JPS635032B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a heme complex coordinated with an imidazole derivative and a gas adsorption/desorption agent. Many heme complexes have been known as substances that have the ability to reversibly adsorb and desorb gas molecules such as oxygen, carbon monoxide, and nitrogen oxides. However, in general, the constituent components of known heme complexes are often materials with poor biocompatibility, such as synthetic porphyrins or basic ligands that have a structure far different from that of in-vivo porphyrins, and moreover, they cannot be used in aqueous solutions. There are few materials that can maintain gas adsorption/desorption ability. Therefore, an object of the present invention is to provide an imidazole derivative-coordinated heme complex that is biocompatible, has superior ability to adsorb and desorb gas molecules, and can maintain its function even in an aqueous solution. The complex of the present invention is an imidazole derivative clathrated in a cyclodextrin, which has a substituent on the nitrogen atom at the 1-position that has a size and hydrophobicity that allow it to be included in the cavity of the cyclodextrin. It is a cyclodextrin inclusion imidazole-coordinated heme complex in which heme is bound to the nitrogen atom through a coordination bond. The above cyclodextrin has 6, 7 or 8
D-glucopyranose units are cyclically glucosidically bonded, and depending on the number of D-glucopyranose units, α-cyclodextrin (6 units), β
-They are called cyclodextrin (7 pieces) and γ-cyclodextrin (8 pieces). This cyclodextrin has a nearly cylindrical structure, and the inside of the cavity is a hydrophobic field. In this invention, α-
Cyclodextrins are preferred. The imidazole derivatives included in such cyclodextrins are fat-soluble and have a size and hydrophobicity that allow them to be included in the cavities of the cyclodextrins, that is, they contain substituents that can stably exist within the cavities of the cyclodextrins. It is located on the nitrogen atom at the 1st position. Such imidazole derivatives preferably have the formula (Here, R ¹ is a methyl group, R ² and R ³ are each independently hydrogen or a methyl group, and A is -(CH ₂ -) _o
or [Formula] n is an integer from 0 to 3, and B is a hydrocarbon group having 1 to 10 carbon atoms, or a group in which one terminal hydrogen atom is substituted with a C ₁ to _{C 3} hydrocarbon ester of carboxylic acid or phthalimide. ). To give a specific example, 1-
Phenethyl-2-methylimidazole, 1-cyclohexyl-2-methylimidazole, 1-benzyl-2-methylimidazole, 1-tosyl-2
-Methylimidazole, 1-(2-ethoxycarbonyl)ethyl-2-methylimidazole, N-
{1-(4,5-dimethyl)imidazolyl}pentylphthalimide, 11-{1-(2-methyl)imidazolyl}undecanoate, or 1,2-
It is dimethylimidazole. The term "inclusion" used in this specification means that the entire imidazole derivative or its 1-position substituent exists relatively stably within the cavity of the cyclodextrin. In the complex of this invention, the heme coordinating with the imidazole is porphyrin and Fe()
Or a complex with Fe(), and a complex with Fe() is preferable as a gas adsorption/desorption agent. In such heme, the central iron is 3 of the imidazole derivative.
