JPH1029994A - Dimerized porphyrin compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a new dimerized porphyrin compound exhibiting an excellent metal ion-catching ability and an excellent energy-converting characteristic, having good bioaffinity and thereby high in a possibility for utilization as a biological energy-converting substance, etc. SOLUTION: This new dimerized porphyrin compound is expressed by the formula [R<1> -R<15> are each H, a halogen; M is a metal ion such as Ag, Al, Ba, Ca, Co, Cr, Fe, Ge, Mg, Mn, Mo, Ni, P, Pb, Pt, Si, W, Zn; (n) is an integer of 2-20]. The compound of the formula can form a coordination compound with any electric charge number ion of a transition metal exhibiting various kinds of electric charge numbers, and can catch and coordinate such a large metal ion as being not able to enter a space in the skeleton of the porphyrin. The compound of the formula thereby has an excellent energy-converting characteristic, and has a high possibility to be utilized as a biological energy-converting substance. The compound is obtained by reacting cystamine dihydrochloride and fluorophenylporphyrin monomethyl ester with ethyl chlorocarbonate and subsequently treating the reaction product with a metal salt compound.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel porphyrin dimerization compound, and more particularly to a metal complex of a porphyrin dimerization compound.

[0002]

2. Description of the Related Art Porphyrin metal complexes mainly synthesized in vivo in animals and plants are derivatives of a porphine skeleton substituted with various groups, and generally have metal ions trapped in the porphine skeleton. As such a porphyrin metal complex, proteins and natural pigments such as hemoglobin as an oxygen carrier, cytochrome as an electron transfer medium, and chlorophyll as a photo-chemical energy conversion medium are known. On the other hand, those artificially synthesized include (1) 2-acryloyloxymethyl-5,10,15,20-tetraphenylporphyrin copper as a recording material, (2) ferrotetraaminophenylporphyrin as an oxygen sensor material, (3) Iron tetraphenylporphyrin and the like as a light-to-electric energy conversion material are known. Still further, mesoporphyrin having a hydrogen atom and / or a halogen atom at any one or more positions of α to δ in the porphine skeleton has a higher metal ion trapping ability of the porphine skeleton and can form various metal complexes. Is also known.

[0003]

Various metal complexes are known for porphyrins having enhanced metal ion-capturing ability, but metal complexes of porphyrin dimerization compounds are not known. An object of the present invention is to provide a novel substance of a porphyrin dimerization compound, more specifically, a metal complex of a porphyrin dimerization compound.

[0004]

Means for Solving the Problems To achieve the above object, the present inventors have made intensive studies and found that the α of the porphine skeleton was
A porphyrin dimerization compound in which each position of ~ δ is substituted with a phenyl group and an alkyl chain of a suitable length having a disulfide group at the phenyl group at the β position, or a suitable porphyrin compound having a disulfide group at the phenyl group at the β position Porphyrin dimerized compounds in which an alkyl chain of a length is bonded, and all or part of the hydrogen atoms of the phenyl group at each position of α, γ, and δ are substituted with halogen atoms, all have high metal ion trapping ability. It has been found that such a porphyrin dimerized compound in which various metal ions are captured by the porphine skeleton is a metal complex of a novel compound, a porphyrin dimerized compound.

That is, the present invention provides a compound represented by the general formula (2)

[0006]

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[In the formula (2), R ^{1 to} R ¹⁵ represent a hydrogen atom and / or a halogen atom, and M represents Ag, Al,
Ba, Ca, Co, Cr, Fe, Ge, Mg, Mn, M
o, any one metal ion selected from the group consisting of Ni, P, Pb, Pt, Si, W and Zn, and n is 2 to 20
Represents an integer. ] The porphyrin dimerization compound shown by these.

