JP7730631B2 - Porous organic cages for quantum sieves - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act Science, Vol. 366, Issue 6465, pp. 613-620,AAAS

The present invention relates to a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture. In particular, porous organic cages (POCs) can be used as quantum sieves for mixtures of hydrogen isotopes to selectively sorb heavy hydrogen isotopes (e.g., diatomic deuterium) over lighter isotopes (e.g., diatomic protium).

STATEMENT REGARDING PRIOR DISCLOSURE BY THE INVENTOR OR ANY CO-INVENTORS
Liu M et al., Barely porous organic cages for hydrogen isotope separation. Science. 2019, 366(6465):613-620. doi:10.1126/science.aax7427 is hereby incorporated by reference (including any supplemental material) and is a prior disclosure made by the present inventor or a co-inventor pursuant to AIA 35 U.S.C. 102(b)(1)(A).

Deuterium (D) and tritium (T) are isotopes of hydrogen (H) that could power nuclear fusion reactors and potentially produce clean energy. Deuterium is also a valuable chemical, used, for example, as a moderator, a non-radioactive isotope tracer, and in neutron scattering experiments. These applications require expensive, high-purity deuterium due to its low natural abundance (0.0156 mol%). Therefore, enrichment of deuterium from hydrogen-containing raw materials is an important industrial process. Tritium is typically produced from lithium (by neutron activation of lithium-6 in a nuclear reactor), while _D2 is commonly produced by electrolysis of heavy water and extracted using the Girdler-sulfide process or by cryogenic distillation at 24 K. Both processes are costly and energy-intensive due to the multiple enrichment steps required. An attractive alternative for purifying deuterium from _H2 / _D2 gas mixtures is the selective adsorption of _D2 in a microporous bed. Dynamic quantum sieving (KQS) using nanoporous solids was first proposed by Beenakker et al. The effect of KQS becomes significant when the difference in size between the hydrogen molecule and the confining space is comparable to the thermal de Broglie wavelength of molecular hydrogen. Quantum sieving has been developed for separating gaseous isotope mixtures such as _D2 / _H2 , but identifying suitable porous solids has proven challenging. This is because KQS requires ultrafine pore openings (approximately 3 Å), which typically result in materials with low pore volumes. Therefore, the low _D2 adsorption capacity makes such processes difficult to scale. Similar selectivity/capacity tradeoffs, or in the case of membranes, selectivity/permeance tradeoffs, are observed in the separation of a wide range of other gases that do not involve KQS.

Various porous materials, including carbon, zeolites, metal-organic frameworks (MOFs), covalent organic frameworks (COFs), and 2D crystals, have been investigated for hydrogen isotope separation. MOFs and COFs have attracted increasing attention due to their crystallinity and synthetically tunable pore size and functional groups. However, even with MOFs or COFs, it is difficult to achieve the exceptionally fine pore size required for KQS. For example, in MOFs, a common strategy for tailoring pore openings is by systematically increasing or decreasing the number of phenylene rings in the organic linker, with each individual increase/decrease being approximately 2.8 Å, a coarser size control than required for KQS.

Liu M et al. Barely porous organic cages for hydrogen isotope separation. Science. 2019, 366(6465):613-620. doi:10.1126/science.aax7427 Advanced Organic Chemistry, by Jerry March, 4th edition, Wiley Interscience, pp. 131-133, 1992. "Advanced Organic Chemistry," 4th ed., J. March, John Wiley and Sons, New York, 2001, Chapter 4 Hasell, T., Cooper, A. Porous organic cages: soluble, modular and molecular pores. Nat Rev Mater 1, 16053 (2016). https://doi.org/10.1038/natrevmats.2016.53 www.ccdc.cam.ac.uk/data_request/cif. https://www.cp2k.org/ http://gle4md.org/http://gle4md.org/ M. Ravichandran, P. R. Ramya, S. Sankar Ganesh, K. Ramesh Naidu and M. M. Rajput, “Optimization of Indigenously Developed Column for the Separation and Analysis of All the Six Hydrogen Isotopic Combinations in Elemental form using Gas Chromatograph”, BARC NEWSLETTER, January-February 2016, pp. 23-26, ISSN 0976-2108 K. Kotoh, M. Tanaka, Y. Nakamura, T. Sakamoto, Y. Asakura, T. Uda, and T. Sugiyama, "Experimental Verification of Hydrogen Isotope Separation by Pressure Swing Adsorption," Fusion Science and Technology, Vol. 54, No. 2, 2008, pp. 411-414, https://doi.org/10.13182/FST08-A1842 Jones, J. T., Hasell, T., Wu, X., Bacsa, J., Jelfs, K. E., Schmidtmann, M., Chong, S. Y., Adams, D. J., Trewin, A., Schiffman, F., Cora, F., Slater, B., Steiner, A., Day, G. M., Cooper, A. I. Nature 2011, 474, 367 pages

Accordingly, it is an object of the present invention to address at least one of the problems inherent in the prior art.

Another object of the present invention is to provide alternative solutions to those presented in the prior art, including, for example, providing alternative approaches to facilitate advances in nuclear fusion or other applications where deuterium isotopes play a key role.

Another object of the present invention is to provide materials and/or synthesis methodologies that allow for the provision of precisely the right pore size to achieve highly selective sorption of a particular target substance (e.g., deuterium) over a non-target substance (e.g., hydrogen).

Another object of the present invention is to provide a material that can be fine-tuned to have an ideal pore size for the target substance (preferably a target gas), preferably towards the end of any synthetic route.

Another object of the present invention is to provide a material that is easy to manufacture.

Another object of the present invention is to provide a material that is easy to process and/or handle, for example, by being sufficiently soluble to allow for convenient handling in a plant (including bulk transfer).

Another object of the present invention is to provide a material that can be produced efficiently and with high yields.

Another object of the present invention is to provide a highly pure target substance, such as highly pure deuterium.

Another object of the present invention is to provide a means for recycling exhaust materials from a nuclear fusion reaction.

Another object of the present invention is to provide a material that is not only selective for a target substance, but that is selective without excessive sorption capacity or excessive reduction in target substance uptake.

Another object of the present invention is to address two or more, preferably three or more, of the aforementioned objectives.

One or more objects of the present invention define certain aspects of the present invention and are addressed by the solutions outlined below. It is recognized that specific embodiments of such aspects described elsewhere in this specification may equally be redefined as aspects of the present invention.

Methods for Preferential Sorption According to an aspect of the present invention, there is provided a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture comprising, consisting essentially of, or consisting of target substances and non-target substances, the method comprising contacting the target mixture with a sorption composition comprising, consisting essentially of, or consisting of a sorption compound.

According to an aspect of the present invention, there is provided a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture comprising, consisting essentially of, or consisting of target substances and non-target substances, the method comprising contacting the target mixture with a sorption composition comprising, consisting essentially of, or consisting of a sorption compound and a co-crystallized compound.

According to an aspect of the present invention, there is provided a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture comprising, consisting essentially of, or consisting of target substances and non-target substances, the method comprising contacting the target mixture with a sorption device containing a sorption composition comprising, consisting essentially of, or consisting of a sorption compound.

According to an aspect of the present invention, there is provided a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture comprising, consisting essentially of, or consisting of target substances and non-target substances, the method comprising contacting the target mixture with a sorption device containing a sorption composition comprising, consisting essentially of, or consisting of a sorption compound and a co-crystallized compound.

The foregoing methods, and any related methods described below, may be used in methods for producing, extracting, purifying, separating, or removing either target and/or non-target substances. Accordingly, the following further aspects of the invention arise:

Methods for Production, Extraction, Purification, Separation, and Removal According to aspects of the present invention, there are provided methods for producing, extracting, or purifying one or more target substances, comprising performing a preferential sorption method as defined herein. Such methods may include, for example, removing the non-target substances by separating the sorption composition from the non-target substances after sorption of the target substances in the sorption composition. Such methods may include, for example, recovering, extracting, or isolating the target substances from the sorption composition by desorbing the target substances from the sorption composition, most preferably after removal of the non-target substances.

Aspects of the present invention provide methods for producing, extracting, or purifying one or more non-target substances, the methods comprising performing a preferential sorption method as defined herein. Such methods may include separating the sorption composition with the target substances sorbed thereto from the non-target substances, e.g., by removing the sorption composition by contact with the non-target substances. The methods may include repeating the preferential sorption method and, optionally, one or more additional method steps (e.g., separating the sorption composition from the non-target substances). In this method, preferably, the "target substances" are indeed selectively removed from a target mixture comprising, consisting essentially of, or consisting of the target substances and non-target substances.

According to an aspect of the present invention, there is provided a method for removing one or more target substances from a target mixture comprising, consisting essentially of, or consisting of the target substances and one or more non-target substances, comprising performing a preferential sorption method as defined herein. Such a method may be performed repeatedly to maximize removal of the target substances. Such a method is particularly useful, for example, when it is desired to remove radioactive tritium from radioactively contaminated water, preferably by subjecting the water to electrolysis to produce gaseous hydrogen isotopes, which are then subjected to the method. Accordingly, another aspect of the present invention provides a method for removing tritium from radioactively contaminated water, comprising subjecting the electrolyzed water to the aforementioned removal method.

According to an aspect of the present invention, there is provided a method for separating one or more target substances from one or more non-target substances, the method comprising performing a preferential sorption method as defined herein. Such a method may suitably include separating the treated target mixture from the sorption composition with the target substances sorbed to the sorption composition. Such a method may most preferably include, after removal of the non-target substances, recovering, extracting, or isolating the target substances from the sorption composition, for example, by desorbing the target substances from the sorption composition. Such a method may include recovering, extracting, or isolating the non-target substances.

According to an aspect of the present invention, there is provided a quantum sieving method comprising selectively sieving one or more target materials over one or more non-target materials from a target mixture comprising, consisting essentially of, or consisting of target materials and non-target materials, the method comprising contacting (or passing) a sorption composition comprising, consisting essentially of, or consisting of a sorption compound and, optionally, a co-crystallized compound with (or through) the target mixture.

Hydrogen Isotope Specific Methods According to aspects of the present invention, there is provided a method for preferentially sorbing one or more target materials over one or more non-target materials from a target mixture comprising, consisting essentially of, or consisting of target materials and non-target materials, the method comprising contacting the target mixture with a sorption composition (or with a sorption device comprising a sorption composition), wherein the sorption composition comprises, consists essentially of, or consists of a sorption compound, and optionally a co-crystallized compound;
the target mixture comprises, consists essentially of, or consists of two or more selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT;
the target substance is selected from the group consisting _of H2, _D2 , _T2 , HD, HT, and DT;
The non-target substance is selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT, provided that the non-target substance excludes the target substance.

According to an aspect of the present invention, there is provided a dynamic quantum sieving (KQS) method, most preferably comprising performing a preferential sorption method as defined herein on a mixture containing two or more hydrogen isotopes.

The target mixture may be or may include products from a nuclear fusion reaction. Thus, the method may be a method of recycling fusion exhaust, as the extract of deuterium and/or tritium-containing molecules may then be reused as input to the fusion process via the methods described above.

Methods Applied to Nuclear Fusion According to an aspect of the present invention, there is provided a method for performing nuclear fusion, comprising obtaining at least one fusion input material by performing one of the methods of the present invention (preferably by isolating one or more target materials or one or more non-target materials obtained therefrom, preferably one or more target materials, preferably deuterium and optionally also tritium), and optionally obtaining one or more further fusion input materials (e.g., tritium, optionally obtainable via an alternative method to that of the present invention), and performing nuclear fusion using the at least one fusion input material, optionally together with the one or more further fusion input materials. Optionally, particularly when performing nuclear fusion using recycled exhaust material, the at least one fusion input material is obtained, for example, by performing one of the methods of the present invention on fusion exhaust material containing two or _more hydrogen species, preferably selected from the group consisting of H2, _D2 , _T2 , HD, HT, and DT. The exhaust material may further comprise helium.

Compounds According to an aspect of the present invention, there is provided a sorption compound, which is preferably a porous organic cage.

According to an aspect of the present invention, a method for producing a sorption compound is provided.

According to an aspect of the present invention, a co-crystallized compound is provided. The co-crystallized compound is preferably a porous organic cage.

Co-crystals are provided according to an embodiment of the present invention. The co-crystals suitably comprise or consist of both a sorption compound and a co-crystallized compound. Preferably, the sorption compound is a separate and distinct compound or molecule from the co-crystallized compound. However, it is envisioned that the co-crystals may comprise covalently bound sorption-co-crystallized compounds, including a sorption compound (or a derivative thereof) covalently bound to a co-crystallized compound (or a derivative thereof).

Preferably, both the sorption compound and the co-crystallized compound are porous, with the co-crystallized compound having larger pores than the sorption compound. Preferably, the sorption compound and the co-crystallized compound co-crystallize.

According to an aspect of the present invention, there is provided a method for producing a co-crystal. The method preferably comprises co-crystallizing a sorption compound and a co-crystallization compound.

Compositions According to aspects of the present invention, there is provided a sorption composition comprising a sorption compound. The sorption composition, in some embodiments, can consist of or consist essentially of the sorption compound.

According to aspects of the present invention, a sorption composition is provided that includes a sorption compound and a co-crystallized compound. In some embodiments, the sorption composition can consist of, or consist essentially of, the sorption compound and the co-crystallized compound.

According to an aspect of the present invention, a cocrystal composition is provided. The cocrystal composition preferably comprises or consists of a cocrystal as defined herein. The sorption composition may be a cocrystal composition.

Sorption Devices According to aspects of the present invention, there is provided a sorption device comprising a sorption composition (or co-crystal composition) as defined herein. The sorption device can be a filtration or scrubbing device. The sorption device can be a cartridge comprising the sorption composition or the co-crystal composition. The sorption device can be incorporated into a larger apparatus. The sorption device can be a cartridge or column comprising the sorption composition (preferably in compacted form). The sorption device can be a membrane or film comprising or consisting of the sorption composition.

According to an aspect of the present invention, there is provided a dynamic quantum sieve (KQS) comprising a sorption composition defined herein.

Method for Fine-Tuning Sorption Compounds for a Target Gas According to an aspect of the present invention, there is provided a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture comprising, consisting essentially of, or consisting of target substances and non-target substances, the method comprising:
A method is provided that includes preparing a pre-functionalized sorption compound, wherein the sorption compound is a porous organic cage comprising an interior cavity with one or more functionalizable groups; optionally protecting some, but not all, of the functionalizable groups in the interior cavity with protecting groups, functionalizing one or more unprotected functionalizable groups, deprotecting the protected functionalizable groups with protecting groups, and optionally thereafter chemically modifying (post-functionalizing) the interior cavity of the sorption compound by further functionalizing one or more unprotected functionalizable groups; and contacting the sorption composition (or a device comprising the sorption composition) with a target mixture, wherein the sorption composition comprises, consists essentially of, or consists of the sorption compound, and optionally a co-crystallization compound.

Other Aspects and Features According to aspects of the present invention, there is provided a sorption compound, co-crystallized compound, sorption composition, co-crystal, co-crystal composition, or sorption device for use in a dynamic quantum sieve.

A feature, including an optional, preferred, and preferred feature, described in connection with one particular aspect of the invention may also be a feature, including an optional, preferred, and preferred feature, of any other aspect of the invention, except where incompatible.

For a better understanding of the present invention and to show how embodiments thereof may be carried into effect, reference will now be made, by way of example, to the following schematic drawings:

Figure 1 shows a dynamic quantum sieve using ultrasmall-pore organic cages. (A) Scheme illustrating the protection-functionalization-deprotection strategy for modifying the interior cage cavity. (B) Complete synthetic route for the modified cage corresponding to the scheme in A. FT, AT, ET, and PT represent products in which the diamine group is linked to formaldehyde, acetone, ethanal (acetaldehyde), and propionaldehyde, respectively. x and y represent different possible linking groups (x = E, F and y = A, E, P). (C) Representative single crystal structures of modified cages showing the available cavity (colored) along with the calculated pore limit envelope for each system. (D) Summary of gas adsorption for different gases (histogram, left axis) and the cage cavity volume (right axis) of a single modified cage, calculated by VOIDOO based on the crystal structure and probe radius = 2.0 Å (30).

Figure 2 shows dynamic quantum sieves using ultrasmall-pore organic cages. (A) Pore confinement envelope for 6ET-RCC3. The image (inset) shows the single-crystal structure of 6ET-RCC3 with the available cage cavity (colored). (B) Hydrogen adsorption (filled) and desorption (open) isotherms for 6ET-RCC3 at different temperatures. (C) Temperature-programmed desorption spectra (TDS) of 6ET-RCC3 obtained after exposure to a 10 mbar 1:1 _D2 / _H2 isotope mixture for a fixed exposure time (t _exp ) of 30 min at different exposure temperatures. Desorption spectra after evacuation at the exposure temperature were measured at a heating rate of 0.1 K/s. (D) _D2 / _H2 selectivity and gas uptake as a function of exposure time at 30 K for CC3, 6FT-RCC3, and 6ET-RCC3.

Figure 3 shows the formation of a cocrystal that improves _D2 / _H2 separation performance. (A) Left: Scheme showing the cocrystal Cocryst1, formed through chiral recognition between two cages to combine capacity and selectivity in a single material. Center: Simplified representation of the crystal structure of Cocryst1, with the pore channels shown in yellow. Right: Single crystal structure of Cocryst1. (B) _H2 and _D2 adsorption (filled) and desorption (open) isotherms for Cocryst1 at different temperatures. (C) _D2 / _H2 isotherm ratio as a function of pressure at different temperatures. (D) TDS for Cocryst1 obtained after exposure to a 10 mbar 1:1 _H2 / _D2 isotope mixture at different exposure temperatures (T _exp ) and for a fixed exposure time (t _exp ) of 30 min. (E) D ₂ /H ₂ selectivity as a function of t _exp at 30 K (red), 40 K (blue), and 50 K (green). (F) TDS on Cocryst1 obtained after exposure to 10 mbar 1:1 H ₂ /D ₂ isotope mixture for different exposure times at 30 K. (G) Equivalents of adsorbed H ₂ (black), D ₂ (red), and selectivity (blue) as a function of t _exp at 30 K.

Figure 4 shows a summary of hydrogen isotope KQS selectivity and adsorption capacity for various porous materials. The list includes carbon (Takeda 3A (40)), MOFs (MFU-4 (18, 40), MOF-5 (40), IFP (41)), COFs (Py@COF-1 (42)), zeolite 5A (16), and porous organic cages (CC3, 6FT-CC3, 6ET-CC3, Cocryst1). The utility of KQS adsorbents lies in the combination of selectivity and capacity, and based on this, cage cocrystals show the most promising performance here.

Figure 5 shows simulations that provide insight into the mechanism of hydrogen isotope separation by porous organic cages. Simulated free energy profiles (A–C) of a single _H2 or _D2 molecule diffusing between the centers of mass of two adjacent cage molecules for 6ET-RCC3 (A), Cocryst1 (B), and CC3 (C), respectively. The free energy profiles were calculated for the diffusion path using the respective crystal structures. Only the two relevant cage molecules involved are shown here. In A, the diffusion path passes through a 6ET-RCC3 cage window with two methyl groups (left cage) and a second 6ET-RCC3 cage window with one methyl group (right cage); in B, the diffusion path passes through a 6ET-RCC3 cage window with one methyl group (left cage) and the adjacent CC3 cage window (right cage). Gray, white, and blue atoms represent carbon, hydrogen, and nitrogen, respectively. The pore space inside the cage molecule is defined by a spherical probe with a diameter of 2.2 Å and colored red. Predicted competitive adsorption of an equimolar H2/D2 mixture (D–F). PIMD simulations (G–I) predict _D2 / _H2 selectivity and gas diffusion in a single, isolated 6ET-RCC3 cage (see Computational Methods below for simulation details). (G) Transition state for transport of quantum _H2 molecules. A single snapshot with an overlay of all 32 replicas in the PIMD simulation is shown, illustrating nuclear quantum fluctuations. Added semitransparent red dots depict fluctuations in _H2 molecule transport obtained from 100 transition state configurations. (H) Relative population of _D2 over _H2 inside the cage versus that in the gas phase as a function of temperature, compared to the observed experimental _D2 / _H2 selectivity. (I) Free energy profile for a single molecule of quantum H ₂ (black) or quantum D ₂ (red) diffusing through a window of isolated 6ET-RCC3 molecules at 50 K. Definitions of the errors in H and I are given in the Computational Methods section subtitled "Path-integral molecular dynamics simulations and free energy calculations."

Figure 6 shows the predicted D2/H2 selectivity calculated using competitive adsorption simulations of equimolar D2/H2 mixtures for 6ET-RCC3 (A), Cocryst1 (B), and CC3 (C) (A to C). Similarly, five independent simulations were performed to predict the average uptake and determine the error bars.

Scheme showing the protection-functionalization-deprotection strategy for modifying the interior cage cavity. Complete synthetic route of the modified cages corresponding to the scheme in A. FT, AT, ET, and PT represent products in which the diamine group is linked to formaldehyde, acetone, ethanal (acetaldehyde), and propionaldehyde, and x and y represent the different possible linking groups (x = E, F and y = A, E, P). Representative single crystal structures of the modified cages showing the available cavities (colored) along with the pore limiting envelope calculated for each system. Summary of gas adsorption for different gases (histogram, left axis) and cage cavity volume (right axis) of a single modified cage, calculated by VOIDOO based on the crystal structure, probe radius = 2.0 Å (30). Confinement envelope of the pore in 6ET-RCC3. The image (inset) shows the single crystal structure of 6ET-RCC3 with the available cage cavity (colored). Hydrogen adsorption (solid) and desorption (open) isotherms of 6ET-RCC3 at different temperatures. Temperature-programmed desorption spectra (TDS) of 6ET-RCC3 obtained after exposure to a 10 mbar 1:1 _D2 / _H2 isotope mixture for a fixed exposure time (t _exp ) of 30 min at different exposure temperatures. Desorption spectra after ejection at the exposure temperature were measured at a heating rate of 0.1 K/s. D ₂ /H ₂ selectivity and gas uptake as a function of exposure time at 30 K for CC3, 6FT-RCC3 and 6ET-RCC3. Left: Scheme showing the cocrystal Cocryst1 formed through chiral recognition between two cages, combining capacity and selectivity in a single material. Center: Simplified representation of the crystal structure of Cocryst1 with the pore channel shown in yellow. Right: Single crystal structure of Cocryst1. Adsorption (filled) and desorption (open) isotherms of _H2 and _D2 for Cocryst1 at different temperatures. D ₂ /H ₂ isotherm ratio as a function of pressure at different temperatures. TDS for Cocryst1 obtained after exposure to 10 mbar 1:1 _H2 / _D2 isotope mixture at different exposure temperatures ( _Texp ) and for a fixed exposure time ( _texp ) of 30 min. _D2 / _H2 selectivity as a function of t _exp at 30K (red), 40K (blue) and 50K (green). TDS in Cocryst1 obtained after exposure to 10 mbar 1:1 H ₂ /D ₂ isotope mixture at 30 K for different exposure times. Equivalent adsorbed H ₂ (black), D ₂ (red), and selectivity (blue) as a function of t _exp at 30 K. Figure 1 shows a summary of hydrogen isotope KQS selectivity and adsorption capacity for various porous materials. The list includes carbon (Takeda 3A (40)), MOFs (MFU-4 (18, 40), MOF-5 (40), IFP (41)), COFs (Py@COF-1 (42)), zeolite 5A (16), and porous organic cages (CC3, 6FT-CC3, 6ET-CC3, Cocryst1). The utility of KQS adsorbents lies in the combination of selectivity and capacity, and based on this, the cage cocrystals show the most promising performance here. Simulated free energy profile of a single H ₂ or D ₂ molecule diffused between the centers of mass of two adjacent cage molecules in 6ET-RCC3(A). Simulated free energy profile of a single _H2 or _D2 molecule diffused between the centers of mass of two adjacent cage molecules in Cocryst1 (B). In CC3(C), simulated free energy profiles of a single H ₂ or D ₂ molecule diffused between the centers of mass of two adjacent cage molecules. Predicted competitive adsorption of equimolar H2/D2 mixtures. Predicted competitive adsorption of equimolar H2/D2 mixtures. Predicted competitive adsorption of equimolar H2/D2 mixtures. Transition state for transport of quantum _H2 molecules. Relative population of D ₂ over H ₂ inside the cage versus that in the gas phase as a function of temperature compared to the observed experimental D ₂ /H ₂ selectivity. Free energy profile for a single molecule of quantum H ₂ (black) or quantum D ₂ (red) diffusing through the window of an isolated 6ET-RCC3 molecule at 50K. Figure 1 shows the predicted D2/H2 selectivity calculated using competitive adsorption simulations of equimolar D2/H2 mixtures on 6ET-RCC3. Predicted D2/H2 selectivities calculated using competitive adsorption simulations of equimolar D2/H2 mixtures on Cocryst1 are shown. The predicted D2/H2 selectivity calculated using competitive adsorption simulations of equimolar D2/H2 mixtures is shown for CC3.

DEFINITIONS Unless otherwise specified, the following terms used in the specification and claims have the following meanings, as specified below.

Unless otherwise specified, the following terms used in this specification and claims have the following meanings as specified below.

Throughout the description and claims of this specification, the words "comprise" and "contain" and variations thereof mean "including, but not limited to," and are not intended to (and do not) exclude other moieties, additives, ingredients, integers, or steps. Throughout the description and claims of this specification, the singular includes the plural unless the context otherwise requires. In particular, when the indefinite article is used, the specification should be understood to contemplate the plural as well as the singular unless the context otherwise requires.

Any feature, integer, property, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the invention is to be understood as applicable to any other aspect, embodiment, or example described herein, except where inconsistent. All features disclosed in this specification (including any accompanying claims, abstract, and drawings), and/or all steps of any method or process so disclosed, may be combined in any combination, except where at least some of such features and/or steps are mutually exclusive. The invention is not limited to the details of any of the foregoing embodiments. The invention extends to any novel single feature, or any novel combination of features, or any novel combination of method or process steps so disclosed, disclosed in this specification (including any accompanying claims, abstract, and drawings).

The reader is directed to all articles and documents related to this application, filed contemporaneously with or prior to this application, and open to public inspection herewith, the contents of all such articles and documents being incorporated herein by reference.

For the avoidance of doubt, it is hereby stated that the information previously disclosed herein under the heading "Background Art" is relevant to the present invention and should be read as part of this disclosure of the present invention.

Unless otherwise specified, any reference herein to an "average" value is intended to relate to the mean value.

When a composition is said to contain multiple specified ingredients (optionally in specified amounts and concentrations), the composition may optionally contain additional ingredients other than those specified. However, in some embodiments, a composition said to contain multiple specified ingredients may actually consist essentially of, or consist of, all of the specified ingredients.

As used herein, when a composition is said to "consist essentially of" a particular component, the composition preferably comprises at least 70 wt% of that component, preferably at least 90 wt% of it, preferably at least 95 wt% of it, and most preferably at least 99 wt% of it. Preferably, a composition said to "consist essentially of" a particular component consists of that component, excluding one or more trace impurities.

When the amount or concentration of a particular component of a composition is specified as a weight percentage (wt% or % w/w), the weight percentage refers to the weight percentage of that component compared to the total weight of the entire composition. It will be understood by those skilled in the art that the total weight percentages of all components of a composition add up to 100 wt%. However, if not all components are listed (e.g., if a composition is said to "comprise" one or more specific components), the balance of the weight percentage can optionally be made up to 100 wt% by unspecified ingredients (e.g., diluents, e.g., water, or other optional but suitable additives). Most preferably, the total weight percentages of the specified components does not exceed 100 wt%, and any resulting wt% combinations are excluded by definition.

The term "substantially free," when used in reference to a component of a composition (e.g., "a composition substantially free of compound X"), refers to a composition to which essentially no such component has been added. When a composition is "substantially free" of a component, the composition preferably contains no more than 0.001 wt% of the component, preferably no more than 0.0001 wt% of the component, preferably no more than 0.00001 wt%, preferably no more than 0.000001 wt%, preferably no more than 0.0000001 wt%, and most preferably no more than 0.0001 parts per billion (by mass) of the component.

The term "completely free," when used in reference to a component of a composition (e.g., "a composition completely free of compound X"), refers to a composition that is free of said component.

Preferably, unless otherwise specified, when a parameter (e.g., pH, pKa, size) or state (e.g., liquid, gas) of a material that may be affected by pressure and/or temperature is referred to, such reference preferably refers to said parameter at standard room temperature and pressure (SATP) without further specification. SATP is a temperature of 298.15 K (25°C, 77°F) and an absolute pressure of 100 kPa (14.504 psi, 0.987 atm).

In this specification, all chemical names may be defined according to IUPAC definitions unless otherwise specified.

As used herein, the term "hydrocarbon" is well understood in the art and refers to compounds containing only carbon and hydrogen. The term "hydrocarbyl" generally refers to any aliphatic, acyclic, or cyclic (including aryl) hydrocarbon group, preferably without heteroatoms. Such compounds include, among others, alkanes, alkenes, alkynes, arenes, and their cyclic counterparts. The term "hydrocarbon" includes anthracene, naphthalene, benzene, and/or their derivatives (e.g., toluene).

As used herein, the terms "carbocyclyl," "carbocycle," or "carbocyclic" generally refer to the radical of a non-aromatic cyclic hydrocarbon group having 3 to 10 ring carbon atoms (i.e., (3-10C) carbocyclyl) in a non-aromatic ring system and zero heteroatoms. Suitable carbocyclyl groups include (3-nC) cycloalkyl and (3-nC) cycloalkenyl. Exemplary embodiments include cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptenyl, cycloheptadienyl, cycloheptatrienyl, cyclooctyl, cyclooctenyl, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octanyl, and the like.

As used herein, the terms "macrocyclyl," "macrocycle," or "macrocyclic" refer to macrocyclic rings known in the art. Such macrocyclic rings are preferably cyclic polymers or polymeric cyclic portions of molecules. Preferably, macrocyclic rings have 9 or more atoms in the ring. Preferably, macrocyclic rings have 3 or more internal electron pair donor atoms. Preferably, macrocyclic rings are cyclic molecules that can coordinate to a central metal species (e.g., Mg2+). Examples include porphyrins.

As used herein, the term "carbohydrate" is well understood in the art and refers to compounds containing only carbon, hydrogen, and oxygen. Such compounds include esters, ketones, aldehydes, sugars, and the like.

