JP2002128782A - Porphyrin aggregate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stable oxygen carrier which has high oxygen-carrying efficiency without adding an axial basic ligand. SOLUTION: This oxygen carrier includes a porphyrin aggregate comprising a porphyrin derivative represented by the general formula (I) [(n) is the number of methylene groups; R1 is an alkylene; R2 is a substituent not inhibiting the coordination of imidazole to the central metal; M is hydrogen atom or a transition metal ion in the 4 to 5 periods; X- is a halide ion selected from chloride ion, bromide ion and iodide ion; (m) is 0 or an integer obtained by subtracting 2 from the valency of the metal ion].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a porphyrin assembly comprising an amphiphilic tetraphenylporphyrin metal complex having a proximal base and an artificial oxygen carrier containing the same.

[0002]

2. Description of the Related Art Iron (II) porphyrin complexes present in hemoglobin and myoglobin can reversibly adsorb and desorb oxygen molecules.
Numerous studies have attempted to realize oxygen adsorption / desorption ability similar to that of the (II) complex by using a synthetic complex (for example, J.
P. Collman, Accounts of Chemical Research, 1977,
10 , 265, F. Basolo, BM Hoffman, JA Ibers, ib
id., 1975, 8 , 384, etc.). In particular, porphyrin iron reported to be able to form stable oxygen complexes under room temperature conditions
As the (II) complex, 5,10,15,20-tetrakis (α, α, α, α-o-pivalamidophenyl) porphyrin iron (II) complex (hereinafter, referred to as FeTpivPP complex) is known. (JP Collman, et al., J. Am.
Chem. Soc., 1975, 97 , 1427).

[0003] When an axial base such as 1-alkylimidazole or 1-alkyl-2-methylimidazole coexists, the FeTpivPP complex is benzene, toluene, N, N-
Molecular oxygen can be reversibly bound at room temperature in an organic solvent such as dimethylformamide. This complex also
When embedded in a bilayer membrane vesicle composed of phospholipids, the same function is exhibited under physiological conditions (aqueous phase, pH 7.4, ≤40 ^° C.) (E. Tsuchida, et al., J. Chem. Soc.,
Dalton Trans., 1984 , 1147). However, this FeTp
Since the ivPP complex has a bulky substituent on only one surface of the porphyrin ring, the ivPP complex is susceptible to attack from a surface that is not protected by the bulky substituent of the porphyrin ring, and gradually has no oxygen binding ability. ) There was a problem that it was oxidized to a complex. For this reason, porphyrin iron (II) complexes that provide stable oxygen complexes in water and at room temperature have been actively developed.

Accordingly, the inventors of the present application have introduced a central iron (I) by introducing a bulky substituent on both sides of a porphyrin ring.
It is considered that the oxidative degradation of I) can be prevented and a more stable oxygen carrier can be provided. As a porphyrin metal complex having a bulky substituent on both surfaces, 5,10,15,20-tetrakis [2,6-bis] (Pivaloyloxy) phenyl]
A porphyrin iron (II) complex (hereinafter referred to as FeTbpivPP complex) has been synthesized and its reversible oxygen bond has been revealed (JP-A-3-128389, JP-A-3-128389).
No. 275687).

However, in such a porphyrin iron (II) complex, the complex equilibrium constant with an imidazole derivative (axial base ligand) required for oxygen coordination is low, so that iron (II) having an oxygen adsorbing / desorbing ability is required. ) In order to obtain a five-coordinate complex, it was necessary to allow the axial base ligand to coexist excessively with the porphyrin iron (II) complex. In general, many imidazole derivatives widely used as axial base ligands are highly toxic in the body, and destabilize the morphology of phospholipid vesicles. Must be as small as possible.

[0006] In response to such a problem, the inventors of the present application have proposed a method for minimizing the amount of the axial base ligand to be added, in which one of the eight ortho positions of the phenyl ring is substituted with an alkylimidazole. FeTbpiv substituted with derivatives
Analogues of PP complex have been synthesized and embedded in phospholipid vesicles to achieve reversible oxygen adsorption / desorption ability. This porphyrin-embedded phospholipid vesicle repeatedly adsorbs and desorbs oxygen under physiological conditions and can transport oxygen for a long time (Japanese Patent Application Laid-Open No. 06-184156).

On the other hand, the present inventors have paid attention to the feature that phospholipids are easily dispersed in water to form bilayer vesicles and form a hydrophobic environment inside the membrane, and have a phospholipid-like structure. An FeTbpivPP analog was synthesized. These FeT
The bpivPP analog has an amphipathic property, and is advantageous in that, when dispersed in water, the porphyrin molecule itself forms an aggregate spontaneously in water, and can form a hydrophobic space around the porphyrin complex. In such a system, a porphyrin aggregate solution with a high concentration can be prepared without using a large amount of phospholipid (E. Tsuchida, et al., J. Chem. Soc., Che.
m. Commun., 1993 , 728; E. Tsuchida, et al., ibi.
d., 1995 , 1063, JP-A-03-275687).

In view of the state of the prior art as described above, the inventors of the present application have conducted intensive studies on the design and synthesis of an oxygen carrier capable of stably adsorbing and desorbing a higher concentration of oxygen. It has been found that the objective can be achieved by introducing a long-chain alkyl group into the ortho-position of the phenyl ring of tetraphenylporphyrin, and further substituting one of them with an imidazolyl group which is an axial base.

[0009]

Means for Solving the Problems The invention of this application has been made based on the above background, and as a result of the above-mentioned research, the inventors of this application have proposed 5,10,1.
5,20-tetrakis [2,6-bis {2,2-dimethyl-ω-[{(2-trimethylammonio) ethoxy]}
Phosphonatoxy] alkanoyloxy {phenyl] porphyrin A substituent necessary for effectively exhibiting oxygen adsorption ability at one position of the ortho position of the phenyl ring of the metal complex, for example, an imidazole derivative which is a basic axial ligand is converted to porphyrin 1 Based on the idea that by introducing an ester bond at a ratio of one molecule to a molecule (a porphyrin having an axial base in the molecule), it is possible to provide a stable oxygen carrier with high oxygen transport efficiency. completed.