It has a coordinate bond with the nitrogen atom at the position. This heme includes complexes of various types of hemin and other porphyrins in the body and iron. As described above, the cyclodextrin-clathrate imidazole-coordinated heme complex of the present invention is composed of an iron complex of porphyrin, which is a biological component, and cyclodextrin (rat,
LD ₅₀ by in vivo administration 1.00g/Kg (α-cyclodextrin), 0.788g/Kg (β-cyclodextrin); DWFrenk et al., American Journal of
Pathology 83 (2), 367 (1976)) and fat-soluble imidazole derivatives. Some fat-soluble imidazoles have pharmacological effects, and are generally considered to be highly toxic based on the results of extensive toxicity tests, but inclusion in cyclodextrin not only makes them water-soluble, but also reduces their apparent toxicity. There is expected. Generally, the complex of imidazole and heme has the formula (Here, [Formula] is a porphyrin planar structure, [Formula] is an iron ( ) complex of this), and has a low spin type hexacoordination structure. On the other hand, an imidazole derivative having a sterically hindered group, such as a complex of 2-methylimidazole and heme, has the formula (Here, [Formula] is a porphyrin structure with the center part protruding upward, and [Formula] is an iron ( ) complex of this structure.) It has a high spin five-coordination structure. A heme complex with a low spin hexacoordination structure of formula () has the disadvantage that when it comes into contact with oxygen, the imidazole coordinated to the sixth coordination site of the central iron must be pushed away in order for oxygen to coordinate. However, in the latter heme complex with a high-spin pentacoordination structure represented by formula (), the sixth coordination site of the central iron is vacant, and gas molecules such as oxygen can quickly bind thereto. Furthermore, it is generally said that in the low spin hexacoordination structure heme of formula (), outer sphere type oxidative deterioration is likely to occur due to the approach of oxygen molecules. The latter high-spin pentacoordination structure is preferable in order to be able to reversibly bond with gas molecules such as It has a five-coordinate structure, which is why it has the ability to stably capture oxygen molecules. By the way, imidazole derivatives having a sterically hindered group generally have significantly weaker coordination bond strength with heme than imidazole that does not have a sterically hindered group, and this can be used to stably form a five-coordinate heme structure. In order to achieve this, it is necessary to use a large molar excess of heme. Therefore, a complex with the structure of formula () is
Considering only the toxicity of imidazole itself, it is extremely difficult to apply it to living organisms. On the other hand, even if the imidazole derivative containing cyclodextrin, which is a component of the complex of the present invention, has a sterically hindered group, its coordination bond strength is significantly reduced as a result of inclusion with cyclodextrin. Improved.
That is, for heme having a low spin five-coordination structure shown by the formula (), for example, the formula (Here, [Formula] is cyclodextrin, A and B are as described above) When a minute amount of the cyclodextrin inclusion imidazole derivative is acted on, a high-spin type five-coordinated heme complex is preferentially produced. . Therefore, the amount of the imidazole derivative itself is small, and since the imidazole derivative is included in cyclodextrin, its toxicity is low and it has biocompatibility. In order to obtain the cyclodextrin inclusion imidazole-coordinated heme complex of the present invention having such characteristics, for example, X-A-B (where X is halogen,
A and B are as described above) and the formula (Here, R ¹ , R ² and R ³ are as described above)
The imidazole derivative represented by the formula (A) is first obtained by bonding with the imidazole represented by the formula (A) by a per se known imidazole 1-substituent introduction reaction (dehydrohalogenation reaction). Next, this derivative is added to an aqueous solution with an appropriate concentration below the saturation concentration of cyclodextrin at a ratio of equal molar or more to cyclodextrin and no more than twice the molar amount, and the mixture is mixed and stirred at around room temperature for several hours, and then frozen. dry. 50℃
