Jean-Paul Battioni

Soybean lipoxygenase-catalyzed oxidations by linoleic acid hydroperoxide: Different reducing substrates and dehydrogenation of phenidone and BW 755C

Phenidone is not a substrate for dioxygenation by soybean lipoxygenase-1 (L1) but reduces L1Fe(III) into L1Fe(II), as shown by EPR spectroscopy. L1 catalyzes the oxidation of phenidone by 13-HPOD, the hydroperoxide formed by dioxygenation of linoleic acid by L1, with formation of 4,5-dehydrophenidone. Two moles of 13-HPOD are used per mole of phenidone dehydrogenated. Other pyrazoline derivatives such as BW 755C, but also, in a more general manner, different compounds containing phenol, aniline, hydrazine, hydroxylamine or hydrazide functions act as reducing substrates for decomposition of 13-HPOD by L1.

Mode of interaction and apparent binding constants of meso-tetraaryl porphyrins bearing between one and four positive charges with DNA

Meso-substituted porphyrins, ((4-N-methyl-pyridyl)n(Ph)4-n)PH2, n = 1 to 4, bearing between 1 and 4 positive charges have been synthetized and studied for their interaction with Calf Thymus DNA. Competition binding experiments using ethidium bromide or one of its dimers show that these porphyrins and some of their Cu(II) or Fe(III)Cl complexes have apparent binding constants between 3 10(5) and 5 10(7) M-1. Fluorescence energy transfer experiments show that not only the tetracationic previously described porphyrin but also the tri- and dicationic porphyrins are able to intercalate into DNA. These data indicate a greater importance of the polyaromatic porphyrin ring than of the number or position of the positive charges for meso-tetra-arylporphyrin interaction with DNA.

Rapid synthesis of radiolabeled porphyrin complexes for medical application

This invention relates to a novel method for the rapid synthesis of radiolabeled porphyrin complexes which are highly useful for biomedical application, i.e. conjugation to protein antibodies for use in tumor imaging and internal radiation therapy.

Peroxidase-like activity of lipoxygenases: different substrate specificity of potato 5-lipoxygenase and soybean 15-lipoxygenase and particular affinity of vitamin E derivatives for the 5-lipoxygenase

Potato 5-lipoxygenase (5-PLO) catalyzes the reduction of 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13-HPOD) in the presence of vitamin E. I mol of vitamin E is required to consume 2 mol of 13-HPOD. The mechanism of the 5-PLO-catalyzed oxidation of vitamin E by 13-HPOD is similar to that previously established for the soybean 15-lipoxygenase (L-1)-catalyzed oxidation of phenidone by 13-HPOD, and seems to involve a one-electron reduction of the O-O bond of 13-HPOD. 5-PLO and L-1 exhibit very different substrate specificities and pH profiles for their peroxidase-like activity. Actually, among the 20 compounds containing various reducible functions and the 10 derivatives of vitamin E which have been studied, only four products containing hydrophobic long chains, ascorbic acid 6-palmitate, the trolox esters of octanol and undecanol, and vitamin E exhibit high peroxidase-like activities for 5-PLO. On the contrary, much more compounds, even not very hydrophobic, are good substrates for the peroxidase-like activity of L-1.

Efficient metalloporphyrin synthesis under mild conditions using N-benzylporphyrins.

Abstract A general method has been developed for nearly quantitative synthesis of N-benzylporphyrins by use of benzyldiphenylsulfonium tetrafluoroborate. The N-benzylporphyrins (including natural, synthetic, water soluble and non-water soluble porphyrins) insert Cu(II), Co(II), Pd(II) and Ni(II) rapidly and then readily lose the N-benzyl group to give non-N-substituted metalloporphyrins. The reactions of Cu(II), Co(II) and Pd(II) are efficient under mild conditions compatible with biological preparations.