[0010] That is, the present application firstly discloses the following general formula (I):

[0011]

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(Where n is the number of methylene groups, R ¹ is an alkylene group, R ² is a substituent that does not inhibit the coordination of imidazole to the central metal, M is a hydrogen atom, X ⁻ is a chloride ion, a bromine ion, iodine A porphyrin aggregate comprising a porphyrin derivative represented by the following formula (1) represents a halogen ion selected from ions, and m is 0).

The invention of the present application also relates to a porphyrin assembly wherein n is an integer of 1 to 18; and a porphyrin assembly wherein R ¹ is an alkylene group of C _{3 to} C _17. And, fourthly, a porphyrin aggregate wherein R ² is a hydrogen atom or a substituent selected from a methyl group, an ethyl group and a propyl group.

Fifth, the invention of this application is characterized by the following general formula (I):

[0015]

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(Where n is the number of methylene groups, R¹Is al
Kylene group, R^TwoInhibits coordination of imidazole to central metal
The substituent that does not harm, M is a transition metal ion in the fourth or fifth cycle.
Yes, X ^-Is chlorine ion, bromide ion, iodine ion
The halogen ion selected from the above, m is the valence of the metal ion
Is an integer obtained by subtracting 2 from the above)
The present invention provides a porphyrin aggregate comprising a porphyrin derivative.

Sixth, the invention of this application relates to the porphyrin aggregate wherein M is Fe or Co in the fifth invention, and seventhly, the valence of Fe is +2 in the sixth invention. Or a porphyrin aggregate having +3 valence, and eighthly, a porphyrin aggregate having +2 valence of Co in the sixth invention.

Ninth, the invention of this application also provides an artificial oxygen carrier containing at least the porphyrin aggregate according to any of the fifth to eighth inventions.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION The invention of this application has the features as described above, and embodiments thereof will be described below.

First, the compound used in the first invention is represented by the following general formula (I)

[0021]

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(Where n is the number of methylene groups, R ¹ is an alkylene group, R ² is a substituent that does not hinder the coordination of imidazole to the central metal, M is two hydrogen atoms or a transition metal of the fourth or fifth cycle. Ion, X ^- is chlorine ion, bromine ion,
Represents a halogen ion selected from iodine ions;
Is 0 or an integer obtained by subtracting 2 from the valence of the metal ion). The derivative in which M is a hydrogen atom in such a derivative is represented by the following general formula (II).

[0023]

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Among these porphyrin derivatives, M
Is a metal in a +2 valence state, and one in which one base ligand is coordinated to M has a high binding ability to oxygen.
It is preferable.

In the porphyrin aggregate of the invention of this application, each porphyrin derivative forming the aggregate has an imidazole derivative at the ortho position of the phenyl ring. Since such a porphyrin derivative can coordinate an intramolecular imidazole to a porphyrin central metal, the porphyrin derivative can exert its own oxygen binding ability without externally adding an axial base ligand. Therefore, in the porphyrin aggregate of the invention of this application, the axial base concentration can be reduced to an extremely low level at the time of use.

In addition, since such a porphyrin derivative has an amphipathic structure on both sides of the porphyrin ring, it can spontaneously form a tissue in water to form an aggregate, and can itself build a hydrophobic environment near the complex portion. At this time, the porphyrin complex is fixed at the center of the hydrophobic region of the bilayer membrane of the phospholipid vesicle. Therefore, such a porphyrin derivative can form a stable oxygen complex even under physiological conditions, and can effectively act as an artificial oxygen carrier such as red blood cells.

When the porphyrin derivative as described above is, for example, a metal ion complex belonging to the fourth period, it also acts as a catalyst for an oxidation-reduction reaction, an oxygen oxidation reaction or an oxygen addition reaction. Therefore, such a porphyrin derivative can be used not only as an artificial oxygen carrier, but also as a gas adsorbent, a redox catalyst, an oxygen oxidation reaction catalyst, and an oxygen addition reaction catalyst.

The porphyrin aggregate of the invention of the present application and the porphyrin derivative constituting the same may be produced by any method, but the following method is preferably exemplified.

[0029] JP-A-03-275687, JP-A-04-110619, or E. Tsuchida, et al.
al., J. Chem. Soc., Dalton Trans., 1991 , 3281, etc. to synthesize 5,10,15,20-tetrakis (2,6-dihydroxyphenyl) porphyrin and then dry it. After dissolving in tetrahydrofuran, an equimolar acid chloride or acid bromide solution in dry tetrahydrofuran is gradually added under an inert gas atmosphere, and the mixture is stirred at room temperature for 6 to 24 hours. After completion of the reaction, the solvent is removed under reduced pressure, and this is extracted with a suitable organic solvent, for example, ethyl acetate. This is washed with water, dried over anhydrous sodium sulfate, filtered, and the solvent is removed under reduced pressure. The obtained product was purified by silica gel column chromatography to give 5- (2-alkanoyloxy-6-hydroxy) phenyl-10,1.
5,20-Tris (2,6-dihydroxyphenyl) porphyrin is obtained.

5- (2-alkanoyloxy-6-hydroxy) phenyl-10,15,20-tris (2,6
-Dihydroxyphenyl) porphyrin and a small excess of 4-
General formula (III) synthesized in a dry tetrahydrofuran solution in which dimethylaminopyridine is dissolved in an atmosphere of an inert gas such as nitrogen or argon according to, for example, JP-A-59-101488.

[0031]

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(Where n is 1 representing the number of methylene groups)
And an acid chloride or acid bromide of β, β-dimethylalkanoic acid represented by an integer of 7 to 18 or more, and stirred at 40 to 60 ° C. for 6 to 24 hours. The solvent was removed under reduced pressure, and the residue was washed with methanol to remove unreacted β, β-
The dimethylalkanoic acid is eluted away. Purification by silica gel column chromatography gave 5- [2-alkanoyloxy-6- (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl] -10,15,20-.
Tris [2,6-bis (ω-benzyloxy-2,2-
Dimethylalkanoyloxy) phenyl] porphyrin is obtained.