After further drying under reduced pressure with heat nearby, the unclathrated imidazole is washed with a suitable low-boiling organic solvent (such as diethyl ether) that dissolves the unclathrated imidazole derivative but does not dissolve the clathrated imidazole derivative. Remove. The resulting clathrate imidazole is dried under reduced pressure at 50° C. to a constant weight to obtain the desired cyclodextrin clathrate imidazole derivative. Finally, this clathrate imidazole derivative is added in water or a mixed solvent of a polar aprotic solvent (for example, N,N-dimethylformamide, N,N-dimethylacetamide, etc.) and water in an equimolar amount or more relative to heme. By mixing with heme, the cyclodextrin inclusion imidazole-coordinated heme complex of the present invention is obtained. The complex of this invention adsorbs and captures gases such as oxygen, carbon monoxide, and nitrogen oxides when it is passed through the solution, and immediately releases the adsorbed gases when an inert gas is passed through it or when it is placed under reduced pressure. do. This can be done repeatedly. Since the present invention has such ability and high biocompatibility, it can be applied, for example, as a material for artificial blood. It can also be used as a catalyst for various chemical reactions such as redox reactions and oxygen addition reactions, especially as a homogeneous water phase catalyst. Hereinafter, this invention will be explained in detail with reference to Examples. Example 1 Phenethyl chloride 28.1g (0.2mol), 2-
32.8 g (0.4 mol) of methylimidazole was mixed and reacted at 200°C for 5 hours. After cooling, the reaction product was dissolved in 200 ml of chloroform. This was washed with the same amount of 10% Na ₂ CO ₃ aqueous solution and the same amount of water, left to dry over anhydrous sodium carbonate, and the solvent was distilled off under reduced pressure. The residual oil was distilled under reduced pressure (bp159-160℃ (5mmHg)) under a nitrogen stream to obtain 1-
15.3g of phenethyl-2-methylimidazole
(yield 41.0%). NMR (TMS, CDCl ₃ ), 2.10 (singlet,
3H, -CH ₃ ), 2.80 (triple line, 2H, J=7Hz,
C H ₂ φ), 3.97 (triple line, 2H, J=7Hz, C
H ₂ CH ₂ φ), 6.64 (double line, 1H, J=1Hz,
Proton at position 5 of imidazole ring), 6.79 (doublet, 1H, J=1Hz, proton at position 4 of imidazole ring), 6.84-7.22 (multiplet, 5H, φ-H)
ppm. MSm/e186 (M ⁺ .) After dissolving 2.92 g (3 x 10 ^-3 mol) of α-cyclodextrin in 25 ml of water, 1.12 g (6 x 10 ^-3 mol) of 1-phenethyl-2-methylimidazole was added. Added. After stirring at room temperature for 3 hours, the mixture is freeze-dried and further dried under reduced pressure at 50°C for 8 hours. After washing the obtained powder twice with 50 ml of diethyl ether, it was further dried under reduced pressure at 50°C for 12 hours to obtain 1-phenethyl-2 as a white powder.
- Obtain 4.00 g (quantitative yield) of a clathrate compound with a molecular ratio of 1:1 of methylimidazole and α-cyclodextrin. In heavy water solvent (D ₂ O), the above clathrate, α-
NMR of cyclodextrin (CD) and 1-phenethyl-2-methylimidazole (PMI)
The following two tables were obtained from the measured results. [Table] (In the above table, α-CD stands for α-cyclodextrin, PMI stands for 1-phenethyl-2
-Represents methylimidazole. ) [Table] In Table 1, the phenyl group and methyl group protons of 1-phenethyl-2-methylimidazole are shifted up the magnetic field in the case of inclusion bodies,
It was found that these groups were contained within the hydrophobic cavity. Furthermore, in Table 2, the 3- and 5-position protons on the inner surface of the cavity of α-cyclodextrin are shifted by a high magnetic field in the case of the inclusion complex, and these protons interact hydrophobically with the phenyl group and methyl group. It was inferred that Furthermore, in the NMR spectrum of the inclusion complex, for example, the integrated intensity ratio of the 1-position proton signal of α-cyclodextrin (5.065 ppm) and the methyl group proton signal of 1-phenethyl-2-methylimidazole (1.909 ppm) is 6:3. It was also confirmed that the inclusion ratio was 1:1. Hemin was dissolved in M/5-Na ₂ CO ₃ -NaHCO ₃ buffer solution (PH=10.0) to prepare a 10 ^-5 M hematin aqueous solution. The resulting solution was placed under a nitrogen atmosphere.
Na ₂ S ₂ O ₄ was added in a molar amount 20 times that of hematin, and the visible absorption spectrum in the wavelength range of 350 to 700 nm was measured. Next, 50 each for hematin,
After coexisting with 100, 200, 500, 1000 times the molar amount of α-cyclodextrin inclusion 1-phenethyl-2-methylimidazole, under the same conditions as above.
