JPS5925766B2 - Surfactant micelles containing iron (2) porphyrin complexes and oxygen adsorbing/desorbing agents - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an aqueous micelle of a surfactant containing a so-called iron()porphyrin complex, and an oxygen adsorbing/desorbing agent comprising the micelle.

Iron ()porphyrin complexes in hemoglobin and myoglobin reversibly adsorb and desorb oxygen molecules.

Many studies have been published to synthesize complexes with oxygen adsorption/desorption functions similar to those of natural porphyrin iron() complexes. An example is J. P●CO
llman, AccOuntsOfChemicalR
esearehlO265 (1977); F. BasO
lO,B. M. Hoffman and J. A. lber
s, AccOuntsOfChemicalResea
rch8384 (1975), etc. In particular, iron()-5,10,15,
20-tetra[α,α,α,α-(0-pivalamidophenyl)]porphyrin complex (J.P. COllman et al., JournalOfAmericanChemica
1SOciety971427 (1975)). However, if even a small amount of water coexists with this complex, it will be immediately oxidized, making it impossible to generate an oxygen complex. For this reason, the development of iron()porphyrin complexes that provide oxygen complexes even in the coexistence of water at room temperature is being promoted. An object of the present invention is to provide a porphyrin iron (4) complex system that can reversibly adsorb and desorb oxygen in an aqueous phase or water-coexisting solvent system at room temperature based on a difference in oxygen partial pressure.
According to this invention, the above object is achieved by: (where R is a group that does not inhibit the coordination of the imidazole group to which it is bonded to the central iron; R2, R3, and R4 are each hydrogen or a hydrophobic substituent; iron ()5,10, at least one of which is a hydrophobic substituent)
, 15,20-tetra[α,α,α,α-(0-pivalamidophenyl)]porphyrin (hereinafter referred to as Fe()Tpi
vPP) complex in an aqueous micelle of a surfactant.

The present inventors thought that by placing an iron()porphyrin complex in a specially designed hydrophobic field, a stable oxygen complex could be formed even in a system where water coexists.

It is certainly easy to imagine adding various types of synthetic surfactants to the system in order to uniformly dissolve or disperse iron complexes containing poorly water-soluble porphyrin as ligands in an aqueous solution; In none of the examples given, the formation of an oxygen complex has not been achieved. The inventors
As a result of various studies, it was found that the basic ligand coordinated to the axial position of the Fe()TpivPP complex has a large effect on the formation of the oxygen complex. That is, Fe(
) The TpivPP complex alone has almost no effect of adsorbing and desorbing oxygen by coordination, and in order to achieve this purpose, it is necessary to coordinate a basic ligand at the axial position. As shown in Formula 1 above, a substituted imidazole represented by the formula is used as a ligand.

Here, R, is Fe()TpivP of the imidazole
It is a group that does not inhibit coordination to P, and methyl, ethyl, and propyl groups (including n-propyl and isopropyl groups) are preferable. R2, R3 and R4 are each hydrogen or a hydrophobic group, and at least one is a hydrophobic group. The hydrophobic group is usually R2 or R3, especially R2. Examples of such hydrophobic groups are:
C, ~C, O alkyl group or trityl group or substituted trityl group or carboxylic acid alkyl ester group'=
5-30, m=0 or 1).

It is important that the substituted imidazole as an axial ligand has the above-mentioned substituent (R1) at the 2-position and a hydrophobic group. According to the research of the present inventors, in a Fe()TpivPP complex having a substituted imidazole that does not have a hydrophobic group, for example, 1,2-dimethylimidazole as an axial ligand, it is possible to incorporate it into an aqueous micelle of a surfactant. oxidizes immediately without forming oxygen complexes. Furthermore, as the number of carbon atoms in the hydrophobic group increases, the inclusion of the complex into micelles becomes better, and it becomes less susceptible to oxidation, resulting in the formation of an oxygen complex. The surfactant used in this invention may be ionic or nonionic as long as it can form micelles.