5- [2-Alkanoyloxy-6- (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl]-dissolved in a suitable solvent (eg, N, N-dimethylformamide, chloroform, dichloromethane). 10,15,20-tris [2,6-bis (ω-
Benzyloxy-2,2-dimethylalkanoyloxy) phenyl] porphyrin, and an excess of imidazole was added thereto under an inert gas atmosphere such as nitrogen or argon.
Stir at 0-80 ° C for 1-12 hours. After cooling, the solvent is removed under reduced pressure, washed with water, and dried over anhydrous sodium sulfate.

After filtration, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography to give 5- [2-hydroxy-6- (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl] -10,15. , 20-Tris [2,6-bis (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl] porphyrin.

Ω- (N-imidazolyl) alkanoic acid hydrochloride is, for example, JP Collman et al., J. Am. Chem. So
c., 1980, 102 , 4182.
Alkyl chain length, it is preferable that the C ₄ -C _8. To this dried tetrahydrofuran solution, under an inert gas atmosphere,
An excess amount of oxalyl dichloride or thionyl chloride is added, and the mixture is stirred at room temperature for 1 to 6 hours. After removing the solvent and excess oxalyl dichloride or thionyl chloride under reduced pressure, the mixture was added to 5- [2-hydroxy-6- (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl]-.
A solution of 10,15,20-tris [2,6-bis (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl] porphyrin and 4-dimethylaminopyridine in dry tetrahydrofuran was added dropwise, and under an inert gas atmosphere, Stir at 40-60 ° C for 8-12 hours. After cooling, the solvent is removed under reduced pressure, washed with water, and dried over anhydrous sodium sulfate. After filtration, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography.
-{Ω- (N-imidazolyl) alkanoyloxy}-
6- (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl] -10,15,20-tris [2,6-bis (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl] porphyrin can get.

5- [2- {ω- (N-imidazolyl) alkanoyloxy} -6- (ω-benzyloxy-2,
2-dimethylalkanoyloxy) phenyl] -10,
15,20-tris [2,6-bis (ω-benzyloxy-2,2-dimethylalkanoyloxy) phenyl]
Porphyrin in a suitable solvent, such as dry chloroform,
It is dissolved in dichloromethane or the like, and a small excess of boron trifluoride-diethyl ether complex and ethanethiol are added thereto under an atmosphere of an inert gas such as nitrogen or argon.
Stir for ~ 6 hours. At this time, the solution changes from magenta to deep blue. After dripping this into water and stirring for 5 to 60 minutes,
Washed with water, dried over anhydrous sodium sulfate, filtered,
The solvent is removed under reduced pressure. Purification by silica gel column chromatography gave 5- [2- {ω- (N-imidazolyl) alkanoyloxy} -6- (ω-hydroxy-
2,2-dimethylalkanoyloxy) phenyl] -1
0,15,20-tris [2,6-bis (ω-hydroxy-2,2-dimethylalkanoyloxy) phenyl]
Get the porphyrin.

The thus obtained 5- [2- {ω- (N-imidazolyl) alkanoyloxy} -6- (ω-hydroxy-2,2-dimethylalkanoyloxy) phenyl]
-10,15,20-Tris [2,6-bis (ω-hydroxy-2,2-dimethylalkanoyloxy) phenyl] porphyrin can be prepared by a conventional method (for example, E. Tsuchida et a
By introducing a central metal by the method described in l., J. Chem. Soc., Dalton Trans., 1993 , 2465), considerable porphyrin metal complexes are obtained. Generally, in the case of an iron complex, a porphinato iron (III) complex is obtained, and in the case of a cobalt complex, a porphinato cobalt (II) complex is obtained.

5- [2- {ω- (N-imidazolyl) alkanoyloxy} -6- (ω-hydroxy-2,2-
Dimethylalkanoyloxy) phenyl] -10,1
5,20-tris [2,6-bis (ω-hydroxy-
2,2-Dimethylalkanoyloxy) phenyl] porphyrin metal complex and triethylamine are dissolved in dichloromethane, and 2-chloro-2-oxo-1,3-dioxa- is dissolved at 0 ° C. in an atmosphere of an inert gas such as nitrogen or argon. 2-phosphorane was added dropwise and at 0 ° C for 1 to 6 hours,
Stir further at room temperature for 1-6 hours. After removing the solvent under reduced pressure,
Redissolve in N, N-dimethylformamide, transfer to a pressure-resistant reaction vessel, add excess trimethylamine,
Stir at 〜6 h for a further 6 to 36 h. After allowing to cool, the pressure-resistant reaction vessel is opened to remove trimethylamine, then the insoluble component is washed with dry diethyl ether and dried under vacuum, and the solvent is removed from the solution component under reduced pressure. The methanol solution was reprecipitated in cold acetone, and further purified by gel column chromatography to obtain 5- [2-Δω
-(N-imidazolyl) alkanoyloxy} -6-
{2,2-dimethyl-ω- (2- [trimethylammonio] ethoxyphosphonatoxy) alkanoyloxy} phenyl] -10,15,20-tris [2,6-bis-2,2-dimethyl-ω- ( A 2- [trimethylammonio] ethoxyphosphonatoxy) alkanoyloxy {phenyl] porphyrin metal complex is obtained.

In the above porphyrin metal complex, iron
(III) When it has a complex form, oxygen coordination activity can be imparted by reducing the central metal from +3 valence to +2 valence using a suitable reducing agent (such as sodium dithionite) by a conventional method. For example, synthesized 5- [2- {ω- (N-imidazolyl) alkanoyloxy} -6- {2,2-dimethyl-ω- (2- [trimethylammonio] ethoxyphosphonatooxy) alkanoyloxy} phenyl] -10,1
5,20-tris [2,6-bis {2,2-dimethyl-
A methanol solution of an ω- (2- [trimethylammonio] ethoxyphosphonatoxy) alkanoyloxydiphenyl] porphyrin iron (III) complex is poured into water, and after purging with nitrogen, carbon monoxide is passed through and an aqueous solution of dithionous acid is added. To obtain an aqueous dispersion of the carbon monoxide complex. Furthermore, when carbon monoxide is desorbed by irradiation with light in a nitrogen atmosphere, the visible absorption spectrum shifts, and the imidazole is coordinated to a five-coordinated deoxy type. When this dispersion is observed with an electron microscope, formation of a spherical aggregate having a particle size of 5 to 10 nm can be confirmed.

