JPS5829787A - Porphyrin having hydrophobic substituent group and its complex - Google Patents

Abstract

NEW MATERIAL:A porphyrin expressed by formulaI[R is >=10C alkyl, formula II (m>=1), etc.], an iron complex thereof expressed by formula III and a complex expressed by formula IV[(L) is basic axial ligand; (x) and (y) are 0 or 1, and (x+y) is 1 or 2]. EXAMPLE:meso-tetra[alpha,alpha,alpha,alpha-(o-lauroylamidophenyl)]porp hyrin. USE:An oxygen carrier capable of adsorbing and desorbing oxygen molecules. PROCESS:5,10,15,20-Tetra[alpha,alpha,alpha,alpha-(o-aminophenyl)]porph yrin is reacted with an acid chloride expressed by the formula R-COCl, e.g. H(CH2)nCOCl (10<=n<=30), in a molar amount of 4 or more times that of the porphyrin to give a porphyrin expressed by formulaI. The central iron is then introduced into the porphyrin expressed by formulaIto afford a complex expressed by formula III. The central iron of the resultant complex is then reduced with a reducing agent in the presence of an axial ligand (L) by the conventional method to give a complex expressed by formula IV.

Description

DETAILED DESCRIPTION OF THE INVENTION The invention relates to porphyrins having hydrophobic substituents and complexes thereof.

Conventionally, many efforts have been made to synthesize complexes with oxygen adsorption and desorption functions similar to those of the iron (In/ruphyrin complexes, which reversibly adsorb and desorb oxygen molecules. Such natural porphyrin iron ω) complexes of hemoglobin and myoglobin. research has been published. Examples include - J.P., Collman, A.
ccounts of ChemicalR*a*ar
eh 10 265 (1977); iP, B
a5oio, B, M.

Hoffman and J.A., Ib@ra, 1bi.
d, 8384 (1975), etc. In particular, iron ω)-5,10 is a porphyrin fR1I) complex that is reported to be able to form a stable oxygen complex under room temperature conditions.
, 15゜20-tetra[α, α, α, α-(0-piparandophenyl)]porphyrin complex (J, P, Col1
man et al Journal of Am@rican C
h@m1cal 8oei*ty 971427 (19
75)). However, this complex is immediately oxidized when water coexists with even a small amount of violet, making it impossible to generate an oxygen complex. The development of iron(II) porphyrin complexes that provide oxygen complexes even in the coexistence of water at room temperature continues to be promoted.

The applicant has discovered that the aforementioned iron (n)-5, 10, 15, 20-tetra [α, α,
α,α-(0-piparamidophenyl)]porphyrin (
Hereinafter, in order for the F(II) Tplv pp ) complex to provide a stable oxygen complex and act as an oxygen carrier, the complex is embedded in, for example, 8 parts of a hydrophobic block of an ABA type block copolymer, or We have discovered that when lipids are included in a hydrophobic double layer membrane, oxidation by water or Hi□ is inhibited, and the desired function can be exerted.
No. 56-89312).

The present inventors developed the above idea and found that if the hydrophobic nature of the porphyrin was increased by replacing the piparoyl group of TpI mapPP with another more hydrophobic substituent, it would be possible to make more available oxygen. The present invention was completed based on the idea that it would be possible to provide a carrier.

The compound of this invention is a hydrophobic substituent represented by the general formula (where R is an alkyl substituted derivative having 10 or more carbon atoms, m is an integer of 1 or more or a substituted derivative, and t is an integer of 0 or 1 or more). porphyrin (meso-tetra[α, α, α, α-(0-substituted amidophenyl]]porphyrin) having A complex in a divalent state and coordinated with one or two basic axial ligands, that is, a complex with the formula (where L is a basic axial ligand, X and y are 0 or 1, and X+y is 1 or 2).

In order to produce the porphyrin represented by formula (4),
Known methods (Jou of J, P, Co11m1n et al.
rnal of th@Am@riean Ch＊m1
eal 5.10 by the method described in oei@ty)
, 15.20-tetra[α,α,α1α-(0-aminophenyl)]poporfin with a specified acid chloride (R-CO
Ct) is reacted at a ratio of 4 times the mole or more. The reaction temperature is usually 0°C to room temperature. Acid chloride (R-COCt)
is an aliphatic carmenic acid chloride represented by the formula H+cH2-y coct (where n is 10 or more and usually 30 or less), (where m is 1 or more and usually 3 or less, R1 is a methic group or an ethyl group) , propyl group, base, bromine,).

Aromatic carmenic acid chloride represented by a benzene term substituent such as base, methoxy group, ethoxy group, pro/coconut group, carmenic acid methyl ester group, cardanic acid ethyl ester group, allyl group, a is an integer from O to 5) The substance or formula is 1 or more and usually 3 or less, b is an integer of O to 10, R2 is R1
There are alicyclic cardanate chlorides represented by groups similar to .