As used herein, the term "alkyl" includes both straight-chain and branched-chain alkyl groups. References to individual alkyl groups, such as "propyl," are specific for the straight-chain version only, and references to individual branched-chain alkyl groups, such as "isopropyl," are specific for the branched-chain version only. For example, "(1-6C)alkyl" includes (1-4C)alkyl, (1-3C)alkyl, propyl, isopropyl, and t-butyl. A similar convention applies to other groups, for example, "phenyl(1-6C)alkyl" includes phenyl(1-4C)alkyl, benzyl, 1-phenylethyl, and 2-phenylethyl.

The term "(m-nC)" or "(m-nC) group" used alone or as a prefix refers to any group having m to n carbon atoms.

An "alkylene," "alkenylene," or "alkynylene" group is an alkyl, alkenyl, or alkynyl group that is positioned between and serves to connect two other chemical groups. Thus, "(1-6C)alkylene" means a linear saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms, e.g., methylene, ethylene, propylene, 2-methylpropylene, pentylene.

"(2-6C)alkenylene" means a linear divalent hydrocarbon group of 2 to 6 carbon atoms containing at least one double bond, or a branched divalent hydrocarbon group of 3 to 6 carbon atoms, e.g., ethenylene, 2,4-pentadienylene.

"(2-6C)alkynylene" means a linear divalent hydrocarbon radical of 2 to 6 carbon atoms or a branched divalent hydrocarbon radical of 3 to 6 carbon atoms containing at least one triple bond, e.g., ethynylene, propynylene, and butynylene.

"(3-8C)cycloalkyl" means a hydrocarbon ring containing 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or bicyclo[2.2.1]heptyl.

"(3-8C)Cycloalkenyl" means a hydrocarbon ring containing at least one double bond, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, or cycloheptenyl, e.g., 3-cyclohexen-1-yl or cyclooctenyl.

"(3-8C)cycloalkyl-(1-6C)alkylene" means a (3-8C)cycloalkyl group covalently attached to a (1-6C)alkylene group, both of which are defined herein.

The term "halo" refers to fluoro, chloro, bromo, and iodo.

The terms "heterocyclyl,""heterocyclic," or "heterocycle" refer to non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic heterocyclic ring systems. The term heterocyclyl includes both monovalent and divalent species. Monocyclic heterocyclic rings contain about 3 to 12 (preferably 3 to 7) ring atoms and 1 to 5 (preferably 1, 2, or 3) heteroatoms selected from nitrogen, oxygen, or sulfur in the ring. Bicyclic heterocycles contain 7 to 17 member atoms, preferably 7 to 12 member atoms, in the ring. Bicyclic heterocycles contain about 7 to about 17 ring atoms, preferably 7 to 12 ring atoms. Bicyclic heterocyclic rings can be fused, spiro, or bridged ring systems. Examples of heterocyclic groups include cyclic ethers, such as oxiranyl, oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers. Nitrogen-containing heterocycles include, for example, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, and tetrahydropyrazolyl. Typical sulfur-containing heterocycles include tetrahydrothienyl, dihydro-1,3-dithiol, tetrahydro-2H-thiopyran, and hexahydrothiepin. Other heterocycles include dihydrooxathiolyl, tetrahydrooxazolyl, tetrahydrooxadiazolyl, tetrahydrodioxazolyl, tetrahydrooxathiazolyl, hexahydrotriazinyl, tetrahydrooxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl, octahydrobenzimidazolyl, and octahydrobenzothiazolyl. Sulfur-containing heterocycles also include oxidized sulfur heterocycles containing SO or SO groups. Examples include the sulfoxide and sulfone forms of tetrahydrothienyl and thiomorpholinyl, such as tetrahydrothienyl 1,1-dioxide and thiomorpholinyl 1,1-dioxide. Suitable values of heterocyclyl groups bearing one or two oxo (=O) or thioxo (=S) substituents are, for example, 2-oxopyrrolidinyl, 2-thioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidinyl, 2-oxopiperidinyl, 2,5-dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl or 2,6-dioxopiperidinyl. Particular heterocyclyl groups are saturated monocyclic 3- to 7-membered heterocyclyls containing 1, 2, or 3 heteroatoms selected from nitrogen, oxygen, or sulfur, such as azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl 1,1-dioxide, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, piperidinyl, homopiperidinyl, piperazinyl, or homopiperazinyl. As those skilled in the art will recognize, any heterocycle can be linked to another group via any suitable atom, for example, via a carbon or nitrogen atom. However, reference herein to piperidino or morpholino refers to a piperidin-1-yl or morpholin-4-yl ring linked via the ring nitrogen.

"Bridged ring system" means a ring system in which two rings share more than two atoms; see, for example, Advanced Organic Chemistry, Jerry March, 4th Edition, Wiley Interscience, pp. 131-133, 1992. Examples of bridged heterocyclyl ring systems include aza-bicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, aza-bicyclo[2.2.2]octane, aza-bicyclo[3.2.1]octane, and quinuclidine.

"Heterocyclyl(1-6C)alkyl" means a heterocyclyl group covalently attached to a (1-6C)alkylene group, both of which are defined herein.

The term "heteroaryl" or "heteroaromatic" refers to an aromatic mono-, bi-, or polycyclic ring incorporating one or more (e.g., 1 to 4, particularly 1, 2, or 3) heteroatoms selected from nitrogen, oxygen, or sulfur. The term heteroaryl includes both monovalent and divalent species. Examples of heteroaryl groups are monocyclic and bicyclic groups containing 5 to 12 ring members, more typically 5 to 10 ring members. A heteroaryl group can be, for example, a 5- or 6-membered monocyclic ring, or a 9- or 10-membered bicyclic ring, e.g., fused 5- and 6-membered rings, or a bicyclic structure formed from two fused 6-membered rings. Each ring can contain up to about four heteroatoms, typically selected from nitrogen, sulfur, and oxygen. Typically, a heteroaryl ring contains up to three heteroatoms, more typically up to two, e.g., a single heteroatom. In one embodiment, a heteroaryl ring contains at least one ring nitrogen atom. The nitrogen atoms in the heteroaryl ring can be basic, as in the case of imidazole or pyridine, or essentially non-basic, as in the case of indole or pyrrole nitrogens. Generally, the number of basic nitrogen atoms present in a heteroaryl group, including any amino group substituents on the ring, is less than five.

Examples of heteroaryl include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazenyl, benzofuranyl, indolyl, isoindolyl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, and isoquinoline. These include aryl, quinazolinyl, quinoxalinyl, cinnolinyl, pteridinyl, naphthyridinyl, carbazolyl, phenazinyl, benzisoquinolinyl, pyridopyrazinyl, thieno[2,3-b]furanyl, 2H-furo[3,2-b]-pyranyl, 5H-pyrido[2,3-d]-o-oxazinyl, 1H-pyrazolo[4,3-d]-oxazolyl, 4H-imidazo[4,5-d]thiazolyl, pyrazino[2,3-d]pyridazinyl, imidazo[2,1-b]thiazolyl, and imidazo[1,2-b][1,2,4]triazinyl. "Heteroaryl" also covers partially aromatic bi- or polycyclic ring systems in which at least one ring is aromatic and one or more of the other rings are non-aromatic, saturated or partially saturated, provided that at least one ring contains one or more heteroatoms selected from nitrogen, oxygen or sulfur. Examples of partially aromatic heteroaryl groups include, for example, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, dihydrobenzthienyl, dihydrobenzfuranyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,3]dioxolyl, 2,2-dioxo-1,3-dihydro-2-benzothienyl, 4,5,6,7-tetrahydrobenzofuranyl, indolinyl, 1,2,3,4-tetrahydro-1,8-naphthyridinyl, 1,2,3,4-tetrahydropyrido[2,3-b]pyrazinyl, and 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazinyl.

Examples of 5-membered heteroaryl groups include, but are not limited to, pyrrolyl, furanyl, thienyl, imidazolyl, furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, and tetrazolyl groups.

Examples of 6-membered heteroaryl groups include, but are not limited to, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, and triazinyl.

Bicyclic heteroaryl groups include, for example:
a) a benzene ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms;
b) a pyridine ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms;
c) a pyrimidine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
d) a pyrrole ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms;
e) a pyrazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
f) a pyrazine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
g) an imidazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
h) an oxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
i) an isoxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
j) a thiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
k) an isothiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;
l) a thiophene ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms;
m) a furan ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms;
n) a cyclohexyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2, or 3 ring heteroatoms, and
o) a group selected from a cyclopentyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2, or 3 ring heteroatoms.

Specific examples of bicyclic heteroaryl groups containing a 6-membered ring fused to a 5-membered ring include, but are not limited to, benzfuranyl, benzthiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzisothiazolyl, isobenzofuranyl, indolyl, isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g., adeninyl, guaninyl), indazolyl, benzodioxolyl, and pyrazolopyridinyl groups.

Specific examples of bicyclic heteroaryl groups containing two fused 6-membered rings include, but are not limited to, quinolinyl, isoquinolinyl, chromanyl, thiochromanyl, chromenyl, isochromenyl, chromanyl, isochromanyl, benzodioxanyl, quinolidinyl, benzoxazinyl, benzodiazinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl, and pteridinyl groups.

"Heteroaryl(1-6C)alkyl" means a heteroaryl group covalently attached to a (1-6C)alkylene group, both of which are defined herein. Examples of heteroaralkyl groups include pyridin-3-ylmethyl, 3-(benzofuran-2-yl)propyl, and the like.

The term "aryl" means a cyclic or polycyclic aromatic ring having 5 to 12 carbon atoms. The term aryl includes both monovalent and divalent species. Examples of aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, and the like. In certain embodiments, aryl is phenyl.

The term "aryl(1-6C)alkyl" means an aryl group covalently attached to a (1-6C)alkylene group, both of which are defined herein. Examples of aryl-(1-6C)alkyl groups include benzyl, phenylethyl, and the like.

This specification also uses some compound terms to describe groups containing more than one functional group. Such terms are understood by those of ordinary skill in the art. For example, heterocyclyl(m-nC)alkyl includes (m-nC)alkyl substituted with heterocyclyl.

Whenever groups having large carbon chains (e.g., (1-12C) alkyl, (1-8C) alkenyl) are disclosed, such groups can optionally be shortened, for example to contain between 1 and 5 carbons (e.g., (1-5C) alkyl or (1-5C) alkenyl), or between 1 and 3 carbons (e.g., (1-3C) alkyl or (1-3C) alkenyl instead of (1-12C) alkyl or (1-8C) alkenyl).

The term "optionally substituted" refers to groups, structures, or molecules that are either substituted or unsubstituted.

When optional substituents are selected from "one or more" groups, it should be understood that this definition includes all substituents selected from one particular group, or substituents selected from two or more particular groups.

The phrase "compounds of the invention" means the compounds disclosed herein, both generically and specifically.

Compounds that have the same molecular formula but differ in the nature or bonding sequence of their atoms or in the arrangement of their atoms in space are called "isomers." Isomers in terms of the arrangement of their atoms in space are called "stereoisomers." Stereoisomers that are not mirror images of one another are called "diastereoisomers," and stereoisomers that are non-superimposable mirror images of one another are called "enantiomers." When a compound has an asymmetric center—for example, a compound bonded to four different groups—a pair of enantiomers can occur. Enantiomers are characterized by the absolute configuration of the asymmetric center and are described by the R- and S-sequencing rules of Cahn and Prelog, or by the way the molecule rotates the plane of polarized light and designating it as dextrorotatory or levorotatory (i.e., as (+)- or (-)-isomers, respectively). Chiral compounds can exist as either individual enantiomers or mixtures thereof. A mixture containing equal proportions of enantiomers is called a "racemic mixture."

The compounds of the present invention may possess one or more asymmetric centers, and such compounds can therefore be produced as individual (R)- or (S)-stereoisomers, or as mixtures thereof. Unless otherwise indicated, the description or designation of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise. Methods for determining stereochemistry and separating stereoisomers are well known in the art (see the discussion in Chapter 4 of "Advanced Organic Chemistry," 4th Edition, J. March, John Wiley and Sons, New York, 2001), for example, by synthesis from optically active starting materials or by resolution of a racemate. Some of the compounds of the present invention may possess geometric isomeric centers (E- and Z-isomers). It should be understood that the present invention encompasses all optical, diastereomeric, and geometric isomers, and mixtures thereof, that possess telomerase inhibitory activity.

The present invention also encompasses compounds of the present invention as defined herein that contain one or more isotopic substitutions. For example, H can be in any isotopic form, including 1H, 2H (D), and 3H (T); C can be in any isotopic form, including 12C, 13C, and 14C; and O can be in any isotopic form, including 160 and 180.

It should also be understood that certain compounds of Formula I may exhibit polymorphism, and that the present invention encompasses all such forms.

Compounds may exist in several different tautomeric forms, and a reference to a compound includes all such forms. For the avoidance of doubt, where a compound may exist in one of several tautomeric forms and only one is specifically described or shown, all others are nevertheless encompassed within the definition of the compound. Examples of tautomeric forms include, for example, the following tautomeric pairs: keto-, enol-, and enolate forms, keto/enol (illustrated below), imine/enamine, amide/iminoalcohol, amidine/amidine, nitroso/oxime, thioketone/enethiol, and nitro/aci-nitro.

Any unqualified reference herein to "hydrogen" refers to protium unless the context indicates otherwise. Any unqualified reference herein to "deuterium" refers to deuterium and/or tritium, but most preferably to deuterium.

Where the context dictates herein (e.g., in the methods of the present invention), references to hydrogen, protium, deuterium, and tritium without limitation preferably refer to their molecular (or diatomic) forms. The same applies to other elemental gases.

As used herein, the term heteroisotopic diatom may include HD (protium-deuterium), HT (protium-tritium), and/or DT (deuterium-tritium), while an isotopic diatom may include protium ( _H2 , also known as dihydrogen, diatomic hydrogen, or elemental hydrogen), deuterium ( _D2 , also known as dideuterium or diatomic deuterium), and/or tritium ( _T2 , also known as ditritium or diatomic tritium). In some embodiments, where the context allows, particularly as is the case with respect to nuclear fusion, reference to unrestricted deuterium molecules, e.g., deuterium and tritium, may include a heteroisotopic diatom containing a single deuterium or tritium atom.

"De Broglie wavelength" is a well-known term relating to the wavelength properties of matter, typically expressed by the equation λ = h/mv
where λ is the de Broglie wavelength, h is Planck's constant, m is the mass of the particle, and v is the velocity at which the particle is moving. Thus, the de Broglie wavelength is inversely proportional to the momentum of the particle. However, for the present invention, references herein to "de Broglie wavelength" generally refer to the thermal de Broglie wavelength (λ _T or λ _th ), which is approximately equivalent to the average de Broglie wavelength of a gas particle in a perfect gas at a specified temperature. Thus, the thermal de Broglie wavelength (λ _th ) can be calculated as follows:

where h is Planck's constant, m is the mass of the gas particle in question, _kB is Boltzmann's constant, and T is temperature in Kelvin. In terms of units, wavelength is meters (m), mass is kilograms (kg), temperature is Kelvin (K), Planck's constant is 6.62607004× ^10-34 Js (joule-seconds or ^m2 kg/s), and Boltzmann's constant is 1.380649× ^10-23 JK ^-1 (joules per Kelvin or ^m2 kg s ^-2K-1 ).
The following thermal de Broglie wavelengths can be calculated like this:
Diatomic protium (H ₂ ) has a mass of 3.35×10 ⁻²⁷ kg, so its de Broglie wavelength is
○λ _th (at 300 K) = 7.1 × 10 ^-11 , 0.071 nm, 0.7 Å.
○λ _th (at 30 K) = 2.24×10 ⁻¹⁰ , 0.224 nm, 2.24 Å.
○λ _th (at 77K) = 1.4×10 ^-10 , 0.14 nm, 1.4 Å.
Diatomic deuterium (D ₂ ) has a mass of 6.7×10 ⁻²⁷ kg, so its de Broglie wavelength is
○λ _th (at 300 K) = 5.02×10 ⁻¹¹ , 0.05 nm, 0.5 Å.
○λ _th (at 30 K) = 1.59×10 ^-10 , 0.16 nm, 1.6 Å.
○λ _th (at 77 K) = 9.90 × 10 ^-11 , 0.099 nm, 0.99 Å.
Diatomic tritium (T ₂ ) has a mass of 10×10 ^-27 kg, so its de Broglie wavelength is
○λ _th (at 300 K) = 4.11 × 10 ^-11 , 0.04 nm, 0.4 Å.
○λ _th (at 30 K) = 1.3 × 10 ^-10 , 0.13 nm, 1.3 Å.
Quantum-scale features, including the cavities in POCs, can interact with matter with comparable thermal de Broglie wavelengths, so dynamic quantum sieves require ultra-small pore openings (approximately 3 Å).

As used herein, the term "particle size" preferably refers to the length of the longest dimension of a particle. Particle size can be measured using methods well known in the art, including laser particle size analyzers and/or electron microscopes (e.g., transmission electron microscopes, TEM, or scanning electron microscopes, SEM).

As used herein, the terms "pore diameter," "cavity size," or "window size" (e.g., pore/cavity window) preferably refer to the length of the smallest dimension of a pore, cavity, or window, respectively. Pore, cavity, and window sizes can be measured using methods known in the art, including laser particle size analysis and/or electron microscopy (e.g., transmission electron microscopy, TEM, or scanning electron microscopy, SEM), or using crystal structures of otherwise calculated forms. However, pore, cavity, and window sizes can also be determined by single crystal analysis and/or molecular dynamics to obtain, for example, the pore confinement envelope (PLE). Thus, pore diameter (or cavity size) can be the pore confinement envelope (PLE) or the pore confinement diameter (PLD). As used herein, the term "cavity size" or any dimension given in relation to a cavity may optionally refer to the size of a "window" of the cavity, which may be smaller than the size of the cavity (or pore) itself, but most preferably the term "cavity size" relates to the cavity or pore itself, and not to a window. The dimension given in relation to the cavity may be alternatively referred to as "pore diameter."

In this specification, when "PLE" is shown as a particular value, this preferably means the PLE centered around that particular value, since the PLE itself is distributed. Alternatively, the PLE value may instead be the same PLD value (if it is easier to calculate PLD geometrically without requiring molecular dynamics simulations).

The distribution (especially its width) in cavity/pore sizes may vary with temperature (i.e., higher temperatures generally result in wider distributions), but generally the static (i.e., statically calculated) pore size, average pore size, or center of the pore confinement envelope does not vary significantly with temperature (e.g., between the SATP and 30 K), particularly if such pores are "permeable"/flexible. Without any temperature limitations, the cavity or pore size specified herein may therefore refer to said cavity/pore size at either the SATP or the relevant "contact temperature."

The "size" of a substance, whether a single atom (atomic size) or a molecule (molecular size), can be estimated by methods well known in the art. Typically, size refers to the longest single dimension or diameter of the hemisphere (or imaginary hemisphere) that the atom or molecule represents. For a single atom, the van der Waals radius can be used to calculate the corresponding atomic size (i.e., the van der Waals diameter, which is twice the van der Waals radius). For a molecule, such as diatomic hydrogen or any of its isotopic permutations, the size or length can be calculated by reference to the bond distances of each atom forming the molecule and the corresponding van der Waals radii. Alternatively, the size of a molecule can be determined by its van der Waals volume. Unless otherwise specified, such sizes are calculated in SATP.

The solubility of a solute can be defined as follows, where the solvent parts and solute parts are parts by mass:

General Points and Advantages of the Invention The present invention arose from the unexpected discovery that porous organic cages can be modified by interior post-functionalization (i.e., modifying the cavity without modifying the exterior) and still crystallize in an isostructural manner. This opens the possibility, with proper post-functionalization (i.e., functionalizing the cavity after the essential framework of the molecule has essentially been assembled), to fine-tune the interior cavity size (and therefore the pore diameter, or the size of the pore window) to obtain potentially valuable interconnected pore networks without weakening the established crystal structure, optionally via a protection-deprotection strategy. The inventors subsequently discovered that the highly advantageous porous organic cages in so many respects can be fine-tuned to obtain pore diameters small enough to potentially enable dynamic quantum sieving of gaseous targets. The inventors then showed that the porous organic cages can be tailored to selectively separate deuterium and hydrogen, thereby paving the way to high-purity deuterium. From such an achievement, it seems plausible to selectively extract tritium or other hydrogen isotopes, including mixed diatomics such as protium-deuterium (HD), protium-tritium (HT), and deuterium-tritium (DT), from mixtures that may further contain helium and/or other by-products, including, for example, fusion emissions.

The present invention therefore solves the problems inherent in the prior art.

The present invention provides a valuable alternative material that, among other things, will substantially and commercially increase the future viability of nuclear fusion.

The present invention allows for easy fine tuning to achieve precise pore sizes that enable highly selective sorption of desired target substances, such as deuterium.

The materials used in this invention are extremely easy to manufacture, as they can be produced efficiently (and generally without the need for any intermediate purification), in high yields, and are soluble, allowing for convenient processing and handling in the liquid state.

Our experiments with cocrystals have revealed that two different porous organic cages can be cocrystallized to yield crystals isomorphous with at least one (if not both) of the input porous organic cages. This opens up additional possibilities for tailoring properties without the usual concerns associated with weakening established crystalline structures (e.g., interconnected porous networks). The inventors therefore conceived of cocrystallizing the aforementioned small pore cage with a large pore cage. In doing so, the inventors found that not only could they increase the sorption volume (at a given temperature and pressure), but also the target selectivity. Without wishing to be bound by theory, this unexpected result may result from the complementary interplay between classical diffusion, quantum tunneling, and wave diffraction.

The present invention therefore further provides a material that exhibits high selectivity and high sorption capacity.

While the present invention can be operated to selectively separate a variety of targets from a mixture, it is particularly suited to extracting deuterium from a mixture containing deuterium and hydrogen. However, using the same principles of the present invention, the porous organic cages can be fine-tuned to target tritium. In this way, the present invention can be operated to treat tritiated water or other tritium by-products resulting from nuclear power plants, including those resulting from accidents such as the Fukushima reactor. Treatment of tritiated (and therefore radioactively contaminated) water may involve subjecting the contaminated water to electrolysis to first generate a gaseous mixture containing _T2 and/or HT (likely an admixture with _H2 ), and then separating the tritiated gas molecules via the method of the present invention.

Methods Involving Sorption of Target Substances The present invention provides a variety of methods involving the sorption of one or more target substances. Such methods always use a sorption composition (or a sorption device comprising said sorption composition) to preferentially sorb the target substance from a target mixture containing the target substance along with one or more non-target substances. The sorption composition preferably selectively (or preferentially) sorbs the target substance over the non-target substances. The properties of the sorption composition (or sorption device) used in these methods are defined herein, and such definition of a sorption composition is applicable to any or all embodiments of these methods.

Methods for Preferential Sorption The present invention provides a method for preferentially sorbing one or more target substances. The method is preferably a method for preferentially (or selectively) sorbing one or more target substances over one or more non-target substances. The method suitably comprises contacting a target mixture as defined herein with a sorption composition. The method may equally comprise contacting the target mixture with a sorption device, the sorption device comprising the sorption composition. The target mixture suitably comprises, consists essentially of, or consists of the target substances and non-target substances. The sorption composition suitably comprises, consists essentially of, or consists of a sorption compound. Preferably, the sorption composition comprises, consists essentially of, or consists of both the sorption compound and the co-crystallized compound.

According to an aspect of the present invention, there is provided a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture comprising, consisting essentially of, or consisting of target substances and non-target substances, the method comprising contacting the target mixture with a sorption composition (or a sorption device comprising the sorption composition), wherein the sorption composition comprises, consists essentially of, or consists of a sorption compound and, optionally, a co-crystallized compound.

The method preferably provides a sorbed composition (i.e., the sorption composition and the target materials sorbed thereto) comprising a treated target mixture containing one or more target materials (and optionally one or more non-target materials) and one or more non-target materials (and optionally one or more target materials). The sorbed composition is preferably enriched in the target materials (relative to the non-target materials) from the treated target mixture. The treated target mixture is preferably enriched in the non-target materials (relative to the target materials) from the sorbed composition. The sorbed composition is preferably released from the sorption composition by desorption, yielding a desorbed composition, preferably after the treated target mixture has been removed by contact with the sorption composition. The desorbed composition is preferably (substantially) identical to the sorbed composition except that it is no longer sorbed within the sorption composition. The desorbed composition may itself become the target mixture in a subsequent round of the method, thereby providing an opportunity for further purification of the target materials.

The target substances, non-target substances, and target mixtures described below (and elsewhere herein) are applicable to any aspect and embodiment of the preferential sorption method, or an entirely separate method incorporating the preferential sorption method. The same applies to the conditions and characteristics of the method, such as contacting conditions, sorption characteristics, and equipment.

Target Materials, Non-Target Materials and Target Mixtures Thereof The target mixture is preferably a gaseous mixture at the SATP. The target mixture is preferably a gaseous mixture at the relevant contact temperature (see below). Preferably, the target material has a melting point below 200K, preferably below 100K, more preferably below 75K, more preferably below 40K, more preferably below 20K, and most preferably below 15K.

Preferably, the target material is the material intended for sorption, while the non-target material is the material designated for separation from the target material, although some non-target material may co-sorb with the target material, preferably in lower relative amounts. Thus, the target mixture may consist of the target material and non-target material, but the target mixture may also include the target material and non-target material, as well as, optionally, additional materials. Such additional materials may include one or more carrier gases and may be intentionally included to facilitate the overall process. Alternatively, the additional materials may be present for some other reason. In such cases, the additional materials are preferably less sorptive than the non-target material (in the case of preferential sorption methods).

In some embodiments, the target and non-target materials may be chemically different, e.g., preferably in terms of their elemental composition. The target and non-target materials may be physically different, e.g., they may have different sizes (e.g., in terms of maximum dimension or effective molecular radius, e.g., larger sized species are at least 2%, preferably at least 5%, and preferably at least 10% larger than smaller sized species in SATP). For example, the target and non-target materials (target/non-target pairs) may be selected from the group consisting of _H2 / _N2 , _H2 /CO, _CH4 / _N2 , and Xe/Kr (in the case of Xe/Kr, either one can be a target while the other is a non-target).

In preferred embodiments, the target material and non-target material are identical except for isotopic differences; for example, the target material and non-target material may preferably be chemically identical in terms of their elemental composition. The target material and non-target material may be (substantially) the same size (e.g., in terms of maximum dimension or effective molecular radius, e.g., a larger size species is at most 2%, preferably at most 1%, preferably at most 0.5% larger in SATP than a smaller size species). In such a scenario, an additional material in the target mixture preferably differs from the target material by more than just isotopic differences; for example, the additional material may be chemically different in terms of their elemental composition and/or the additional material may be physically different in terms of size.

Preferably, the target material is heavier (in terms of atomic weight or molecular weight, whichever is applicable) than the non-target material. In preferred embodiments, the target material comprises an isotopically differentiated form of the non-target material. Suitably, in such embodiments, the isotopic form of the target material is a heavier isotope than that of the non-target material.

Preferably, the de Broglie wavelength of the target substance in SATP is between 0.1 and 3.5 Å. Preferably, the de Broglie wavelength of the target substance in SATP is between 0.2 and 2.0 Å. Preferably, the de Broglie wavelength of the target substance in SATP is between 0.3 and 1.0 Å. Preferably, the de Broglie wavelength of the target substance in SATP is between 0.3 and 0.8 Å.

Preferably, the de Broglie wavelength of the target material at the contact temperature is between 0.2 and 4.0 Å. Preferably, the de Broglie wavelength of the target material at the contact temperature is between 0.3 and 3.5 Å. Preferably, the de Broglie wavelength of the target material at the contact temperature is between 0.5 and 2.5 Å. Preferably, the de Broglie wavelength of the target material at the contact temperature is between 1 and 3.0 Å. Preferably, the de Broglie wavelength of the target material at the contact temperature is between 1 and 2.0 Å. Preferably, the de Broglie wavelength of the target material at the contact temperature is between 1.2 and 1.9 Å. Preferably, the de Broglie wavelength of the target material at the contact temperature is between 1.4 and 1.7 Å.

Preferably, the de Broglie wavelength of the non-target material at the contact temperature is between 1 and 5.0 Å. Preferably, the de Broglie wavelength of the non-target material at the contact temperature is between 2 and 4.0 Å.

Preferably, in SATP, the difference between the de Broglie wavelength of the target substance and that of the non-target substance is at least 0.1 Å. Preferably, at the contact temperature, the difference between the de Broglie wavelength of the target substance and that of the non-target substance is at least 0.2 Å, and more preferably at least 0.4 Å.

Preferably, the target substance has a shorter (or lower) de Broglie wavelength than the non-target substance. Preferably, in SATP, the target substance has a de Broglie wavelength that is at least 0.1 Å smaller than the non-target substance. Preferably, at the contact temperature, the target substance has a de Broglie wavelength that is at least 0.2 Å smaller, more preferably at least 0.4 Å smaller, than the non-target substance.

Preferably, in the SATP, the difference between the de Broglie wavelength of the target substance and that of the additional substance is at least 0.1 Å, more preferably at least 0.2 Å. Preferably, at the contact temperature, the difference between the de Broglie wavelength of the target substance and that of the additional substance is at least 0.2 Å, more preferably at least 0.4 Å, and more preferably at least 0.6 Å.

Preferably, the target material has a shorter (or lower) de Broglie wavelength than any additional material. Preferably, the non-target material has a shorter (or lower) de Broglie wavelength than any additional material, although in some embodiments they may be similar, e.g., within +/- 0.5 Å.

Preferably, the de Broglie wavelength of the target substance in SATP is within +/- 5 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target substance in SATP is within +/- 4 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target substance in SATP is within +/- 3.5 Å of the cavity size of the sorption compound. More preferably, the de Broglie wavelength of the target substance in SATP is within +/- 2 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target substance in SATP is within +/- 1 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target substance in SATP is within +/- 0.5 Å of the cavity size of the sorption compound.

Preferably, the de Broglie wavelength of the target material at the contact temperature is within +/- 5 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target material at the contact temperature is within +/- 4 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target material at the contact temperature is within +/- 3.5 Å of the cavity size of the sorption compound. More preferably, the de Broglie wavelength of the target material at the contact temperature is within +/- 2 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target material at the contact temperature is within +/- 1 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target material at the contact temperature is within +/- 0.5 Å of the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target material at the contact temperature is within +/- 0.4 Å of the cavity size of the sorption compound.