The porphyrin derivative constituting the porphyrin aggregate of the invention of the present application is capable of reversibly binding and desorbing oxygen in a solution. Therefore, when oxygen gas is blown into the porphyrin aggregate solution produced by the above method, its visible absorption spectrum changes immediately, and the formation of an oxygenated complex can be confirmed. When nitrogen gas is blown into the oxygenated complex solution, the visible absorption spectrum changes from the oxygenated spectrum to the deoxy-type spectrum, and adsorption and desorption of oxygen can be confirmed. In the porphyrin derivative as described above, the oxygen absorption and desorption can be continuously performed as described above.

Further, 5- [2- {ω- (N-imidazolyl) alkanoyloxy} -6- {2,2-dimethyl-ω- (2- [trimethylammonio]] synthesized by the method described above. Ethoxyphosphonatoxy) alkanoyloxy {phenyl] -10,15,20-tris [2,6-bis {2,2-dimethyl-ω- (2- [trimethylammonio] ethoxyphosphonatoxy) alkanoyloxy} phenyl ] A porphyrin iron (III) complex and a methanol solution of a phospholipid such as dipalmitoylphosphatidylcholine are mixed, the solvent is removed, vacuum-dried, water is added thereto, and ultrasonic irradiation is performed with a probe-type ultrasonic stirrer, By aerating carbon monoxide and adding an aqueous solution of dithionite for reduction, an vesicle dispersion of the carbon monoxide complex can be obtained. Further, when carbon monoxide is desorbed by irradiation with light in a nitrogen atmosphere, a five-coordinated deoxy-type porphyrin aggregate in which one imidazole is coordinated is obtained. When this dispersion is observed with an electron microscope, the particle size is 30 to
The formation of a uniform bilayer vesicle of 100 nm can be confirmed.

In such a porphyrin aggregate solution,
As soon as oxygen gas is blown, the spectrum changes and the formation of an oxygenated complex can be confirmed. When nitrogen gas is blown into this oxygenated complex solution, a reversible change from oxygenated to deoxy can be confirmed from the visible absorption spectrum. Note that the operation of blowing oxygen and then blowing nitrogen can be repeated to continuously perform oxygen adsorption / desorption.

The porphyrin derivative produced by the above method (and a system in which it is embedded in a bilayer vesicle composed of phospholipid molecules, a system in which it is mixed with a phospholipid-coated fat emulsion, and A system in which the molecules are molecularly aggregated, etc.) rapidly forms a stable oxygen complex upon contact with oxygen. Further, these complexes adsorb and desorb oxygen according to the oxygen partial pressure.
Since this oxygen adsorption / desorption can be performed reversibly and repeatedly, the porphyrin aggregate of the present invention effectively functions as an oxygen adsorption / desorption agent or an oxygen carrier.

Since the porphyrin derivative forming the porphyrin aggregate of the invention of this application has a substituent capable of coordinating with the central metal of porphyrin at the ortho position of the phenyl ring, the porphyrin derivative can be prepared without externally adding an excessive axial ligand. It can be an active compound. For this reason, the porphyrin aggregates of the invention of this application can be used not only as a homogeneous or heterogeneous redox reaction catalyst or as a gas adsorbent, but also as a highly safe artificial oxygen. It is preferably used as a carrier.

Hereinafter, the present invention will be described in detail with reference to examples. It goes without saying that the invention of this application is not limited to the following embodiments.

[0046]

EXAMPLES <Example 1> 1.50 g of valeric acid (8.28
mmol) in 3.55 mL (41.4) of oxalyl dichloride.
mmol), and the mixture was stirred at room temperature for 1 hour and 30 minutes under a nitrogen atmosphere. After confirming the formation of the acid chloride in the IR spectrum (1700 cm ⁻¹ due to the carbonyl of the carboxylic acid)
Near peak disappeared, and peak of acid chloride was 1800c
m- ¹ ), and the excess oxalyl dichloride was removed under reduced pressure to obtain a pale yellow liquid valeric acid chloride. Separately, JP-A-03-275687 or JP-A-04-11
5,1 obtained according to the method described in
0.5 g (673 μmol) of 0,15,20-tetrakis (2,6-dihydroxyphenyl) porphyrin and 58.0 mg (471 μl) of 4-dimethylaminopyridine
mol) was dissolved in distilled tetrahydrofuran (400 ml), and 63.0 μL of the above valerate chloride under a nitrogen atmosphere.
(471 μmol) in distilled tetrahydrofuran (1
00 mL) was added dropwise over 2 hours.

After stirring at room temperature for 12 hours, the solvent was removed under reduced pressure, and the residue was extracted with ethyl acetate, which was washed several times with water. After dehydration and filtration with anhydrous sodium sulfate, the solvent was removed under reduced pressure, and this was added to chloroform / methanol (8 /
1 (volume / volume)), and white insolubles were filtered through a glass filter.

After concentrating the filtrate, fractionation and purification were performed using a silica gel column (chloroform / methanol (8/1 (volume / volume)), and the desired product was recovered and dried in vacuo.

Thus, red-purple 5- (2-valeroyloxy-6-hydroxy) phenyl-10,15,
20-tris (2,6-dihydroxyphenyl) porphyrin was obtained in a yield of 104 mg (18.7% yield).

The analysis results of the above porphyrin were as follows: FAB-mass spectrum (m / z): 826 Thin layer chromatography (Merck silica gel plate,
Chloroform / methanol (8/1 (volume / volume)): Rf: 0.35 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1735 (ν _{C = O}
(ester)).

Visible absorption spectrum (CH ₃ OH, λ _max :
nm): 417, 513, 548, 587, 640.