In the present invention, M in the general formula (2) is represented by the following formula:
A porphyrin dimerization compound characterized by being any one of metal ions selected from the group consisting of Mn, Fe, Cr, Mg, Co, and Zn.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The porphyrin dimerization compound according to the present invention is represented by the above formula (2), wherein the positions of α, γ and δ of the porphine skeleton are each substituted by a phenyl group. Or the hydrogen of the phenyl group is completely or partially substituted with a halogen atom such as chlorine, fluorine, bromine or iodine, that is, R ^{1 to} R ¹⁵ in the formula (2) are hydrogen atoms Or / and a halogen atom, and a metal ion represented by M in the formula (2), ie, Ag, Al,
Ba, Ca, Co, Cr, Fe, Ge, Mg, Mn, M
o, any one metal ion selected from the group consisting of Ni, P, Pb, Pt, Si, W and Zn, preferably Mn, F
e, a metal ion selected from the group consisting of Cr, Mg, Co, and Zn is coordinated, and the β position of the porphine skeleton is substituted with a phenyl ring, and disulfide is used as a side chain bonded to the phenyl group. An alkyl chain of a suitable length having a group, that is, an alkyl chain having n in the formula (2) wherein n is any integer of 2 to 20 is bonded.

Incidentally, such a porphyrin dimerization compound can be synthesized by utilizing a known synthesis method of other porphyrin derivatives. For example, when n in the formula (2) is In the case of synthesizing the porphyrin dimerized compound of No. 2, Traz is used as a raw material with benzaldehyde, 4-acetoxybenzaldehyde and pyrrole as raw materials.
ylor et al. (J. Am. Chem. So
c. , 101 (1979) pp. 6716-6731)
A triphenylporphyrin monomethyl ester is synthesized in the same manner as described above, and potassium hydroxide is added thereto to produce triphenylporphyrin carboxylic acid. Ethyl carbonate is added to the triphenylporphyrin carboxylic acid, and then cystamine dihydrochloride is further added to obtain triphenylporphyrin disulfide. By using pentafluorobenzaldehyde instead of benzaldehyde as a raw material, pentafluorophenylporphyrin disulfide can be obtained in the same manner as described above. After dissolving this triphenylporphyrin disulfide or pentafluorophenylporphyrin disulfide in acetic acid or nitric acid, Ag, A
1, Ba, Ca, Co, Cr, Fe, Ge, Mg, M
Acetate hydrate or nitrate hydrate of a desired metal selected from the group of n, Mo, Ni, P, Pb, Pt, Si, W and Zn, preferably Mn, Fe, Cr, Mg, Co and Zn The metal triphenylporphyrin dimerized compound: (MTPP-
C ₂ -S) _2, or metal pentafluorophenyl porphyrin dimer compound: (can be obtained MPFPP-C ₂ -S) _2. When the product (solute) after the solvent extraction is a mixture, it can be easily separated by a general separation operation, for example, column chromatography or the like.

As an example of the case where a porphyrin dimerization compound in which n in the formula (2) is an integer of 3 to 20 is synthesized, for example, thiourea is added to bromoalcohol as a raw material, refluxed in hexanol and dried. Thereafter, potassium hydroxide and sulfuric acid are added to the dried product, iodine ethanol is added to the obtained mercapto alcohol, and p-trisyl chloride and then phthalimide potassium are added to prepare bisphthalimidyl disulfide. Hydrazine monohydrate and hydrochloric acid are added thereto to obtain a bisaminoalkyl disulfide. This is added to a stirred solution of triphenylporphyrin carboxylic acid, methylene chloride and ethyl chlorocarbonate prepared in the same manner as described above to obtain triphenylporphyrin disulfide.
In this method, pentafluorophenyl porphyrin disulfide can be obtained by using pentafluorophenyl porphyrin carboxylic acid prepared by using a method by Traylor or the like instead of the triphenyl porphyrin carboxylic acid. After dissolving the thus obtained triphenylporphyrin disulfide or pentafluorophenylporphyrin disulfide in acetic acid or nitric acid, Ag, Al, Ba, Ca, C
o, Cr, Fe, Ge, Mg, Mn, Mo, Ni, P,
Group of Pb, Pt, Si, W, Zn, preferably Mn, F
e, a metal triphenylporphyrin dimerization compound by adding an acetate hydrate or a nitrate hydrate of a desired metal selected from the group of e, Cr, Mg, Co, and Zn and removing the solvent by an extraction operation: MTPP-C _n -S) _2, or metal pentafluorophenyl porphyrin dimer compound: (MP
Can be obtained FPP-C _n -S) _2. When the product (solute) after solvent extraction is a mixture, a general separation operation,
For example, it can be easily separated by column chromatography or the like.