Preferably, the de Broglie wavelength of the target material at the contact temperature is smaller than the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the target material at the contact temperature is smaller than the cavity size of the sorption compound by at most 5 Å, preferably at most 4 Å, preferably at most 3.5 Å, preferably at most 2 Å, preferably at most 1 Å, preferably at most 0.5 Å, preferably at most 0.4 Å.

Preferably, the de Broglie wavelength of the non-target material at the contact temperature is greater than the cavity size of the sorption compound. Preferably, the de Broglie wavelength of the non-target material at the contact temperature is greater than the cavity size of the sorption compound by at most 5 Å, preferably at most 4 Å, preferably at most 3.5 Å, preferably at most 2 Å, preferably at most 1 Å, preferably at most 0.5 Å, preferably at most 0.4 Å.

Preferably, the non-target material has a shorter (or lower) de Broglie wavelength than the additional material at the contact temperature, although in some embodiments they may be similar, e.g., within +/- 0.5 Å.

Preferably, the size (e.g., molecular size) of the target substance is smaller than the cavity size of the sorption compound. Preferably, the size (e.g., molecular size) of the non-target substance is smaller than the cavity size of the sorption compound. Preferably, the sizes (e.g., molecular size) of the target substance and the non-target substance are approximately the same, preferably substantially the same, preferably within +/-0.5 Å, more preferably +/-0.3 Å, more preferably +/-0.2 Å, more preferably +/-0.1 Å, more preferably +/-0.05 Å, and more preferably +/-0.01 Å.

Preferably, the size of the additional material is larger than the cavity size of the sorption compound. Preferably, the size of the additional material is larger than the non-target material. However, the size of the additional material (e.g., a carrier gas or material different from the target and non-target materials) may be within +/- 0.5 Å of the non-target material.

Preferably, both the target material and the non-target material comprise or consist of isotopically identified materials, with the isotopes of the target material being heavier than those of the non-target material. Most preferably, both the target material and the non-target material comprise or consist of isotopically identified hydrogen molecules, with the isotopes of the target material being heavier than those of the non-target material.

Isotopic quantum sieving tends to be more selective when the difference between the de Broglie wavelengths of the target and non-target materials is large. Because the thermal de Broglie wavelength is inversely proportional to the square root of the mass of the material, the differences in de Broglie wavelengths are greatest between protium and tritium isotopes, but they are also quite significant between protium and deuterium isotopes.

Preferably, the preferential sorption methods described herein are for separating target materials from non-target materials, more preferably for separating isotopes of hydrogen (e.g., separating different isotopic forms of molecular hydrogen into homo- or hetero-isotopes), and most preferably for separating one or more heavier hydrogen isotopes (e.g., separating one or more heavier isotopic forms of molecular hydrogen) from one or more lighter hydrogen isotopes (e.g., separating one or more heavier isotopic forms of molecular hydrogen). In terms of increasing weight, the three most common and stable isotopes of hydrogen are protium ( ¹ H or 3 H), deuterium ( ² H or 3 D), and tritium ( ³ H or 3 T). Preferably, therefore, the target material comprises or consists of a form of molecular hydrogen comprising or consisting of either or both deuterium atoms ( ^2H or D) and/or tritium atoms ( ^3H or T), which may include _D2 , HD, _T2 , HT, and/or DT. Preferably, the non-target material is or comprises molecular protium ( ^1H2 or _H2 ). In some embodiments, however, _it may be desirable to separate tritium from either protium and/or deuterium, or both, in which case the target material is preferably tritium, while the non-target material is either protium and/or deuterium, or both.

In some embodiments, the target mixture may comprise, consist essentially of, or consist of heteroisotopic diatomics (or mixed diatomics) and/or isotopic diatomics (plain diatomics). For example, heteroisotopic diatomics may include HD (protium-deuterium), HT (protium-tritium), and/or DT (deuterium-tritium), while isotopic diatomics may include protium ( _H2 , also known as dihydrogen, diatomic hydrogen, or elementary hydrogen), deuterium ( _D2 , also known as dideuterium or diatomic deuterium), and/or tritium ( _T2 , also known as tritium or diatomic tritium).

In preferred embodiments, the target substance is selected from the group consisting of _D2 , _T2 , HD, HT, and DT. In particularly preferred embodiments, the target substance is _D2 . In another embodiment, the target substance is _T2 . In some embodiments, the target substance may comprise heteroisotopic hydrogen molecules.

In a preferred embodiment, the non-target substance is selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT, provided that the non-target substance excludes the target substance. Preferably, the non-target substance is or includes _H2 .

In preferred embodiments, the target mixture comprises, consists essentially of, or consists of two or more selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT. In some embodiments, the target mixture comprises, consists essentially of, or consists of three or more selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT. In particularly preferred embodiments, the target mixture comprises or consists of _H2 and _D2 .

For nuclear fusion, the exhaust (output) gas may include a mixture of two or more of _H2 , _D2 , _T2 , HD, HT, and DT (some of which may be target material and others may be non-target material), and possibly additional material, such as helium (He). Such an exhaust mixture may constitute a target mixture for the present invention. In such a scenario, the target material may include any one or more of _D2 , _T2 , HD, HT, and DT, while the non-target material may include one or more of _H2 , _D2 , _T2 , HD, HT, and DT other than that of the target material, and the additional material may optionally include helium.

In particularly preferred embodiments, the target mixture comprises, consists essentially of, or consists of _H2 and _D2 , the target material is or comprises _D2 , and the non-target material is or comprises _H2 .

In certain embodiments, the target mixture comprises, consists essentially of, or consists of _H2 and _T2 , the target material is or comprises _T2 , and the non-target material is or comprises _H2 .

Contact Conditions - Temperature, Pressure, Exposure Time, and Other Conditions Like the sorbent materials (e.g., sorption compounds and/or co-crystallized compounds) employed in the present invention, the conditions used in the methods of the present invention can be selected to optimize selectivity and/or to optimize sorption volume/capacity (i.e., to sorb the largest possible volume of target substance). Most preferably, however, the conditions can be selected for an optimal balance between both selectivity and sorption capacity. This is especially the case when multiple sorption rounds are envisioned (i.e., the sorbed material is fed back into the sorption process for further purification or further target substance selection).

The method preferably involves contacting the target mixture with the sorption composition (or a sorption device containing the sorption composition) at a specific contact temperature. The contact temperature is preferably the temperature of the target mixture during (or immediately before) the contacting. The contact temperature can be the same as, or substantially the same as, the temperature of the sorption composition or sorption device. During contacting, the temperature of the sorption composition or sorption device can preferably be within 100 K of the temperature of the target mixture, more preferably within 50 K, more preferably within 20 K, and most preferably within 5 K. The temperature of the sorption composition or sorption device can be controlled separately from the temperature of the target mixture to facilitate, for example, processing (e.g., freezing after the contacting step to maintain the sorbed content within the composition but separate the target mixture therefrom, thereby avoiding premature desorption).

The contact temperature affects the de Broglie wavelength (i.e., thermal de Broglie wavelength) of the target material, non-target materials, and optional additional materials. Furthermore, decreasing the contact temperature increases the difference between the de Broglie wavelengths of the target and non-target materials. Therefore, quantum sieves are generally more selective at lower temperatures. Therefore, the contact temperature is preferably set to preferentially sorb the target material based on the match between the cavity size of the sorption compound and the de Broglie wavelength of the target material at the contact temperature.

The contact temperature, and in particular the temperature of the sorption composition (or sorption device), can affect the cavity size distribution of the sorbed compound (and indeed the co-crystallized compound) because elevated temperatures increase vibrational freedom, causing cavities to temporarily assume larger sizes, which can affect (i.e., decrease) selectivity and can also affect the overall sorption capacity (again, impairing selectivity). Furthermore, higher temperatures can rapidly produce equilibrium (i.e., thermodynamic) sorption scenarios, which can result in lower selectivity; in other words, kinetic control can result in higher selectivity.

Preferably, the target mixture is a gaseous mixture in the SATP. Preferably, the target mixture remains a gaseous mixture at the contact temperature. Preferably, the contact temperature exceeds the melting point of the target material. Preferably, the contact temperature exceeds the melting point of the non-target material.

The contact temperature is preferably at least 15 K, preferably at least 20 K, preferably at least 25 K. The contact temperature is preferably at most 300 K, preferably at most 200 K, preferably at most 100 K. In certain embodiments, the contact temperature is between 15 and 100 K, preferably between 20 and 80 K. In certain embodiments, the contact temperature is between 20 and 60 K. In certain embodiments, the contact temperature is between 25 and 40 K, preferably between 25 and 35 K.

The method preferably involves contacting the target mixture with the sorption composition (or a sorption device containing the sorption composition) at a specific contact pressure. The contact pressure may be optimized for a specific contact temperature. While elevated pressure may increase overall (i.e., all materials) sorption, there may be an optimum pressure for selectivity. In such embodiments, the contact temperature may preferably be between 0.1 and 500 mbar, more preferably between 1 and 100 mbar, and most preferably between 5 and 50 mbar (especially at the lowest temperatures). However, in some circumstances (e.g., in embodiments of the invention involving cocrystals), elevated pressure may increase selectivity. Thus, desirably, the contact pressure may be at least 10 mbar, preferably at least 100 mbar, more preferably at least 500 mbar, and even more preferably at least 900 mbar. The contact pressure may be at most 10,000 mbar, preferably at most 5,000 mbar, preferably at most 2,000 mbar, preferably at most 1,100 mbar.

The method may include contacting the target mixture with the sorption composition (or a sorption device containing the sorption composition) at varying contact pressures. For example, the method may include pressure swing adsorption. In such embodiments, the contact pressure may be varied from a relatively high pressure to a relatively low pressure. At the relatively high pressure, preferential sorption of the target material is promoted, while desorption of the target material (potentially miscible with a proportion of non-target material) is promoted at the relatively low pressure. Between the two pressure changes, the target mixture is removed (optionally flowed downstream or stored in another vessel or apparatus in preparation for a subsequent round of the method) for the desorbed target material, and potentially subjected to a subsequent round of the method (in the same or a different vessel or apparatus, optionally downstream) to further purify the target material. Alternatively, varying contact pressure (which may follow a preprogrammed envelope over a predetermined time period) may facilitate sorption and desorption in a manner that results in greater selectivity and/or greater overall sorption volume; for example, this may allow for a degree of "shuffling" that generally favors sorption of the target substance. It is contemplated that temperature swing adsorption can be practiced with or without pressure swing adsorption, preferably while achieving the same results.

The method preferably involves contacting the target mixture with the sorption composition (or a sorption device containing the sorption composition) for a specific contact time (or exposure time). Longer contact times necessarily promote an increase in overall sorption volume, but this may decrease sorption selectivity (depending on other conditions and the sorption material in question, e.g., when pressure and/or temperature swing adsorption is operated, and then higher selectivity is obtained due to the extended process). Longer contact times favor thermodynamic control, while shorter contact times favor kinetic control. Thus, the contact time can be selected to optimize either or both sorption volume and/or selectivity, but most preferably, the contact time is selected for an optimal balance between the two. The contact time is preferably 1 min or more, preferably 5 min or more. The contact time is preferably 1,200 min or less, preferably 800 min or less, preferably 600 min or less, and preferably 120 min or less. The inventors have indeed discovered that the sorption compositions of the present invention, in contrast to prior art compositions, tend to maintain selectivity over extended contact times, thereby enabling longer contact times and subsequently facilitating an increase in overall sorption volume.

The method may include contacting the target mixture with the sorption composition (or sorption device containing the sorption composition) by pumping (or passing) the target mixture through the sorption composition (or sorption device), preferably in a continuous (potentially cyclical) manner. In embodiments, the sorption device is or includes a column or cartridge containing the sorption composition, optionally mixed with another solid material that facilitates gas flow; thus, the sorption composition (optionally mixed with another solid) may preferably act as the stationary phase. Following contact, the stationary phase may exhibit a sorption gradient of target vs. non-target substances to be sorbed. In certain embodiments, the sorption composition or sorption device may perform a chromatographic function; thus, a chromatographic apparatus (e.g., a gas chromatographic apparatus) may include the sorption composition or sorption device.

In some embodiments, the sorption composition (or sorption device) is a membrane or film.

Sorption Properties Sorption of the target substance is preferably via physical adsorption.

The method preferably provides a sorption volume (or sorption uptake) of target and/or non-target substances (i.e., 1 mmol of target/non-target substance per gram of sorption composition or per gram of combined sorbed compounds and/or co-crystallized compounds) of at least 1 mmol/g, more preferably at least 2 mmol/g, more preferably at least 4 mmol/g, and more preferably at least 6 mmol/g, at 1 bar and the relevant contact temperature.

The method preferably achieves a sorption selectivity of target material relative to non-target material (i.e., ratio, e.g., molar, volumetric, or mass ratio of sorbed target material to sorbed non-target material, preferably a molar ratio) of at least 1.5, preferably at least 2, more preferably at least 3, more preferably at least 6, and most preferably at least 7. The method can optionally be adjusted to achieve such selectivity at the expense of or in favor of overall sorption volume (i.e., uptake). Selectivity is preferably determined by TDS after exposing the sorption composition to a target mixture (most preferably a 1:1 mixture of target material/non-target material, e.g., _D2 / _H2 ).

Apparatus Suitable apparatus for carrying out the methods of the present invention may preferably comprise a sealed container, an inlet (preferably for the target mixture), an outlet (preferably for the treated target mixture, i.e., the target mixture depleted in some sorbed substance), a fluid pathway through the sealed container fluidly connecting the inlet to the outlet (optionally by controllably interrupted means or discontinuous means, for example, via one or more intermediate valves), and a sorption composition (or a sorption device comprising the sorption composition) located within the container along the fluid pathway. The sorption composition (or sorption device) is preferably located at a sorption station (where sorption can occur). The sorption composition is preferably contained within, for example, a sorption device, cartridge, or column introduced (optionally removably) along the fluid pathway, such that the target mixture is preferably constrained to pass therethrough. Preferably, the apparatus includes a temperature control mechanism for the target mixture, particularly for controlling the temperature of the target mixture during contact with the sorption composition. Preferably, the apparatus includes a sorption composition temperature control mechanism for controlling the temperature of the sorption composition, particularly during contact with the sorption composition, and potentially thereafter (e.g., temporarily cooling the sorption composition while the treated target mixture is removed by contact therewith, followed by desorption, thereby releasing the target material sorbed to the sorption composition). Preferably, the target mixture temperature control mechanism is operable independently of the sorption composition temperature control mechanism. Preferably, the apparatus includes a target mixture pressure control mechanism for controlling the pressure of the target mixture, particularly during contact. The pressure control mechanism may be operable to vary the pressure to facilitate pressure swing adsorption.

The apparatus may include two or more sorption stations containing sorption compositions (or sorption devices). Second and subsequent sorption stations may be configured to receive the further purified, desorbed target material (which may contain some non-target material) as an input target mixture, and the treated (product) target mixture is separated from the process.

Methods for Producing, Extracting, or Purifying One or More Target Substances Preferably, the preferential sorption methods defined herein are used to produce, extract, or purify target substances, although non-target substances may also be purified (or enriched) via the same process. A method for producing, extracting, or purifying a target substance may in fact constitute a method for enriching a mixture in target substances. Similarly, the same method may provide a method for enriching a mixture in non-target substances, i.e., a processed target mixture. The same method may also provide a method for separating target substances from non-target substances.

According to an aspect of the invention, there is provided a method of producing, extracting or purifying one or more target substances (or enriching a mixture in one or more target substances), comprising:
a. performing a preferential sorption method as defined herein to obtain a sorbed composition comprising one or more target substances (and optionally one or more non-target substances), and a treated target mixture comprising one or more non-target substances (and optionally one or more target substances);
b. Separating or removing the treated target mixture by contact with a sorption composition;
c. desorbing the sorbed composition from the sorption composition to obtain a desorbed composition.

The method may further include repeating steps a through c by re-feeding the desorbed composition to the method for preferential sorption as the target mixture. In this manner, the target substance may be repeatedly enriched or purified.

The method may further include isolating the desorbed composition or isolating the target substance.

Prior to carrying out the preferential sorption method, the method may include pre-filtering the target mixture, preferably via a membrane or other such filtration device. Such pre-filtration preferably removes some additional substances, e.g., target substances and/or a portion of additional substances larger than non-target substances.

Separating or Removing the Treated Target Mixture Separating or removing the treated target mixture by contact with the sorption composition preferably comprises pumping the treated target mixture from the sorption composition, preferably via an outlet.

Preferably, the sorption composition, and any sorbed composition sorbed thereto, may be further cooled prior to and/or during separation or removal of the treated target mixture. Preferably, the sorption composition is cooled independently of the treated target mixture. Cooling the sorption composition preferably maintains (or enhances the retention of) the sorbed composition sorbed on the sorption composition while the treated target mixture is removed (e.g., under vacuum).

Desorption Desorbing the sorbed composition from the sorption composition suitably involves either or both elevated temperature and/or reduced pressure.

The temperature of the sorption composition can be increased via a temperature control mechanism associated with the sorption composition (e.g., a heating/cooling element associated with the sorption composition or sorption device) and/or a temperature control mechanism associated with the target mixture, although the latter may be less effective at low pressures. Therefore, desorption preferably involves the direct application of heat to the sorption composition or sorption device, or a direct temperature increase (compared to the contact temperature), preferably via a separate heating/cooling mechanism that may be separately applied to the target mixture.

Desorption may preferably involve an increase in temperature of at least 10 K, preferably at least 30 K, preferably at least 40 K.

The reduced pressure may involve only the creation of a vacuum. Desorption may involve a reduced pressure (preferably in some container or void space surrounding or in contact with the sorption composition or sorption device) of preferably at least 1 mbar, preferably at least 10 mbar, preferably at least 50 mbar, preferably at least 200 mbar, preferably at least 500 mbar.

Preferably, desorption is induced after separation/removal of the treated target mixture.

Repeating steps a-c may suitably involve using the desorbed composition as the target mixture in a subsequent round of the method. The desorbed composition may be contacted with the same sorption composition (or sorption device) as used in the preceding round, or with a different sorption composition (or sorption device), suitably in a different part of the apparatus (e.g., a second or subsequent sorption station, see above). Suitably, the sorbed and desorbed compositions are further enriched in the target material compared to those in previous rounds of the method. Thus, successive repetitions of steps a-c of the method suitably further enrich the sorbed or desorbed composition in the target material and/or further increase the purity of the ultimately isolated target material.

Methods for Producing, Extracting, or Purifying One or More Non-Target Substances While the preferential sorption methods defined herein can be used to produce, extract, or purify target substances, the same methods can also be used to produce, extract, purify, or enrich non-target substances in a target mixture. In such a scenario, the preferential sorption essentially removes the target substances from the target mixture, thereby leaving the treated target mixture enriched in the non-target substances.

According to an aspect of the invention, there is provided a method for producing, extracting or purifying one or more non-target substances (or enriching a mixture in one or more non-target substances), comprising:
a. performing a preferential sorption method as defined herein to obtain a sorbed composition comprising one or more target substances (and optionally one or more non-target substances), and a treated target mixture comprising one or more non-target substances (and optionally one or more target substances); and
b. separating the treated target mixture by contact with a sorption composition.

The method may further include repeating steps a-b by feeding the treated target mixture to a method that preferentially sorbs the target mixture. In this manner, non-target substances may be repeatedly enriched or purified within the treated target mixture. Furthermore, in this manner, the "target substances" are preferably selectively removed from the target mixture.

The method may further include isolating the treated target mixture or isolating non-target material.

Prior to carrying out the preferential sorption method, the method may preferably include pre-filtering the target mixture, preferably via a membrane or other such filtration device. Such pre-filtration preferably removes some additional material, e.g., a portion of the additional material that is larger than the target material and/or non-target material.

Separating or Removing the Treated Target Mixture Separating or removing the treated target mixture by contact with the sorption composition preferably comprises pumping the treated target mixture from the sorption composition, preferably via an outlet.

Preferably, the sorption composition, and any sorbed composition sorbed onto the sorption composition, may be further cooled prior to and/or during separation or removal of the treated target mixture. Preferably, the sorption composition is cooled independently of the treated target mixture. Cooling the sorption composition preferably maintains (or enhances the retention of) the sorbed composition sorbed onto the sorption composition while the treated target mixture is removed (e.g., under vacuum).

Repeating steps a-b may suitably involve using the treated target mixture as the target mixture in a subsequent round of the method. The treated target mixture may be contacted with the same sorption composition (or sorption device) as used in the preceding round, or with a different sorption composition (or sorption device), suitably in a different part of the apparatus (e.g., a second or subsequent sorption station, see above). If the same sorption composition (or sorption device) is used, preferably any sorbed composition is desorbed therefrom to produce a desorbed composition, which is then removed by contact with the sorption composition (or sorption device) and then any further contact thereof with the treated target mixture. Preferably, the treated target mixture is thus further enriched in non-target materials compared to that in the previous round of the method. Successive repetitions of steps a-b of the method therefore suitably further enrich the treated target mixture in non-target materials and/or further increase the purity of the non-target materials that are ultimately isolated.

Methods for Removing Target Materials According to one aspect of the present invention, there is provided a method for removing one or more target materials from a target mixture comprising, consisting essentially of, or consisting of the target materials and one or more non-target materials, comprising performing a preferential sorption method as defined herein. The method may be a method for producing, extracting, or purifying one or more non-target materials (or a method for enriching a mixture in one or more non-target materials). Such a method may be performed repeatedly to maximize removal of target materials. Such a method is particularly useful, for example, when it is desired to remove radioactive tritium from radioactively contaminated water, preferably by subjecting the water to electrolysis to produce gaseous hydrogen isotopes, which are then subjected to the method. Accordingly, another aspect of the present invention provides a method for removing tritium from radioactively contaminated water, comprising subjecting the electrolyzed water to the aforementioned removal method.

Compositions and Compounds According to certain aspects of the present invention, there are provided sorption compositions comprising sorption compounds. The sorption compositions, in some embodiments, can consist of or consist essentially of the sorption compounds.

Preferably, the sorption composition further comprises a co-crystallized compound. In some embodiments, the sorption composition can consist of, or consist essentially of, the sorption compound and the co-crystallized compound.

The co-crystallized compound may be a compound of the same class as the sorption compound, provided that the co-crystallized compound is a different compound from the sorption compound.

Preferably, the sorption composition comprises a co-crystal, and suitably the co-crystal comprises a sorption compound co-crystallized with a co-crystallizing compound. In some embodiments, the sorption composition can consist of, or consist essentially of, the co-crystal.

According to one aspect of the present invention, a co-crystal composition is provided. The co-crystal composition preferably comprises or consists of a co-crystal as defined herein. A sorption composition can be a co-crystal composition, and vice versa.

Other than the sorption compound and/or co-crystallized compound, the sorption composition preferably does not include any other sorbent materials. Indeed, the sorption composition preferably does not include any other sorbent materials capable of sorbing non-target or additional substances.

Other than the sorption compound and/or co-crystallized compound, the sorption composition preferably does not include any other sorbent material capable of sorbing the target substance, particularly at the contact temperature. However, in some embodiments, the sorption composition may include an additional sorbent material capable of sorbing the target substance. The additional sorbent material is capable of sorbing the target substance at the contact temperature, preferably resulting in alternative sorbent pores that optionally exhibit different selectivity than the sorption compound (or co-crystal). Such additional sorbent material may optionally be co-crystallized with the sorption compound and/or co-crystal. The additional sorbent material may be more capable (e.g., in terms of relative sorption capacity/volume) of sorbing the target substance at temperatures above the contact temperature and/or pressures below the contact pressure, preferably thereby increasing the temporary retention of the target substance within the sorption composition while separating the treated target mixture therefrom.

The sorption composition may include additional non-sorbent materials.

The sorption composition may be a highly flowable, preferably crystalline, solid. However, the sorption composition may also be formulated as granules. The sorption composition may be compressed. The sorption composition may also be formulated as a membrane or film.

Sorption Compound The sorption compound is preferably a porous compound, as the sorption compound preferably comprises pores. The porous compound preferably has porous molecules packed in the solid state which create the pores, and the sorption compound preferably exhibits solid-state porosity. The pores are preferably permeable to liquids and/or gases, most preferably gases.

The sorption compound preferably comprises a multidimensional (at least two, preferably three) interconnected porous network, preferably via interconnected voids. Such pores may preferably be external pores arising from disordered or inefficient packing (perhaps due to an "unwieldy" molecular structure) or from predisposed intermolecular interactions (e.g., electrostatic, dipolar, hydrogen bonding) that energetically favor a low-density crystalline structure. External pores are pores between adjacent molecules rather than within their own individual molecules. Alternatively, such pores may preferably be intrinsic pores arising from cavities within the porous molecules themselves, such intrinsic voids being independent of the overall crystalline structure, or at least less dependent thereon than are the external pores or voids. Intrinsic pores tend to occur in porous cages, where molecules with invariant voids are confined within their own molecular structure. A "window" defines an access point to a pore, and certain dimensions given herein for pore diameter or cavity size may optionally refer to the window size. A porous compound may include or consist of either or both internal and/or external pores (or voids).

The sorption compound preferably comprises at least one internal cavity. The internal cavity is preferably chemically modifiable or is otherwise formed by chemically modifying the same internal cavity of a precursor compound, for example, by functionalizing a modifiable group located within the internal cavity.

The sorption compound is preferably a porous compound other than a metal-organic framework (MOF), a porous coordination polymer (PCP), a covalent organic framework (COF), or a porous organic polymer (POP). The sorption compound is preferably other than a hydrogen-bonded organic framework (HOF). The sorption compound is preferably a porous compound other than one characterized as an extended solid in which the molecular components are held together by strong covalent and/or coordinate (e.g., dative) bonds.

The sorption compound is preferably a porous organic cage (POC). Any suitable POC can be used.

The sorption compound is preferably soluble. The sorption compound is preferably soluble, freely soluble, or very soluble in organic solvents. The sorption compound is preferably soluble, freely soluble, or very soluble in polar organic solvents. The sorption compound is preferably soluble, freely soluble, or very soluble in polar aprotic organic solvents. The sorption compound is preferably soluble, freely soluble, or very soluble in polar protic organic solvents. The sorption compound is preferably soluble, freely soluble, or very soluble in methanol, chloroform, dichloromethane, tetrahydrofuran (THF), dimethylformamide (DMF), and/or N-methyl-2-pyrrolidone (NMP). The sorption compound (and, where relevant, the co-crystallized compound) can be tailored for solubility in a preferred solvent (including water) through, for example, appropriate functionalization of the surrounding (i.e., interfacially contacting) groups; for example, to increase aqueous solubility, the periphery of the porous organic cage can be functionalized with polar, protic, ionizable, or ionized/ionic groups.

The sorption compound is preferably soluble, freely soluble, or very soluble in a solvent having a dielectric constant (as SATP) between 4.5 and 35. The sorption compound is preferably soluble, freely soluble, or very soluble in chloroform. The sorption compound is preferably soluble, freely soluble, or very soluble in methanol.

Porous organic cages
The POC is a covalently bonded cage. The POC has at least one, potentially a single, internal cavity (e.g., at least one cavity per cage molecule, potentially a single cavity). The POC is preferably capable of crystallizing into a crystalline POC.

Cage molecules are preferably distinguished from external porous molecules by their internal (intrinsic) cavity. Preferably, however, POCs exclude cavitands (e.g., cucurbiturils) and cryptophanes. POCs are preferably cages rather than macrocycles. POCs preferably do not contain metal atoms or metal ions.

Porous organic cages (POCs) are individual molecules with internal cavities that typically crystallize to form porous solids, with the pore structure preferably determined by the internal cavities and crystalline packing of the molecules. Fine-tuning of the pore structure therefore preferably involves modifications to the interior of the molecule without significantly affecting the overall crystalline packing. Therefore, modifications to the interior of the molecule preferably do not significantly affect the overall cage shape and/or cage size.

The porous organic cages are preferably shape-persistent, e.g., they are preferably resistant to collapse (e.g., pore collapse).

As per the review article in the Examples section mentioned below (Hasell, T., Cooper, A. Porous organic cages: soluble, modular and molecular pores. Nat Rev Mater 1, 16053 (2016). https://doi.org/10.1038/natrevmats.2016.53), the POC is preferably selected from the group consisting of imine cages, diamine cages (preferably structurally stabilized diamine cages, e.g. functionalized diamine cages), triptycene cages, carbon-carbon cages, boron ester cages, porphyrin box cages, alkyne metathesis cages, linked cages, cage MOFs, modular cage cocrystals, porous organic alloys, quadruple linked cages, porous liquids and any combination thereof. Preferably, the POC is selected from the group consisting of a [4+6] imine cage, an [8+12] imine cage, a diamine cage (preferably a structurally stabilized diamine cage, e.g., a functionalized diamine cage), a triptycene cage, a carbon-carbon cage, an [8+12] boron ester cage, a porphyrin box cage, a [4+6] alkyne metathesis cage, a linked cage, a cage MOF, a modular cage cocrystal, a porous organic alloy, a quadruple linked cage, a porous liquid, and any combination thereof.

The internal cavity of a POC is preferably chemically modifiable (e.g., to modify the chemical structure or functional groups present within the cavity) and/or formed by chemically modifying the same internal cavity of a precursor compound, e.g., by functionalizing modifiable groups located within the internal cavity. Thus, a POC can be defined by reference to the precursor compound and any functionalization thereof. The precursor compound is preferably identical to the sorption compound except for the functionalization of the internal cavity, i.e., the sorption compound is distinguished from its precursor compound by the functionalization of the internal cavity.

The internal cavity of the POC is preferably a functionalized internal cavity, which preferably contains one or more functionalized groups (i.e., one or more groups derived from one or more corresponding pre-functionalized groups), or preferably a set (e.g., pair) of functionalized groups comprising two or more functionalized groups or sets (e.g., pairs) of functionalized groups. The functionalized internal cavity can be homofunctionalized (e.g., with all functionalized groups functionalized by the same means, preferably with the same functional group), or heterofunctionalized (e.g., with functionalized groups functionalized by different means, preferably with different functional groups).