Na ₂ S ₂ O ₄ reduction was performed and the spectrum was measured. From the obtained continuous change spectrum, Miller
According to Dorough's equation, the complex equilibrium constant K of the complex formed between heme and the clathrate ligand is 7.64×10 ² l・
mol ^-1 was determined. This value is K=2.8 when 1.2-dimethylimidazole is used as a ligand.
Compared to ×10 ¹ l·mol ^-1 , the coordination ability to heme is significantly improved. According to the above procedure, a M/5-Na ₂ CO ₃ -NaHCO ₃ solution (PH = 10.0) of hematin 10 ^-5 M and imidazole 10 ^-2 M was prepared, and dithionite was added under a nitrogen gas atmosphere. By reducing λ _nax
Visible absorption spectra of the low-spin hexacoordination structure at 426, 528, and 558 nm were observed. When 1/5 amount of α-cyclodextrin clathrated 1-phenethyl-2-methylimidazole ligand of imidazole was added to the obtained solution, the spectrum immediately shifted to λ _nax 432, 557 nm and became high. Formation of a spin-type pentacoordination complex was observed. This result shows that the coordination ability of 1-phenethyl-2-methylimidazole clathrated with α-cyclodextrin to heme is even better than that of imidazole without sterically hindered groups, and it is possible to It has characteristics completely different from that of a ligand. Hemin 1.2×10 ^-4 M, α-cyclodextrin inclusion 1-phenethyl-2-methylimidazole 2.4×10 ^-2 M N,N-dimethylformamide/water (PH=7) = 9/1 (v/v ) The solution was reduced by adding 6 times the molar amount of Na ₂ S ₂ O ₄ to hemin under a nitrogen atmosphere. The obtained heme complex solution was heated to -30
After cooling to ℃ and introducing 1 atm of oxygen,
Visible spectral changes occur rapidly, and λ _nax
Oxygen complex spectra of 410, 545, and 577 were obtained.
When nitrogen gas was blown into this, the visible spectrum returned to its original reduced form (λ _nax 432, 557 nm). When carbon monoxide was blown into the obtained heme complex, carbon monoxide complex spectra of λ _nax 418, 538, and 566 were observed. These visible spectral behaviors are comparable to spectral changes associated with gas adsorption and desorption of hemoglobin in water at room temperature (Table 3). [Table] Imidazole, 2-methylimidazole, etc.
Compared to the fact that conventional systems using low-molecular-weight ligands do not form any oxygen complexes under the same conditions as above and are quickly oxidized, or the half-life of oxygen complexes is several minutes or less, the half-life of the oxygen complex is long. , an improved heme complex with excellent oxygen bond stability. Examples 2-8 Several imidazole derivatives with hydrophobic substituents were prepared and included in cyclodextrins according to the method of Example 1. The coordination ability of the prepared clathrate imidazole to heme (complex stability constant) and the gas adsorption properties of the clathrate imidazole coordination heme complex were also investigated using exactly the same method as used in Example 1. Details are shown in Table 4. In the table, imidazoles No. 4 and No. 6 were clathrated with the addition of a small amount of acetic acid. The greater the complex stability constant K, the higher the stability of the produced oxygen complex, and it was unstable when imidazole clathrates No. 4 and No. 8, which had smaller values, were used. [Table] The imidazole derivatives of Examples 2 to 7 were each synthesized as follows. (2) Cyclohexylmethyl bromide 35.4g (0.2
After mixing 32.8 g (0.4 mol) of 2-methylimidazole and reacting at 200°C for 8 hours, 1-cyclohexyl-2-
25.0 g (yield 70.0%) of methylimidazole was obtained. NMR (TMS, _CDCl3 ), 0.6-2.0 (broad multiplet,
11H, [formula]), 2.35 (single line, 3H, - CH ₃ ), 3.61 (double line, 2H, J = 7Hz, - CH ₂
-), 6.69 (singlet, H, proton at 5th position of imidazole ring), 6.81 (singlet, H, proton at 4th position of imidazole ring) ppmMSm/e178 (M ⁺ .) (3) Benzyl chloride 25.3g (0.2 mol), Add 16.4 g (0.2 mol) of 2-methylimidazole to 100 ml of n-butanol and add 9.6 g of sodium hydroxide.