By introducing a central iron into the thus obtained formula porphyrin by a conventional method, an iron complex represented by the formula ω), namely 5.10,15.20-meso-tetra [α, α, α, α
-(0-1f-converted amidophenyl)]porphinate iron is obtained.

In order to obtain the complex represented by the formula (0), the central iron of the iron complex represented by the formula (B) is substituted with a suitable reducing agent in the presence of an axial ligand by a conventional method. The ligand is represented by the formula (where R1 is a group that does not inhibit the coordination of the imidazole, preferably hydrogen, methyl group, ethyl group, and propyl group (including isomers), and R1 to Rd are hydrogen or any substituted an imidazole represented by a group such as an alkyl group, a trityl group, a carmenic acid ester group), or an imidazole represented by the formula (where R and R1 are the same groups as R1, and Rf~.Rh is a group similar to R6-R6) There is pirinone.

When the complex of the formula (0) comes into contact with oxygen, it coordinates in place of one of the axial ligands to form an oxygen complex, which desorbs oxygen under degassing.

This oxygen adsorption/desorption can be repeated reversibly and acts as an oxygen adsorption/desorption agent and an oxygen carrier.

Example 1 (4) Meso-tetra(〇-aminophenyl)/rufin (mixture of 4 isomers) was synthesized by a known method, and silica powder (acetone/ether = 1/1 volume) was synthesized. The α, α, α, α-isomers were extracted and isolated using the following method.

(B) Meso-tetra[α, α, α, α-(0-aminophenyl]porphine approximately o, 3 tr 'k included t
A solution of 300 ml of acetone ether (1/1) was stirred under water cooling.

Add to this 2-1 dry pyricin, then 2.5 lauroyl chloride.
- was added, and the mixture was stirred for 1 hour under water cooling, and then stirred for 2 hours at room temperature. The tA liquid obtained by evaporation was dissolved in CHC/-, 200-, washed with dilute ammonia water, washed with water, treated with gelite, and washed with water.

This was dehydrated with Na2SO4, filtered, and the filtrate was evaporated to dryness in a bath below 30°C. This was fractionated and purified using a silica dull column, and benzene/ether (7/'3)
(Volume t/volume) The purpose of the effluent was completed and it was evaporated to dryness. Purification using a silica column was performed again.

Yield 0.56 fr (yield 901). This was further refined by two people (BioBsads
8X-8, benzene).

Electric field desorption mass spectrum measurement: M+1 (1403) (C
Molecular weight of 92H12□N804: 1402). Elemental analysis value (heavy 414): C78,66 (78,7)i, H8,5
2 (8,7), N7.60 (8,0) However, the values in parentheses indicate calculated values for C92H12□N804.

13C-Nuclear magnetic resonance spectrum (solvent CDCl3°TM
S standard) δ (pprn): 170.5 (1) -
147.0 (2), 138.0 (3), 134.8 (4
).

131.6(5), 129.8(6), 122.
8(7).

121.1 (8), 11-5.0 (9), 37.0 (1
0).

31.8(11), 29.4.29.2 and 28.9(
12, 13, 14), 25.0 (15).

22.6 (16), 14.0 (17) However, the numbers in parentheses indicate the carbon in the manure.

Meso-tetra [α, α, α, α-(
0-Lauroilua (dophenyl)] Porphy 70, 33
Dissolve fr in 25 dK of dry tetrahydrofuran and N2
Replacement was made. To this, 0.1 d of 2,6-lutisone
Next, 0.3 fr of ferrous bromide (FeBr2) was added, and a direct current was applied while heating. After 2 hours, more FeBr2
After heating for 2 hours, evaporate to dryness, and purify the remaining solid with a basic alumina column using chloroform as the effluent solvent.
After adding r and shaking, the mixture was washed with water. chloroform layer with Na25
After dehydration treatment with O4, it was evaporated to dryness and once dried under reduced pressure. This was purified by column (B amount oB@ada 5X
-8, benzene). Thin layer chromatography (Merck silica glucose, benzene/ether = 1/1):
Rf=0.89 (mono spot). Electric field desorption mass spectrum measurement: M + 1 = 1457 (C, 2H,
2oN804F@, molecular weight 1456). Elemental analysis value (
Weight 4): C71,50 (71,9), N7.61 (7
, 8), N 7.03 (7, 3) However, the values in parentheses indicate the calculated values for C92H12 (IN60.F@Br.
ffl) *2930, 2860 (Van
, Vm (CH2)), 1680 (amide I absorption band), isso (ve-baphenyl nucleus), 760
(δCH2 (out-of-plane) (〇-substituted phenyl nucleus.

Example 3 Iron-mesotet 2 [α, α.