Examples of surfactants include sodium dodecyl sulfate,
Anionic surfactants such as sodium dodecylsulfonate, sodium dodecyl-N-sarcosinate and disodium N-laurylglutamate, cetyltrimethylammonium bromide, tetradecylammonium bromide and dodecylpyrimidinium chloride, di(
Cationic surfactants such as n-octyl)dimethylammonium bromide, as well as palmitoyl lysolecithin, dodecyl-N-betaine, polyoxyethylene alcohol, polyoxyethylene isoalcohol, polyoxyethylene p-t-octylphenol, polyoxyethylene Nonionic surfactants such as nonylphenol, polyoxyethylene esters of fatty acids, polyoxyethylene solpit esters and polyoxyethylene nonylphenol ethers. All of these are commercially available. To clathrate Fe()TpivPP into surfactant micelles, TpivPPFe(l) and an excess amount (e.g. 5 to 100 times the mole) of substituted imidazole are added in an inert atmosphere (e.g. nitrogen gas) in an appropriate amount. It is dissolved in a solvent such as toluene or benzene, and the central iron of FeTpivPP is reduced to a divalent state using a reducing agent such as sodium dithionite. Then, a sufficient amount of surfactant to solubilize Fe()TPivPP, for example, 1000 grams or more per mole of Fe()TPivPPl, is added, and the solvent is distilled off. These operations are performed by blowing in CO gas, but are preferably performed under an inert atmosphere such as nitrogen gas. The CO gas can finally be easily removed by thermal degassing. Next, this is added to an aqueous medium (e.g., water, phosphate buffered water, physiological saline) under an inert gas atmosphere and shaken vigorously to form surfactant micelles containing Fe()TPlVPP. is obtained. The concentration of surfactant is generally 0.1 wt/v% or more. Further, it is desirable that the aqueous medium has a pH value of 5 or more and 9 or less. The thus obtained micelles according to the present invention exhibit the reversible oxygen adsorption/desorption function of Fe()TplvPP clathrated therein, and the TpivPPFe() forms an oxygen complex even in a system where room temperature sewage coexists.

Therefore, this micelle system is useful as an oxygen adsorption/desorption agent that operates well at room temperature and in the presence of water. Examples of this invention will be described below. Example 1 In a nitrogen gas atmosphere, 5,10,15,20-tetra[α,α,α,α-(0-pivalamidophenyl)-
Porphyne] Iron (111) bromide (hereinafter referred to as Fe(
(abbreviated as NTpivPP-Br) 1719 (8.7×
10-4rrm01e) and N-n-lauryl-2-methylimidazole (4.3 x 10-2 mm01e) were dissolved in 5ml of benzene, and 57rL1 of an aqueous solution in which excess sodium dithionite was dissolved was added and shaken.

After standing still, the benzene layer was separated, and a small amount of three molecular sieves was added for dehydration treatment. Benzene was completely removed from this benzene solution using a vacuum pump, and the obtained solid was mixed with 8% (w/l) Triton X-100 (polyoxyethylene nonyl phenol ether trade name, hereinafter T
(abbreviated as X-100) phosphate buffered water (PH7.O)
Add 10ml solution, shake vigorously to dissolve, 5,1
0,15,20-tetra[α,α,α,α-(0-pivalamidophenyl)porphin]iron()-mono(N-n-
A homogeneous micellar aqueous solution of the lauroyl-2-methylimidazole complex was obtained. The visible absorption spectrum of the solution under nitrogen gas is shown in spectrum a in FIG. The shape of the absorption spectrum and the absorption maximum wavelength matched the literature values, confirming the preparation of the above-mentioned complex as intended. Example 2 To the micelle aqueous solution obtained in Example 1 (under nitrogen gas atmosphere),
When oxygen gas is blown at room temperature, spectrum b in Figure 1 is obtained.
I got it.

The absorption spectra obtained were consistent with literature values for oxygenated complexes in anhydrous toluene solution. By bubbling nitrogen gas into this oxygenated complex solution or freezing and degassing the solution, a reversible change from spectrum b to spectrum a was observed, confirming reversible oxygen adsorption and desorption. Furthermore, the half-life of the oxygen complex was determined to be about 1 hour at room temperature, as determined by tracking changes over time in the absorption spectrum of the oxygen complex obtained. Example 3 FeTpivPP-Brl. O immediate (8.7X10-7M
A solution of 5 ml of benzene containing 11η (50 times equivalent) of 1-lauryl-2-methylimidazole and 1-lauryl-2-methylimidazole was reduced with an aqueous solution containing excess Na2s and O4 under N2, and then CO gas was bubbled (for 10 minutes) to form a CO complex. After standing still, separate the organic layer under CO and add molecular sieves 4λ
It was dried.

This solution was transferred under CO into a 5d solution of TX-100 (0.49) in benzene, previously saturated with CO gas bubbles (15 min), and the combined benzene solution was evaporated with a vacuum pump to remove the TX-100 solution of the CO complex. And so.