The internal cavity of the POC is preferably derived from a pre-functionalized internal cavity (which may itself be partially functionalized), preferably via functionalization of a pre-functionalized internal cavity, preferably a functionalized internal cavity. It will be understood by those skilled in the art that a pre-functionalized internal cavity can be functionalized by a variety of means to obtain a desired functionalized internal cavity.

The pre-functionalized internal cavity preferably contains one or more functionalizable groups (e.g., a functionalizable group containing a reactive heteroatom, e.g., an amine group or a hydroxyl group, or a reactive carbon atom, e.g., a carboxylate, a ketone, an aldehyde, or an imine) or one or more sets (e.g., pairs) of functionalizable groups (e.g., a diamine pair). The pre-functionalized internal cavity preferably contains two or more functionalizable groups (e.g., a functionalizable group containing a reactive heteroatom, e.g., an amine group or a hydroxyl group, or a reactive carbon atom, e.g., a carboxylate, a ketone, an aldehyde, or an imine) or two or more sets (e.g., pairs) of functionalizable groups (e.g., a diamine pair). One or more (but not necessarily all) of the functionalizable groups are preferably functionalized in the resulting functionalized internal cavity of the POC. Such functionalizable groups, particularly those containing reactive heteroatoms (e.g., amine or diamine groups), are preferably functionalized via alkylation, acylation, acetalization, hemiacetalization, aminalization, and/or hemiaminalization. Such functionalizable groups, particularly those containing reactive carbon atoms (e.g., carboxylate groups, ketones, aldehydes, imines), are preferably functionalized via esterification, amidation, acetalization, hemiacetalization, aminalization, and/or hemiaminalization.

In a homofunctionalized interior cavity, all of the functionalized groups are functionalized by the same means, but not necessarily all functionalizable groups. For example, a homofunctionalized interior cavity may include a polydiamine configuration in which some (at least two), but not all, diamine pairs are identically functionalized by cycloaminalization (i.e., to form cyclic aminals) with the same aldehyde or ketone.

In a heterofunctionalized interior cavity, some of the functionalized groups are functionalized to other functionalized groups by different means, but not all functionalizable groups need to be functionalized. For example, a heterofunctionalized interior cavity may include a polydiamine configuration in which some (at least two), but not all, diamine pairs are functionalized by cycloaminalization (i.e., to form cyclic aminals), but at least one diamine pair is functionalized to another diamine pair with a different aldehyde or ketone.

In some embodiments, all of the functionalizable groups in the internal cavity are functionalized. However, in other embodiments, some, but not all, of the functionalizable groups in the internal cavity are functionalized; for example, the internal cavity can be partially functionalized (e.g., a partially functionalized internal cavity).

Functionalizing a precursor compound to ultimately form a sorption compound can involve directing functionalization of one, some, or all of the functionalizable groups. However, in some embodiments, functionalization can involve temporarily functionalizing (protecting) one or more of the functionalizable groups to form temporary functionalized groups, functionalizing one or more other functionalizable groups to form permanent functionalized groups, defunctionalizing (or deprotecting) the temporary functionalized groups to form defunctionalized groups, and optionally functionalizing the defunctionalized groups to form other permanent functionalized groups (optionally functionalized to other permanent functionalized groups by the same or different means, preferably different means).

Functionalization preferably involves functionalization of the functionalizable group with one or more functionalizing substances (or compounds). In homofunctionalized embodiments, such functionalization preferably involves only a single functionalizing substance. In heterofunctionalized embodiments (or indeed embodiments involving temporary functionalization/protection), such functionalization may preferably involve two or more functionalizing substances. When two or more functionalizing substances are to be used, these may be independently selected from any of the functionalizing substances defined herein (e.g., see below; two or more different molecular linkages or molecular linker compounds may be incorporated).

The functionalization of the precursor compound to form the sorption compound preferably comprises the steps of:
i) functionalizing one or more functionalizable groups (or one or more sets or pairs of functionalizable groups) with a first functionalizing agent to obtain one or more first functionalized groups;
ii) functionalizing one or more other functionalizable groups (or one or more other sets or pairs of functionalizable groups) with a second functionalizing agent to obtain one or more second functionalized groups;
iii) defunctionalizing (or deprotecting) one or more of the first functionalized groups to obtain one or more first defunctionalized groups, preferably corresponding to the functionalizable groups to be regenerated;
iv) optionally re-functionalizing one or more of the first defunctionalized groups with a third functionalizing agent that is the same as or different from either the first or second functionalizing agent to obtain one or more third functionalized groups;
v) defunctionalizing (or deprotecting) one or more of the second functionalized groups to obtain one or more second defunctionalized groups, preferably corresponding to the functionalizable groups to be regenerated;
vi) optionally re-functionalizing one or more of the second defunctionalized groups with a functionalizing agent that is the same as or different from any of the first, second, or third functionalizing agents to obtain one or more fourth functionalized groups.

Preferably, functionalization of the precursor compound includes at least step i), and in some embodiments, only step i) (steps i) through vi), thereby obtaining a homo-functionalized sorption compound formed from a single functionalizing material.

In some embodiments, functionalization of the precursor compound includes at least steps i) and ii), and in some embodiments, only steps i) and ii) (steps i) through vi) to obtain a heterofunctionalized sorption compound formed from two different functionalizing materials.

In some embodiments, functionalization of the precursor compound includes at least steps i), ii), and iii), and in some embodiments, only steps i), ii), and iii) (steps i) through vi), thereby obtaining a homo-functionalized sorption compound formed from a single functionalizing substance (preferably less functionalized, and possibly with a smaller cavity size than a corresponding method involving only step i) using the same functionalizing substance).

In some embodiments, functionalization of the precursor compound includes at least steps i), ii), iii), and iv), and in some embodiments, only steps i), ii), iii), and iv) (steps i) through vi), thereby obtaining a heterofunctionalized sorption compound formed from two different functionalized substances (second and third functionalized substances). In such embodiments, step i) acts as a protecting step, introducing the first functionalized substance as a protecting group that is subsequently removed in step iii).

In some embodiments, further refinement may be performed where the second functionalization is also a protecting step, and such embodiments may include all of steps i) through v) or all of steps i) through vi).

The steps of the above method can be repeated to further refine the results.

The functionalizable groups of the internal cavity are preferably appropriately functionalized to obtain the desired cavity size. Therefore, functionalizing the internal cavity preferably constitutes fine-tuning of the internal cavity and/or cavity size (and/or cavity window size).

The precursor (or parent) compound to the sorption compound preferably defines the maximum cavity size of any of its functionalized derivatives in terms of its pre-functionalized internal cavity. Therefore, the functionalizable groups of the internal cavity of the precursor compound can preferably be functionalized to reduce the internal cavity size. Therefore, functionalization preferably involves adding functionalizable groups. Preferably, functionalization involves reacting functionalizable groups (otherwise known herein as "reactive moieties" or "reactive units") with a functionalizing substance/compound (otherwise known herein as "reactive moieties" or "reactive units"). For example, the functionalizable group can be part of or is a reactive unit containing a reactive moiety, such as a diamine moiety, and the functionalizing agent can be a reactive unit having a reactive moiety (e.g., a carbonyl group), such as an aldehyde (e.g., formaldehyde), which can react with the functionalizing agent to produce a formaldehyde-linked aminal. Suitable precursor compounds can be prepared to allow fine tuning via functionalization to obtain a desired cavity size. Thus, the interior cavity size of the precursor compound can be large enough to accommodate the desired size reduction. Alternatively, the precursor compound can be functionalized with a functionalizing agent of appropriate size to obtain an interior cavity having a desired size.

The precursor compound preferably comprises one or more reactive units, each of which may comprise one or more (preferably two or more, most preferably two) different reactive moieties (e.g., amine moieties). The precursor compound preferably comprises multiple reactive units, such that the precursor compound preferably comprises at least six reactive moieties (e.g., amine groups, or half as many diamine groups), preferably at least 10, preferably at most 40, preferably at most 20, and most preferably 12 reactive moieties. The reactive units themselves are preferably linked, preferably by covalent bonds, via associated linker units.

The reactive units are open chains that can be linked together to form: chains that optionally contain one or more ring systems (e.g., carbocyclic, aryl, heterocyclic, heteroaryl), optionally as members of the reactive unit, the linker, or as optional substituents thereof;
a macrocycle, also optionally containing one or more ring systems as described above, and/or
A cage also optionally containing one or more ring systems as described above.

The functionalizing agent is preferably a molecular linking compound. As noted above, when more than one functionalizing agent is used, preferably more than one molecular linking compound is used.

The molecular linking compound preferably includes one or more moieties (e.g., carbonyl moieties). The molecular linking compound preferably includes a single reactive moiety (e.g., carbonyl), but the single reactive moiety may preferably be capable of reacting with two reactive moieties of a precursor compound to form a molecular linkage (or crosslink) between the two reactive moieties.

Preferably, the reaction between the precursor compound and the molecular linking compound is
reacting a precursor compound (or a synthetic equivalent thereof) comprising one or more reactive units with a molecular linking compound (or a synthetic equivalent thereof) comprising one or more reactable units to form a sorption compound (or a precursor thereof, e.g., where subsequent deprotection or other conversion steps are required to obtain a final product comprising one or more linking units);
the reactive unit(s) of the precursor compound comprise one or more (preferably two or more, most preferably two) different reactive moieties (e.g., amines);
one or more reactable units of the molecular linker compound include one or more reactable moieties (e.g., carbonyl, protected carbonyl, dihalo);
The one or more linking units of the sorption compound include one or more moieties characterized by the product of a reaction between a precursor compound and a reactive unit of the molecular linking compound.

The aforementioned reaction between a precursor compound and a molecular linking compound can be applied in the above-described context of functionalizing a precursor compound to form a sorption compound involving any, some, or all of steps i) through vi) outlined above, and the functionalizing, defunctionalizing, and/or refunctionalizing can optionally involve multiple different molecular linking compounds and multiple different linking units in the final sorption compound. Thus, the aforementioned reaction can optionally be repeated with different reactable units (e.g., with different molecular linking compounds) to obtain a heterofunctionalized sorption compound.

Preferably, corresponding reactive and reactable moieties are susceptible to react together (to form a covalent bond therebetween) under appropriate conditions. Preferably, one of the reactive or reactable moieties is electrophilic, while the other of the reactive or reactable moieties is nucleophilic. Preferably, a single reactable moiety reacts with at least two (preferably two) reactive moieties. A single linking unit is preferably formed by a single molecular linking molecule (or a single reactable moiety of a single molecular linking molecule) reacting with at least two (preferably only two) reactive moieties of a precursor compound.

The sorption compound (preferably stabilized compound) therefore preferably comprises one or more linking units, where each linking unit preferably corresponds directly to the post-reaction form of a reactive unit of the precursor compound. The linking units are therefore preferably covalently linked (as in the corresponding precursor compound) via associated linker units (preferably the same linkers as defined in relation to the precursor compound). The sorption compound preferably comprises multiple linking units (which may be identical in the case of homo-functionalized sorption compounds or different in the case of hetero-functionalized sorption compounds), so that the sorption compound preferably comprises at least 3 linking units, preferably at least 5, preferably at most 20, preferably at most 10, and most preferably 6 linking units. Furthermore, the linking units are preferably linked together in the same way as the reactive units of the original precursor compounds, i.e. to form an open chain, but optionally containing one or more ring systems (e.g. carbocyclic, aryl, heterocyclic, heteroaryl), optionally as members of the linking unit, linker or as optional substituents thereof; a macrocycle, also optionally containing one or more ring systems as described above; and/or
A cage also optionally containing one or more ring systems as described above.

The number and chemical structure of the reactive units of the precursor compound and/or the linking units of the sorption compound can be readily varied by one skilled in the art through appropriate synthetic modifications. Such parameters can be varied, as desired, to alter pore size, pore selectivity (in terms of selectivity for a particular guest compound), and/or other properties. Similarly, the chemical structure (e.g., size or molecular weight) of the molecular linking compound can also be readily varied to affect pore size, pore selectivity, and/or other properties of the final sorption compound. Thus, the precursor compound (and its porous precursor, if relevant) and molecular linking compound are preferably appropriately selected to obtain, after the aforementioned reaction, a sorption compound that is more stable than the precursor compound and has at least sufficient porosity for the desired application (e.g., pores of sufficient shape and size to allow the sorption compound to act as a host for the selected guest compound).

Preferably, the portions of the precursor compound other than the "reactive moiety" are (substantially) inert, preferably inert, to certain reactive moieties of the molecular linking compound, and particularly under the prevailing reaction conditions, preferably inert to both electrophiles and nucleophiles.

Preferably, the portions of the molecular linking compound other than the "reactive portion" are (substantially) inert, preferably inert, to certain reactive portions of the precursor compound, and particularly under the prevailing reaction conditions, preferably inert to both electrophiles and nucleophiles.

Preferably, a linker or its substituents of the precursor compound are (substantially) inert, preferably inert, to a reactive moiety of the precursor compound or a reactable moiety of the molecular linking compound, and in particular, under the prevailing reaction conditions, are preferably inert to both electrophiles and nucleophiles.

In certain embodiments, the reaction is
Formula A

A precursor compound (or a synthetic equivalent thereof) containing one or more reactive units defined by formula B

(or a synthetic equivalent thereof) wherein
n is an integer between 1 and 4,
each _R and _R group is independently hydrogen or an optionally substituted substituent, and any pair of R and _R groups are optionally joined together to form a carbocyclic, heterocyclic, _aryl , or heteroaryl ring;
each _R and _R group is independently hydrogen or an optionally substituted substituent, and any pair of R and _R groups is optionally joined together to form a carbocyclic, heterocyclic, _aryl , or heteroaryl ring;
formula C

to produce a sorption compound containing one or more linking units defined by

In the above situation, formula C is formula D

It is sometimes said to contain a "molecular linkage" that can be defined as two groups.

Formula C is:

(where Tie is a molecular linkage defined by formula D)

The foregoing reactions can be applied in the above-described context of functionalizing precursor compounds to form sorption compounds involving any, some, or all of steps i) through vi) outlined above, where the functionalizing, defunctionalizing, and/or refunctionalizing can optionally involve multiple different molecular linking compounds (and multiple different linking units) independently selected from the definitions above. Thus, the foregoing reactions can optionally be repeated with different reactable units (e.g., with different molecular linking compounds resulting in different linking units) to obtain heterofunctionalized sorption compounds. In such a context, either or both of R and _{R of} the different molecular linking compounds are different.

The units of formula A and C are represented in divalent form by bonds (which may be considered groups or "connectable bonds") intersected by square brackets. These units may be possible repeating units when the compound in question contains two or more of said units (which is the common case). As explained in detail below, the precursor compound and its corresponding sorption compound may preferably contain multiple units of formula A and formula C, respectively, linked together via their "connectable bonds" (preferably to form open-chain, macrocyclic, or caged compounds/molecules), preferably via intervening linkers. Such linkers may link two or more units of formula A and/or C together, and in some embodiments, link three such units. Thus, the linkers are preferably multivalent (e.g., divalent, trivalent).

The sorption compound preferably comprises one or more units of formula C and, optionally, zero, one or more units of formula A, preferably linked together via an intervening linker.

According to the present invention, the aforementioned units of formula A, B and C (and molecular linkages of formula D), and by extension the corresponding compounds (or synthetic equivalents thereof), as well as any linkers therebetween, may have any structure as defined herein, unless otherwise specified, wherein n, R _A1 , R _A2 , R _B1 , and R _B2 each have any of the meanings defined herein above or in the following paragraphs.
(1) n is an integer between 2 and 3
(2) n is 2
(3) each R _A1 and R _A2 is independently selected from hydrogen or any inert group (e.g., inert to electrophiles, preferably to carbonyls, preferably inert in relation to molecular linking compounds), and R _A1 and R _A2 combine such that they together form a carbocyclic, aryl, heterocyclic, or heteroaryl ring, and preferably each R _A1 /R _A2 pair (i.e., attached to the same carbon atom) contains an inert group having a collective molecular weight of less than 200, preferably less than 100, preferably less than 70;
(4) R _A1 and R _A2 are independently selected from the group consisting of hydrogen, (1-2C) alkyl, or R _A1 and R _A2 are joined such that they together form a carbocyclic ring.
(5) R _A1 and R _A2 are linked together so that they together form a (3-8C)cycloalkyl ring.
(6) R _A1 and R _A2 are linked together so that they together form a cyclohexane ring
(7) Each R and _R is independently selected from hydrogen or any inert group (e.g., inert to nucleophiles, preferably to amines, preferably inert with respect to the precursor compound), and _R and _R combine such that they together form a carbocyclic, aryl, heterocyclic, or heteroaryl ring, and preferably each _R / _R pair (i.e., attached to the same carbon atom) contains an _inert group having a collective molecular weight of less than 100, preferably less than 50, preferably less than 31, preferably less than 5.
(8) R _B1 and R _B2 are independently selected from the group consisting of hydrogen, (1-3C) alkyl, or R _B1 and R _B2 are optionally joined so that they together form a carbocycle, heterocycle, aryl ring, or heteroaryl ring.
(9) R _B1 and R _B2 are independently selected from the group consisting of hydrogen and (1-2C) alkyl.
(10) R _B1 and R _B2 are independently selected from the group consisting of hydrogen, methyl, and ethyl.
(11) R _B1 and R _B2 are independently selected from the group consisting of hydrogen and methyl.
(12) R _B1 and R _B2 are both hydrogen.
(13) R _B1 and R _B2 are both methyl.
(14) R _B1 is hydrogen and R _B2 is methyl
(15) R _B1 is hydrogen and R _B2 is ethyl
(16) The precursor compound and/or the sorption compound each contain at least three units of formula A and/or formula C.
(17) The precursor compound and/or the sorption compound each contain at least 5 units of formula A and/or formula C.
(18) The precursor compound and/or the sorption compound each contain at most 20 units of formula A and/or formula C, more preferably at most 10 units of formula A and/or formula C, respectively.
(19) The precursor compound and/or the sorption compound contain six units of formula A and/or formula C, respectively;
(20) Units of formula A and/or formula C are directly or indirectly covalently linked together (preferably in series and/or in parallel, i.e., linear or branched) to form open chain, macrocyclic and/or cage structures.
(21) Units of formula A and/or formula C are directly or indirectly covalently linked together to form macrocyclic and/or cage structures.
(22) Units of formula A and/or formula C are directly or indirectly covalently linked together to form a cage structure (e.g., an organic cage molecule).
(23) The units of formula A and/or formula C are covalently linked together via between 1 and 8 intervening atoms (preferably carbon atoms), preferably between 4 and 6 intervening atoms (preferably carbon), most preferably 5 intervening carbon atoms.
(24) The units of formula A and/or formula C are covalently linked together via an intervening linker of formula -L ₁ -
(25) -L ₁ - is a polyvalent group representing the aforementioned number of intervening atoms between adjacent units of formula A and/or formula C.
(26) -L ₁ - is selected from the group consisting of polyvalent hydrocarbons (linear or branched), polyvalent carbocycles, polyvalent heterocycles, polyvalent arenes, polyvalent heteroarenes, polyvalent mono-/poly-hydrocarbyl-carbocycles, polyvalent mono-/poly-hydrocarbyl-heterocycles, polyvalent mono-/poly-hydrocarbyl-arenes and polyvalent mono-/poly-hydrocarbyl-heteroarenes (mono-/poly- indicating that the ring system in question contains one or more hydrocarbyl substituents, respectively).
(27) -L ₁ - is selected from the group consisting of polyvalent (1-8C)alkanes, polyvalent (2-8C)alkenes, polyvalent (3-8C)cycloalkanes, polyvalent mono-/poly-[(1-8C)alkyl]-(3-8C)cycloalkanes, polyvalent (3-8C)cycloalkenes, polyvalent mono-/poly-[(1-8C)alkyl]-(3-8C)cycloalkenes, polyvalent heterocycles, polyvalent mono-/poly-[(1-8C)alkyl]-heterocycles, polyvalent arenes, polyvalent mono-/poly-[(1-8C)alkyl]-arenes, polyvalent heteroarenes and polyvalent mono-/poly-[(1-8C)alkyl]-heteroarenes.
(28)-L ₁ - is selected from the group consisting of polyvalent (4-6C)alkanes, polyvalent (4-6C)alkenes, polyvalent (5-6C)cycloalkanes, polyvalent mono-/poly-[(1-2C)alkyl]-(5-6C)cycloalkanes, polyvalent (5-6C)cycloalkenes, polyvalent mono-/poly-[(1-2C)alkyl]-(5-6C)cycloalkenes, polyvalent heterocycles, polyvalent mono-/poly-[(1-2C)alkyl]-heterocycles, polyvalent arenes, polyvalent mono-/poly-[(1-2C)alkyl]-arenes, polyvalent heteroarenes and polyvalent mono-/poly-[(1-2C)alkyl]-heteroarenes.
(29)-L ₁ - is selected from the group consisting of polyvalent poly-[(1-2C)alkyl]-(5-6C)cycloalkanes, polyvalent poly-[(1-2C)alkyl]-(5-6C)cycloalkenes, polyvalent poly-[(1-2C)alkyl]-heterocyclyls, polyvalent poly-[(1-2C)alkyl]-arenes and polyvalent poly-[(1-2C)alkyl]-heteroarenes.
(30)-L ₁ - is a polyvalent poly-[(1-2C)alkyl]-arene
(31) -L ₁ - is a trivalent tri-[(1-2C)alkyl]-arene
(32) -L ₁ - is selected from the group consisting of benzene-trimethylene
(33) -L ₁ - is selected from the group consisting of benzene-1,3,5-trimethylene;
(34) The molecular linking compound is selected from formaldehyde and/or acetone.
(35) The molecular linking compound is formaldehyde.
(36) Any one or more of the R _A1 , R _A2 , R _B1 , R _B2 and -L ₁ - groups may optionally be substituted (preferably so long as the corresponding molecules of the collapsible and molecularly linked react together to produce a porous material whose physical structure is more stable than that of the precursor compound and whose pores are sufficiently available to accommodate one or more guest compounds);
(37) In any of the aforementioned R _A1 , R _A2 , R _B1 , R _B2 and -L ₁ - groups, any of the CH, CH ₂ or CH ₃ groups optionally carries on each said CH, CH ₂ or CH ₃ group one or more substituents selected from halogeno, hydroxy, mercapto, amino, cyano, carboxy, carbamoyl, ureido, (1-3C) alkyl, hydroxy(1-3C) alkyl, (1-3C) alkoxy, halo(1-3C) alkoxy, (1-3C) alkylthio, (1-3C) alkylamino and di-[(1-3C) alkyl] amino.
(38) In any of the aforementioned R _A1 , R _A2 , R _B1 , R _B2 and -L ₁ - groups, any of the CH, CH ₂ or CH ₃ groups optionally carries one or more substituents on each of said CH, CH ₂ or CH ₃ groups selected from halogeno, hydroxy, mercapto, amino, methyl, hydroxymethyl, methoxy, trifluoromethoxy, trichloromethoxy, methylthio, methylamino and dimethylamino.
(39) In any of the foregoing R _A1 , R _A2 , R _B1 , R _B2 and -L ₁ -, all of the CH, CH ₂ or CH ₃ groups are unsubstituted.

In certain embodiments, R _A1 , R _A2 and -L ₁ - are selected such that the precursor compound comprises multiple reactive units of formula A ₁ , each reactive unit being indirectly linked (through its connectable bond, also represented by a square bracket) to an adjacent, different reactive unit via an intervening linker unit of formula A _1L .

(Wherein, ring A is a carbocyclic ring, an aryl ring, a heterocyclic ring, or a heteroaryl ring,

Ring L is a polyvalent hydrocarbon (linear or branched), polyvalent carbocycle, polyvalent heterocycle, polyvalent arene, polyvalent heteroarene, polyvalent mono-/poly-hydrocarbyl-carbocycle, polyvalent mono-/poly-hydrocarbyl-heterocycle, polyvalent mono-/poly-hydrocarbyl-arene or polyvalent mono-/poly-hydrocarbyl-heteroarene (it should be implied from this specification that the linker of formula A _1L in the brackets indicated for both species is attached to the reactive unit of formula A ₁ , but it should also be implied that for the linker, the relevant bond or group available for connection may be derived from the core ring structure or, if applicable, from one of the hydrocarbyl substituents of the core ring), and either group of formula A ₁ or A _1L is optionally substituted as defined herein. In this embodiment, the precursor compound preferably comprises units of formula A ₁ and A _1L in a molar ratio of 3:2 (e.g., 6 units of A ₁ and 4 units of A _1L ), respectively. For application of this embodiment, ring A can be replaced with a (2-3C) alkylene group between the relevant amine moieties to produce an alkylenediamine. The corresponding sorption compound preferably comprises at least one (preferably at least two, preferably six, preferably all) reactive units of formula A ₁ , each of which is a hydroxyl group of formula C ₁

The compound has the same structure as the precursor compound, except that the linking unit is: (wherein R _B1 and R _B2 have any of the definitions provided herein).

In certain embodiments, R _A1 , R _A2 and -L ₁ - are selected such that the precursor compound comprises at least three reactive units of formula A ₁ , each reactive unit being indirectly linked to an adjacent different reactive unit via an intervening linker unit of formula A _1L ;
Ring A is a (5-6C) cycloalkane;
ring L is a polyvalent poly-[(1-2C)alkyl]-(5-6C)cycloalkane, a polyvalent poly-[(1-2C)alkyl]-(5-6C)cycloalkene, a polyvalent poly-[(1-2C)alkyl]-heterocyclyl, a polyvalent poly-[(1-2C)alkyl]-arene or a polyvalent poly-[(1-2C)alkyl]-heteroarene;
Either group of formula A ₁ or A _1L is optionally substituted as defined herein.

In certain embodiments, R _A1 , R _A2 -L ₁ -, ring A, and ring L are selected such that the precursor compound comprises multiple reactive units of formula A ₂ , each reactive unit being indirectly linked to an adjacent different reactive unit via an intervening linker unit of formula A _2L ;

Either the groups of formula _A2 or _A2L are optionally substituted as defined herein, but most preferably they are unsubstituted. In this embodiment, the precursor compound preferably comprises units of formula _A2 and _A2L in a 3:2 molar ratio (e.g., six units of _A2 and four units of _A2L ), respectively. For application of this embodiment, the cyclohexane rings can be replaced with (2-3C) alkylene groups between the relevant amine moieties to produce alkylenediamines, and optionally the benzene rings of the linker are replaced with heteroarene rings. The corresponding sorption compound preferably comprises at least one (preferably at least two, preferably six, preferably all) reactive units of formula _A2 , each of which is a group of formula _C2

(wherein R _B1 and R _B2 have any of the definitions provided herein, but most preferably are both hydrogen or both methyl) linking units. Preferably, when R _B1 and R _B2 are both hydrogen (i.e., derived from a formaldehyde molecular linking compound), two or more, preferably all, reactive units of the precursor compound are linking units. Preferably, when R _B1 and R _B2 are both methyl (i.e., derived from an acetone molecular linking compound), only one reactive unit of the precursor compound is a linking unit.

Preferably, the sorption compounds of the present invention have a structure directly corresponding to (or based directly on) any of the embodiments and/or definitions set forth herein relating to precursor compounds, having two or more of the reactive moieties of the precursor compound reacted with a molecular linking compound to form the corresponding molecular linkages between the reactive moieties. This is self-evident from the above, where a reactive unit of Formula A directly corresponds to a linking unit of Formula C. The sorption compounds also preferably contain the same linkers that connect the reactive/linking units in the same manner as the corresponding precursor compounds. Preferably, each reactive unit of the precursor compound contains two reactive moieties. Preferably, any, some, or all of the molecular linkages between the reactive moieties are between two reactive moieties within the same reactive unit. Thus, preferably, the sorption compound is its corresponding precursor compound with one or more reactive units converted into linking units. The sorption compound may contain both reactive units and linking units, so long as at least one linking unit is present. In a preferred embodiment, the sorption compound contains two or more linking units. In certain embodiments, the sorption compound comprises two or more, preferably three or more, preferably five or more, preferably six linking units, and preferably is (substantially) free of reactive units (i.e., all reactive units have reacted to form linking units).

The sorption compound preferably comprises one or more units of formula C (or a formula defined thereunder) and zero, one or more units of formula A (or a formula defined thereunder), optionally preferably linked together via an intervening linker.

Preferably, the sorption compound comprises c units of formula C (or a formula defined accordingly) and a units of formula A (or a formula defined accordingly), optionally linked together via an intervening linker. The sum of c and a is preferably at least 2, preferably at least 3, preferably at most 18, preferably at most 12, most preferably 6, c is at least 1 and a is 0, 1 or more (a is most preferably 0 or 1). The units of formula A are therefore not functionalized and therefore do not contain any molecular linkages (of formula D). Preferably, the units of formula C, and, where applicable, formula A, are linked together, optionally via an intervening linker, in a way to form a cage with an internal cavity. The molecular linkages of formula D, and preferably any of the relevant _R and _R groups, are preferably located within the cavity or at its interface.

In certain embodiments, a sorption compound comprising c units of formula C (or formulas defined accordingly) and a units of formula A (or formulas defined accordingly) contains only a single type of molecular linkage (of formula D). In some embodiments, the sorption compound contains only a single type of molecular linkage (of formula D), where c is either 0 or 1 (most preferably 0), while c is between 4 and 12 (most preferably c is 6). Examples of such embodiments include when the single molecular linkage of formula D (and thus the molecular linkage compound used to form it) is selected from the group consisting of:
R _B1 and R _B2 are both hydrogen (e.g. linked by formaldehyde);
R _B1 and R _B2 are both methyl (e.g., linked by acetone), and
R _B1 is hydrogen and R _B2 is methyl (eg linked with acetaldehyde).