After refluxing the boiling point for 3 hours in the presence of
%) was obtained. NMR (TMS, CDCl ₃ ), 2.31 (singlet, 3H,
―CH ₃ ), 5.00 (single line, 2H, ―CH ₂ ―), 6.82
(double line, 1H, imidazole ring 5-position proton),
6.93 (doublet, 1H, proton at 4 position of imidazole ring), 6.9-7.4 (multiplet, 5H, φ-H) ppm MSm/e172 (M ⁺ .) (4) 2-methylimidazole 16.4 in 100ml of anhydrous pyridine (0.2 g) and 38.1 g of p-toluenesulfonyl chloride were added, and the mixture was stirred at room temperature overnight. After distilling off the solvent under reduced pressure, it is treated in a conventional manner and recrystallized from diethyl ether-petroleum ether to obtain 1-tosyl-2.
- Obtain 36.8 g (yield 78%) of methylimidazole. IR (KBr) 1375, 1200-1155 cm ^-1 (νSO ₂ ) NMR (TMS, CDCl ₃ ), 2.40 (singlet, 3H, imidazole ring - CH ₃ ), 2.48 (singlet, 3H, phenyl ring - _{CH 3} ) , 6.79 (double line, H, imidazole ring 5-position proton), 7.23 (double line, 2H,
[Formula]), 7.30 (double line, H, proton at 4-position of imidazole ring), 7.66 (double line,
2H, [Formula]) ppmM Sm/ e236 (M ⁺ .) (5) 2-methylimidazole 16.4 g (0.2 mol),
Mix 21.3g (0.4mol) of acrylonitrile,
After boiling under reflux for 3 hours, excess acrylonitrile was distilled off under reduced pressure. Dissolve the residue in 95% ethanol, add 20 ml of concentrated hydrochloric acid and boil under reflux for 4 hours. Neutralize by adding 10% Na ₂ CO ₃ aqueous solution under ice cooling. After extraction with 300ml of chloroform three times
Dry and filter _{over Na2CO3} . After the liquid was distilled off under reduced pressure, the residue was crystallized at dry ice-mutanol temperature, and the resulting pale yellow crystals were ground and collected in diethyl ether. Drying under reduced pressure over P ₂ O ₅ at room temperature yielded 16.8 g of 1-(2-ethoxycarbonyl)ethyl-2-methylimidazole (yield:
46%) get. IR (KBr) 1740 (ν _C=O , ester) 1185 (ν _CO ,
ester) cm ^-1 NMR (TMS, CDCl ₃ ) 1.20 (triple line, 3H,
-CH ₂ CH ₃ ) 2.31 (- doublet, 3H, imidazole ring - CH ₃ ), 2.64 (triplet, 2H, -C H
₂ CH ₂ CO ₂ -), 4.06 (quartet, 2H, -C H
₂ CH ₃ ), 4.11 (triple line, 2H, CH ₂ CH 2 _{CO 2} -),
6.87, 6.85 (each singlet, 2H, imidazole ring proton) ppm MSm/e182 (M ⁺ .) (6) (i) 25 g of acetoin and 125 ml of formamide were mixed and boiling refluxed for 4 hours. After cooling, fractional distillation was carried out under reduced pressure to collect bp165°C (11 mmg), which was then recrystallized from diethyl ether-methanol to obtain 4,5
-Dimethylimidazole 13.5g (yield 49.5
%) was obtained. MSm/e96 (M ⁺ .) NMR (TMS, CDCl ₃ ) 1.82 (singlet, 6H,
-CH ₃ ), 6.74 (singlet line, H, imidazole ring 2-position proton), 11.04 (broad line, H, NH)
ppm. (ii) 60 g of potassium phthalimide was suspended in 250 g of pentamethylene bromide, and the reaction was heated and stirred at 200°C for 12 hours. After cooling, steam distillation was performed to remove unreacted pentamethylene bromide.