¹ H-nuclear magnetic resonance spectrum (CD ₃ O
D): δ (ppm) -0.1 to 0.2 (4H, m,-
(CH ₂ ) _2- ), 0.9 (3H, t, CH _3- ), 1.
_{2 (2H, t, -CH 2} -COO -), 6.7~7.6
(12H, m, phenyl-H), 8.8 (8H,
s, pyrrole β-H). <Example 2> 20-benzyloxy-2,2- obtained according to the method described in JP-A-59-101488.
1.60 g (3.52 mmol) of dimethyleicosanoic acid
Was dissolved in 3 mL of benzene, oxalyl dichloride (1.50 mL, 17.6 mmol) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 1 hour and 30 minutes. Confirmation of acid chloride by IR spectrum (disappearance of peak at 1700 cm ^-1 )
Thereafter, excess oxalyl dichloride was removed under reduced pressure to obtain a light yellow solid acid chloride. To this was added 5- (2-valeroyloxy-6-hydroxy) phenyl-10,15,20-tris (2,6-dihydroxyphenyl) porphyrin 10
A solution of 4 mg (126 μmol) and 430 mg (3.52 mmol) of 4-dimethylaminopyridine in distilled tetrahydrofuran (5 mL) was added dropwise, and the mixture was heated at 60 ° C. under a nitrogen atmosphere.
For 12 hours. After allowing to cool, the solvent was removed under reduced pressure, extracted with chloroform / water, dried over anhydrous sodium sulfate, filtered, and the solvent was removed again under reduced pressure.

Methanol was added to the residue, and the mixture was heated to 40 ° C., and unreacted 20-benzyloxy-2,2-dimethyleicosanoic acid was filtered off as an insoluble component. After the eluate was concentrated, it was fractionated and purified on a silica gel column (chloroform / dimethyl ether (45/1 (volume / volume)), and the target product was collected and dried in vacuo.

Thus, magenta 5- [2-valeroyloxy-6- (20-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl] -10,1
5,20-tris [2,6-di (20-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl]
Porphyrin was obtained in a yield of 334 mg (69.5%).

The results of the analysis of the porphyrins described above were as follows: thin layer chromatography (Merck silica gel plates,
Chloroform / dimethyl ether (45/1 (vol / vol)): Rf: 0.54 (monospot).

Infrared absorption spectrum (cm ^-1 ): 1758
(Ν _{C = O} (ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 415, 509, 538, 584, 639.

¹ H-nuclear magnetic resonance spectrum (CDC
l ₃ ): δ (ppm) -3.0 (2H, s, inner)
-H), -1.2 to -0.5 (42H, m, dimet
hyl), 0.7-1.6 (233H, m,-(C
_{H 2) 16 -, CH 3} - (CH 2) 3 -COO -), 3.5
_{(14H, t, -CH 2 O} -), 4.5 (14H, s,
—OCH ₂ Ph), 7.2 to 7.8 (47H, m, ph)
enyl-H), 8.8 (8H, s, pyrrolβ-
H). <Example 3> 5- [2-valeroyloxy-6- (20
-Benzyloxy-2,2-dimethyleicosanoyloxy) phenyl] -10,15,20-tris [2,6
-Di (20-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin 334 mg
(87.3 μmol), 475 mg of imidazole (6.
98 mmol) was added with 15 mL of dimethylformamide, and the mixture was stirred at 80 ° C. for 2 hours under a nitrogen atmosphere. After removing the solvent under reduced pressure, it was extracted and washed with chloroform / water, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure.

The residue was purified by fractionation on a silica gel column (chloroform / dimethyl ether (45/1 (volume / volume)).
The desired product was collected and dried under vacuum. The red-purple 5
-[2-hydroxy-6- (20-benzyloxy-
2,2-dimethyleicosanoyloxy) phenyl]-
185 mg of 10,15,20-tris [2,6-di (20-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin was obtained (yield: 56.6).
%).

The porphyrin analysis results described above were as follows: thin layer chromatography (Merck silica gel plates,
Chloroform / dimethyl ether (45/1 (vol / vol))): Rf: 0.50 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1758 (ν _{C = O}
(ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 415, 509, 538, 584, 639.

The ¹ H-nuclear magnetic resonance spectrum (CDC
l ₃ ): δ (ppm) -3.0 (2H, s, inner)
-H), -1.0 to -0.5 (42H, m, dimet
hyl), 0.5-1.6 (224H, m,-(C
_{H 2) 16 -), 3.4} (14H, t, -CH 2 O-),
_{4.5 (14H, s, -OCH 2} Ph), 7.1~7.
8 (47H, m, phenyl-H), 8.8 (8H,
s, pyrrol β-H). <Example 4> 202 mg (988 µmol) of 5- (imidazol-1-yl) valeric acid salt was dissolved in 3 mL of distilled tetrahydrofuran, and 0.862 mL (9.88 mmol) of oxalyl dichloride was added under an argon atmosphere. Stir for 1 hour and 30 minutes. Excess oxalyl dichloride was removed under reduced pressure to obtain light brown solid 5- (imidazol-1-yl) valeric acid chloride. In addition, 5-
[2-hydroxy-6- (20-benzyloxy-2,
2-dimethyleicosanoyloxy) phenyl] -1
0,15,20-tris [2,6-di (20-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin 185 mg (49.4 μmo)
l), 241 mg of 4-dimethylaminopyridine (1.
98 mmol) of distilled tetrahydrofuran (5 mL) was added dropwise, and the mixture was stirred at 60 ° C. for 12 hours. After cooling, the solvent was removed under reduced pressure, extracted and washed with chloroform / water, dehydrated with anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure, and the mixture was subjected to silica gel column (chloroform / methanol (30/1 (volume / volume))). The desired product was collected by fractionation purification and dried in vacuo.

Thus, magenta 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (2
0-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl] -10,15,20-tris [2,
6-di (20-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin was obtained in a yield of 11
3 mg (58.8% yield) was obtained.

The analysis results of the above porphyrins were as follows: thin layer chromatography (Merck silica gel plate,
Chloroform / methanol (30/1 volume / volume))): Rf: 0.68 (monospot).

Infrared absorption spectrum (cm ^-1 ): 1758
(Ν _{C = O} (ester)).

Visible absorption spectrum (CH ₃ OH, λ _max :
nm): 415, 509, 536, 585, 640.