In certain embodiments, a sorption compound comprising c units of formula C (or formulas defined therein) and a units of formula A (or formulas defined therein) comprises two or more (most preferably exactly two) different types of molecular linkages (of formula D). In such embodiments, preferably a is either 0 or 1 (most preferably 0) and c is between 4 and 12 (c is most preferably 6). Thus, one or more units of formula C comprise one type of molecular linkage (of formula D), while one or more other units of formula C comprise a different type of molecular linkage (of formula D). Examples of such embodiments using different molecular linkages of formula D (and therefore molecular linkage compounds used to form same) are selected from the group consisting of:
i.e., a first molecular linkage in which _R and _R are both hydrogen (e.g., formaldehyde linked), and a second molecular linkage in which _R is hydrogen and R is _methyl (e.g., acetaldehyde linked), preferably in a molar ratio of the first molecular linkage to the second molecular linkage between 1:6 and 12:1, most preferably between 2:1 and 6:1, and most preferably 5:1.
ii. a first molecular linkage in which _R and _R are both hydrogen (e.g., linked by formaldehyde) and a second molecular linkage in which R and _R are both _methyl (e.g., linked by acetone), preferably the molar ratio of the first molecular linkage to the second molecular linkage is between 1:6 and 12:1, most preferably between 2:1 and 6:1, most preferably 5:1;
iii. A first molecular linkage where _R and _R are both hydrogen (e.g., linked by formaldehyde), and a second molecular linkage where _R is hydrogen and _R is ethyl (e.g., linked by propionaldehyde), preferably the molar ratio of the first molecular linkage to the second molecular linkage is between 1:6 and 12:1, most preferably between 2:1 and 6:1, and most preferably 5:1.

In certain embodiments, a sorption compound comprising c units of formula C (or a formula defined therein) and a units of formula A (or a formula defined therein) comprises two or more (most preferably exactly two) different types of molecular linkages (of formula D), one type of molecular linkage being larger (preferably having more carbon atoms) than the other type of molecular linkages.

In certain embodiments, the precursor compound is defined by formula A3 (referred to elsewhere herein and in related citations as RCC3):

For all of the foregoing embodiments, the precursor compound is optionally formed by reduction of the corresponding porous precursor compound (i.e., an imine compound), e.g., by converting each amine moiety of the reactive unit to a nitrogen atom, which forms a direct imine bond with the carbon atom adjacent to the linker, thereby attaching the bond to the linker. For example, a precursor compound of formula A3 can be formed by reduction of a precursor compound of formula E3.

The bold line corresponds to that of formula A3.

As can be seen, the precursor compound of formula A3 (RCC3) has six pairs of diamines, each of which can be aminalized via the aforementioned molecular linking compounds to form the corresponding molecular linkages bridging each diamine pair. Therefore, the sorption compound of formula C can be defined according to formula C3:

where Tie/ _H2 refers to either a diamine group linked with Tie or a diamine group not linked with the single hydrogen carried by each diamine nitrogen, Tie is a molecular linkage defined by formula D, and the sorption compound contains at least one Tie.

Sorption compounds of formula C3 comprise c units of formula _C2 and a units of formula _A2 , all linked together via four intervening linkers of formula _A2L , where the sum of c and a is 6, c is an integer between 1 and 6, and a is an integer between 0 and 5. As previously explained, when two or more Tie groups are present, the Tie groups can be the same or different. Sorption compounds of formula C3 herein are also referred to as xXT-yYT-zZT-RCC3, where XT, YT, and ZT represent different Tie groups, x, y, and z similarly represent the respective numbers of each Tie group present in the molecule, and each of x, y, and z can be an integer between 0 and 6, provided that the sum of x, y, and z is an integer between 1 and 6.

In certain embodiments, the sorption compound of formula C3 contains only a single type of molecular linkage (the Tie group of formula D). Examples of such embodiments (and thus the molecular linkage compound used to form the sorption compound) include those where the single molecular linkage of formula D is selected from the group consisting of:
R _B1 and R _B2 are both hydrogen (e.g. linked by formaldehyde), e.g. 6FT-RCC3 or 5FT-RCC3;
R _B1 and R _B2 are both methyl (e.g. linked by acetone), e.g. 1AT-RCC3, and
R _B1 is hydrogen and R _B2 is methyl (eg linked with an acetaldehyde), such as 6ET-RCC3.

In certain embodiments, the sorption compound of formula C3 comprises two or more (most preferably exactly two) different types of molecular linkages (Tie groups of formula D). Examples of such embodiments having different molecular linkages of formula D (and therefore molecular linkage compounds used to form the sorption compound) are selected from the group consisting of:
i.e., a first molecular linkage in which _R and _R are both hydrogen (e.g., formaldehyde linked), and a second molecular linkage in which R is _hydrogen and _R is methyl (e.g., acetaldehyde linked), e.g., 1ET-5FT-RCC;
ii. a first molecular linkage where _R and _R are both hydrogen (e.g., linked by formaldehyde), and a second molecular linkage where R and _R are both methyl (e.g., linked by acetone), e.g., 1AT- _5FT -RCC; and
iii. A first molecular linkage where _R and _R are both hydrogen (e.g., linked by formaldehyde), and a second molecular linkage where _R is hydrogen and R is ethyl (e.g., linked by propionaldehyde), e.g., 1PT-5FT- _RCC3 .

In certain embodiments, the sorption compound is selected from the group consisting of 6FT-RCC3, 5FT-RCC3, 6ET-RCC3, 1AT-RCC3, 1ET-5FT-RCC3, 1AT-5FT-RCC3, and 1PT-5FT-RCC3.

In certain embodiments, the sorption compound is selected from the group consisting of 5FT-RCC3, 6ET-RCC3, 1ET-5FT-RCC3, 1AT-5FT-RCC3, and 1PT-5FT-RCC3.

In certain embodiments, the sorption compound is as defined anywhere herein, provided that the sorption compound is not 6FT-RCC3 or 1AT-RCC3.

In certain embodiments, the sorption compound is 6ET-RCC3, which corresponds to a sorption compound of formula C3, in which all Tie groups are identical, R _B1 of the Tie groups is hydrogen, R _B2 of the Tie groups is methyl (e.g., linked by acetaldehyde), c is 6, and a is 0.

When the sorption compound is chiral, it may be a racemic mixture or may be enantiomerically pure (or enantiomerically enriched) as a single enantiomer. Where applicable, the (major) enantiomer of the sorption compound is preferably of opposite chirality to that of any corresponding co-crystallized compound.

Crystal Structure and Isomorphous Crystallization The sorption compound is preferably crystallized to obtain sorption compound crystals or crystalline sorption compounds. The crystalline sorption compound preferably comprises intrinsic voids (i.e., internal cavities). The crystalline sorption compound also preferably comprises external voids (preferably between individual sorption compound molecules). The combination of intrinsic and external voids preferably results in an interconnected three-dimensional (3D) porous network comprising continuous porous channels.

The sorption compound preferably has a diamondoid pore network.

Cavity Size The sorption compound preferably has an internal cavity capable of accommodating a guest, in this case preferably a target substance. The internal cavity is preferably sized to accommodate the target substance (or target substances).

The cavity size preferably corresponds to the smallest dimension of the internal cavity, which is considered the "pore size." The cavity size is preferably larger than the size (or largest dimension) of the target material. The cavity size may be larger than the size (or largest dimension) of non-target materials. The size of the target material may be determined as defined herein in relation to the "size" of the material.

The sorption selectivity advantages associated with the present invention are realized when the size difference between the target compound (or non-target compound, particularly when the atomic or molecular sizes of the target and non-target compounds are the same or similar) and the cavity size is comparable to the thermal de Broglie wavelength of the target compound (and/or non-target compound). Therefore, when hydrogen is the non-target compound, the advantages of the present invention can be realized with a cavity size (or pore diameter) of 5 Å or less.

Preferably, the cavity size is similar to the de Broglie wavelength, preferably the thermal de Broglie wavelength, of the target material. The cavity size is preferably numerically closer to the de Broglie wavelength, preferably the thermal de Broglie wavelength, of the target material than to the de Broglie wavelength, preferably the thermal de Broglie wavelength, of non-target materials. The cavity size is believed to increase selectivity for the target material over non-target materials.

Preferably, the aforementioned size, whether it be the cavity size or the size of the target substance (or its corresponding molecule), is an average (e.g., median, or other statistical average, e.g., Boltzmann mean) size.

The cavity size can be determined by measurement (e.g., by molecular dynamics (MD) simulation) or calculation, taking into account molecular flexibility, to ascertain the time-averaged pore limit envelope (PLE) rather than a single static pore diameter (e.g., PLD). A particular PLE value preferably refers to the PLE centered around that value.

Preferably, the difference between the cavity size of the sorption compound at the SATP or at the contact temperature and the size of the target substance (e.g., the van der Waals diameter or effective van der Waals diameter of the atoms or molecules) is within +/- 5 Å, preferably within +/- 4 Å, preferably within +/- 3.5 Å, preferably within +/- 2 Å, preferably within +/- 1 Å, preferably within +/- 0.5 Å of the de Broglie wavelength of the target substance at the SATP or at the contact temperature, respectively. Preferably, the difference between the cavity size of the sorption compound at the SATP or at the contact temperature and the size of the target substance (e.g., the van der Waals diameter or effective van der Waals diameter of the atoms or molecules) is at most 0.4 Å, preferably at most 0.3 Å, preferably at most 0.2 Å of the de Broglie wavelength of the target substance at the SATP or at the contact temperature, respectively.

Preferably, the cavity size of the sorption compound in the SATP is within +/- 5 Å of the de Broglie wavelength of the target substance in the SATP. Preferably, the cavity size of the sorption compound in the SATP is within +/- 4 Å of the de Broglie wavelength of the target substance in the SATP. Preferably, the cavity size of the sorption compound in the SATP is within +/- 3.5 Å of the de Broglie wavelength of the target substance in the SATP. More preferably, the cavity size of the sorption compound in the SATP is within +/- 2 Å of the de Broglie wavelength of the target substance in the SATP. Preferably, the cavity size of the sorption compound in the SATP is within +/- 1 Å of the de Broglie wavelength of the target substance in the SATP. Preferably, the cavity size of the sorption compound in the SATP is within +/- 0.5 Å of the de Broglie wavelength of the target substance in the SATP.

Preferably, the cavity size of the sorption compound at the contact temperature is within +/- 5 Å of the de Broglie wavelength of the target material at the contact temperature. Preferably, the cavity size of the sorption compound at the contact temperature is within +/- 4 Å of the de Broglie wavelength of the target material at the contact temperature. Preferably, the cavity size of the sorption compound at the contact temperature is within +/- 3.5 Å of the de Broglie wavelength of the target material at the contact temperature. More preferably, the cavity size of the sorption compound at the contact temperature is within +/- 2 Å of the de Broglie wavelength of the target material at the contact temperature. Preferably, the cavity size of the sorption compound at the contact temperature is within +/- 1 Å of the de Broglie wavelength of the target material at the contact temperature. Preferably, the cavity size of the sorption compound at the contact temperature is within +/- 0.5 Å of the de Broglie wavelength of the target material at the contact temperature. Preferably, the cavity size of the sorption compound at the contact temperature is within +/- 0.4 Å of the de Broglie wavelength of the target material at the contact temperature.

Preferably, the cavity size in SATP is at most 6.0 Å. Preferably, the cavity size in SATP is at most 5.0 Å. Preferably, the cavity size in SATP is between 0.1 and 4.0 Å. Preferably, the cavity size in SATP is between 0.2 and 3.5 Å. Preferably, the cavity size in SATP is between 0.3 and 3.0 Å. Preferably, the cavity size in SATP is between 0.5 and 2.5 Å. Preferably, the cavity size in SATP is between 1 and 2.4 Å. Preferably, the cavity size in SATP is between 1.5 and 2.3 Å. Preferably, the cavity size in SATP is between 1.6 and 2.1 Å. In certain embodiments, the cavity size is between 1.9 and 2.0 Å.

Preferably, the cavity size at the contact temperature is at most 6.0 Å. Preferably, the cavity size at the contact temperature is at most 5.0 Å. Preferably, the cavity size at the contact temperature is between 0.1 and 4.0 Å. Preferably, the cavity size at the contact temperature is between 0.2 and 3.5 Å. Preferably, the cavity size at the contact temperature is between 0.3 and 3.0 Å. Preferably, the cavity size at the contact temperature is between 0.5 and 2.5 Å. Preferably, the cavity size at the contact temperature is between 1 and 2.4 Å. Preferably, the cavity size at the contact temperature is between 1.5 and 2.3 Å. Preferably, the cavity size at the contact temperature is between 1.6 and 2.1 Å. In certain embodiments, the cavity size is between 1.9 and 2.0 Å.

The sorption compound is preferably porous to protium, preferably at SATP and/or preferably at the relevant contact temperature. The sorption compound is preferably porous to deuterium, preferably at SATP and/or preferably at the relevant contact temperature. The sorption compound is preferably porous to protium and deuterium, preferably at SATP and/or preferably at the relevant contact temperature.

When the sorption compound crystallizes to provide sorption compound crystals or a crystalline sorption compound, the sorption compound preferably includes external voids that are larger than the cavity size, although in some embodiments the external voids may be slightly smaller than the cavity size. Preferably, the size of the external voids of the sorption compound is within 1 Å of the cavity size of the sorption compound, preferably within 0.5 Å, and preferably within 0.2 Å.

Methods for Preparing Sorption Compounds The present invention provides a method for preparing a sorption compound, comprising reacting a precursor compound, as defined herein, with a molecular linking compound.

The present invention provides a method for preparing a sorption compound, comprising obtaining a precursor compound as defined herein, the precursor compound being a porous organic cage comprising an internal cavity carrying one or more functionalizable groups, and functionalizing one or more of the functionalizable groups to modify (preferably reduce) the size of the internal cavity. Preferably, functionalization of the internal cavity does not alter the crystalline structure of the sorption compound.

The functionalizable groups of the internal cavity are preferably appropriately functionalized to obtain the desired cavity size. Thus, functionalizing the internal cavity preferably constitutes fine-tuning of the internal cavity and/or cavity size (and/or cavity-window size).

The functionalization of the precursor compound to form the sorption compound is preferably carried out by
i) functionalizing one or more functionalizable groups (or one or more sets or pairs of functionalizable groups) with a first functionalizing agent to obtain one or more first functionalized groups;
ii) functionalizing one or more other functionalizable groups (or one or more other sets or pairs of functionalizable groups) with a second functionalizing agent to obtain one or more second functionalized groups;
iii) defunctionalizing (or deprotecting) one or more of the first functionalized groups to obtain one or more first defunctionalized groups, preferably corresponding to the functionalizable groups to be regenerated;
iv) optionally re-functionalizing one or more of the first defunctionalized groups with a third functionalizing agent that is the same as or different from either the first or second functionalizing agent to obtain one or more third functionalized groups;
v) defunctionalizing (or deprotecting) one or more of the second functionalized groups to obtain one or more second defunctionalized groups, preferably corresponding to the functionalizable groups to be regenerated;
vi) optionally re-functionalizing one or more of the second defunctionalized groups with a functionalizing agent that is the same as or different from any of the first, second, or third functionalizing agents to obtain one or more fourth functionalized groups.

Preferably, functionalization of the precursor compound includes at least step i), and in some embodiments, only step i) (steps i) through vi), thereby obtaining a homo-functionalized sorption compound formed from a single functionalizing material.

In some embodiments, functionalization of the precursor compound includes at least steps i) and ii), and in some embodiments, only steps i) and ii) (steps i) through vi) to obtain a heterofunctionalized sorption compound formed from two different functionalizing materials.

In some embodiments, functionalization of the precursor compound includes at least steps i), ii), and iii), and in some embodiments, only steps i), ii), and iii) (steps i) through vi), thereby obtaining a homo-functionalized sorption compound formed from a single functionalizing material (although preferably less functionalized and, optionally, having a smaller cavity size than a corresponding method involving only step i) using the same functionalizing material).

In some embodiments, functionalization of the precursor compound includes at least steps i), ii), iii), and iv), and in some embodiments, only steps i), ii), iii), and iv) (steps i) through vi), thereby obtaining a heterofunctionalized sorption compound (second and third functionalized compounds) formed from two different functionalized substances. In such embodiments, step i) acts as a protecting step, introducing the first functionalized substance as a protecting group that is subsequently removed in step iii).

In some embodiments, further refinement can be performed where a second functionalization is also a protecting step, and such embodiments can include all of steps i) through v) or all of steps i) through vi).

The functionalization of the precursor compound to form the sorption compound may suitably include:
functionalization with a single linking compound, whether partial (i.e. functionalization of some but not all of the functionalizable groups within the internal cavity) or complete (i.e. functionalization of all of the functionalizable groups within the internal cavity);
- partial functionalization with a first linking compound, where the first linking compound is larger (sterically) than the second linking compound, followed by functionalization with a second linking compound;
- partial functionalization with a first linking compound, where the first linking compound is larger (sterically) than the second linking compound, followed by functionalization with a second linking compound, and then defunctionalization (deprotection) of the first linking compound;
- partial functionalization with a first linking compound, where the first linking compound is larger (sterically) than the second linking compound, followed by functionalization with a second linking compound, then defunctionalization (deprotection) of the first linking compound, and refunctionalization with a third linking compound.

The method for preparing the sorption compound may suitably include reacting RCC3 with formaldehyde (or a synthetic equivalent thereof, such as paraformaldehyde, or an acetal or hemiacetal of formaldehyde) to produce the sorption compound 6FT-RCC3.

The method for preparing the sorption compound may suitably include reacting RCC3 with acetaldehyde (or a synthetic equivalent thereof) to produce the sorption compound 6ET-RCC3.

The method for preparing the sorption compound may suitably include reacting RCC3 with acetone (or a synthetic equivalent thereof) to produce the sorption compound 1AT-RCC3.

The method for preparing the sorption compound may suitably include reacting RCC3 with acetone (or a synthetic equivalent thereof) to form the sorption compound 1AT-RCC3, and then reacting 1AT-RCC3 with formaldehyde (or a synthetic equivalent thereof) to form the sorption compound 1AT-5FT-RCC3.

The method for preparing the sorption compound may suitably include reacting RCC3 with acetone (or a synthetic equivalent thereof) to form the sorption compound 1AT-RCC3, then reacting 1AT-RCC3 with formaldehyde (or a synthetic equivalent thereof) to form the sorption compound 1AT-5FT-RCC3, and then removing (deprotecting) the acetone linkage to form 5FT-RCC3.

The method for preparing the sorption compound may suitably include reacting RCC3 with acetone (or a synthetic equivalent thereof) to form the sorption compound 1AT-RCC3, then reacting 1AT-RCC3 with formaldehyde (or a synthetic equivalent thereof) to form the sorption compound 1AT-5FT-RCC3, then removing (deprotecting) the acetone linkage to form 5FT-RCC3, and then reacting 5FT-RCC3 with acetaldehyde (or a synthetic equivalent thereof) to form the sorption compound 1ET-5FT-RCC3.

The method for preparing the sorption compound may suitably include reacting RCC3 with acetone (or a synthetic equivalent thereof) to form the sorption compound 1AT-RCC3, then reacting 1AT-RCC3 with formaldehyde (or a synthetic equivalent thereof) to form the sorption compound 1AT-5FT-RCC3, then removing (deprotecting) the acetone linkage to form 5FT-RCC3, and then reacting 5FT-RCC3 with propionaldehyde (or a synthetic equivalent thereof) to form the sorption compound 1PT-5FT-RCC3.

All reactions are preferably carried out in solution.

The present invention provides a method for preparing a sorption compound, comprising the steps of:
The sorption compound is a porous organic cage comprising an interior cavity having one or more functionalizable groups, and optionally chemically modifying the interior cavity of the sorption compound (post-functionalizing) by protecting some, but not all, of the functionalizable groups in the interior cavity with protecting groups, functionalizing one or more unprotected functionalizable groups, deprotecting the protected functionalizable groups, and optionally subsequently further functionalizing one or more unprotected functionalizable groups.

The present invention provides a method for fine-tuning the internal cavity of a porous organic cage, comprising obtaining a precursor compound as defined herein, which precursor compound is a porous organic cage comprising an internal cavity carrying one or more functionalizable groups, and selectively functionalizing one or more of the functionalizable groups to fine-tune (preferably reduce) the size of the internal cavity. Preferably, functionalization of the internal cavity does not alter the crystalline structure of the sorption compound. The method of fine-tuning preferably comprises carrying out the steps of the method for preparing a sorption compound as defined herein. The method may further comprise subsequently using the sorption compound in a sorption method (or other related method, e.g., an extraction method) as defined herein.

According to one aspect of the present invention, there is provided a method for preferentially sorbing one or more target substances over one or more non-target substances from a target mixture comprising, consisting essentially of, or consisting of target substances and non-target substances, the method comprising:
preparing a pre-functionalized sorption compound, wherein the sorption compound is a porous organic cage containing an interior cavity having one or more functionalizable groups;
Optionally chemically modifying the interior cavity of the sorption compound (post-functionalizing) by protecting some, but not all, of the functionalizable groups in the interior cavity with protecting groups, functionalizing one or more unprotected functionalizable groups, deprotecting the protected functionalizable groups with protecting groups, and optionally then further functionalizing one or more unprotected functionalizable groups; and
Methods are provided that include contacting a sorption composition (or a device comprising a sorption composition) with a target mixture, wherein the sorption composition comprises, consists essentially of, or consists of a sorption compound and, optionally, a co-crystallized compound.

Co-crystallized Compounds Co-crystallized compounds may be defined according to any of the definitions set forth herein relating to sorption compounds, with the sole proviso that the co-crystallized compound is a different, i.e., chemically distinct, compound from the sorption compound (or molecule) (although they may be similar or identical in any, some, or all other respects). Thus, the co-crystallized compound preferably comprises a multidimensional (at least two-dimensional, preferably three-dimensional) interconnected (preferably via interconnected voids) porous network. Co-crystallized compounds preferably comprise endogenous pores arising from cavities within their own porous molecules, and such endogenous voids are preferably independent of the overall crystalline structure. Co-crystallized compounds may comprise either endogenous and/or external pores (or voids), or both. Sorption compounds preferably comprise at least one endogenous void. Sorption compounds are preferably porous organic cages (POCs).

While the co-crystallized compound is preferably different from the sorption compound, the co-crystallized compound preferably crystallizes in a (substantially) isomorphous manner with the sorption compound, i.e., the co-crystallized compound preferably has (substantially) the same crystal structure as the sorption compound. Both the co-crystallized compound and the sorption compound preferably have a diamondoid pore network. Preferably, the individual crystal structures of the sorption compound and the co-crystallized compound have the same symmetry (even if they differ slightly in size). Preferably, the individual crystal structures of the sorption compound and the co-crystallized compound have the same space group. Preferably, the individual crystal structures of the sorption compound and the co-crystallized compound have the same unit cell structure. The combination of the internal and external porosity of the co-crystallized compound preferably results in an interconnected three-dimensional (3D) porous network containing continuous porous channels.

The co-crystallized compounds are preferably shape-persistent, e.g., they are preferably resistant to collapse (e.g., pore collapse).

The co-crystallized compound preferably has an internal cavity capable of accommodating a guest, which in this case is preferably the target substance. The internal cavity of the co-crystallized compound is preferably sized to accommodate the target substance (or one or more target substances).

The co-crystallized compound preferably has a cavity size larger than that of the sorption compound, preferably at least 0.2 Å larger, preferably at least 0.5 Å larger, preferably at least 1 Å larger, preferably at least 2 Å larger, preferably at least 2.5 Å larger. The co-crystallized compound preferably has a cavity size larger than that of the sorption compound, preferably at most 30 Å larger, preferably at most 20 Å larger, preferably at most 10 Å larger, preferably at most 5 Å larger, preferably at most 4 Å larger, preferably at most 3 Å larger. The co-crystallized compound preferably has a cavity size between 0.5 and 4 Å, preferably between 1 and 3 Å larger than that of the sorption compound.

Preferably, the cavity size of the co-crystallized compound in SATP is at most 30 Å. Preferably, the cavity size of the co-crystallized compound in SATP is at most 20 Å. Preferably, the cavity size of the co-crystallized compound in SATP is between 1 and 15 Å. Preferably, the cavity size of the co-crystallized compound in SATP is between 2 and 10 Å. Preferably, the cavity size of the co-crystallized compound in SATP is between 3 and 7 Å. Preferably, the cavity size of the co-crystallized compound in SATP is between 4 and 5 Å.

Preferably, the cavity size of the co-crystallized compound at the contact temperature is at most 30 Å. Preferably, the cavity size of the co-crystallized compound at the contact temperature is at most 20 Å. Preferably, the cavity size of the co-crystallized compound at the contact temperature is between 1 and 15 Å. Preferably, the cavity size of the co-crystallized compound at the contact temperature is between 2 and 10 Å. Preferably, the cavity size of the co-crystallized compound at the contact temperature is between 3 and 7 Å. Preferably, the cavity size of the co-crystallized compound at the contact temperature is between 4 and 5 Å.

The co-crystallized compound is preferably porous to protium, preferably in SATP, and/or preferably at the relevant contact temperature. The co-crystallized compound is preferably porous to deuterium, preferably in SATP, and/or preferably at the relevant contact temperature. The co-crystallized compound is preferably porous to protium and deuterium, preferably in SATP, and/or preferably at the relevant contact temperature.

When a co-crystallized compound is crystallized to obtain a crystal of the co-crystallized compound or a crystalline co-crystallized compound, the co-crystallized compound preferably comprises an external void that is larger than the cavity size of the co-crystallized compound, although in some embodiments the external void may be slightly smaller than the cavity size. Preferably, the size of the external void of the co-crystallized compound is within 3 Å, preferably within 2 Å, and preferably within 1 Å of the cavity size of the co-crystallized compound.

The co-crystallized compound is preferably less selective than the sorption compound (per se) in terms of preferentially sorbing the target substance over non-target substances. The co-crystallized compound preferably exhibits a sorption selectivity for the target substance relative to the non-target substances (i.e., the ratio, e.g., molar ratio, volume ratio, or mass ratio, preferably molar ratio) of the sorbed target substance to the sorbed non-target substances (per se) of at most 3, preferably at most 2, preferably at most 0.5.

The co-crystallized compound preferably exhibits a higher sorption capacity for the target substance (and preferably also for non-target substances) than the sorption compound, particularly at the relevant contact temperature. The co-crystallized compound preferably has a sorption capacity (i.e., is capable of sorptive uptake) of the target substance and/or non-target substance at 1 bar, at the relevant contact temperature (or at SATP), of at least 1 mmol/g (i.e., 1 mmol of target/non-target substance per gram of co-crystallized compound) greater than that of the sorption compound, more preferably at least 2 mmol/g greater than that of the sorption compound.

The co-crystallized compound preferably exhibits structural similarity to the sorption compound, but has a larger internal cavity. Preferably, the internal cavity of the co-crystallized compound does not involve functionalized or functionalizable groups present in the sorption compound and/or the precursor compound related to the sorption compound, respectively. The internal cavity of the co-crystallized compound preferably cannot be chemically modified in the same way as the internal cavity of the sorption compound.

When both the sorption compound and the co-crystallized compound are chiral, both are preferably enantiomerically pure (or enantiomerically enriched) as a single enantiomer, with the single enantiomer of the sorption compound being of the opposite chirality to that of the co-crystallized compound (e.g., one is the R-enantiomer and the other is the S-enantiomer).

Preferably, the sorption compound and the co-crystallized compound are from the same or related classes of compounds. For example, if the sorption compound is a boron ester cage, the co-crystallized compound is also preferably a boron ester cage. However, in certain embodiments, the sorption compound is a diamine cage while the co-crystallized compound is an imine cage. In certain embodiments, the sorption compound is a [4+6] functionalized diamine cage and the co-crystallized compound is a [4+6] imine cage.

In certain embodiments, the co-crystallized compound has the formula E

(In the formula,
n is an integer between 1 and 4,
each _R and _R group is independently hydrogen or an optionally substituted substituent, and any pair of _R and _R groups is optionally joined together to form a carbocyclic, heterocyclic, aryl or heteroaryl ring;
Suitably, the units of formula E are linked together via a linker (ie are not directly bonded).

The units of formula E are represented in a divalent form by bonds (which may be considered groups or "connectable bonds") crossed by square brackets. These units may be possible repeat units if the compound in question contains two or more of said units (which is the common case). The co-crystallization compound preferably comprises multiple units of formula E linked together via their "connectable bonds", preferably via an intervening linker (preferably to form an open-chain, macrocyclic or caged compound/molecule, most preferably a cage). Such a linker may link two or more units of formula E together, and in some embodiments, three such units. The linker is therefore preferably multivalent (e.g., divalent, trivalent). The linkers n, _R and _R of the co-crystallization compound preferably have any of the definitions specified in connection with the sorption compound. Most preferably, the sorption compound comprises one or more linking units of formula C and the co-crystallized compound comprises one or more linking units of formula E, where the two compounds match in all other respects (e.g., identical linkers, n, R _A1 and R _A2 ).

In certain embodiments, R _A1 , R _A2 and L ₁ - are such that the co-crystallized compound has the formula E ₁

wherein ring A is a carbocyclic ring, an aryl ring, a heterocyclic ring, or a heteroaryl ring;
Either the group of formula _E1 or A _1L is selected to include multiple reactive units of formula (optionally substituted as defined herein), each reactive unit being indirectly linked (through its connectable bond, also represented by a square bracket) via an intervening linker unit of an adjacent unique unit of formula A _1L . In this embodiment, the co-crystallized compound suitably includes units of formula _E1 and A _1L in a 3:2 molar ratio (e.g., 6 units of A ₁ and 4 units of A _1L ), respectively. For application of this embodiment, ring A is replaced with a (2-3C) alkylene group between the relevant imine moieties to form an alkylenediimine.

In certain embodiments, R _A1 , R _A2 -L ₁ -, ring A, and ring L are selected such that the co-crystallized compound comprises multiple reactive units of formula E ₂ , each reactive unit having the formula A _2L

is indirectly linked to adjacent different reactive units via an intervening linker unit of
Either the group of formula _E2 or _A2L is optionally substituted as defined herein, but most preferably is unsubstituted. In this embodiment, the co-crystallized compound preferably comprises units of formula _E2 and _A2L in a molar ratio of 3:2 (e.g., 6 units of _A2 and 4 units of _A2L ), respectively. For application of this embodiment, the cyclohexane rings can be replaced with (2-3C) alkylene groups between the relevant imine moieties to form alkylenediimines, and optionally the benzene rings of the linker are replaced with heteroarene rings.

In certain embodiments, the co-crystallized compound has the formula E3

(where the bold line corresponds to that of formula A3). This imine compound is also referred to herein as CC3.

The co-crystallization compound is preferably CC3.

Co-crystals The present invention provides co-crystals comprising a sorption compound as defined herein and a co-crystallized compound as defined herein, in which the sorption compound and the co-crystallized compound are co-crystallized together.