VITAMIN E DERIVATIVES AS NEW POTENT INHIBITORS OF MICROSOMAL LIPID PEROXIDATION

Several synthetic Vitamin E derivatives are strong inhibitors of lipid peroxidation induced in rat liver microsomes either chemically by ferrous ions and ascorbate or enzymatically by NADPH and carbon tetrachloride. The relative activities of these inhibitors are consistent with their intrinsic antioxidant properties, as peroxyl radicals scavengers. Among them, a 3,4-dihydro-6-hydroxy-2H-1-naphtopyran with IC50 around 0.08 microM is one of the most potent yet known inhibitor of lipid peroxidation.

Réactions des dérivés de l'iode(III) avec les ferroporphyrines et le cytochrome P-450: Formation de complexes σ-aryles du fer(III) et de N-aryl-porphyrines du fer(II) à partir de sels de diaryliodonium

Abstract Diaryliodonium salts ArAr′I + X − , such as diphenyliodonium chloride or iodide ( a and 4b ), p -chlorophenyl(2-thienyl)iodonium chloride ( 5 ) and bis(2-thienyl)iodonium chloride ( 6 ), oxidize Fe II (TPP) (TPP = tetraphenylporphyrin) to give the corresponding ferric porphyrin complex. In the presence of an excess of reducing agent (iron powder), compounds 4 and 5 react with Fe(TPP) to give the σ-aryl complexes, Fe III (TPP)(Ar) (with Ar  C 6 H 5 and p -ClC 6 H 4 , respectively). Using of an excess of 4a or 4b , gave in addition the Fe II (N-C 6 H 5 -TPP)(Cl or I) complexes. Reaction of compounds 4 , 5 and 6 with the hepatic cytochromes P-450 in the presence of NADPH or sodium dithionite, also gave σ-aryl ferric complexes characterized by a Sorek peak around 480 nm.

Isolation of σ-alkyl-iron(III) or carbene-iron(II) complexes from reduction of polyhalogenated compounds by iron(II)-porphyrins: the particular case of halothane CF3CHClBr

FeII(TPP)(TPP = tetraphenylporphyrin), in the presence of an excess of sodium dithionite, reacts with CF3CCl3 and halothane CF3CHClBr, leading respectively to the carbene FeII(TPP)(CCICF3) and σ-alkyl-FeIII(TPP)-(CHCICF3) complexes, the latter being the first isolated σ-alkyl-FeIII(porphyrin) complex involving a halogen substituent on the carbon bound to iron.

Synthèse de complexes σ-vinyliques de ferriporphyrines et leur oxydation en N-vinyl-porphyrines: Rétention de la stéréochimie de la double liaison

Various σ-vinyl(meso-tetraarylporphyrin)iron(III) complexes have been obtained by reaction of the vinylic Grignard reagents R1R2CCHMgBr (R1  R2  C6H5, R1  R2  CH3, R1  H, R2 n-C4H9 and R1  n-C4H9, R2  H) with FeIII(meso-tetraarylporphyrin)(ClO4 complexes. The N-vinyl porphyrins derived from these σ-vinyl(porphyrin)iron(III) complexes by monoelectronic FeCl3 oxidation were isolated and completely characterized. This two-step route from vinylic Grignard reagents to the corresponding N-vinylporphyrins occurs with retention of the stereochemistry of the double bond of the starting organometallic compound. It is highly probable that each of the two steps involved occurs with retention of this stereochemistry.

Intermediate formation of a σ-alkyl iron(III) complex in the reduction of 4-nitrobenzyl chloride catalysed by iron(II)-prophyrins

Formation of the σ-alkyl FeIII(TPP)(CH2C6H4NO2-4) complex (TPP = tetraphenylporphyrin) during reduction of 4-nitrobenzyl chloride (1) by sodium ascorbate catalysed by Fe(TPP)(Cl) was detected by visible spectroscopy, and its invollement as an intermediate intne reduction of (1) to 4-nitrotoluene was deduced from a study of the characteristics of this reaction.