The ¹ H-nuclear magnetic resonance spectrum (CD ₃ O
D): δ (ppm) -3.0 (2H, s, inner-
H), -1.4 to -0.4 (42H, m, dimeth
yl), 0.5~1.6 (230H, m , - (CH 2)
₁₆ -,-(CH ₂ ) _3- ), 3.4 (14H, t, -CH
_{2 O -), 4.2 (2H} , d, -CH 2 -imidazo
le), 4.5 (14H, s , -OCH 2 Ph), 6.
6-7.2 (3H, m, imidazole-H),
7.2 to 7.8 (47H, m, phenyl-H),
8.8 (8H, s, pyrrol β-H). Example 5 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (20-benzyloxy-2,2-dimethyleicosanoyloxy) phenyl]
-10,15,20-tris [2,6-di (20-benzyloxy-2,2-dimethyleicosanoyloxy)
Phenyl] porphyrin 113 mg (29.1 μmo
l) was dissolved in 3 mL of dry dichloromethane, and under a nitrogen atmosphere, boron trifluoride-diethyl ether complex 0.51 m
L (4.07 mmol), ethanethiol 3.01 mL
(40.7 mmol), and the mixture was stirred at room temperature for 2 hours.

The solution changed from reddish purple to deep blue as the reaction proceeded. This was added dropwise to ice water, and the mixture was further stirred for 10 minutes, extracted and washed with chloroform / water, dehydrated with anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. Fractionation and purification were performed using a silica gel column (chloroform / methanol (10/1 (volume / volume)), and the target product was collected and dried in vacuo.
Thus, magenta 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] -10, 15,20-tris [2,6-di (2
[0-Hydroxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin was obtained in a yield of 68.3 mg (72.1%).

The results of the analysis of the porphyrins described above were as follows: thin layer chromatography (Merck silica gel plates,
Chloroform / methanol (10/1 (vol / vol)): Rf: 0.47 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1756 (ν _{C = O}
(ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 415, 509, 538, 585, 645.

¹ H-nuclear magnetic resonance spectrum (CD ₃ O
D): δ (ppm) -3.0 (2H, s, inner-
H), -1.5 to -0.5 (42H, m, dimethy)
yl), 0.5~1.5 (230H, m , - (CH 2)
_{16 -, - (CH 2)} 3 -), 3.5 (14H, t, -C H
_{2 OH), 4.2 (2H,} d, -CH 2 -imidazo
le), 6.6-7.2 (3H, m, imidazol
e-H), 7.2-7.8 (12H, m, phenyl)
-H), 8.7 (8H, s, pyrrol β-H). Example 6 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (20-hydroxy-
2,2-dimethyleicosanoyloxy) phenyl]-
6,8.3 mg (20.9 μmol) of 10,15,20-tris [2,6-di (20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin is dissolved in 6 mL of toluene, and the mixture is dissolved in an argon atmosphere. Iron pentacarbonyl 220 μL (1.68 mmol), iodine 1
Add 0.6 mg (41.9 μmol), and add 2 mg at 100 ° C.
Stirred for hours. After confirming the introduction of central iron by a visible absorption spectrum, the mixture was allowed to cool, and an aqueous sodium chloride solution was added to stop the reaction. This was extracted and washed with chloroform / aqueous sodium chloride solution, dehydrated with anhydrous sodium sulfate, filtered, and then the solvent was removed under reduced pressure. Fractionation and purification were performed using a silica gel column (chloroform / methanol (10/1 (volume / volume)), and the target product was collected and dried in vacuo.

Thus, 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (20
-Hydroxy-2,2-dimethyleicosanoyloxy) phenyl] -10,15,20-tris [2,6-
Di (20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin iron (III) complex was obtained in a yield of 42.1 mg (60.0%).

The results of the analysis of the porphyrins described above were as follows: thin layer chromatography (Merck silica gel plates,
Chloroform / methanol (10/1 (volume / volume))): Rf: 0.43 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1754 (ν _{C = O}
(ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 416, 504, 571. Example 7 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (20-hydroxy-
2,2-dimethyleicosanoyloxy) phenyl]-
10,15,20-tris [2,6-di (20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin iron (III) complex 42.1 mg (12.5 mg)
μmol [mol]) was dissolved in 7 mL of dichloromethane, and 3.07 μL (220 μmol) of triethylamine was dissolved.
Was added. Under a nitrogen atmosphere, 21.7 μL (220 μmol) of a phosphorylation reagent (2-chloro-2-oxo-1,3-dioxa-2-phosphorane) was added dropwise at 0 ° C.
The mixture was stirred for 1 hour and further at room temperature for 2 hours. After the solvent was removed under reduced pressure, the residue was dissolved again in 7 mL of dimethylformamide, and transferred to a pressure-resistant reaction vessel.
L (3.52 mmol) was added, and the mixture was stirred at room temperature for 1 hour and further at 60 ° C. for 12 hours.

At the end of the reaction, the solution became almost transparent, and a brown precipitate precipitated at the bottom of the container. After cooling, the container was opened, and excess trimethylamine was evaporated. The precipitate was washed with diethyl ether, and the solvent was removed under reduced pressure.

The obtained solid was dissolved in methanol, dropped into cold acetone / water (4/1 (volume / volume)) and reprecipitated to roughly purify, and finally a gel column (benzene / methanol (2 / 1 (vol / vol)). Thus, 5- [2- {5- (imidazol-1-yl)
Valeroyloxy} -6- {20- (2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethyleicosanoyloxy} phenyl] -10,15,
20-tris [2,6-di {20- (2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethyleicosanoyloxy} phenyl] porphyrin iron
(III) Complex was obtained in a yield of 37.6 mg (66.7% yield).

[0081] Analysis results of porphyrins described above were as follows: Infrared absorption spectrum ^{(cm -1): 1754 (ν} C = O ( _{ester)), 1228,1088 (ν P =} O ( phosphate ester)).

Visible absorption spectrum (CH ₃ OH, λ _max :
nm): 415, 507, 582. <Example 8> Instead of 20-benzyloxy-2,2-dimethyleicosanoic acid in Examples 2 to 5, 16-
Except that benzyloxy-2,2-dimethylpalmitic acid is used, and that 6- (imidazol-1-yl) caproic acid is used instead of 5- (imidazol-1-yl) valerate. According to the same method, 5
-[2- {6- (imidazol-1-yl) caproyloxy} -6- (16-hydroxy-2,2-dimethylpalmitoyloxy) phenyl] -10,15,20-
Tris [2,6-di (16-hydroxy-2,2-dimethylpalmitoyloxy) phenyl] porphyrin was obtained quantitatively.