The co-crystal is formed by co-crystallizing (or re-crystallizing) the sorption compound and the co-crystallizing compound, preferably from a mixture thereof, more preferably from a solution thereof. Preferably, the sorption compound and the co-crystallizing compound are mixed in a molar ratio suitable to achieve the target molar ratio in the co-crystal.

The co-crystal preferably crystallizes in a (substantially) isomorphous manner with the sorption compound and/or co-crystallizing compound. The co-crystal preferably has a diamondoid pore network. Preferably, the co-crystal has the same symmetry (even if slightly different in size) as the sorption compound and/or co-crystallizing compound. Preferably, the co-crystal has the same space group as the sorption compound and/or co-crystallizing compound. Preferably, the co-crystal has the same unit cell structure as the sorption compound and/or co-crystallizing compound. The co-crystal preferably comprises an internal void (internal cavity) provided by the internal cavities of the sorption compound and the co-crystallizing compound, and therefore preferably comprises two different internal cavities of different sizes (see above for the cavity sizes of the respective sorption compound and co-crystallizing compound, which preferably correspond to the cavity sizes in the co-crystal). The co-crystal preferably also comprises an external void. The combination of internal and external voids of the co-crystallized compounds preferably results in an interconnected three-dimensional (3D) porous network containing continuous porous channels.

The cocrystals are preferably shape-persistent, e.g., they are preferably resistant to collapse (e.g., pore collapse).

The co-crystal preferably has a relatively small internal cavity and a relatively large internal cavity, either of which is capable of accommodating a guest, in this case the guest is preferably the target substance. The small internal cavity is preferably provided by the sorption compound (and the properties of which are preferably defined herein in relation to the sorption compound), while the large internal cavity is preferably provided by the co-crystallization compound (and the properties of which are preferably defined herein in relation to the co-crystallization compound). Any external voids are preferably larger than the small internal cavity.

The sorption compound and the co-crystallization compound are most preferably different molecules, although in some embodiments the two compounds may optionally be covalently linked via a linker to form a sorption-co-crystallization compound (preferably having two different types of internal cavities with different sizes as described above), and the co-crystal may in such circumstances comprise or consist of the sorption-co-crystallization compound.

The co-crystal is preferably porous to protium, preferably in SATP, and/or preferably at the relevant contact temperature. The co-crystal is preferably porous to deuterium, preferably in SATP, and/or preferably at the relevant contact temperature. The co-crystal is preferably porous to protium and deuterium, preferably in SATP, and/or preferably at the relevant contact temperature.

The cocrystal is preferably more selective than the sorption compound in terms of preferentially sorbing the target substance over the non-target substances. The cocrystal preferably exhibits a sorption selectivity for the target substance relative to the non-target substances (i.e., the ratio, e.g., molar ratio, volume ratio, or mass ratio, preferably molar ratio, of the sorbed target substance to the sorbed non-target substances) of at least 3, preferably at least 5, and preferably at least 7.

The cocrystal preferably exhibits a higher sorption capacity for the target substance (and preferably also for non-target substances) than the sorption compound, particularly at the relevant contact temperature. The cocrystal preferably has a sorption capacity (i.e., is capable of sorptive uptake) of the target substance and/or non-target substance at 1 bar at the relevant contact temperature (or SATP) that is at least 1 mmol/g (i.e., 1 mmol of target/non-target substance per gram of cocrystal) greater than that of the sorption compound, more preferably at least 2 mmol/g greater than that of the sorption compound.

Within the co-crystal, the sorption compound and the co-crystallized compound, if chiral, preferably have opposite chirality. This preferably allows for "chiral recognition" that promotes a more closely packed crystal structure.

The co-crystal preferably exhibits a modified crystal structure relative to the sorption compound molecules and the co-crystallized compound molecules.

The co-crystal is preferably configured to sorb the target substance in both the internal cavity provided by the sorption compound and the internal cavity provided by the co-crystallized compound at the relevant contact temperature and pressure.

The molar ratio of sorption compound to co-crystallized compound in the co-crystal is preferably between 10:1 and 1:10, more preferably between 5:1 and 1:5, and more preferably between 3:1 and 1:3. In certain embodiments, the molar ratio of sorption compound to co-crystallized compound in the co-crystal is about 1:1.

Detailed Embodiments of the Invention In particular embodiments of the method of the invention, the sorption compound is a porous organic cage having a functionalized internal cavity with a size within +/- 1 Å of the de Broglie wavelength of the target substance at the contact temperature in question at SATP, the co-crystallized compound is a porous organic cage with an internal cavity size at SATP that is at least 1 Å larger than the internal cavity size of the sorption compound, the sorption composition comprises a co-crystal of the sorption compound and the co-crystallized compound, the target compound is or comprises deuterium and/or tritium, the non-target compound is or comprises protium, and the contact temperature is 20-80K.

In a specific embodiment of the method of the present invention, the sorption compound is a porous organic cage having a functionalized internal cavity in SATP with a size within +/- 1 Å of the de Broglie wavelength of the target substance at the contact temperature; the co-crystallized compound is a porous organic cage in SATP with an internal cavity size at least 1 Å larger than the internal cavity size of the sorption compound; the sorption composition comprises a co-crystal of the sorption compound and the co-crystallized compound; the target compound is deuterium, the non-target compound is or comprises protium, and the contact temperature is 20 to 80 K.

In certain embodiments of the method of the present invention, the sorption compound is a functionalized polydiamine cage, preferably in which one, some, or all (but not necessarily all) of the diamine units are functionalized (preferably by molecular linkages).

In a specific embodiment of the method of the present invention, the sorption compound is a functionalized polydiamine cage in SATP having an internal cavity size between 1 and 2.4 Å, the co-crystallized compound is a polydiimine cage in SATP having an internal cavity size at least 1 Å larger than the internal cavity size of the sorption compound, the sorption composition comprises a co-crystal of the sorption compound and the co-crystallized compound, the target compound is or comprises deuterium and/or tritium, the non-target compound is or comprises protium, and the contact temperature is 20 to 80 K.

In a specific embodiment of the method of the present invention, the sorption compound is a functionalized polydiamine cage in SATP having an internal cavity size between 1 and 2.4 Å, the co-crystallized compound is a polydiimine cage in SATP having an internal cavity size at least 1 Å larger than the internal cavity size of the sorption compound, the sorption composition comprises a co-crystal of the sorption compound and the co-crystallized compound, the target compound is deuterium, the non-target compound is or comprises protium, and the contact temperature is 20 to 80 K.

In a specific embodiment of the method of the present invention, the sorption compound is 6ET-RCC3, the co-crystallized compound is CC3, the sorption composition comprises a co-crystal of the sorption compound and the co-crystallized compound, the target compound is or comprises deuterium and/or tritium, the non-target compound is or comprises protium, the contact temperature is 25 to 35 K, and the contact pressure is 10 to 1100 mbar.

In a specific embodiment of the method of the present invention, the sorption compound is 6ET-RCC3, the co-crystallized compound is CC3, the sorption composition comprises a co-crystal of the sorption compound and the co-crystallized compound, the target compound is deuterium, the non-target compound is or comprises protium, the contact temperature is 25 to 35 K, and the contact pressure is 10 to 1100 mbar.

The present invention is further illustrated by the following non-limiting examples, experiments, and results, from which it will become apparent that certain specific features may be combined with any of the aspects and embodiments of the invention described elsewhere herein. Before proceeding with a detailed discussion of the experiments, the relevant materials, protocols, methods, and compounds will first be identified.

The inventors' aforementioned prior disclosure, Liu M et al., Barely porous organic cages for hydrogen isotope separation. Science. 2019, 366(6465):613-620. doi:10.1126/science.aax7427, describes the same or similar examples and nomenclature, abbreviations, and terminology used below, which will be clarified by reference to this document or its appendices. Similarly, additional data and explanations will be found in appendices to this disclosure. Additionally, certain citations within this disclosure may be relevant to enabling the production of the relevant compounds, compositions, and materials discussed below.

Materials Nomenclature: The organic cage molecules were named according to the "linking" molecule that reacts with the six diamine groups of RCC3. Thus, FT, AT, ET, and PT represent products in which the diamine group is linked with formaldehyde, acetone, ethanal (acetaldehyde), and propionaldehyde. The preceding number indicates how many diamine groups of RCC3 react in this manner; for example, 1AT-5FT-RCC3 is the product formed by sequentially reacting RCC3 with one acetone molecule (1AT) followed by five formaldehyde molecules (5FT).

1,3,5-Triformylbenzene was purchased from Manchester Organics, UK. All other chemicals were purchased from Sigma-Aldrich and used as received. CC3 (covalent cage 3), RCC3 (reduced covalent cage 3), 1AT-RCC3, and 6FT-RCC3 were prepared in their homochiral forms using chirally pure (1S,2S)-(+)-1,2-diaminocyclohexane (31) according to previously reported procedures.

Formation of Cocryst 1 (CC3-S/6ET-RCC3-R cocrystal). CC3-S was dissolved in DCM (5 mg/mL) and added to an equimolar solution of 6ET-RCC3-R in dichloromethane (5.75 mg/mL). The solutions were mixed by direct addition at room temperature with stirring. No precipitate was observed upon mixing, but the solution became cloudy after approximately 10 minutes. The cocrystal Cocryst 1 was collected by filtration (Whatman® membrane filter PTFE, 0.2 μm pore size). Crystals suitable for single-crystal X-ray diffraction were grown by vapor diffusion of acetone into equimolar solutions of CC3-S and 6ET-RCC3-R in _CHCl3 .

Analysis Protocol Solution NMR
The ¹ H NMR spectrum of the solution was recorded at 400.13 MHz using a Bruker Avance 400 NMR spectrometer. The ¹³ C NMR spectrum was recorded at 100.6 MHz.

Fourier transform infrared spectroscopy (FTIR)
IR spectra were collected on a Bruker Tensor 27 spectrometer. Samples were analyzed as KBr disks for 16 scans at a resolution of 4 cm ⁻¹ . Spectra were recorded in transmission mode.

thermogravimetric analysis
TGA analysis was performed using a Q5000 IR analyzer (TA instruments) with an automated vertical overhead thermobalance. Samples were heated at a rate of 5°C/min.

Powder X-ray Diffraction. Laboratory powder X-ray diffraction (PXRD) patterns were collected in transmission mode on samples held in aluminum well plates by Mylar films on a Panalytical Empyrean diffractometer equipped with a high-throughput screening (HTS) XYZ stage, an X-ray focusing mirror, and a PIXcel detector, using Cu-Kα (λ = 1.541 Å) radiation. PXRD patterns were measured over a 2θ range of 5–50°, with approximately 0.013° increments, over a 1 h period. For indexing, samples were placed in borosilicate glass capillaries, and PXRD patterns were recorded in transmission mode on a Panalytical Empyrean diffractometer equipped with a sample spinner to improve powder averaging. High-resolution synchrotron PXRD data for Cocryst1 (CC3-S/6ET-RCC3-R) were collected using the I11 beamline at the Diamond Light Source (λ = 0.825015 Å) equipped with a Mythen II position-sensitive detector. The sample was placed in a borosilicate glass capillary, which was rocked to improve powder averaging during data acquisition.

Electron Microscopy. Imaging of the crystal morphology was accomplished using a Hitachi S-4800 cold field emission scanning electron microscope (FE-SEM) operating in both scanning and transmission modes. Scanning mode samples were prepared by depositing dried crystals onto 15 mm Hitachi M4 aluminum stubs using high-purity adhesive carbon tabs, followed by coating with a 2 nm layer of gold using an Emitech K550X automated sputter coater. Imaging was performed at an 8 mm working distance and 3 kV operating voltage using a combination of upper and lower secondary electron detectors. Transmission mode samples were prepared by dispersing cage particles in a methanol suspension and depositing a carbon-coated copper grid (300 mesh) and were imaged at a 30 kV working voltage and 7 mm working distance.

Gas sorption analysis: To determine gas sorption isotherms, gases of the following purity were used: hydrogen (99.9995% - BOC gas) and carbon dioxide (SCF grade - BOC gas). Surface area and pore size distribution were measured by nitrogen adsorption and desorption at 77.3 K using a Micromeritics ASAP 2020 volumetric sorption analyzer. Samples were degassed offline at 80 °C for 15 h under vacuum (10-5 bar) prior to analysis and subsequently degassed in the analysis port under vacuum and also at 80 °C. Carbon dioxide isotherms were measured at 289 K using the same degassing procedure using a Micromeritics 2420 volumetric sorption analyzer.

Single-crystal X-ray diffraction. Single-crystal X-ray data sets were measured using a Rigaku MicroMax-007 HF rotating anode diffractometer (Mo-Kα radiation, λ = 0.71073 Å, Kappa 4 circle goniometer, Rigaku Saturn 724+ detector) at beamline 11.3.1 at the Advanced Light Source, Berkeley, USA, using silicon monochromated synchrotron radiation (λ = 0.7749 Å or 1.0332 Å, PHOTON100 CMOS detector), or at beamline I19 at the Diamond Light Source, Didcot, UK, using silicon double-crystal monochromated synchrotron radiation (λ = 0.6889 Å, Dectris Pilatus 2M detector). Unless specified in the detailed modification section, desolvated single crystals activated by removing the solvent under dynamic vacuum at 353 K were mounted on a MiTeGen loop and flash-cooled to 100 K under a stream of dry nitrogen gas. Empirical absorption corrections were performed with the program SADABS using the multiscan method (49). For synchrotron X-ray data collected at the Diamond Light Source (λ = 0.6889 Å), data reduction and absorption corrections were performed with xia2 (50). The structure was solved with SHELXT (51) and refined by full-matrix least-squares |F| ² with SHELX (52) interfaced through the program OLEX2 (53). All non-H-atoms were refined anisotropically unless otherwise specified, and H-atoms were fixed to their geometrically estimated positions and refined using the riding model unless otherwise specified. The captured CIF, including structure factors, is available free of charge from the Cambridge Crystallographic Data Centre (CCDC) via www.ccdc.cam.ac.uk/data_request/cif.

Hydrogen Isotope Adsorption/Separation Measurements Adsorption experiments were performed using a fully automated Sieverts iQ2 instrument (Quantachrome Instruments). The calibration cell was a blank run performed over the same temperature and pressure range as each experiment, with corrections related to the nonlinearity of the sample volume and adsorbed material. Approximately 20 mg of sample was activated under vacuum at 343 K for 5 hours to remove any solvent molecules. The sample temperature was controlled using an attached cryocooler based on the Gifford-McMahon cycle. The cooling system allowed us to measure temperatures from 20 to 300 K with an estimated error of <0.05 K.

Selective adsorption after exposure to a _D2 / _H2 isotope mixture was directly measured by setting up an in-house designed temperature-programmed desorption spectrometry (TDS) system. In a typical process, approximately 4 mg of sample was placed in a sample holder and activated at 343 K under vacuum for 5 h. An equimolar _D2 / _H2 isotope mixture was then applied to the sample at a fixed temperature (exposure temperature, T _exp ) for a selected exposure time (t _exp ). The sample was then cooled to 20 K to expel the free gas and preserve the adsorption state. Finally, during heating from 20 K to room temperature at a heating rate of 0.1 K/s, the desorbed gas was continuously detected using a mass spectrometer (QMS), which recognizes the pressure increase in the sample chamber as gas desorbs. The area under the desorption peak is proportional to the amount of gas desorbed, which can be quantified after careful calibration of the TDS instrument.

Calibration of the Mass Spectrometer Signal _. A solid polycrystalline piece of diluted Pd alloy _Pd95Ce5 (approximately 0.5 g) was used for calibration. Prior to calibration, the alloy was etched with aqua regia to remove the oxide layer. It was then heated to 600 K under high vacuum to remove any hydrogen that may have been absorbed during the etching procedure. It was then weighed and inserted into the sample chamber. At 350 K, the chamber was filled with 40 mbar pure _H2 or pure _D2 for 1.5–2.5 h. Since H and D preferentially bind to cerium atoms at low loading pressures in this diluted alloy, the alloy could be handled briefly under ambient conditions. After loading, the alloy was cooled to room temperature and weighed. It was then returned to the sample chamber and a conventional TDS measurement was performed at 0.1 K/s. After desorption, the alloy was cooled back to RT and reweighed. The mass difference between the unloaded and loaded states was equal to the mass uptake of hydrogen or deuterium, respectively.

Calculation method
2.10.1 Pore Confinement Envelope Molecular dynamics (MD) simulations were used to calculate the time-averaged pore confinement envelope (PLE) for the isomorphous series of post-synthetic modified cages in this study. Individual frames from these MD simulations were extracted, and the pore confinement diameter (PLD) for each was determined using the high-throughput geometry-based analysis tool Zeo++ (55). A histogram of these values forms the PLE for each system studied here and is displayed in Figure 1C. The PLE reveals the flexibility of the equilibrium crystal structure, intramolecular vibrations, and surrounding molecular motions. For MD simulations, the experimental single crystal structure was used as the starting configuration. MD simulations were performed using DL_POLY_2.20, a 2 × 2 × 2 supercell (56). All cage crystals were modeled using the OPLS force field with a cutoff distance of 10 Å. The NPT ensemble was used, with a Hoover barostat and thermostat, both with a time constant of 0.5 ps, at 1 atm and 298 K. Using a time step of 0.5 fs, the system was first equilibrated for 100 ps, followed by a 2 ns generation run, with frames generated every 1 ps. This MD trajectory was used to generate the PLE for the system.

2.10.2 Adsorption and Diffusion Simulations To account for quantum diffraction effects in classical molecular simulations, the so-called Feynman-Hibbs (FH) effective potential can be used. (44) The quadratic FH potential U _FH (r) acts on some classical model potential U _C (r),

where r _ij is the separation distance between particles i and j, h is the reduced Planck constant, k _B is the Boltzmann constant, T is the temperature, and μ _ij is the reduced mass, which is equivalent to m _i m _i /(m _i +m _i ), where m i and m j are the masses of the particles. In our simulations of hydrogen adsorption/diffusion, at temperatures below 77 K, U _c (r) took the form of a Lennard-Jones (LJ) potential. With a simple charge-charge Coulomb potential, the total (non-bonded) interaction energy is

where ε _ij and σ _ij are the LJ potentials at full depth and core diameter, respectively, q _i and q _j are the partial atomic charges, and ε ₀ is an electric constant.

Using the model proposed by Levesque et al. (57), hydrogen is described as a rigid two-site molecule with a fixed HH bond distance of 0.74 Å, partial atomic charges placed on the two hydrogen atoms, and the center of mass of the hydrogen molecule, which reproduces the quadrupole moment of molecular hydrogen in the gas phase. Although the same force field parameters (Levesque et al.) are used for both _H2 and _D2 , the interactions around them may still differ due to the use of an FH effective potential. A real-space cutoff of 12.0 Å was applied to all LJ interactions, but long-range Coulomb interactions were handled by the Ewald summation method with a relative accuracy of ^10-6 . The Lorentz-Berthelot combination rule was used to calculate the LJ cross parameters for host-guest and guest-guest interactions. For all simulated porous organic cage crystals, one cell unit of the experimental crystal structure was used, and periodic boundary conditions were applied in three dimensions. In the case of a flexible host simulation, the experimental crystal structure was used as the starting configuration. The OPLS force field (58) was used to assign force field parameters (for both bonded and nonbonded interactions) and to assign partial atomic charges to all cage molecules.

RASPA 2.0 (59), a molecular simulation software for adsorption and diffusion in flexible nanoporous materials, was used throughout this study. Gas adsorption simulations were performed using a hybrid grand canonical Monte Carlo (GCMC)/molecular dynamics (MD) scheme, which allowed for direct sampling of host motion in the adsorption simulation. Hybrid GCMC/MD moves consisted of MD paths calculated in an isenthalpic (NPH) constant-pressure ensemble. Each MD move consisted of five time steps of 0.5 fs each, with a probability of 2% in the simulation. MD runs allowed the molecular cage crystal to relax upon loading with guest molecules, and the newly relaxed configurations were either accepted or rejected according to the MC sampling rules. Other trial MC moves included insertions, deletions, translations, rotations, reinsertions, and identity swaps (in the case of gas mixtures). These moves were attempted randomly with equal probability. All GCMC/MD and GCMC simulations involved an equilibration period of 800,000 cycles followed by a production run of 200,000 cycles, with one cycle consisting of n MC transfers, where n was equal to the number of adsorbate molecules (or 20, whichever was larger). In a typical GCMC/MD simulation performed here, the sampled MD path spanned approximately 1 ns in total.

2.10.3 Free Energy Profiles of Gas Diffusion in Cage Crystals Nanometer-scale molecular diffusion confinement, such as that presented in the crystal structures simulated here, can be so slow that the time scale for a particle hopping from one free energy minimum to the next becomes too large for routine application of molecular dynamics simulations. For example, a guest molecule can be confined inside a cage molecule, and the actual time required to escape the cage window is small compared to the time spent inside the cage. Such processes can be considered activated processes, which can alternatively be probed by rare-event simulation methods, such as transition state theory (TST). A comprehensive demonstration of the method for studying adsorbate transport in nanoporous adsorbents is presented by Dubbeldam et al. (60).

The free energy profiles (Figures 5A-C) were calculated using Monte Carlo simulations with the Widom particle insertion method in the canonical (NVT) ensemble. During the simulation, the probe molecule (i.e., _H2 or _D2 ) was inserted into many random positions in the cage crystal structure, and the energy required or gained by each molecular insertion into the system was measured. This energy was mapped to the reaction coordinate q,
βF(q)=-ln〈e ^-βΔU 〉 _N
to generate a free energy profile,
where β=1/(k _B T), k _B is the Boltzmann constant, T is the temperature, and 〈e ^−βΔU 〉 _N is the average Boltzmann factor over all N sampled positions in the plane perpendicular to the reaction coordinate q.

2.11 Host-Guest Binding Energy. Path-integral molecular dynamics (PIMD) simulations, combined with quantum-mechanical interaction evaluations, further probed the diffusion behavior of _H2 and _D2 in the cage molecules, explicitly accounting for both electronic and nuclear quantum mechanical properties. Because path-integral simulations are typically two orders of magnitude more expensive than classical nuclear treatments, we focused only on isolated 6ET-RCC3 cage molecules with a single gas molecule (i.e., _H2 or _D2 ) diffusing from the cage. Further computational cost reduction was achieved by using the self-consistent charge density functional tight-binding DFTB3 method (61) with a UFF-based dispersion correction scheme (62) to calculate interactions from electronic structure evaluations.

We benchmarked the DFTB3-UFF method, which describes the energy metabolism of our host-guest system (i.e., 6ET-RCC3 with _H2 or _D2 ) against the DFT-D3 method with BLYP and PBE density functionals. The 3OB parameterization was used for all DFTB3 calculations. (63) For DFT-based calculations, the MOLOPT-DZVP basis set was used for all elements along with Goedecker-Teter-Hutter pseudopotentials. (64, 65) The plane wave auxiliary basis method was defined with an energy cutoff of 500 Ry, and the Gaussian basis set selection method involved a relative cutoff of 50 Ry. During each self-consistent field cycle, the electronic structure was minimized to a tolerance of ^10-8 Hartree. Calculations were performed with the CP2K simulation package (https://www.cp2k.org/). The host-guest binding energy was calculated using
E _bond = E(host...guest)-E(host)-E(guest)
where E(host...guest), E(host), and E(guest) are the total energies of the guest-loaded 6ET-RCC3 host, the unloaded 6ET-RCC3 host, and the isolated guest molecule ( _H2 or _D2 ), respectively. Table S6 reports all the binding energies obtained using the different methods, clearly demonstrating that the DFTB3-UFF method is not only computationally efficient but also able to correctly describe the system. Therefore, all PIMD simulations use the DFTB3-UFF method to evaluate the electronic structure.

2.12 Minimum Energy Paths for _H2 Dispersion through Cage Windows We performed climbing image nudged elastic band (CI-NEB) calculations to determine the minimum energy paths (MEPs) for a single _H2 molecule transitioning through each of the four windows of the 6ET-RCC3 cage molecule. The same DFTB3-UFF settings described above were used for all CI-NEB calculations.

2.13 Path-Integral Molecular Dynamics Simulations and Free Energy Calculations. As discussed above, direct simulation of periodic cage crystal structures with PIMD is challenging due to the large size of the systems (e.g., cocrystal structures contain over 1,500 atoms in the unit cell). Because molecular cage crystals assemble through the packing of individual cage molecules, many properties related to the porosity of the crystal structure closely follow the properties of the constituent molecular subunits; for example, the pore-limiting diameter in the CC3 crystal structure is governed by the size of the cage window. This allows us to study isolated cage molecules to understand the properties of cage crystals, which have previously been shown to capture essential features of the diffusion process (66).

Statistical mechanics. To characterize the quantum Boltzmann statistics of the nuclear degrees of freedom, we used imaginary-time path-integral molecular dynamics (PIMD). (67) This technique is based on an isomorphism between the quantum statistical mechanics of a system and the classical statistical mechanics of so-called ring polymers, which consist of multiple replicas of the system. (68) This method accurately describes the statistics of zero-point fluctuations and quantum tunneling, but does not include effects arising from indistinguishable identical atoms. This approximation can be problematic for atoms in _H2 or _D2 molecules at low temperatures. (69) However, including exchange effects in PIMD simulations raises the issue of pathological manifestations. (70) Subsequent corrections reveal that this is not straightforward. We therefore assumed distinguishable atoms and performed all simulations with the understanding that the approximation may not be accurate.

Relative population of _D2 over _H2 inside the 6ET-RCC3 cage. At a particular temperature, the relative population of _D2 over _H2 inside the cage is a measure of the relative preference of _D2 over _H2 , which can be compared to experimental _D2 / _H2 selectivity. To calculate the relative population, we consider the reversible replacement of _H2 molecules inside the cage with _D2 molecules in the gas phase.

The equilibrium constant (α) of this substitution describes the relative abundance of _D2 over _H2 inside the cage throughout the gas phase at temperature T,
-k _B Tin(α)={[A[D2(cage)]-[A[H2(cage)]-[A[D2(gas)]-[A[H2(gas)]}
(71) where A represents the Helmholtz free energy of the system and _kB is the Boltzmann constant. The free energy difference is calculated by thermodynamic integration over the mass (72),

where _mD2 and _mH2 are the atomic masses of the _D2 and _H2 molecules, respectively, and T(m; cage/gas) is the expected quantum kinetic energy of the guest molecule with atomic mass m in the cage or gas phase. The entire system was discretized at three points selected using the quadrature method of Ceriotti and Markland (73). PIMD simulations were used to calculate the quantum kinetic energies of the _H2 and _D2 molecules inside the cage and in the gas phase. Simulations were performed using i-PI in the NVT ensemble at temperatures T = 30 K, 40 K, 50 K, 77 K, and 100 K (74). Quantum fluctuations were forced using a PIGLET thermostat with the following parameters (75):

These parameters were obtained from the online repository, http://gle4md.org/. Force evaluation was performed using the DFTB+ code (76). The equations of motion were integrated using the BAOAB scheme with a time step of 0.5 fs (77). Simulations were run for 20 ps, with the quantum kinetic energy sampled at each step. The error in the relative population was calculated by error propagation from the quantum kinetic energy, which was calculated as the standard error of the time series obtained from the PIMD simulation (Figure 5H).

Free energy profiles for the diffusion of _H2 and _D2 through cage windows. The free energy profiles were calculated using a combination of PIMD and umbrella sampling (78). The cage window of 6ET-RCC3, which has the weakest energy barrier as assessed by CI-NEB calculations, was investigated. The order parameter is
S = (r _guest - r _cage ) (r _window - r _cage ) / [(r _window - r _cage )] ²
where r _guest , r _cage , and r _window are the position vector of the guest molecule, the cage center, and the window center, respectively. s = 0, s = 1, and s > 1 correspond to the guest molecule located at the center of the cage, the guest molecule located at the center of the window in the transition state with respect to the guest molecule, and the guest molecule outside the cage, respectively. The cage is an approximately irregular octahedron with four windows facing the phenyl rings. The window center is defined as the center of mass of the three carbon atoms. The cage molecule center is defined as the center of mass of the six carbon atoms.

A total of 50 harmonic restraints were used, uniformly centered between s = 0.0 and s = 4.5. The harmonic force constants were set to K = 150 kJ mol ⁻¹ and K = 500 kJ mol ⁻¹ for the first 40 restraints and the remaining 10 restraints, respectively. To prevent the guest molecules from scattering from the cage molecules,

The wall was applied.

PIMD simulations were performed at 50 K using i-PI, with Plum ED (79) biasing the center-of-mass Hamiltonian of the ring polymer. The calculation settings were kept identical to those in the previous position. Simulations were run for 10 ps at each constraint. The unbiased free energy curves were obtained using the weighted histogram analysis method implemented by Grossfield (80). This process was repeated four times using different starting configurations and different random number seeds to obtain averaged free energy profiles with error bars (Figure 5I).

Further Techniques Applicable in Relation to the Present Invention Although not necessarily specifically practiced in the experiments discussed below, the following techniques may be practiced to further utilize the present invention and/or to demonstrate further embodiments.

Gas chromatographic quantification and separation of diatomic hydrogen isotopes.
M. Ravichandran, P.R. Ramya, S. Sankar Ganesh, K. Ramesh Naidu, and M.M. Rajput, "Optimization of Indigenously Developed Column for the Separation and Analysis of All the Six Hydrogen Isotopic Combinations in Elemental Form using Gas Chromatograph," BARC NEWSLETTER, January-February 2016, pp. 23-26, ISSN 0976-2108, describes a gas chromatography apparatus and method for separating homo- and hetero-diatomic hydrogen isotopes, such as _H2 , HD, HT, _D2 , DT, and _T2 , from their mixtures (typically mixed with helium carrier gas) and then quantifying them based on their differential affinity for a treated gamma-alumina stationary phase and their differences in thermal conductivity. This is envisioned to be particularly useful when deploying the technology of the present invention to separate the products of nuclear fusion.

