Etsuo Hasegawa

Syntheses and properties of vinyl monomers containing a meso-tetraphenylporphin ring and their copolymers

Abstract To synthesize polymer-covalently bonded meso-tetraphenylporphin derivatives, two porphyrin vinyl monomers, viz., 5-mono( p -acrylamidophenyl)-10,15,20-triphenylporphin and 5,10,15,20-tetra( α , α , α , α - o -methacrylamidophenyl)porphin, were prepared and characterized by elemental analyses, nuclear magnetic resonance, infrared and mass spectrometry. The porphin-bonded polymers were synthesized by radical copolymerization of the porphin monomers with styrene and other monomers and purified by gel permeation chromatography. The spectral properties of these compounds in the Q-band region are also discussed.

Liposomal heme as oxygen carrier under semiphysiological condition

Abstract To prepare a potent synthetic oxygen carrier in aqueous media, the iron(II) picket fence porphyrin complex with one hydrophobic imidazole was incorporated into a lipid bilayer of phosphatidylcholine. The incorporation was confirmed by gel permeation chromatography and ultracentrifugation, which indicates the complex being trapped in the multilayer liposome. The liposomal iron(II) porphyrin complex could bind molecular oxygen reversibly in neutral aqueous media and in the serum of a rat blood at 25°C.

Complexes between synthetic polymer ligands and ferri- and ferro-protoporphyrin IX

Abstract The complexes of synthetic polymer ligands, i.e. poly- l -lysine, poly-4-vinyl-pyridine, poly- N -vinyl-2-methylimidazole and the higher branched polyethyleneimine, with ferri- or ferro-protoporphyrin IX were studied from the standpoint of polymer ligand effects by comparison with those of their monomeric model ligand complexes and poly-γ-benzyl- l -glutamate containing an imidazole nucleus at the chain end. The coordination numbers and formation constants were determined optically and their structures were also estimated. The coordination number of a poly- l -lysine complex was two, but those of other polymer ligand complexes were one. One of the polymer effects, which was indicated by the large formation constants of the polymer complexes, was caused by the increment of the local ligand concentration around the polymer chain. Another was caused by the conformational effect of an α-helical structure in the poly- l -lysine complexes. The interaction of a poly- l -lysine-heme complex with molecular oxygen was also studied. An observed pseudo-allosteric phenomenon may be due to the specific structure of a poly- l -lysine complex which is different from those of other polymer-ligand complexes.

Clearance and tissue distribution of functionalized polymeric liposomes from the blood stream of rats

Polymeric liposomes containing a synthetic porphinato-iron-imidazole complex (hemoglobin or red blood cell model) were labeled by introducing 1,2-di[1-14C]palmitoyl-sn-glycero-3-phosphocholine into their polymerized bilayers. After intravenous injection into rats, their clearance from a blood stream was measured. The apparent half-life time (50% disappearance time) was about 14 +/- 2 h. Their tissue distribution was determined with time by whole autoradiographic measurement.

Metal-ligand bonding properties of double-sided porphyrin complexes : influence of bulky ester groups

Metal–ligand bonding properties of double-sided porphyrinato-iron(II) and -cobalt(II) complexes have been characterized by ESR, IR, and Mossbauer spectroscopy. The smaller AN value for a 1-methyl-imidazole (mim) adduct of 5,10,15,20-tetra(2,6-dipivaloyloxyphenyl)porphyrinatocobalt(II) compared to that of 5,10,15,20-tetra(2,6-di-tert-butylacetoxyphenyl)porphyrinatocobalt(II) suggested that the cobalt–imidazole bond is weak. The ESR spectrum of the dioxygenated double-sided series in fluid toluene indicated that an electrostatic interaction between the bound dioxygen and the ester fences was rarely found. The relaxation of steric strain on the rear side of the ring plane for axial imidazole bonding resulted in a lowering of the bound CO and O2 stretching frequencies of iron(II) complexes. This indicates that the π-back donation from the dπ orbital of the iron to the π* orbital of the bound gaseous ligand could be controlled by the strength of the iron–imidazole bonding, which is regulated by the structure of the rear pocket on the macrocycle. The co-ordination structure of various ligands in double-sided porphyrinatoiron complexes is also discussed by means of Mossbauer parameters.