The results of the analysis of the porphyrins described above were as follows: thin layer chromatography (Merck silica gel plates,
Chloroform / methanol (10/1 (vol / vol)): Rf: 0.45 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1755 (ν _{C = O}
(ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 416, 510, 538, 584, 645.

¹ H-nuclear magnetic resonance spectrum (CD ₃ O
D): δ (ppm) -2.9 (2H, s, inner-
H), -1.5 to -0.5 (42H, m, dimethy)
yl), 0.5~1.6 (176H, m , - (CH 2)
_{12 -, - (CH 2)} 4 -), 3.5 (14H, t, -C H
_{2 OH), 4.2 (2H,} d, -CH 2 -imidazo
le), 6.6-7.2 (3H, m, imidazol
e-H), 7.2-7.8 (12H, m, phenyl)
-H), 8.8 (8H, s, pyrrol β-H). <Example 9> 5- [2- {6- (imidazol-1-yl) caproyloxy} -6- (1) synthesized in Example 8
6-hydroxy-2,2-dimethylpalmitoyloxy) phenyl] -10,15,20-tris [2,6-
Di (16-hydroxy-2,2-dimethylpalmitoyloxy) phenyl] porphyrin in toluene solution,
Reaction with cobalt octacarbonyl and iodine under an argon atmosphere to give 5- [2- {6- (imidazol-1-yl) caproyloxy} -6- (16-hydroxy-
2,2-dimethylpalmitoyloxy) phenyl] -1
0,15,20-tris [2,6-di (16-hydroxy-2,2-dimethylpalmitoyloxy) phenyl]
Porphyrin cobalt (II) complex was obtained quantitatively.

The results of the porphyrin analysis described above were as follows: thin-layer chromatography (Merck silica gel plates,
Chloroform / methanol (10/1 (volume / volume))): Rf: 0.43 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1755 (ν _{C = O}
(ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 403, 521, 553. <Example 10> In Example 7, 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (2
0-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] -10,15,20-tris [2,6-
According to a completely similar method except that the cobalt (II) complex synthesized in Example 9 was used instead of the di (20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin iron (III) complex. -[2- {6- (imidazol-1-yl) caproyloxy} -6- {16
-(2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethylpalmitoyloxy {phenyl] -10,15,20-tris [2,6-di} 16-
(2-Trimethylammonioethoxyphosphonatoxy) -2,2-dimethylpalmitoyloxy {phenyl] porphyrin cobalt (II) was obtained quantitatively.

[0090] Analysis results of porphyrins described above were as follows: Infrared absorption spectrum ^{(cm -1): 1754 (ν} C = O ( _{ester)), 1229,1086 (ν P =} O ( phosphate ester)).

Visible absorption spectrum (CH ₃ OH, λ _max :
nm): 405, 524, 558. <Example 11> Instead of 20-benzyloxy-2,2-dimethyleicosanoic acid in Examples 2 to 5, 3-
Following exactly the same procedure except using benzyloxy-2,2-dimethylpropionic acid, 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (3
-Hydroxy-2,2-dimethylpropanoyloxy)
[Phenyl] -10,15,20-tris [2,6-di (3-hydroxy-2,2-dimethylpropanoyloxy) phenyl] porphyrin was obtained quantitatively.

The porphyrin analysis results described above were as follows: thin layer chromatography (Merck silica gel plate,
Chloroform / methanol (6/1 (volume / volume)): Rf: 0.40 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1756 (ν _{C = O}
(ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 417, 512, 546, 582, 634.

¹ H-nuclear magnetic resonance spectrum (CD ₃ O
D): δ (ppm) -3.3 (2H, s, inner-
H), -0.1 to -0.4 (42H, m, dimethy)
yl), 0.8~1.5 (20H, m , -C H 2 OH,
-(CH ₂ ) _3- ), 3.6 (2H, m, -CH ₂ -im
idazole), 6.6-7.2 (3H, m, imi)
dazole-H), 7.4-7.9 (12H, m, p
henyl-H), 8.8 (8H, s, pyrrolβ)
-H). <Example 12> In Example 6, 5- [2-５−5-
(Imidazol-1-yl) valeroyloxy} -6-
(20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] -10,15,20-tris [2,
Instead of using 6-di (20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin, 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (3 -Hydroxy-2,2-dimethylpropanoyloxy) phenyl] -10,15,2
According to a similar method except that 0-tris [2,6-di (3-hydroxy-2,2-dimethylpropanoyloxy) phenyl] porphyrin is used, 5- [2- {5- (imidazol-1-yl)] is used. Valeroyloxy} -6- (3
-Hydroxy-2,2-dimethylpropanoyloxy)
Phenyl] -10,15,20-tris [2,6-di (3-hydroxy-2,2-dimethylpropanoyloxy) phenyl] porphyrin iron (III) complex was obtained quantitatively.

The analysis results of the above porphyrins were as follows: thin layer chromatography (Merck silica gel plates,
Chloroform / methanol (6/1 (volume / volume)): Rf: 0.32 (monospot).

Infrared absorption spectrum (cm ^-1 ): 3300
~ 3800 (ν _OH (alcohol)), 1753 (ν _{C = O}
(ester)).

Visible absorption spectrum (CHCl ₃ , λ _max :
nm): 418, 509, 586. <Example 13> In Example 7, 5- [2- {5- (imidazol-1-yl) valeroyloxy} -6- (2
0-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] -10,15,20-tris [2,6-
According to a completely similar method except that the iron (III) complex synthesized in Example 12 was used instead of the di (20-hydroxy-2,2-dimethyleicosanoyloxy) phenyl] porphyrin iron (III) complex. -[2- {5- (imidazol-1-yl) valeroyloxy} -6- {3-
(2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethylpropanoyloxy {phenyl] -10,15,20-tris [2,6-di} 3-
(2-Trimethylammonioethoxyphosphonatoxy) -2,2-dimethylpropanoyloxy {phenyl] porphyrin iron (III) was obtained quantitatively.

[0099] Analysis results of porphyrins described above were as follows: Infrared absorption spectrum ^{(cm -1): 1754 (ν} C = O ( _{ester)), 1229,1087 (ν P =} O ( phosphate ester)).