After further heating to 95° C., CO was removed using a vacuum pump for 30 minutes to obtain a reduced product. Vacuum frozen and degassed (1 x 10-4t0r
r14 times) 0.05M phosphate buffer (PH7.O) 1
0 ml was added to this and vigorously shaken to obtain a homogeneous micellar aqueous solution of the reductant. 0. Immediately after gas was bubbled (20 seconds), the visible spectrum was measured to track changes over time in the generated oxygen complex.

It was 50 minutes during the half life τ. Example 4 FeTpivPP-BrO. 8Tr9, 1-trityl-
A benzene 5a solution containing 50 equivalents of 2-methylimidazole and 0.11 times diphenyl oxide was reduced with an aqueous Nas2q solution under N2, separated, dried over 4λ molecular sieves, and evaporated.

4% (w
/v) TX-100-0.05M phosphate buffer solution 10d
was added and shaken to uniformly dissolve. At room temperature, the reduced body-micelle aqueous solution was brought into contact with 02 gas and shaken to form an oxygen complex, and the change over time was followed, and it was confirmed that the oxygen complex had a half-life of about 30 minutes. Example 5 Exactly the same method as in Example 3 except that methylly[1-(2-methyl)imidazolyl]undecanoate (50 times the molar amount of FeTpivPP) was used instead of 1-lauryl-2-methylimidazole. Accordingly, 5,10
, 15.20-tetra-[α,α,α,α-(0-pivalamidophenyl)porphyrin]iron()-mono{methyl-11-[1-(2-methyl)imidazolyl]undecanoate} complex A uniform aqueous solution of dissolved micelles was obtained.

Formation of an oxygen complex was similarly confirmed. The half life at room temperature was about 1 hour. The imidazole derivatives used in Examples 1 to 5 were synthesized as follows. [1] 1
-Synthesis of n-lauryl-2-methylimidazole 19 gr (0.23 mol) of 2-methylimidazole and 25 gr (0.10 mol) of lauryl bromide were mixed and heated to 200°C.
The reaction was heated for 0 hours.

After cooling, 500 d of 10% K2CO3 aqueous solution was added and stirred, followed by ether extraction (2 x 300 d). The organic layers were combined and saturated NaHCO3 aqueous solution (2 x 200 ml),
After washing with saturated NaCl aqueous solution, the liquid was separated and Na2sO4
It was dried. After removing the solvent by evaporation, the oily residue was transferred to a silica gel column (500 gr, CHC1, /MeOH=1
After purification with B.0/1), further distillation under reduced pressure was performed. p. l56~
A 158° C./4 liter Dkg fraction was collected. Yield 20gr1 Yield 79%. Mass spectrum M+=250, 1H-NMR
Spectrum (CDCl3, TMS) S (purchase): 6.88
(D, J=1Hz), 6.76 (D, -J21Hz):
Protons at positions 4 and 5 of the imidazole nucleus; 3.89 (2H
, t, J=7Hz): 11th position N-CH2-CH2; 2.
36(3H-S); -CH3 at 2nd position: IR spectrum (
NaCl plate) Cm-1: 3400, 2930, 2860
,1525,1500,1465,1425,1375
, 1280, 1145, 995, 720, 1680. [
2] Synthesis of 1-trityl-2-methylimidazole 2-
4.3 gr (0.023 mol) of methylimidazole-silver salt was suspended and stirred in 50 d of toluene, and trityl chloride7.
0gr (0.025 mol) was added and heated under reflux for 10 hours.The mixture was returned to room temperature to remove insoluble matter, and the solution was concentrated by evaporation.

The residue was purified using a silica gel column (200 gr,
CHC113/MeOI-1:20/1).

The target product was synthesized by recrystallization from 2benzene-n-heptane system. Yield 3.34gr1 Yield 45%. Mass spectrum M+=324.1H-NMR spectrum (CDC
l3, TMS) S (corner): 7.00-7.40 (15H
, m, phenyl nucleus), 6.86 and J6.76 (1H,
1H, d, J = 1Hz 1 imidazole nucleus 4th and 5th positions),
1.67 (3H,S, -CH3 at the 2nd position of imidazole).