Kinetics of binding of O2 and CO to ‘double-sided’ porphyrinatoiron(II) complexes

The kinetics of binding of O2 and CO to double-sided porphyrinatoiron(II) complexes having ester pockets on both sides of the porphyrin plane has been studied. The specific environment created by the four ester groups around the central iron(II) ion of 5,10,15,20-tetrakis(2,6-di-tert-butylacetoxyphenyl)porphyrinatoiron(II)2 results in binding which is not affected by solvation. The lower binding affinity for CO of 5,10,15,20-tetrakis(2,6-dipivaloyloxyphenyl)porphyrinatoiron(II)1 compared to that of 5,10,15,20-tetra (o-pivalamidophenyl)porphyrinatoiron(II) is attributed to the unfavourable steric repulsions between the axial imidazole ligand and the pivaloyloxy groups, and is reflected in decreased association and increased dissociation rates. On the other hand, axial base ligation to 2 is not inhibited by the tert-butylacetoxy groups. Therefore, the lower binding affinity for O2 exhibited by 2 compared to that of an amide fenced porphyrin complex is ascribed to the loss of local polarity in the cavity. The less-polar ester groups of the double-sided porphyrinatoiron complex result in an increased rate of dissociation of O2. The activation energy for gaseous ligand association to complex 2 was determined.

Synthesis of polymerizable glycerophosphocholines and their polymerized vesicles

SummaryThree types of polymerizable glycerophosphocholines have been prepared. They have a styrene group through a spacer having a ketone, ether or amide group. The ketone-and ether-type compounds form nonpolymerized and polymerized vesicles depending on the chain length of the alkyl group at the 2-position of glycerol. The polymerized vesicles are stable for months.

Polymerizable glycerophosphocholines containing terminal 2,4-hexadienyloxy groups and their polymerized vesicles(1)

SummaryPolymerizable glycerophosphocholines containing one or two 2,4-hexadienyloxy groups at the terminal of the acyl chains were prepared. Those were 1-[11-(2,4-hexadienyloxy)undecanoyl]-2-0-alkyl-rac-glycero-3-phosphocholines 1, 1-acyl-2-[11-(2,4-hexadienyloxy)undecanoyl]-sn-glycero-3-phosphocholines 2 and 1,2-bis[11-(2,4-hexadienyloxy)undecanoyl]-sn-glycero-3-phosphocholine 3. Those having one hexadienyloxy group formed small unilamellar vesicles. One having two groups formed lipid bilayers, but not unilamellar vesicles. 1 and 2 could form stable microcapsules (polymerized vesicles) with the diameters ranging from 20 to 40 nm.

Interactions of functionalized polymeric liposomes having a porphinato-iron complex with some biological cells and components in vitro

The hemocompatibility of functionalized polymeric liposome particles (diameter: 20-32 nm), which have a synthetic porphinato-iron complex in their polymerized bilayers and can carry oxygen, was studied in vitro. The ultramicroparticles did not induce hemolysis, platelet aggregation and plasma coagulation directly and were stable against hydrolysis by phospholipases A2 and D.

Cooperative reactions of poly-l-lysine-heme complex with molecular oxygen, carbon monoxide or cyanide ion

The interaction of the alpha-helical poly-L-lysine-heme complex with molecular oxygen, carbon monoxide, or cyanide ion was studied. Binding equilibrium curve and activation parameters for the reactions were determined. Sigmoid responses were observed for the absorption of molecular oxygen or carbon monoxide by the complex and the cooperative parameter was found to be 2.1. This indicated a cooperative interaction between hemes situated on a cylindrical alpha-helix of poly-L-lysine. But those of other polymer-ligand-heme complexes were 1.0. The cooperative reaction mechanism, in which an alpha-helical poly-L-lysine plays an important role, was suggested.