Add diethyl ether and water to the residue and shake vigorously. Separate the diethyl ether layer. After extracting the aqueous layer with diethyl ether twice, the diethyl ether solution was collected and washed with water, followed by drying over anhydrous sodium sulfate overnight. After that, the solvent component was distilled off under reduced pressure, and the residue was recrystallized from ethanol to obtain 48 g (yield: 50%) of N-(5-bromopentyl)phthalimide. IR (KBr) 1780, 1720 cm ^-1 (ν _C=O , phthalimidocarbonyl) NMR (TMS, CDCl ₃ ) 2.1-1.3 (multiplet,
Broad, 6H, NCH ₂ ( CH ₂ ) ₃ CH ₂ Br),
3.38 (triplet, 2H, -C H ₂ Br), 3.66 (triplet, 2H, NC H ₂ -), 8.27 (multiplet, 4H,
φ-H)ppm. MSm/e296 (M ⁺ .) (iii) Dissolve 10 g of 4,5-dimethylimidazole in tetrahydrofuran, add 6.4 g of 50% sodium hydride under nitrogen, and boil under reflux for 1 hour. N
A solution of 35.5 g of -(5-bromopentyl)phthalimide in tetrahydrofuran (150 ml) was added dropwise at room temperature over 1 hour, followed by boiling under reflux for 3 hours. After removing the insoluble components and distilling off the solvent components under reduced pressure, a silica gel column (6 cmφ x 45 cm, CHCl ₃ /CH ₃ OH = 20/1 (v/
v) solvent) and purified using N-{1-(4,5
18 g (yield: 55.6%) of dimethyl)imidazolyl}pentylphthalimide was obtained. IR (KBr) 1775, 1720 cm ^-1 (ν _C=O , phthalimidocarbonyl) NMR (TMS, CDCl ₃ ) 1.3-1.7 (broad, multiplet, 6HNCH ₂ (CH ₂ ) ₃ CH ₂ N), 2.11
(Single line, 6H, -CH ₃ ), 3.62 (Triple line, 2H,
[Formula]), 3.71 (triplet, 2H, [Formula]), 7.27 (singlet, H, proton at 2-position of imidazole ring), 7.78 (multiplet, 4H,
φ-H) ppm MSm/e311 (M ⁺ .) (7) 25 g of 11-bromoundecanoic acid and 100 g of benzene
Stir at room temperature for 4 hours in the presence of 13 ml of oxalyl chloride. Next, 50 ml of methanol was added, and the mixture was allowed to stand overnight and then treated in a conventional manner to obtain 23 g (yield: 87.5%) of 11-bromoundecanoic acid methyl ester. 8.2g of 2-methylimidazole to 2.4g of NaH/
Slowly add the suspension to 200ml of DMF. After the addition, the mixture was heated at 90°C for 1 hour, and the previously obtained 11-bromoundecanoic acid methyl ester was added dropwise. Subsequently, after heating and stirring at 90°C for 2 hours, the usual procedure was carried out. Silica gel column (6cmφ×27cm, CHCl ₃ /
Purification using CH ₃ CH=9/1 (v/v) yields 9.5 g (41% yield) of methyl 11-{1-(2-methyl)imidazolyl}undecanoate. IR (liquid film) 1740cm ^-1 (ν _C=O , ester) NMR (TMS, CDCl ₃ ), 1.28 (singlet, 12H,
NCH ₂ CH ₂ (CH 2 ) ₆ CH ₂ CH ₂ CO ₂ -), 1.68 (multiline, wide, 4H _, NCH ₂ CH ₂ ( _{CH 2} ) ₆ C H
₂ CH ₂ CO ₂ -), 2.31 (triple line, 2H, - CH ₂ CO ₂
--), 2.37 (singlet, 3H, imidazole ring --
CH ₃ ), 3.66 (singlet, 3H, - COOCH ₃ ), 3.80
(Triple line, 2H, NC H ₂ -), 6.80 (Double line,
H, proton at the 5th position of the imidazole ring), 6.90 (double line, H, proton at the 4th position of the imidazole ring) ppm. MSm/e280 (M ⁺ .).