Pressure Swing Absorption. Pressure swing absorption (PSA) is well known in the art and operates on the basis of the tendency of gases to adsorb onto solid surfaces under high pressure, followed by desorption therefrom at reduced pressure. While PSA processes often seek to enrich a gas mixture in a "target" gas by selectively removing "non-target" gases therefrom, the reverse is also entirely feasible and particularly applicable to the present invention, e.g., selectively extracting and selectively sorbing it to purify the "target" gas. Utilizing two adsorption devices facilitates a substantially continuous process of enriching a mixture in a particular gas or selectively extracting a target gas. Indeed, if the "target" gas is the sorbed species, this target gas can be used (upon depressurization) to partially pressurize the second device following desorption. Furthermore, the desorbed target gas (which may need further purification to remove non-target gases) can be introduced (or reintroduced) in the same process (either through the same device or through further similar downstream devices, in-line or separately). K. Kotoh, M. Tanaka, Y. Nakamura, T. Sakamoto, Y. Asakura, T. Uda, and T. Sugiyama, "Experimental Verification of Hydrogen Isotope Separation by Pressure Swing Adsorption," Fusion Science and Technology, Vol. 54, No. 2, 2008, pp. 411-414, https://doi.org/10.13182/FST08-A1842, describes pressure swing absorption technology applicable to the present invention.

Different types of porous organic cages applicable to the invention
Hasell, T., Cooper, A. Porous organic cages: soluble, modular, and molecular pores. Nat Rev Mater 1, 16053 (2016). https://doi.org/10.1038/natrevmats.2016.53 is a review article that not only defines the term "porous organic cage" as distinct from other porous compounds (e.g., MOFs, zeolites), but also illustrates the scope of the term by exploring a non-exhaustive range of different types of porous organic cages. The experiments detailed below are specific subtypes of porous organic cage compounds, and those skilled in the art will readily recognize that the principles of the present invention are more broadly applicable.

Synthesis of the relevant compound
CC3 (cage 3) was prepared in its homochiral form, CC3-R, as previously reported (Jones, JT, Hasell, T., Wu, X., Bacsa, J., Jelfs, K.E., Schmidtmann, M., Chong, S.Y., Adams, D.J., Trewin, A., Schiffman, F., Cora, F., Slater, B., Steiner, A., Day, G.M., Cooper, A.I. Nature 2011, 474, 367). 1AT-RCC3 and 6FT-RCC3 were prepared in their homochiral forms using chirally pure (1S,2S)-(+)-1,2-diaminocyclohexane (31) according to previously reported procedures.

Synthesis of RCC3: Imine cage CC3-R (926 mg, 0.83 mmol) was dissolved in a _CHCl3 /methanol mixture (1:1 v/v, 50 mL) by stirring. When the solution became clear, sodium borohydride (1.00 g, 26.5 mol) was added, and the reaction was stirred at room temperature for an additional 12 h. Water (2 mL) was then added, and the reaction was stirred for an additional 12 h. The solvent was then removed under vacuum. The resulting white solid was extracted with chloroform (2 x 50 mL), and the combined organic phases were then washed with water (2 x 100 mL). The _CHCl3 phase was dried over anhydrous _MgSO4 and then removed under vacuum. Amine cage 1 (crude yield = 900 mg, 95.1%) was obtained as a white solid. ^1H NMR ( _CDCl3 , 400 MHz) δ 7.12 (s, 12H, -ArH), 3.81 (d, 12H, _-ArCH2 ), 3.59 (d, 12H, _-ArCH2 ), 2.18 (m, 12H, CH from cyclohexane), 0.95 - 1.98 (m, 48H, _CH from cyclohexane) ppm; ^13C NMR ( _CDCl3 , 100 MHz): δ 141.2, 124.9, 61.2, 50.7, 32.0, 25.0 ppm. IR (KBr pellet, ν) 2922 (s), 2850 (s), 1603 (w), 1446 (s), 1354 (w), 1338 (w), 1153 (m), 1113 (s), 856 (s), 789 (m), 750 (m), 714 (m), 525 (w) cm ^-1 . MS (ES+) 1141.9 ([M+H] ⁺ ).

Crystal data for RCC3·14.68(H ₂ O). Formula C ₇₂ H _137.36 N ₁₂ O _14.68 , M = 1406.21 g·mol ⁻¹ , cubic space group F4 ₁ 32, colorless crystals a = 25.71(1) Å, V = 16999(13) Å ³ , ρ = 1.092 g·cm ⁻³ , μ = 0.077 mm ⁻³ , F(000) = 6034, crystal size = 0.25 × 0.20 × 0.15 mm ³ , T = 100(2) K, measured reflections 33042 (2.63 < Θ < 25.01°), 1274 unique (R _int = 0.0466), 1070 (I > 2σ(I)), observed reflections R ₁ = 0.0759 and total reflection R ₂ = 0.0863, total reflection wR ₂ = 0.0863. = 0.2324, max/min residual electron density = 0.493 and -0.275e·Å ⁻³ , data/restraints/parameters = 1274/0/100, GOF = 1.054.

RCC3·14.68( _H2O ) crystallized from MeOH/ _H2O solution. The structure was resolved and refined in the chiral cubic space group F4 ₁ 32 with an asymmetric unit consisting of 1/12 of the RCC3 fragment. The residual electron density was highly diffuse, so _H2O was tentatively assigned as the solvent and its occupancy was determined using _FVAR during refinement. _H2O solvent molecules were refined without proton atoms, but these were included in the refined formula unit.

To obtain a large amount of crystalline RCC3 for subsequent analysis, a solution of RCC3 was dissolved in _CHCl3 and allowed to slowly evaporate over two days. Powder X-ray diffraction (PXRD) confirmed that the solvated material was phase-identical to the single-crystal structure. Different desolvation methods were investigated to activate the RCC3 solvate, including high/low temperature vacuum, _N2 flow, solvent exchange, and supercritical _CO2 drying. However, none of these activation states maintained the crystallinity of RCC3 upon solvation; instead, the authors isolated amorphous solids in all cases, which exhibited an absence of Bragg reflections in the PXRD patterns.

Synthesis of AT-RCC3. The reduced amine cage RCC3 (50 mg, 0.044 mmol) was dissolved in 3 mL of acetone in a 10 mL vial. The vial was sealed and left to stand. Single crystals of AT-RCC3 gradually appeared on the wall and bottom of the vial after about 30 min. After 12 h, the crystals were collected by filtration and washed with acetone (2 × 100 mL). Yield: 39 mg, 75.4%. (Note: The filtrate can be allowed to stand for >12 h to collect an additional crystal crop, thus improving this 75% yield.) ¹ H NMR (CDCl ₃ , 400 MHz) δ 7.35 - 6.83 (m, 12H, -ArH), 4.00 - 3.04 (m, 12H, -ArCH ₂ ), 2.49 - 0.7 (m, 12H, -ArCH ₂ ), 2.18 (m, 60H, CH and CH ₂ from cyclohexane), 0.95 - 1.98 (m, 48H, CH ₂ from cyclohexane) ppm; ¹³ C NMR (CDCl ₃ , 100 MHz): δ 141.2, 127.7, 125.0, 61.4, 51.8, 50.8, 50.0, 31.8, 30.9, 25.0, 23.9 ppm. IR (KBr pellets, ν) 2927 (s), 2855 (m), 1605 (w), 1449 (m), 1374 (w), 1355 (w), 1337 (w), 1293 (w), 1206 (w), 1158 (w), 1110 (w), 1074 (w), 1001 (w), 862 (w), 789 (w), 736 (w) cm ^-1 . MS (ES+) 1181.9 ([M+H] ⁺ ).

Crystal data for AT-RCC3·7.5(H ₂ O). Formula C ₇₅ H ₁₂₇ N ₁₂ O _7.5 , M = 1301.77 g·mol ⁻¹ , cubic space group F4 ₁ 32, colorless crystals a = 25.469(1) Å, V = 16520(2) Å ³ , ρ = 1.047 g·cm ⁻³ , μ = 0.068 mm ⁻³ , F(000) = 5648, crystal size = 0.18 × 0.18 × 0.12 mm ³ , T = 100(2) K, measured reflections 29022 (1.38 < Θ < 23.24°), 993 unique (R _int = 0.0508), 955 (I > 2σ(I)), observed reflections R ₁ = 0.0848 and total reflection R ₂ = 0.0868, total reflection wR ₂ = 0.0848. = 0.2534, max/min residual electron density = 0.485 and -0.250 e·Å ⁻³ , data/restraints/parameters = 993/17/92, GOF = 1.166.

Crystal data for AT-RCC3·4.5(H ₂ O). Formula C ₇₅ H ₁₂₁ N ₁₂ O _4.5 , M = 1262.84 g·mol ⁻¹ , cubic space group F4 ₁ 32, colorless crystals a = 25.612(5) Å, V = 16801(6) Å ³ , ρ = 0.998 g·cm ⁻³ , μ = 0.063 mm ⁻³ , F(000) = 5528, crystal size = 0.18 × 0.18 × 0.12 mm ³ , T = 300(2) K, measured reflections 26066 (1.38 < Θ < 20.88°), 759 unique (R _int = 0.0767), 708 (I > 2σ(I)), observed reflections R ₁ = 0.0828 and R ₂ = 0.0928 _. = 0.2501, max/min residual electron density = 0.346 and -0.377 e·Å ⁻³ , data/restraints/parameters = 759/14/95, GOF = 1.125.

Crystal data for AT-RCC3. Formula C ₇₂ H ₁₁₂ N ₁₂ , M = 1181.76 g·mol ⁻¹ , cubic space group F4 ₁ 32, colorless crystals a = 25.456(6) Å, V = 16495(7) Å ³ , ρ = 0.952 g·cm ⁻³ , μ = 0.057 mm ⁻³ , F(000) = 5168, crystal size = 0.18 × 0.18 × 0.12 mm ³ , T = 350(2) K, measured reflections 25340 (2.26 < Θ < 20.82°), 730 unique (R _int = 0.0940), 570 (I > 2σ(I)), observed reflections R ₁ = 0.1097 and total reflection R ₁ = 0.1260, total reflection wR ₂ = 0.3059, max/min residual electron density = 0.412 and -0.171 e·Å ⁻³ , data/restraints/parameters = 730/14/81, GOF = 1.287.

Synthesis of FT-RCC3 Paraformaldehyde (52 mg, 20 eq.) was dissolved in _CH3OH (10 mL) and stirred at 70 °C. To this clear solution, RCC3 (100 mg) dissolved in _CH3OH (10 mL) was added. Upon addition of RCC3, a white precipitate appeared. The reaction was stirred at 70 °C for an additional 2 h. The reaction was cooled to room temperature and the precipitate was collected by filtration. After washing with _CH3OH (3 × 10 mL) and drying under vacuum, FT-RCC3 (52 mg, 70%) was obtained. ^1H NMR ( _CDCl3 , 400 MHz) δ 7.11 (s, 12H, -ArH), 3.99 (d, _12H , -ArCH2), 3.23 (s, 12H, _-NCH2N- ), 3.19 (d, 12H, -ArCH2), 2.27 (d, _12H , CH of cyclohexane), 1.96 (d, 12H, CH of cyclohexane ₎ , 1.80 (d, 12H, _CH of cyclohexane), 1.28 (m, 24H, _CH of cyclohexane) ppm; ^13C NMR ( _CDCl3 , 100 MHz): δ 140.1, 123.6, 77.2, 68.8, 57.3, 29.4, 24.4 ppm. IR (KBr pellets, ν) 2925 (s), 2858 (m), 2803 (w), 1605 (m), 1436 (s), 1348 (w), 1336 (s), 1313 (w), 1292 (m), 1215 (m), 1187 (s), 1122 (m), 1094 (w), 1066 (w), 1039 (w), 1006 (m), 952 (w), 908 (m), 858 (m), 835 (s), 751 (s), 684 (m), 666(w), 584 (m), 541 (w), 453 (m) cm ^-1 . MS (ES+) 1213.9 ([M+H] ⁺ ). C ₇₈ Exact calculated mass of H ₁₀₉ N ₁₂ : 1213.8898. Measured mass: 1213.8894.

Crystal data for FT-RCC3·4(MeOH)·2(CHCl ₃ ). Formula C ₈₄ H ₁₂₆ Cl ₆ N ₁₂ O ₄ , M = 1580.67 g·mol ⁻¹ , cubic space group F4 ₁ 32, colorless crystals a = 25.370(3) Å, V = 16329(3) Å ³ , ρ = 1.286 g·cm ⁻³ , μ = 0.268 mm ⁻³ , F(000) = 6784, crystal size = 0.06 × 0.06 × 0.05 mm ³ , T = 30(2) K, measured reflections 11627 (2.66 < Θ < 26.35°), 1382 unique (R _int = 0.0740), 1040 (I > 2σ(I)), observed reflections R ₁ = 0.1455 and R ₂ = 0.1720, total reflection wR ₂ = 0.1720. = 0.4196, max/min residual electron density = 0.819 and -0.465e·Å ⁻³ , data/restraints/parameters = 1382/0/85, GOF = 1.769.

Single crystals of FT-RCC3 crystallized from a _CHCl3 /MeOH solution in the chiral cubic space group _F4132 . The crystals were small and diffracted weakly. X-ray diffraction data of suitable quality were obtained using a synchrotron radiation source at beamline I19, Diamond Light Source, UK. A collection temperature of 30 K significantly improved the quality of the data. One _CHCl3 molecule, disordered across two positions, was found in the interstitial cavity between two cage windows. Additional electron density was modeled as MeOH solvent. No restraints were used during purification. The exact occupancies of _CHCl3 and MeOH solvent should be considered tentatively assigned due to their close contact. At higher collection temperatures (>275 K), single crystals of FT-RCC3 diffracted weakly.

Synthesis of 1AT-5FT-RCC3
Solid 1AT-RCC3 (200 mg, 0.17 mmol) was ground to a fine powder and transferred into an open 12 mL glass vial. The open vial containing the cage was then placed into a larger 50 mL glass container containing solid paraformaldehyde (200 mg). The glass container was sealed and then heated in an oil bath at 60 °C to generate a gaseous formaldehyde atmosphere. [Caution: Formaldehyde is a Class I human carcinogen and should only be handled in a contained environment by trained personnel wearing appropriate protective equipment.] The reaction was sealed at 60 °C for 12 hours, after which the reaction was cooled to room temperature. The solid in the vial was collected and dried under dynamic vacuum at 40 °C to remove surface-adsorbed formaldehyde. 1AT-5FT-RCC3 (crude yield = 205 mg, 97.5%) was obtained as a crystalline white solid. ^1H NMR ( _CDCl3 , 400 MHz) δ 7.20-6.95 (m, 12H, -ArH), 4.14-3.86 (m, _12H , -ArCH2), 3.45-3.00 (m, 12H, -ArCH2 and _10H , _-NCH2N- ), 2.20-2.40 (m, 12H, CH of cyclohexane), 2.15-1.75 (m, 24H, CH of cyclohexane ₎ , 1.40-1.00 (m, _24H , CH of cyclohexane), 0.85-0.40 (m, 6H, _CH3 ) ppm; ^13C NMR (CDCl3 _, 100 MHz): δ 140.1, 123.6, 78.4, 68.8, 57.8, 57.3, 30.9, 29.4, 24.4 ppm. IR (KBr pellets, ν) 2925 (s), 2857 (s), 2795 (w), 1669 (w), 1605 (m), 1446 (s), 1349 (w), 1335 (s), 1313 (w), 1291 (m), 1216 (w), 1185 (m), 1121 (m), 1065 (w), 1039 (w), 1005 (m), 953 (w), 907 (m), 859 (m), 834 (m), 736 (w), 685 (m), cm ^-1 . MS (ES+) 1241.9 ([M+H] ⁺ ). Exact mass calculated for [C ₈₀ H ₁₁₃ N ₁₂ ] ⁺ : 1241.921. Found: 1241.849.

Synthesis of 5FT-RCC3
1AT-5FT-RCC3 (100 mg, 0.081 mmol) was dissolved in 20 mL of a CHCl ₃ :MeOH mixture (1:1, v:v). One drop of water was added, and the mixture was vigorously stirred at room temperature for 12 h. After removing the solvent under reduced pressure and subsequently drying under dynamic vacuum at 60 °C, 5FT-RCC3 (91 mg, 94.0%) was isolated as a white solid. ^1H NMR ( _CDCl3 , 400 MHz) δ 7.55-6.75 (m, 12H, -ArH), 4.16-2.95 (m, 24H, -ArCH2 and _10H , _-NCH2N- ), 2.50-0.85 (m, 12H, CH from cyclohexane and 48H, _CH2 from cyclohexane). ^13C NMR ( _CDCl3 , 100 MHz): δ 140.1, 123.6, 78.4, 68.8, 57.3, 29.4, 24.4 ppm. IR (KBr pellet, ν) 2923 (s), 2854 (m), 1668 (w), 1605 (w), 1447 (m), 1349 (w), 1336 (m), 1313 (w), 1292 (w), 1215 (w), 1184 (m), 1121(w), 1066 (w), 1039 (w), 1006 (m), 950 (w), 908 (m), 858 (w), 835 (m), 749 (s), 684 (w), 666 (w) cm ^-1 . MS (ES+) 1201.8 ([M+H] ⁺ ). Exact mass calculated for [C ₇₇ H ₁₀₉ N ₁₂ ] ⁺ : 1201.813. Found: 1201.890.

Synthesis of 1ET-5FT-RCC3
Ethanal (acetaldehyde, 15.7 mg, 0.36 mmol) in 10 mL of CHCl₃/MeOH (50:50, v:v) mixture and stirred at 0 °C.₃5FT-RCC3 (128 mg, 0.11 mmol) in HCl/MeOH (50:50, v:v) was added to the above solution at 0 °C. After stirring the reaction mixture at room temperature, a white precipitate gradually appeared. After removing the reaction solvent under vacuum, 1ET-5FT-RCC3 (126 mg, 96.3%) was isolated as a white solid.¹H NMR (CDCl₃, 400 MHz) δ 7.50 - 6.99 (m, 12H, -ArH), 4.05 - 3.95 (m, 12H, -ArCH₂), 3.54-3.16 (m, 12H, -ArCH₂; 10 H, -NCH₂N- and 1H, -N₂CHCH₃-), 2.10-2.40 (m, 12H, cyclohexane CH), 2.15-1.75 (m, 24H, cyclohexane CH₂), 1.40-1.10 (m, 24H, CH of cyclohexane₂), 0.86 (m, 3H, CH₃) ppm;¹³C NMR (CDCl₃, 100 MHz): δ 140.0, 123.6, 78.2, 68.7, 57.3, 30.9, 29.4, 24.4 ppm. IR (KBr pellets, ν) 2925 (s), 2857 (s), 2798 (w), 1606 (m), 1436 (s), 1349 (w), 1336 (s), 1313 (w), 1293 (m), 1218 (w), 1190 (m), 1122 (m), 1094 (w), 1066 (w), 1039 (w), 1006 (m), 953 (w), 908 (m), 859 (m), 836 (m), 753 (w), 685 (m) cm^-1MS (ES+) 1227.9 ([M+H]⁺). [C₇₉H₁₁₁N₁₂]⁺Exact calculated mass: 1227.905. Measured mass: 1227.837.

Synthesis of 1PT-5FT-RCC3
Dissolve propionaldehyde (5.0 mg, 0.09 mmol) in 5 mL of CHCl₃/MeOH (50:50, v:v) mixture and stirred at 0 °C.₃5FT-RCC3 (50.0 mg, 0.04 mmol) in HCl/MeOH (50:50, v:v) was added to the above solution at 0 °C. After the mixture was stirred at room temperature, a white precipitate gradually appeared. After removing the solvent and drying under vacuum, 1PT-5FT-RCC3 (49 mg, 94.8%), a white solid, was recovered.¹H NMR (CDCl₃, 400 MHz) δ 7.50-6.98 (m, 12H, -ArH), 4.25-3.75 (m, 12H, -ArCH₂), 3.49-3.15 (m, 12H, -ArCH₂; 10H, -NCH₂N- and 1H, -N₂CHCH₂CH₃-), 2.50 -1.50 (m, 12H, cyclohexane CH; m, 24H, cyclohexane CH₂), 1.40-1.01 (m, 24H, cyclohexane CH₂), 0.88 (m, 5H, CH₂CH₃) ppm;¹³C NMR (CDCl₃, 100 MHz): δ 140.0, 123.6, 78.2, 68.7, 57.3, 30.9, 29.4, 24.4 ppm.⁺). [C₈₀H₁₁₃N₁₂]⁺Exact calculated mass: 1241.921. Measured mass: 1241.850.

Synthesis of 6ET-RCC3 Acetaldehyde (200 mg, 4.55 mmol) was dissolved in MeOH (10 mL) and the solution was stirred at 0 °C. RCC3 (500 mg, 0.438 mmol) in MeOH (20 mL) was added to the above solution. Upon addition of RCC3, a white precipitate appeared. The reaction was stirred at room temperature for another 2 h. The precipitate was collected by filtration. After washing the precipitate with MeOH (3 × 10 mL) and drying the product under vacuum, 6ET-RCC3 (472 mg, 83.0%) was obtained. ^1H NMR ( _CDCl3 , 400 MHz) δ 7.50-6.74 (m, 12H, -ArH), 4.23-3.05 (m, _6H , -NCHCH3N and m, 24H, _-NCH2Ar- ), 2.75-2.15 (m, 12H, _CH2 of cyclohexane), 2.10-1.75 (m, 24H, _CH2 of cyclohexane), 1.47-1.12 (m, 24H, _CH2 of cyclohexane), 0.50-0.15 (m, 18H, _CH3 ) ppm; ^13C NMR ( _CDCl3 , 100 MHz): δ 140.4, 128.2, 126.6, 125.7, 123.1, 79.7, 69.4, 65.7, 52.4, 29.5, 29.4, 24.7, 20.5, 18.0 ppm. MS (ES+) 1296.9759 ([M+H] ⁺ ). Exact mass calculated for [C ₈₄ H ₁₂₁ N ₁₂ ] ⁺ : 1297.9837. Found: 1297.9727.

Experimental Status Deuterium (D) is used as a neutron moderator, as a non-radioactive isotope tracer, and in neutron scattering experiments. These applications require expensive, highly purified deuterium due to its low natural abundance (0.0156 mol%). Typically, _D is produced by electrolysis of heavy water and extracted using the Girdler-sulfide method (2) or by cryogenic distillation at 24 K (3). Both processes are costly and energy-intensive, as multiple enrichment steps are required (4).

An attractive alternative method for purifying _D2 from _H2 / _D2 gas mixtures is the selective adsorption of _D2 in microporous beds (5). Dynamic quantum sieving (KQS) using nanoporous solids was first proposed by Beenakker et al. (6). The KQS effect becomes significant when the difference in size between the hydrogen molecule and the confined space is comparable to the thermal de Broglie wavelength of molecular hydrogen, _λT = h/( _2πmkBT ) ^1/2 . Quantum sieving has been developed to separate gaseous isotope mixtures such as _D2 / _H2 (7), but identifying suitable porous solids is challenging. This is because KQS requires ultrafine pore openings (approximately 3 Å) (8, 9), which typically result in materials with low pore volumes. Therefore, the low _D2 adsorption capacity makes such processes difficult to scale. Similar selectivity/capacity tradeoffs, or in the case of membranes, selectivity/permeance tradeoffs, are observed in the separation of a wide range of other gases that do not involve KQS ( 10 – 13 ).

Various porous materials, including carbon (14, 15), carbon nanotubes (16), zeolites (17, 18), metal-organic frameworks (MOFs) (7, 19-20), covalent organic frameworks (COFs) (21), and 2D crystals (22), have been investigated for hydrogen isotope separation. MOFs and COFs have attracted increasing attention due to their crystallinity and synthetically tunable pore size and functional groups. (23) However, even with MOFs or COFs, it is difficult to achieve the exceptionally fine pore size required for KQS. For example, in MOFs, a common strategy for tailoring pore openings is to systematically increase or decrease the number of phenylene rings in the organic linker, with each individual increase/decrease being approximately 2.8 Å (24), a coarser size control than that required for KQS.

Porous organic cages (POCs) (25, 26) are discrete molecules that have previously been used to separate xylene isomers (27), noble gases (28), and chiral molecules ( ₂₈ ). POCs may also be promising candidates for _H /D separations. However, unlike MOFs and COFs, it is difficult to tune the pore size in POCs by simply varying the constituent linkers. Because POCs are discrete molecules, slight changes in their structure can have profound effects on the solid-state packing of the cage and, therefore, the pore structure. (25) Modifying only the interior of the cage molecule, rather than the cage structure itself, can avoid altering the crystal packing. Internal functionalization can be performed. For example, Mastalerz et al. described postsynthetic modification of the interior of an organic cage using six Williamson etherifications. (29) This internal modification affected the cage shape, which in turn altered the crystal packing pattern.

Experiments, Results and Discussion The experiments discussed below were performed in the context described above and utilize the materials, analytical protocols, computational methods and synthesized compounds described above.

Systematic Tuning of Organic Cage Pore Size through Postsynthetic Modification. We synthesized a series of internally post-functionalized porous organic cages that crystallized in an isomorphous manner. Specifically, we used a protection-deprotection strategy to generate cages with five of the six internal reactive sites in the cage cavity functionalized using our previously reported formaldehyde “ligation” method (31) (Figure 1, A and B). After deprotection, a single unreacted diamine group was reacted with a series of aldehyde or ketone precursors, allowing us to achieve ultrafine control over the overall cage cavity size and, therefore, the pore envelope (Figure 1C). This method allowed us to systematically tune the size and shape of the cage pores at the atomic level without affecting the external cage shape and size or its crystalline packing. Using this strategy, the authors tuned the pore size in a series of POCs from 3.5 to 1.95 Å, a useful cutoff range for separating gas pairs such as H ₂ /N ₂ , H ₂ /CO, CH ₄ /N ₂ , and Xe/Kr (8).

Previously, we reported that the organic cage RCC3, which has six diamine groups, reacted with six formaldehyde molecules to form 6FT-RCC3 through the formation of a cyclic aminal ring (31). Here, we reacted RCC3 with six equivalents of acetaldehyde to form a new cage, 6ET-RCC3 (reaction a, Figure 1B), in which the bulky ethylidene bridge was replaced by six methylene bridges in 6FT-RCC3. In contrast, RCC3 reacted with only a single acetone molecule to form 1AT-RCC3 (31) (reaction b, Figure 1B), and steric hindrance prevented further reaction in the cage cavity.

Based on this result, we developed a protection-deprotection strategy to react the five unfunctionalized diamine groups in 1AT-RCC3 with gaseous formaldehyde in the solid state via a single-crystal-single-crystal reaction to form a new dual "linked" cage molecule, 1AT-5FT-RCC3 (reaction d, Figure 1B, and Figure S1). Solid-state synthesis is essential here because when 1AT-RCC3 is mixed with formaldehyde in solution ( _CHCl3 or MeOH), a single acetone "protecting group" is transferred to give 6FT-RCC3 (reaction c in Figure 1B and Figure S2). Due to the chemical instability of 1AT-5FT-RCC3, which leads to the formation of various imidazolidine rings, we were able to selectively hydrolyze a single propyl linkage by stirring in CHCl ₃ :MeOH (1:1, v/v), thereby synthesizing the new deprotected cage 5FT-RCC3 (reaction e in Figure 1B, Figure S3). After deprotection, we then reacted the vacant diamine group in 5FT-RCC3 with acetaldehyde and propionaldehyde to synthesize two new cages, 1ET-5FT-RCC3 and 1PT-5FT-RCC3 (reaction f, Figure 1B). All reactions proceeded with nearly 100% conversion and no additional purification steps.

The parent cage RCC3 in this study was derived from the shape-persistent imine precursor CC3 (25, 27, 28), which crystallized from most organic solvents to form a microporous solid with a diamondoid pore network. To diffuse guests through this pore network, the guests must pass through the intrinsic cage cavities, which act as tetrahedral attachment points. (26) Therefore, functionalization of the cage cavity interior provides a route to systematically fine-tuning the pore size without altering the fundamental shape and crystallization habits of the cage molecule. (33) All cages were isomorphous to CC3, as determined by powder X-ray diffraction (PXRD) and single-crystal X-ray diffraction. The high crystallographic symmetry of the structure (cubic F4 ₁ 32) allowed the authors to determine whether all cages possessed the same diamondoid pore structure, although different "linking" groups were arranged in the micropore structure.

To allow for the effect of molecular flexibility on the diffusivity of small gas molecules through these structures, we used molecular dynamics (MD) simulations to calculate time-averaged pore confinement envelopes (PLEs) rather than measuring a single static pore diameter. (28) These calculations showed that post-synthetic modification resulted in PLEs ranging from 1.95 Å (6ET-RCC3) to 3.50 Å (6FT-RCC3), yielding a tunability window of 1.55 Å (Figure 1C). In this context, this tunability window is equivalent to the van der Waals (vdW) radius of a single nitrogen atom across the entire series of isomorphous cages.

We studied the gas sorption properties of these cages with four different gases (Figure 1D). As expected, a positive correlation between the cage cavity volume and the overall gas uptake was observed, especially under near-saturated gas conditions (e.g., _N2 at 77 K, orange bars in Figure 1D). For example, 5FT-RCC3, which has the largest cage cavity in this series, exhibited the highest uptake for all four gases studied. In contrast, 1AT-5FT-RCC3 exhibited lower gas uptake, and 6ET-RCC3 completely size-excluded krypton (Kr) and xenon (Xe).

This synthetic strategy has also been used to tailor gas selectivity for difficult-to-separate gas pairs, such as Xe and Kr (34, 35). Xenon is heavier and more polarizable than Kr and tends to form stronger vdW interactions with most sorbents, unless the pores are specifically adapted for Kr adsorption. Preferential Kr adsorption is extremely rare. For example, only one MOF, FMOFCu, selectively adsorbs Kr over Xe at temperatures below 0 °C (35).

While most of these organic cages also exhibit higher uptake of Xe than Kr, 1AT-5FT-RCC3 exhibited opposite uptake of these two gases. The ideal Kr/Xe molar selectivity was evaluated, which could be switched at temperatures below 0°C. The authors attribute this effect to 1AT-5FT-RCC3 possessing a cavity that is ideally suited to accommodate Kr but too small for Xe. By inserting an additional methyl group to form 6ET-RCC3, the cavity became too small to adsorb either gas.