α, α-(0-2 uroylamidophenyl)]4rufin・Br5×10 moles and 1.5×10 moles of 1,2-nomethylimitasole were dissolved in toluene 7-ML, and after replacing with N2 gas, Excess Na2S2O4
5 d of water was added thereto, thoroughly shaken, and allowed to stand still. Molequilla-Xigos 41 with benzene layer separated and deoxidized
The desired F.(If)porphyrin complex (formula (
A solution of dry benzene (corresponding to 0%) with 10""M water was prepared. This visible absorption spectrum is
Shown by the curved line in the figure・This is λmix 560 nm e
535 A five-coordinated deoxy complex with nrn (shoulder), i.e. F@1)-meso-tetra[α, α, α, α-(
0-lauroylamidophenyl) L/rufin-nanino(
1,2-methylimidazole). When this was brought into contact with oxygen gas, a spectral change was immediately observed, and λmhx 549 nm (oxygen complex) was obtained (curve b). Visible absorption (from the change in color over time, 25
The stability of this oxygen complex at 0.degree. C. was greater than 20 minutes. Moreover, the stability of this oxygen complex at -10C was more than 1 hour.

Example 4 A deoxy fiber solution was prepared in the same manner as in Example 3 except that nibenzene was used instead of toluene and 0.1 fr of styrene was added. This was freeze-dried to remove benzene and obtain polystyrene particles containing a fraction of the complex. To this, add 10 ml of nitrogen gas saturated water.
5g/g was added to prepare solid particle dispersion water. As shown in curve C in Figure 2, under N2, the 5-coordinate r-oxy form (F・(■)-meso-tetra[α, α, α
, α-(0-lauroylamidophenyl)]/rufin-mono 1,2-dimethylimidazole) m form) (λmax 560 nm, 532
nm (dust)) was obtained. When 0□ gas was introduced into this solid dispersion water, the spectrum of the oxygenated complex (λwax
550 am) (curve d). In addition, CO
As soon as the gas was introduced, a spectrum (λrnax 530 am) corresponding to the F·(II) CO complex was obtained (curve e). The stability of the oxygen complex in water at 25° C. was more than 10 hours.

Example 5 5.10,15.20-tetra(α, α, α,
α-(0-Cyclohexanoylandphenyl)) porphyry tank synthesized 0 element analysis value (weight t%): C77
,13(77,6),f(6,71(6,6),N 1
0.22 (10,1) However, the value in parentheses is C72H
Calculated values for 74N804 are shown. Electric field desorption mass (
Cuttle: M+1-1115 (Molecular Lid 1114).

Practical 6 A central iron was introduced into the 5,10,15°20-tetra(α,α,α,α-(0-cyclohexanoylandophenyl))/rufin synthesized in Example 5 according to Example 2. . Elemental analysis value (heavy in): C68,87 (69,
2), H5,71 (5,8), N8.82 (8,9),
However, the values in parentheses are C72) [74NaOa F@
Calculated values for B r are shown.

Example 7 5.1 was carried out in the same manner as in Example 1 (B) except that phenylacetic acid chloride was used instead of lauroyl chloride.
0,15.20-tetra(α,α.

After synthesizing α,α-(0-phenylacetylamidophenyl))porphyrin, central iron was introduced according to Example 2. Electric field desorption mass (Kutoruni M + 1-1200
(Molecular lid 1200 of C, 6H66N, 04F). Elemental analysis value (weight): C70°92 (71-3), H4
, 65(4,4), N8.41C8,8). However, the numbers in parentheses indicate calculated values for C76H54NB04F@Br.

Actual opening 1 The same reaction was carried out and purified using 9 except for 9.

Elemental analysis value (quantity): C81,53 (81,2), H
10,61 (10,7), H5,02 (5,1), values in parentheses indicate calculated values of C148H234N804. A central iron was introduced into this according to Example 2. Elemental analysis value (weight 4): C76,18 (76,6), 1 (1
0,,37 (10,1), N4.81 (4,8), however, the values in parentheses indicate the calculated values of CH4BH252NB04F@Br.

[Brief explanation of the drawing]

Figures 1 and 2 are graphs showing the visible absorption spectrum before and after oxygenation of the porphyrin iron complex of the present invention. Applicant's agent: Takehiko Suzue, patent attorney
~

Claims (5)

[Claims] (1) General formula (here, an alkyl group having RB carbon atoms number lO or more, -+
CH2−+i group or its benzene product substituted derivative,
m is an integer of 1 or more, or a porphyne having a hydrophobic substituent represented by -(CH2h (◇ or its cyclohexane-substituted derivative, t is an integer of 0 or 1 or more) and a complex in which an iron ion is coordinated thereto; A complex in which the iron ion is in a divalent state and is coordinated with a basic axial ligand. (2) 4-luphyrin and its complexes according to claim 1, in which the alkyl group has up to 30 carbon atoms. (3) 4 as described in claim 1, where m is up to 3
Lufilin and its complexes. (4) 4 as described in claim 1, where t is up to 3
Lufilin and its complexes. (5) The basic axial ligand is I5! %1FFill, which is a lysine derivative! The complex according to item 1 of the desired range.