[0012]

【Example】

Example 1 Commercially available cystamine dihydrochloride 2.75 × 1
0 ^-4 mol and fluorophenyl porphyrin was prepared in a similar manner by Traylor like monomethyl ester 1.38 × 10 ^-4 mol and methylene chloride 8ml
And 2.07 × 10 ⁻⁴ mol of ethyl chlorocarbonate. This methylene chloride - with distilled water, silica gel column chromatography by pentafluorophenyl porphyrin disulfide by separation and purification: yield the _{(PFPP-C 2 -S) 2} . (P
Confirmation of FPP-C ₂ -S) ₂ was performed by nuclear magnetic resonance.
^{The data of 1} H-NMR (δ ppm, CDCl ₃ ) is 8.
77-8.83 (16H), 8.33 (8H), 7.4
0 (2H), 4.10 (4H), 3.24 (4H),-
2.90 (4H). The pentafluorophenylporphyrin disulfide is then 3.36 × 10 ⁻⁴ m
was dissolved in 8.5 ml of acetic acid, and 3.36 × 10 ⁻⁴ mol of manganese acetate tetrahydrate was added thereto. The solvent was removed by solvent extraction, and the solution was removed using a chloroform-methanol eluent. The resulting product was separated and purified by alumina column chromatography to obtain a final product. The obtained final product was analyzed by UV / vis absorption spectrum.
Since absorption was observed at 58.5 nm and 555.0 nm, the final product was a manganese pentafluorophenylporphyrin dimerization compound represented by the formula (3): (MnPF
Was confirmed to be a PP-C ₂ -S) _2. (Yield about 72
%)

[0013]

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Example 2 Thiourea 6.63 × 10 ^-2
was dissolved in 30.26 ml of ethanol and refluxed to give 0.052 mol of 6-bromo-1-hexanol.
The mixture was refluxed in a nitrogen atmosphere to remove the solvent, and further dried under vacuum to obtain isothiuronium hexanol hydrobromide. This is 7N potassium hydroxide 47.3m
After refluxing in a nitrogen atmosphere, 10N sulfuric acid 3
The reaction system was acidified with 0 ml and diethyl ether was added to the reaction system to extract the solvent, followed by vacuum drying to obtain 6-mercapto-1-hexanol. This 6-mercapto-1-hexanol (0.052 mol) has a concentration of 50 mg /
After adding 80 ml of iodine ethanol solution, diethyl ether was added to extract the solvent, the solvent was distilled off, the mixture was stirred in at least the same amount of hexane, allowed to stand, and the precipitate was decanted. And bis (6-hydroxyhexyl) disulfide was obtained by vacuum drying. This bis (6-hydroxyhexyl)
0.0238 mol of disulfide was dissolved in a solution of 20 ml of tetrahydrofuran and 10 ml of triethylamine, and 0.095 mol of p-tosyl was added. After stirring for about 24 hours, the solvent was extracted with methylene chloride and distilled water. The solvent was distilled off and dried to obtain bis (6
-Tosylhexyl) disulfide was obtained. Bis (6-tosylhexyl) disulfide is converted to dimethylformamide 1
Dissolved in 100 ml of potassium phthalimide.
095 mol was added and the mixture was refluxed in a nitrogen atmosphere. To this, methylene chloride (500 ml) was added, followed by filtration, and the filtrate was dried under vacuum to obtain bis (6-phthalimidyl) disulfide powder. This is ethanol 40ml under nitrogen atmosphere
Was added thereto, and 4.695 ml of 0.095 mol of hydrazine monohydrate was added thereto, and the mixture was refluxed in a nitrogen atmosphere, and further adjusted with hydrochloric acid so that the pH of the reaction system became 3, and then refluxed again. 100 ml of ethanol was added to the mixture, followed by filtration. The solvent was extracted from the obtained filtrate using methylene chloride-1N sodium hydroxide, and then dried under vacuum.
Separation and purification by silica gel column chromatography using a methanol-aqueous ammonia eluent gave bis (6-aminohexyl) disulfide: (H ₂
(NC ₆ -S) ₂ was obtained. This was dissolved in a solution obtained by adding 0.011 mol of triethylamine to 2 ml of methylene chloride to prepare bis (6-aminohexyl) disulfide dihydrochloride. This bis (6-aminohexyl) disulfide dihydrochloride 2.75 × 10 ⁻⁴ mol
Was prepared in the same manner as in Traylor et al., With pentafluorophenylporphyrin monomethyl ester 1.3.
8 × 10 ⁻⁴ mol, 8 ml of methylene chloride and 2.07 × 10 ⁻⁴ mol of ethyl chlorocarbonate were added to a mixed solution. This was subjected to solvent extraction using methylene chloride-distilled water, and the reaction product obtained by evaporating the solvent was separated and purified by silica gel column chromatography using a chloroform-methanol eluent to obtain pentafluorophenylporphyrin disulfide: ( PFPP-C ₆ −
S) ₂ was obtained. Checking (PFPP-C ₆ -S) ₂ was performed by nuclear magnetic resonance. ¹ H-NMR (δ ppm, CDC
data of l ₃₎ is, 8.82-8.89 (16H),
8.18-8.28 (8H), 6.57 (2H),
63 (4H), 2.78 (4H), 1.25-1.57
(16H) and -2.87 (4H). The pentafluorophenylporphyrin disulfide
36 × 10 ⁻⁴ mol was dissolved in 8.5 ml of acetic acid. After adding 3.36 × 10 ⁻⁴ mol of manganese acetate tetrahydrate to this, the solvent was removed by solvent extraction to give chloroform-
The final product was obtained by separation and purification by alumina column chromatography using a methanol eluent. When the final product was analyzed by UV / vis absorption spectrum, absorption was observed at 458.5 nm and 557.5 nm. Therefore, the final product was a manganese pentafluorophenylporphyrin dimerization compound represented by the formula (4): (M
it was confirmed that the nPFPP-C ₆ -S) _2. (Yield about 69%)