IR spectrum (KBr tablet) Cm-1:3350,3
070,3030,1600,1520,1490,3
1450, 1395, 1305, 1240, 1180,
1140, 1070, 1035, 1000, 980, 9
10,88,865,760,750,7000 [3]
Synthesis of methyl 11-[1-(-methyl)imidazolyl]undecanoate 25 g of 11-promoundecanoic acid
The mixture was stirred at room temperature for 4 hours in the presence of 13 ml of oxalyl chloride in 100 d of benzene.

Next, 50 ml of methanol was added and left overnight, followed by treatment in a conventional manner to obtain 11-promoundecanoic acid methyl ester 23.
gr (yield 87.5%) was obtained.

8.2g of 2-methylimidazole, 2.4g of NaH
The previously obtained 11-
23 gr of promoundecanoic acid methyl ester were added.

Further, the mixture was heated and stirred at 90° C. for 2 hours, and then processed according to a conventional method. This was applied to a silica gel column (CHCl3/Me
OH=9/1). Yield 9.5gr, Yield 4
1%. Mass spectrum M+=28001RS vector (
liquid film) 1740 cm-1 (DO=o ester). 1H-
NMR spectrum (CDCl3, TMS) S(PPOl
): 1.28(S, l2H,', NNCH2CH2(C
H2)6CH2CH2C0-), 1.68(M,4H,
]NCH2CH2(CH2)6CH2CH2C0-),
2.31 (T, 2H, -CH2COO-), 2.37 (
S,3H, imidazole-CH3), 3.66(S,
3H, -COOCH3), 3.80(T, 2H, 〉NC
H2-), 6.80 (D, lHl proton at 5th position of imidazole ring), 6.90 (D, lH, proton at 4th position of imidazole ring).

Example 6 8% (w/v) Triton x-1 used in Example 1
8% (w/v) cetyltrimethylammonium bromide phosphate buffer (PH
7. O) 5,10,15,20-tetra [α, α, α
, α-(0-pivalamidophenyl)porphyrin]iron (
)-mono(N-n-lauroyl-2-methylimidazole) complex was obtained, and it was confirmed that the shape of its visible absorption vector and the absorption maximum wavelength were consistent with the literature values.

Further, oxygen gas was blown into this solution according to Example 2, and reversible adsorption and desorption of oxygen was confirmed.

The half-life of the oxygen complex was about 40 minutes at room temperature.

[Brief explanation of the drawing]

FIG. 1 is a visible absorption spectrum diagram of TpivPPFe() included in a surfactant micelle according to the present invention due to oxygen injection.

Claims (1)

[Claims] 1 Formula ▲ Numerical formula, chemical formula, table, etc. ▼ (Here, R_1 is a group that does not inhibit the coordination of imidazole to the central iron, R_2, R_3, and
4 is hydrogen or a hydrophobic substituent, at least one of which is a hydrophobic substituent)
-5,10,15,20-tetra [α, α, α, α-(
o-pivalamidophenyl)] A water-based micelle of a surfactant characterized by including a porphyrin complex. 2. The micelle according to claim 1, wherein R_1 is a methyl group, an ethyl group, or a propyl group. 3 R_3 and R_4 are each hydrogen, R_2
The micelle according to claim 1 or 2, wherein is a C_5 to C_3_0 alkyl group, a trityl group, a substituted trityl group, or a carboxylic acid alkyl ester group. 4 1000 surfactants per mole of porphyrin complex
The micelles according to any one of claims 1 to 3, which are present in an amount of gram or more. 5 Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (Here, R_1 is a group that does not inhibit the coordination of the imidazole group to the central iron, R_2, R_3, and R
_4 is hydrogen or a hydrophobic substituent, at least one of which is a hydrophobic substituent)
I) -5,10,15,20-tetra [α, α, α, α
An oxygen adsorbing/desorbing agent comprising an aqueous micelle of a surfactant characterized by including a -(O-pivalamidophenyl)porphyrin complex.6 Claims in which R_1 is a methyl group, an ethyl group, or a propyl group. The oxygen adsorbing/desorbing agent according to item 5. 7 R_3 and R_4 are each hydrogen, and R_2
The oxygen adsorbing/desorbing agent according to claim 6 or 7, wherein is a C_5 to C_3_0 alkyl group, a trityl group, a substituted trityl group, or a carboxylic acid alkyl ester group. 8 1000 surfactants per mole of porphyrin complex
The oxygen adsorbing/desorbing agent according to any one of claims 5 to 7, wherein the oxygen adsorbing/desorbing agent is present in an amount of gram or more.