Claims (1)

[Claims] 1. An imidazole derivative clathrated in cyclodextrin, which has a substituent on the nitrogen atom at the 1-position having a size and hydrophobicity that allows it to be included in the cavity of the cyclodextrin, at the 3-position. A cyclodextrin inclusion imidazole-coordinated heme complex in which heme is bound to the nitrogen atom by a coordination bond. 2. The complex according to claim 1, wherein the cyclodextrin is α-cyclodextrin. 3 The imidazole derivative has the formula (Here, R ¹ is a methyl group, R ² and R ³ are each independently hydrogen or a methyl group, and A is -(CH ₂ -) _o
or [Formula] n is an integer from 0 to 3, and B is a hydrocarbon group having 1 to 10 carbon atoms, or a group in which one terminal hydrogen atom is substituted with a C ₁ to _{C 3} hydrocarbon ester of carboxylic acid or phthalimide. ) The complex according to claim 1 or 2. 4 The imidazole derivative is 1-phenethyl-2-
Methylimidazole, 1-cyclohexyl-2-
Methylimidazole, 1-benzyl-2-methylimidazole, 1-tosyl-2-methylimidazole, 1-(2-ethoxycarbonyl)ethyl-
2-methylimidazole, N-{1-(4,5-
4. The complex according to claim 3, which is dimethyl)imidazolyl}pentylphthalimide, 11-{1-(2-methyl)imidazolyl}undecanoate, or 1,2-dimethylimidazole. 5. The complex according to any one of claims 1 to 4, which is an iron () or iron () complex of porphyrin in which heme is a biological component. 6 An imidazole derivative clathrated in cyclodextrin, which has a substituent on the nitrogen atom at the 1st position that has a size and hydrophobicity that allow it to be included in the cavity of the cyclodextrin, but has heme at the nitrogen atom at the 3rd position. A gas adsorption/desorption agent consisting of a cyclodextrin inclusion imidazole coordination heme complex bound by coordination bonds. 7. The gas adsorption/desorption agent according to claim 6, wherein the cyclodextrin is α-cyclodextrin. 8 The imidazole derivative has the formula (Here, R ¹ is a methyl group, R ² and R ³ are each independently hydrogen or a methyl group, and A is -(CH ₂ -) _o
or [Formula] n is an integer from 0 to 3, and B is a hydrocarbon group having 1 to 10 carbon atoms, or a group in which one terminal hydrogen atom is substituted with a C ₁ to _{C 3} hydrocarbon ester of carboxylic acid or phthalimide. ) The gas adsorption/desorption agent according to claim 6 or 7. 9 Imidazole derivative is 1-phenethyl-2-
Methylimidazole, 1-cyclohexyl-2-
Methylimidazole, 1-benzyl-2-methylimidazole, 1-tosyl-2-methylimidazole, 1-(2-ethoxycarbonyl)ethyl-
2-methylimidazole, N-{1-(4,5-
9. The gas adsorption/desorption agent according to claim 8, which is dimethyl)imidazolyl}pentylphthalimide, 11-{1-(2-methyl)imidazolyl}undecanoate, or 1,2-dimethylimidazole. 10. The gas adsorption/desorption agent according to any one of claims 6 to 9, wherein the heme is iron () or an iron () complex of porphyrin, which is a biological component.