Visible absorption spectrum (CH ₃ OH, λ _max :
nm): 417, 512, 587. <Example 14> 5- [2- ｛5- synthesized in Example 7
(Imidazol-1-yl) valeroyloxy} -6-
{20- (2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethyleicosanoyloxy} phenyl] -10,15,20-tris [2,6-
0.54 mg of di {20- (2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethyleicosanoyloxy} phenyl] porphyrin iron (III) complex
(0.12 μmol) was converted into a 60 μL methanol solution, which was poured into 3 mL of water, replaced with nitrogen, gas was passed through carbon monoxide, and an aqueous solution of dithionite was added to reduce the solution. An aqueous dispersion was obtained (λ _max : 428, 544 nm).

Further, when carbon monoxide is desorbed by light irradiation in a nitrogen atmosphere, the visible absorption spectrum becomes λ _max :
It migrated to 441, 538, and 562 nm, and became a five-coordinate deoxy type in which one imidazole was coordinated.

Observation with an electron microscope of this dispersion confirmed formation of a spherical aggregate having a particle size of about 8 nm.

As soon as oxygen gas was blown into this solution, the spectrum changed, and a spectrum at λ _max : 423, 549 nm was obtained. This indicated the formation of an oxygenated complex. By blowing nitrogen gas into this oxygenated complex solution for 1 minute, the visible absorption spectrum was reversibly changed from the oxygenated spectrum to the deoxy-type spectrum, and it was confirmed that oxygen absorption and desorption occurred reversibly. Was. Note that the operation of blowing oxygen and then blowing nitrogen was repeated, whereby oxygen absorption / desorption could be performed continuously. The life (half-life) of this oxygenated complex was 4 to 6 hours at 25 ° C. <Example 15> 5- [2- ｛5- synthesized in Example 7
(Imidazol-1-yl) valeroyloxy} -6-
{20- (2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethyleicosanoyloxy} phenyl] -10,15,20-tris [2,6-
0.54 mg of di {20- (2-trimethylammonioethoxyphosphonatooxy) -2,2-dimethyleicosanoyloxy} phenyl] porphyrin iron (III) complex
(0.12 μmol), and 4.4 mg (6.0 μmol) of dipalmitoylphosphatidylcholine in 60 μl.
A methanol solution of L was added to, for example, a 5 mL round bottom flask, and a thin film was formed on the inner wall of the flask by a rotary evaporator.

After vacuum drying, 3 mL of water was added, and the mixture was irradiated with a probe-type ultrasonic stirrer for 5 minutes. After the replacement with nitrogen, carbon monoxide was aerated and reduced by adding an aqueous solution of dithionite to obtain an vesicle dispersion of the carbon monoxide complex (λ _max : 430, 546 nm). Further, when carbon monoxide is desorbed by light irradiation in a nitrogen atmosphere, the visible absorption spectrum becomes λ _max : 442, 540,
It shifted to 567 nm, and became a five-coordinated deoxy type in which one imidazole was coordinated. Electron microscopic observation of this dispersion confirmed formation of uniform bilayer vesicles having a particle size of 30 to 100 nm.

As soon as oxygen gas was blown into this solution, the spectrum changed, and a spectrum at λ _max : 424, 550 nm was obtained. This indicated the formation of an oxygenated complex. By blowing nitrogen gas into this oxygenated complex solution for 1 minute, the visible absorption spectrum was reversibly changed from the oxygenated spectrum to the deoxy-type spectrum, and it was confirmed that the absorption and desorption of oxygen occurred reversibly. Note that the operation of blowing oxygen and then blowing nitrogen was repeated, whereby oxygen absorption / desorption could be performed continuously.

[0106]

As described above in detail, according to the invention of this application, since it has an amphipathic structure itself, it can self-assemble in water to form an organization, and can form a phase with phospholipid bilayer vesicles. A porphyrin aggregate comprising a porphyrin derivative having high solubility and advantageous in embedding in a hydrophobic region between bilayer membranes is provided. The porphyrin aggregate of the invention of this application has one imidazole derivative that functions as an axial base at the ortho position of the phenyl ring of tetraphenylporphyrin having an amphiphilic long-chain alkyl group, and therefore has a high oxygen carrying ability in an aqueous phase system. It can be demonstrated.
Such a porphyrin aggregate effectively acts as a gas adsorbent, an oxygen adsorbing / desorbing agent, a redox catalyst, an oxygen oxidation reaction catalyst, and the like, in addition to the artificial oxygen carrier.

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 4C050 PA05 4C086 AA01 AA03 CB04 MA01 MA04 NA14 ZA52 ZC02

Claims (9)

[Claims] 1. The following general formula (I): (Where n is the number of methylene groups, R ¹ is an alkylene group, R ²
Is a substituent that does not inhibit the coordination of imidazole to the central metal, M is two hydrogen atoms, X ^- is a halogen ion selected from chloride ion, bromine ion and iodine ion, and m represents 0). A porphyrin aggregate comprising a derivative. 2. The porphyrin aggregate according to claim 1, wherein n is an integer of 1 to 18. 3. The porphyrin aggregate according to claim 1, wherein R ¹ is a C ₃ -C ₁₇ alkylene group. 4. The porphyrin aggregate according to claim 1, wherein R ² is a hydrogen atom or a substituent of any of a methyl group, an ethyl group, and a propyl group. 5. The following general formula (I):(Where n is the number of methylene groups, R¹Is an alkylene group, R^Two
Is a substitution that does not interfere with the coordination of imidazole to the central metal
And the group M is a transition metal ion of the fourth or fifth cycle, and X ^-Is
Selected from chloride ion, bromide ion, iodine ion
Halogen ion, m is 2 minus the valence of metal ion
Porphyrin derivative represented by
A porphyrin aggregate, comprising: 6. The porphyrin aggregate according to claim 5, wherein M is Fe or Co. 7. The porphyrin aggregate according to claim 6, wherein the valence of Fe is +2 or +3. 8. The porphyrin aggregate according to claim 6, wherein the valence of Co is +2. 9. An artificial oxygen carrier containing at least the porphyrin aggregate according to any one of claims 5 to 8.