Separation of Hydrogen Isotopes Using Ultrasmall Opening Cages Efficient KQS requires a porous solid in which the difference between the opening size and the diameter of the gas is comparable to the de Broglie wavelength. The kinetic diameter of hydrogen is 2.89 Å, and previous studies suggest that the optimal opening size for achieving KQS using a rigid framework is less than 3.40 Å. (21) Obtaining porous materials with pore openings in this range is quite difficult; only materials with pore diameters <3.00 Å have been reported to separate _D2 and _H2. (7)

Molecular dynamics simulations suggested that 6ET-RCC3 possesses a pore-confined envelope (PLE) (28) centered at 1.95 Å but exhibiting a relatively broad time-averaged size distribution, close to the minimum molecular dimension of _H2 (2.2 Å, Figure 1C). The hydrogen adsorption isotherm obtained from 6ET-RCC3 exhibited hysteresis between 30 and 60 K (Figure 2B). _{The H2} uptake reached a maximum at 50 K (4.8 mmol/g at 1 bar). We observed the same phenomenon with _D2 adsorption. The hysteresis was maximum at 30 K and decreased with increasing temperature, suggesting a broadening of the equilibrium.

We also compared the H ₂ adsorption behavior of two other organic cages, CC3 (25) and 6FT-RCC3, calculating pore envelopes of approximately 4.5 Å and 3.4 Å, respectively. Both CC3 and 6FT-RCC3 exhibited reversible type I adsorption isotherms, typical of nanoporous materials without dynamic diffusion barriers. The two cages showed an increase in H ₂ uptake with decreasing temperature, with maximum uptakes of 8.0 and 8.2 mmol/g at 1 bar and 30 K. Unlike 6ET-RCC3, no hysteresis was observed in CC3 or 6FT-RCC3. This difference suggests that the methyl groups in the 6ET-RCC3 cavity are responsible for its temperature-dependent flexibility, since this is the only structural difference between 6FT-RCC3 and 6ET-RCC3.

The hydrogen isotope separation performance of 6ET-RCC3 was verified by low-temperature temperature-programmed desorption spectroscopy (TDS). The _H2 and _D2 desorption rates of 6ET-RCC3 (Fig. 2C) were collected at a rate of 0.1 K/s during heating in vacuum (10 mbar) after pre-exposure to a 1:1 _H2 / _D2 mixture at various exposure temperatures (T _exp ) between 30 and 77 K for 10 min of exposure time (t _exp ). The area under the desorption peak is proportional to the amount of desorbed gas; therefore, the selectivity for _D2 over _H2 can be obtained from the ratio of the peak areas (7).

TDS measurements showed that the uptake of _H2 and _D2 in 6ET-RCC3 increased with increasing temperature until it reached a maximum at a T _exp of 60 K, then decreased again at 77 K. The selectivity, S _D2/H2 , decreased with increasing T _exp , reaching a maximum of 3.9 at 30 K, a separation performance significantly better than previous reports of dynamic quantum sieves (7, 36). The onset temperature of gas desorption was nearly identical to the exposure temperature, since the chamber was evacuated at T _exp before cooling to 20 K. No desorption peaks were observed above 60 K at T _exp = 30 K, implying no deep penetration into the structure at this temperature. At higher T _exp , the desorption spectrum occasionally shifted to higher temperatures, which the authors attributed to an increased penetration depth of gas molecules deeper into the cage structure. Consistent with the observations from pure gas isotherms, the properties of 6ET-RCC3 can be attributed to the temperature-dependent opening of the pore opening, a behavior similar to that observed in MFU-4 previously reported (7), which exhibited different effective opening sizes at different _T. This flexibility improved the accessibility of the isotope molecules to the pores at higher exposure temperatures.

Figure 2D shows the S _{D2 /H2} and total amount of adsorbed gas for 6ET-RCC3, 6FT-RCC3, and CC3 as a function of t _exp at T _exp = 30 K. 6ET-RCC3 showed an increase in uptake with longer t _exp , revealing impeded diffusion. At 30 K, S _{D2 /H2} decreased from 3.9 to 3.3 with longer t _exp ranging from 10 to 300 min of exposure, which is a typical KQS reaction. The KQS effect is based on diffusion limitation of the lighter isotope, and equilibrium is reached for both isotopes with longer exposure times. For 6ET-RCC3, the total uptake at 30 K was only 0.8 mmol/g at t _exp of 300 min, which is related to the hysteresis observed in the isotherm experiments at 30 K. The overall gas uptake obtained for CC3 and 6FT-RCC3 at 30 K was much higher (8.0 mmol/g), which is consistent with the adsorption results. For the large pore materials CC3 and 6FT-RCC3, S _{D2 /H2} was lower and remained constant at _1.2 and 2.1, respectively, at different t _exp , while maintaining a barrier-free and rapid diffusion of H2 and _D2 .

Improved quantum sieving performance in two-component cage cocrystals. These single-component cage crystals exhibited either good selectivity but poor gas capacity (6ET-RCC3) or good gas capacity but poor selectivity (CC3 and 6FT-RCC3). To achieve optimal isotope separation, an ideal KQS material should combine large cavities with narrow pore openings to preserve more _D2 and increase kinetic separation. Taking advantage of the chiral recognition assembly of individual cage molecules (37), we designed a cocrystal structure combining two different cages. 6ET-RCC3 was selected as the diffusion barrier to block _H2 diffusion and achieve the KQS effect, and CC3 was selected as the partner cage to provide sufficient pore space for high gas adsorption (Figure 3A).

The structure of the cocrystal Cocryst1 (6ET-RCC3-R/CC3-S, 1:1) is shown in Figure 3A (right). Four selective 6ET-RCC3 cages surrounded each CC3 conserved cage, as the cage cavities formed the connection points of the diamondoid pore network. Gas molecules diffusing through the cocrystal were forced to pass through the small pores in the 6ET-RCC3.

Cocryst1 was studied using high-resolution adsorption experiments of _D2 and _H2 collected between 30 and 77 K (Figure 3B). The amount of gas absorbed at 1 bar showed a maximum for both gases at 40 K. As for 6ET-RCC3, the hysteresis in Cocryst1 was higher at lower temperatures, especially at 30 K, due to a larger diffusion barrier; at higher temperatures, both _H2 and _D2 molecules diffused more rapidly due to the temperature-dependent opening of the openings.

The _D2 / _H2 ratio calculated for each point on the isotherm as a function of pressure is presented in Figure 3C. Cocryst1 exhibited a maximum _D2 / _H2 uptake ratio of 3.5 at 30 K and 25 mbar, which is consistent with the lack of equilibrium at 30 K, implying that the cocrystal possessed good separation ability. To the best of our knowledge, the _D2 / _H2 uptake ratio of Cocryst1 is the maximum value calculated from pure gas adsorption isotherms (7, 21, 36, 38, 39).

We investigated the actual gas separation by TDS. Cocryst1 was exposed to a 1:1 _H2 / _D2 mixture at 10 mbar for 30 min at various exposure temperatures. TDS spectra generated at T _exp 30, 40, and 50 K are shown in Figure 3D. The uptake after exposure to the gas mixture increased with increasing exposure temperature until reaching a maximum in combined gas uptake at 40 K. In contrast to 6ET-RCC3, Cocryst1 showed desorption up to 80 K at T _exp = 30 K, indicating gas permeation of the cage at low exposure temperatures. The uptake then decreased until no desorption peak was observed at 77 K. _{S D2/H2} reached a maximum of 7.7 at 30 K and then dropped to lower values at 40 and 50 K (Figure 3E). At a constant exposure temperature of 30 K, thermally activated flexibility was again observed. As the exposure time increased from 10 to 600 min, the S _D2/H2 ratio remained near 8.0 (7.8 to 8.2), while the _D2 uptake increased from 0.4 to 4.7 mmol/g (Figure 3F and G), indicating impeded diffusion. X-ray diffraction data indicate that Cocryst1 remained highly crystalline and did not change its structure during the TDS measurements.

The kinetics of pure _H2 and _D2 gas uptake was studied by TDS after exposure times varying from 10 to 1200 min at 30 K. For both gases, Cocryst1 showed a significant increase in uptake with longer exposure times. On the other hand, _D2 uptake was almost identical between 600 and 1200 min of exposure, and _H2 also increased with longer exposure times. This may indicate a completely different diffusion mechanism from _H2 , as _D2 reaches saturation faster.

The _H2 / _D2 separation properties of Cocryst1 were excellent, with an S _D2/H2 ratio of approximately 8.0, combined with significantly improved _D2 uptake (4.7 mmol/g) relative to 6ET-RCC3. Experimental S _D2/H2 values for various reported porous KQS adsorbents are compared in Figure 4 and Table S2. Of these, only two other porous solids combined a selectivity greater than 3 with a gas uptake greater than 1.0 mmol/g (dashed lines in Figure 4). The cage cocrystal exhibited the best combination of selectivity and _D2 uptake reported to date.

Molecular Simulation of Hydrogen Isotope Separation in Organic Cages. To further probe the separation mechanism, we simulated equilibrium adsorption isotherms for an equimolar mixture of _H2 and _D2 in CC3, 6ET-RCC3, and Cocryst1 by combining grand canonical Monte Carlo (GCMC) simulations with a Feynman-Hibbs (FH) effective potential. (43) We also used a hybrid GCMC/molecular dynamics scheme, which allows for direct sampling of host motion in adsorption simulations, which has previously been shown to be important for gas adsorption in porous organic cages. (28, 44) The simulated competitive adsorption isotherms (Figure 5, D to F) are in good agreement with experiment, confirming both the experimental adsorption data and the TDS results. All three cage crystals were predicted to be selective for _D2 over _H2 , with selectivity increasing as the temperature decreased. Furthermore, calculations suggest that, in agreement with experiments, Cocryst1 exhibits the high _D2 selectivity of 6ET-RCC3 while achieving a higher gas uptake capacity associated with the CC3 partner cage.

The diffusion of hydrogen isotopes in CC3, 6ET-RCC3, and Cocryst1 was investigated and interpreted by comparing the free energy barriers for _H2 and _D2 in a given crystal structure at infinite dilution. In the approximation of transition state theory, the molecular diffusivity can be derived from the rate constant for a molecule to hop the free energy barrier. Figures 5A–C show the free energy profiles for the diffusion path between the center of mass of a cage molecule and the center of mass of an adjacent cage, traveling between two cage windows. In CC3 (Figure 5C), both _H2 and _D2 easily moved between the two cage molecules in a nearly barrier-free passage. In contrast, the dense cage cavity and narrow window opening in 6ET-RCC3 resulted in a sharp peak in the free energy barrier (Figure 5A), strongly reducing the molecular diffusivity compared to CC3.

When two methyl groups are located in a single 6ET-RCC3 cage window, the pore space becomes too far apart and the diffusion barrier becomes too large to cross (Figure 5A, off-scale, left cage). In a window with only one methyl group (Figure 5A, right cage), the pore space penetrates seamlessly between the cages, and the free energy barrier for _H2 and _D2 is substantially reduced. Importantly, a 6ET-RCC3 cage window containing a single methyl group results in different diffusion barriers for _D2 and _H2 , acting as a dynamic sieve. This feature also applies to Cocryst1 (Figure 5B). In Cocryst1, the large CC3 cavity also provides favorable dynamic relaxation, improving _D2 kinetics and resulting in higher _D2 uptake.

Analysis of the various pore structures and the calculated diffusion barriers (Figure 5, A to I) explained why the selectivity for Cocryst1 was twice that of 6ET-RCC3 (S _D2/H2 = 8.2 vs. 3.9). The small channels in 6ET-RCC3 allowed single-file diffusion. Once molecules penetrated the pores, they could not pass between the isotopes in the channels. Therefore, desorption after exposure to the 1:1 mixture exhibited identical maximum temperatures for both isotopes (Figure 2C), and gas molecules exited in the order they entered, whereas the maximum for pure gas desorption appeared to be lower for _D2 than for _H2 (Figure 2B). Therefore, the KQS effect could only occur at the entrance of the pore opening at the cage crystal surface, without further exchange once inside the channels.

In contrast, Cocryst1 consists of a combination of a large storage pore and a small separation pore, separated by a differential diffusion barrier (Figure 5I). The penetration from the small opening to the next larger cavity provides an additional sieving effect, allowing _D2 molecules to pass through adjacent _H2 molecules, unlike the single-file pores of 6ET-RCC3. Counterintuitively, Cocryst1 significantly improved _D2 / _H2 selectivity, albeit by half the small window of 6ET-RCC3.

We further combined path-integral molecular dynamics (PIMD) simulations with quantum mechanical interaction evaluations to probe the adsorption and diffusion behavior of _H2 and _D2 in the 6ET-RCC3 cage molecule, explicitly accounting for both electronic and nuclear quantum mechanical properties (Figure 5, G to I). PIMD simulations predicted a binding free energy for _D2 that was approximately 0.50 kJ mol ^-1 lower than _that for H2 over the temperature range of 30 to 77 K. This difference in binding free energy resulted in a relative population of _D2 over _H2 inside the cage of 4.21 at 50 K (Figure 6B), which rose to 24.65 at 30 K. Qualitative agreement was observed between these simulated relative populations and the measured _D2 / _H2 selectivity over the temperature range of 30 to 77 K (Figure 5H). We also evaluated the free energy barriers for single molecules of quantum _H2 and quantum _D2 diffusing from the 6ET-RCC3 cage molecule (Figure 5I). These simulations show that nuclear quantum effects make _H2 less stable inside the cage compared to _D2 , resulting in a higher free energy barrier for _H2 diffusing through the cage window. The different barrier heights can be understood as a result of the different degrees of zero-point fluctuations that make the effective size of _H2 larger than that of _D2 , making it more difficult for _H2 to pass through the window opening.

Conclusions: When the field of porous organic cages (POCs) began, particular emphasis was placed on generating materials with large pore volumes and high surface areas relative to competing solids, such as MOFs. (25, 45-47) Our work suggests that there may be benefits in designing “slightly porous” solids. (46) While this approach itself has yielded materials with low gas capacities, by pairing small and large pore cages in a single cocrystal, such as 6ET-RCC3, we have evaluated materials with unprecedented gas separation properties. This strategy can be extended to obtain even better performance, for example, by introducing a storage cage with a larger capacity than CC3, provided that the differential diffusion barrier between the cages is preserved.

Our approach allows for extremely fine tuning of pore size, the entire tunability window for this series of cages spanning the diameter of a single nitrogen atom, and is ideally suited for applications such as KQS. The synthetic method involves a multistep organic synthesis (Figure 1B), including protection and deprotection steps, with each step proceeding in near 100% yield. Because no intermediates needed to be purified, there is good potential for scaling up the amount of material produced for practical separations.

Computational studies (Figs. 5 & 6) helped to explain the excellent H ₂ /D ₂ separation performance of the cocrystal.

[References]

EMBODIMENTS - NUMBERED PARAGRAPHS The following numbered paragraphs represent embodiments of the invention that are not claimed.
1. A method for extracting one or more target substances from a target mixture comprising one or more target substances and one or more non-target substances, comprising contacting the target mixture with a sorption composition at a predetermined contact temperature to preferentially sorb the target substances over the non-target substances, thereby obtaining a sorbed composition and a treated target mixture;
the sorption composition comprises a sorption compound, the sorption compound being a porous organic cage containing an interior cavity having a cavity size within +/- 4 Å of the thermal de Broglie wavelength of the target material at a contact temperature;
the sorbed composition comprises a sorption composition having the target substance or a mixture that is relatively enriched in the target substance compared to the target mixture, sorbed onto a sorption composition;
the treated target mixture is relatively enriched in the non-target material compared to the target mixture;
The method, wherein the target material has a shorter thermal de Broglie wavelength than the non-target material.
2. The method of paragraph 1, wherein the contacting is carried out at a contact temperature between 20K and 80K.
3. The method of any of the preceding paragraphs, further comprising separating the sorbed composition from the treated target mixture.
4. The method of paragraph 2 or 3, further comprising repeating the method of paragraph 2 by again supplying the treated target mixture as a target mixture to the method of paragraph 2 using either the same batch of the sorption composition or a different batch of the sorption composition.
5. The method of any preceding paragraph, further comprising recovering the target material or a mixture relatively enriched in the target material compared to the target mixture from the sorbed composition.
6. The method of paragraph 3, or any paragraph dependent thereon, further comprising repeating the method by re-supplying the recovered target material, or a mixture relatively enriched in target material compared to the target mixture, to the method of paragraph 3 as a target mixture using either the same batch of the sorption composition or a different batch of the sorption composition.
7. The method of any of the preceding paragraphs, wherein the interior cavity of the porous organic cage has a cavity size within +/- 2 Å of the thermal de Broglie wavelength of the target material at the contact temperature.
8. The target mixture comprises, consists essentially of, or consists of two or more selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT;
the target substance is selected from the group consisting of _D2 , _T2 , HD, HT, and DT;
The method of any of the preceding paragraphs, wherein the non-target substance is selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT, with the proviso that the non-target substance excludes the target substance.
9. The method of any of the preceding paragraphs, wherein the target substance comprises _D2 and/or _T2 and the non-target substance comprises _H2 .
10. The method of any of the preceding paragraphs, wherein the target substance is _D2 and the non-target substance comprises _H2 .
11. The method of any of the preceding paragraphs, wherein the interior cavity of the porous organic cage is a functionalized interior cavity derived from a pre-functionalized interior cavity, the pre-functionalized interior cavity comprising two or more functionalizable groups, one or more of which functionalizable groups are functionalized in the functionalized interior cavity.
12. The method of paragraph 11, wherein the functionalizable group comprises a reactive heteroatom that is functionalized via alkylation, acylation, acetalization, hemiacetalization, aminalization, and/or hemiaminalization, or wherein the functionalizable group comprises a reactive carbon atom that is functionalized via esterification, amidation, acetalization, hemiacetalization, aminalization, and/or hemiaminalization.
13. The method of paragraph 11, wherein the interior cavity of the porous organic cage is a homofunctionalized interior cavity.
14. The method of paragraph 11, wherein the interior cavity of the porous organic cage is a heterofunctionalized interior cavity.
15. The method of paragraph 11, wherein the interior cavity of the porous organic cage is a partially functionalized interior cavity.
16. The sorption compound is formed by functionalizing one, some, or all of the functionalizable groups in an internal cavity of a precursor compound with one or more functionalizing agents, the precursor compound being identical to the sorption compound except for the functionalization of the internal cavity, and the functionalization of the precursor compound is carried out by the following steps:
i) functionalizing one or more functionalizable groups (or one or more sets or pairs of functionalizable groups) with a first functionalizing agent to obtain one or more first functionalized groups;
ii) functionalizing one or more other functionalizable groups (or one or more other sets or pairs of functionalizable groups) with a second functionalizing agent to provide one or more second functionalized groups;
iii) defunctionalizing (or deprotecting) one or more of said first functionalized groups to obtain one or more first defunctionalized groups, preferably corresponding to the functionalizable groups to be regenerated;
iv) optionally re-functionalizing one or more of the first defunctionalized groups with a third functionalizing agent that is the same as or different from either the first or second functionalizing agent to obtain one or more third functionalized groups;
v) defunctionalizing (or deprotecting) one or more of said second functionalized groups to obtain one or more second defunctionalized groups, preferably corresponding to the functionalizable groups to be regenerated;
12. The method of paragraph 11, comprising one or more of the steps of: vi) optionally re-functionalizing one or more of the second defunctionalized groups with a functionalizing agent that is the same as or different from any of the first, second or third functionalizing agents to provide one or more fourth functionalized groups.
17. The method of paragraph 16, wherein the functionalization of the precursor compound comprises only step i) of steps i) to vi), thereby obtaining a homo-functionalized sorption compound formed from a single functionalizing material.
18. The method of paragraph 16, wherein the functionalization of the precursor compound comprises only steps i) and ii) of steps i) to vi), thereby obtaining a heterofunctionalized sorption compound formed from two different functionalizing substances.
19. The method of paragraph 16, wherein the functionalization of the precursor compound comprises only steps i), ii), and iii) of steps i) to vi), thereby obtaining a homo-functionalized sorption compound formed from a single functionalizing material.
20. The method of paragraph 16, wherein the functionalization of the precursor compound comprises only steps i), ii), iii) and iv) of steps i) to vi), thereby obtaining a heterofunctionalized sorption compound formed from two different functionalizing substances (second and third functionalizing substances).
21. The method of any of the preceding paragraphs, wherein the cavity size of the sorption compound in the SATP is between 0.5 and 5 Å.
22. The method of any of the preceding paragraphs, wherein the cavity size of the sorption compound in the SATP is between 1 and 2.4 Å.
23. The method of any of the preceding paragraphs, wherein the sorption compound is a functionalized polydiamine cage.
24. The sorption compound comprises one or more linking units of formula C and zero, one or more non-linking units of formula A, wherein the linking units of formula C and/or the non-linking units of formula A are optionally linked together via an intervening linker;
Formula C is

is defined by
Formula A is:

is defined by
wherein Tie is a molecular linkage defined by formula D;

where n is an integer between 1 and 4;
each _R and _R group is independently hydrogen or an optionally substituted substituent, and any pair of R and _R groups are optionally joined together to form a carbocyclic, heterocyclic, _aryl , or heteroaryl ring;
The method of any of the preceding paragraphs, wherein each _R and _R group is independently hydrogen or an optionally substituted substituent, and any pair of _R and _R groups is optionally joined together to form a carbocyclic, heterocyclic, aryl, or heteroaryl ring.
25. The sorption compound comprises one or more linking units of formula C ₁ and zero, one or more non-linking units of formula A ₁ , wherein the linking units of formula C ₁ and/or the non-linking units of formula A _1L are linked together via an intervening linker of formula A _1L ;
Formula _C1 is

is defined by
Formula _A1 is

is defined by
wherein ring A is a carbocycle, an aryl ring, a heterocycle, or a heteroaryl ring;
The formula A _1L is

is defined by
wherein ring L is a polyvalent hydrocarbon (linear or branched), polyvalent carbocycle, polyvalent heterocycle, polyvalent arene, polyvalent heteroarene, polyvalent mono-/poly-hydrocarbyl-carbocycle, polyvalent mono-/poly-hydrocarbyl-heterocycle, polyvalent mono-/poly-hydrocarbyl-arene or polyvalent mono-/poly-hydrocarbyl-heteroarene;
25. The method of paragraph 24, wherein any of the groups of formula C ₁ , A ₁ and/or A _1L are substituted or unsubstituted.
26. The sorption compound comprises one or more linking units of formula C2 and zero, one or more non-linking units of formula _A2 , wherein the linking units of formula _C2 and/or the non-linking units of formula _A2 are linked together via an intervening linker of formula _A2L ;
Formula _C2 is

is defined by
Formula _A2 is

is defined by
The formula A _2L is

is defined by
26. The method of paragraph 25, wherein any of the groups of formula _C2 , _A2 or _A2L is substituted or unsubstituted.
27. The sorption compound is defined by formula C3:

27. The method of paragraph 26, wherein Tie/ _H2 denotes either a diamine group linked with Tie or a diamine group not linked with a single hydrogen carried by each diamine nitrogen, and Tie is a molecular linkage defined by formula D, and the sorption compound comprises at least one Tie.
28. The sorption compound of formula C3 contains only a single type of molecular linkage, and the single molecular linkage of formula D is selected from the group consisting of:
R _B1 and R _B2 are both hydrogen (e.g. linked by formaldehyde), e.g. 6FT-RCC3 or 5FT-RCC3;
R _B1 and R _B2 are both methyl (e.g. linked by acetone), e.g. 1AT-RCC3, and
R _B1 is hydrogen and R _B2 is methyl (e.g. linked with acetaldehyde), e.g. 6ET-RCC3
28. The method of paragraph 27, wherein the compound is selected from the group consisting of:
29. The sorption compound of formula C3 comprises two or more different types of molecular linkages of formula D, wherein the different molecular linkages of formula D are selected from the group consisting of:
vii. a first molecular linkage in which _R and _R are both hydrogen (e.g., formaldehyde linked), and a second molecular linkage in which R _is hydrogen and R is methyl (e.g., acetaldehyde linked), such as 1ET-5FT- _RCC ;
viii. A first molecular linkage in which _R and _R are both hydrogen (e.g., linked by formaldehyde), and a second molecular linkage in which R and _R are both methyl (e.g., linked by acetone), e.g., 1AT-5FT- _RCC3 ; and
ix. The method of paragraph 27, wherein _R and _{R are} selected from a first molecular linkage where both are hydrogen (e.g., linked by a formaldehyde), and a second molecular linkage where R _is hydrogen and _R is ethyl (e.g., linked by a propionaldehyde), e.g., 1PT-5FT-RCC3.
30. The method of any of the preceding paragraphs, wherein the sorption compound is 6ET-RCC3.
31. The method of any of the preceding paragraphs, wherein the sorption composition comprises a co-crystal, the co-crystal comprising the sorption compound and a co-crystallized compound, the co-crystallized compound comprising an internal cavity, and the cavity size of the internal cavity is larger than the internal cavity of the sorption compound.
32. The method of paragraph 31, wherein the individual crystals of the sorption compound are isomorphous with the individual crystals of the co-crystallized compound.
33. The method of paragraph 32, wherein the individual crystals of the co-crystal are isomorphous with the individual crystals of the sorption compound.
34. The method of paragraph 33, wherein the co-crystallized compound has a cavity size at least 2 Å greater than that of the sorption compound.
35. The method of paragraph 33, wherein both the sorption compound and the co-crystallized compound are chiral, each of which is enantiomerically enriched in a single enantiomer, the single enantiomer of the sorption compound being of opposite chirality to that of the co-crystallized compound, in that one is the R-enantiomer and the other is the S-enantiomer.
36. The co-crystallization compound is, where appropriate, one or more units defined by formula E, optionally linked together via an intervening linker;

During the ceremony,
n is an integer between 1 and 4,
each _R and _R group is independently hydrogen or an optionally substituted substituent, and any pair of R and _R groups are optionally joined together to form a carbocyclic, heterocyclic, _aryl , or heteroaryl ring;
32. A method according to paragraph 31, wherein suitably the units of formula E are linked together via a linker (ie not directly bonded).
37. The co-crystallized compound is one or more units defined by formula E ₁ linked together via an intervening linker of formula A _1L ;
The units of formula _E1 are:

is defined by
wherein ring A is a carbocycle, an aryl ring, a heterocycle, or a heteroaryl ring;
The formula A _1L is

is defined by
wherein ring L is a polyvalent hydrocarbon (linear or branched), polyvalent carbocycle, polyvalent heterocycle, polyvalent arene, polyvalent heteroarene, polyvalent mono-/poly-hydrocarbyl-carbocycle, polyvalent mono-/poly-hydrocarbyl-heterocycle, polyvalent mono-/poly-hydrocarbyl-arene or polyvalent mono-/poly-hydrocarbyl-heteroarene;
37. The method of paragraph 36, wherein any of the groups of formula _E1 and/or _A1L are substituted or unsubstituted.
38. The co-crystallization compound is one or more units defined by formula _E2 linked together via an intervening linker of formula _A2L ;
The units of formula _E2 are:

is defined by
The formula A _2L is

37. The method of paragraph 36, wherein:
39. The method of paragraph 38, wherein the co-crystallized compound is CC3.
40. The method of paragraph 31, wherein the sorption compound is selected from the group consisting of 6FT-RCC3, 5FT-RCC3, 6ET-RCC3, 1AT-RCC3, 1ET-5FT-RCC3, 1AT-5FT-RCC3, 1PT-5FT-RCC3, and the co-crystallized compound is CC3.
41. The method of paragraph 40, wherein the sorption compound is 6ET-RCC3 and the co-crystallized compound is CC3.
42. The method of paragraph 31, wherein the molar ratio of sorption compound to co-crystallized compound in the co-crystal is between 5:1 and 1:5.
43. The target mixture comprises, consists essentially of, or consists of two or more selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT;
the target substance is selected from the group consisting of _D2 , _T2 , HD, HT, and DT;
the non-target substance is selected from the group consisting of _H2 , _D2 , _T2 , HD, HT, and DT, provided that the non-target substance excludes the target substance;
the cavity size of the sorption compound in the SATP is between 1 and 2.4 Å;
6. The method of paragraph 5, wherein the sorption compound is a functionalized polydiamine cage.
44. The method of paragraph 43, wherein the sorption composition comprises a co-crystal, the co-crystal comprising the sorption compound and a co-crystallized compound, the co-crystallized compound being a polydiimine cage comprising an internal cavity, the cavity size of the internal cavity being larger than the internal cavity of the sorption compound.
45. The method of paragraph 44, wherein the sorption compound is 6ET-RCC3 and the co-crystallized compound is CC3.

Claims (8)

1. A method for extracting one or more target substances from a target mixture comprising one or more target substances and one or more non-target substances, the method comprising:
the method comprising contacting the target mixture with a sorption composition at a predetermined contact temperature to preferentially sorb the target material over the non-target material to obtain a sorbed composition and a treated target mixture;
the method further comprising recovering the target material or a mixture relatively enriched in the target material compared to the target mixture from the sorbed composition;
the sorption composition comprises a co-crystal, the co-crystal comprising a sorption compound and a co-crystallized compound;
the sorption compound is 6ET-RCC3 and the co-crystallized compound is CC3;
the sorbed composition comprises a sorption composition having the target substance or a mixture that is relatively enriched in the target substance compared to the target mixture, sorbed onto a sorption composition;
the treated target mixture is relatively enriched in the non-target material compared to the target mixture;
the target substance is selected from the group consisting of D2 , T2 _, HD, HT, and DT _;
the target mixture comprises, consists essentially of, or consists of two or more selected from the group consisting of H2, D2, T2, HD, _HT , _and DT _;
the non-target substance is selected from the group consisting of H2, D2, T2, HD, HT, and DT, _provided that _the non _- target substance excludes the target substance ;
method. The method of claim 1, wherein the contacting is carried out at a contact temperature between 20K and 80K. The method of claim 1 or 2, further comprising separating the sorbed composition from the treated target mixture. The method of claim 2 or 3, further comprising repeating the method by feeding the treated target mixture back into the method of claim 2 as a target mixture using either the same batch of the sorption composition or a different batch of the sorption composition. 5. The method of claim 3 or 4, further comprising repeating the method by re-supplying the recovered target material, or a mixture relatively enriched in the target material compared to the target mixture, to the method of claim 3 as a target mixture using either the same batch of the sorption composition or a different batch of the sorption composition. 6. The method of claim 1, wherein the target substance comprises _D2 and/or _T2 , and the non-target substance comprises H2. 7. The method of claim 1, wherein the target substance is _D2 and the non-target substance comprises _H2 . 10. The method of claim 1 , wherein the molar ratio of sorption compound to co-crystallized compound in the co-crystal is between 5:1 and 1:5.