[0015]

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Example 3 3.36 × 10 ⁻⁴ mol of pentafluorophenylporphyrin disulfide prepared in the same manner as in Example 1 was dissolved in 8.5 ml of acetic acid, and zinc acetate dihydrate was added to the solution. 36 × 10 ⁻⁴ mol was added, the solvent was removed by solvent extraction, and the product was separated and purified by alumina column chromatography using a chloroform-methanol eluent to obtain a final product. When the obtained final product was analyzed by UV / vis absorption spectrum, absorption was observed at 420.5 nm and 552.0 nm. Therefore, the final product was a zinc pentafluorophenylporphyrin diamine represented by the formula (5). dimerized compound: was identified as _{(ZnPFPP-C 2 -S) 2} . (Yield about 71%)

[0017]

(Equation 5)

Example 4 3.36 × 10 ⁻⁴ mol of pentafluorophenylporphyrin disulfide prepared in the same manner as in Example 2 was dissolved in 8.5 ml of acetic acid. After adding 3.36 × 10 ⁻⁴ mol of zinc acetate dihydrate thereto, the solvent was extracted to remove the solvent, and the mixture was separated and purified by alumina column chromatography using a chloroform-methanol eluent to give a final product. The product was obtained. When the final product was analyzed by UV / vis absorption spectrum, absorption was observed at 420.5 nm and 552.5 nm. Therefore, the final product was a zinc pentafluorophenylporphyrin dimerized compound represented by the formula (6): (ZnP
It was confirmed that the FPP-C ₆ -S) _2. (Yield about 6
9%)

[0019]

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[0020]

The metal complex of the novel porphyrin dimerization compound according to the present invention can coordinate any charge of a transition metal which can show various charge numbers, and further has a porphine skeleton. Because it can also capture and coordinate large metal ions that can not enter the space inside,
It is highly likely that it has excellent energy conversion properties, and since it is a dimerized compound having a disulfide group, it has biocompatibility, so it is highly likely to be used as an energy conversion substance in vivo .

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Claims (2)

[Claims] 1. A compound of the general formula (1) [In the formula (1), R ^{1 to} R ¹⁵ represent a hydrogen atom and / or a halogen atom, and M represents Ag, Al, Ba, Ca,
Co, Cr, Fe, Ge, Mg, Mn, Mo, Ni,
P is a metal ion selected from the group consisting of P, Pb, Pt, Si, W and Zn, and n represents an integer of 2 to 20. ] The porphyrin dimerization compound shown by these. 2. M is Mn, Fe, Cr, Mg, Co,
The porphyrin dimerization compound according to claim 1, wherein the porphyrin dimerization compound is any one metal ion selected from the group consisting of Zn.