J.C. Chottard

Specific platinum chelation by the guanines of the deoxyhexanucleotide d(T-G-G-C-C-A) upon reaction with cis-[Pt(NH3)2(H2O)2](NO3)2☆

Abstract The stoichiometric reaction between d-TpGpGpCpCpA (d(T-G-G-C-C-A)) and cis -[Pt(NH3)2(H2O)2](NO3)2 (8.4 × 10−6 to 1.3 × 10−4M in water at pH 5.5–6) gives a single complex. High pressure gel permeation chromatography and pH-dependent 1H NMR analyses of the nonexchangeable base protons, show that it is a platinum chelate with the cis -PtII(NH3)2 moiety bound to the two N7 atoms of the adjacent guanines. A 3 × 10−3M reaction gives the same platinum chelate, via the formation of intermediate complexes, together with unsoluble adducts.

On the nature and reactivity towards substrates of the active oxygen hemoprotein complexes involved in the reaction of peroxidases and cytochrome P- 450 with two-electron oxidants

Two sets of results are presented which contribute to the understanding of the nature and reactivity of the active oxygen complexes formed during reactions of catalase, horseradish peroxidase, and cytochrome P- 450 with two-electron oxidants. n nThe one-electron oxidation of vinylidene carbene complexes of iron porphyrins [FeII→ Cue5fbCAr2] ← [FeIVue5fbCue5fbCAr2], by FeCl3 or CuCl2, leads to stable complexes which exhibit visible spectra very similar to those of catalase and horseradish peroxidase compounds I. This suggests a common formulation [porphyrin Fe = X] +· for the carbene complexes, X = Cue5fbAr2, and for the hemoprotein compounds I, X = O. n nFrom model studies, evidence has been obtained in favor of the formation of a stable iron-carbene bond after oxidation of 1,3-benzodioxole by the active oxygen cytochrome P-450 complex. n nFrom these data, a stepwise mechanism for substrate oxidation by two-electron oxidants, catalyzed by cytochrome P-450, involving the possible formation of unstable iron—carbon α bond, is proposed. This mechanism exhibits a close similarity with that of hydrocarbon oxidations by peroxy-compounds catalyzed by copper or iron salts.

2-methyl-2-nitrosopropane and nitrosobenzene as nitrogen-bonded platinum(II) ligands. Molecular structure of {PtCl2[(CH3)3C(NO)]2} ☆

Abstract Two series of 2-methyl-2-nitrosopropane and nitrosobenzene complexes of platinum(II) have been synthesized including: {PtCl3[(CH3)3C(NO)]}−K+ (I), [PtCl3(C6H5NO)]−K+(II); various trans- {PtCl2[(CH3)3C(NO)]L} complexes with L ue5fb various pyridines (III (Z)), nitrosobenzene (IV), and 2-methyl-2-nitrosopropane (V); various trans-[PtCl2(C6H5NO)L] complexes with L ue5fb various pyridines (VI (Z)) and nitrosobenzene (VII); trans and cis isomers of [PtCl2−(C6H5NO)(PR3)] complexes (VIII–XI). The X-ray structure of V, which is the first determined for a platinum(II)—nitrosoalkane complex, establishes its trans configuration and the N-coordination of 2-methyl-2-nitrosopropane to the metal. In complexes III (Z), change from 2,4,6-trimethyl- to 4-nitro-pyridine increases the Nue5f8O bond strength of 2-methyl-2-nitrosopropane, but this is not significant in the case of the nitrosobenzene complexes VI (Z). Both X-ray and IR data favour nitrosoalkyl- and nitrosoaryl-platinum rather than platinum nitroxide structures and imply a small back donation from platinum(II) to the nitroso ligands. The nitroso compounds appear to have a π-accepting ability smaller than that of ethylene and larger than that of the pyridines.

A heme model study of carbon tetrachloride metabolism: mechanisms of phosgene and carbon dioxide formation.

Summary A biphasic model system for the cytochrome P450-iron(II)-catalyzed reductions, based on iron-porhyrin partially maintained in the ferrous state in the presence of dioxygen and a reducing agent in excess, is shown to convert CCl 4 mainly to phosgene and products derived from the free radical CCl 3 . The results indicate that phosgene derives from reaction of dioxygen either with intermediate Fe-CCl 3 σ — or Fe ← CCl 2 carbene — complexes, depending upon the nature of the reducing agent. From these results, a mechanism for metabolic conversion of CCl 4 to CO 2 and for some toxic effects of CCl 4 is proposed.

Iron-porphyrin catalysis of the oxidative dealkylation of para-nitro-anisole and 7-ethoxycoumarin by cumylhydroperoxide: a possible model for the corresponding cytochrome P 450-dependent reactions

Abstract A biphasic system containing an iron porphyrin, Fe (TPP) (C1) ∗ or [Fe(TPP)] 2 O, efficiently catalyzes the cumyl-or tertiobutyl-hydroperoxide-supported dealkylation of p-nitroanisole and 7-ethoxycoumarin to the corresponding phenol and formaldehyde. Stoichiometric amounts of iron porphyrin and hydroperoxide give a quantitative reaction. Catalytic amounts of iron porphyrin give reaction rates and yields which are proportional to substrate concentration. With increasing hydroperoxide concentrations, the rates level offto limit values and the yield rapidly decreases. The maximum rates obtained approach those of the reactions mediated by cytochrome P 450-dependent monooxygenases.

Coupure de liaison s silicium—carbone par des complexes du platine(II) : II. Reactions des silanes, CH2CH(CH2)n SiMe3 (n = 0, 1 et 2)

Abstract A fast coordination is the first step of the reaction between vinyl-, allyl- and but-3-ene-1-yl-trimethylsilanes and teh dime [Pt2Cl4(C2H4)2]. It is followed by the cleavage of the activated Sue5f8C bond of the first two silanes. The nature of the Pt(II) complexes giving this reaction and the comparison of their activity with that of protic acids is discussed. It is shown that the cleavage of the Siue5f8C(sp2) bond of but-2-ene-2-yltrimethylsilanes is stereospecific.

Carbon-13 NMR studies of C2H5N13C binding to various hemoproteins.

Abstract The addition of an excess of C2H5N13C to myoglobin and human adult and fetal hemoglobins, gives three characteristic NMR spectra with new 13C resonances respectively at δ = −10,56 ppm, δ = −7,03 and −7,95 ppm and δ = −6,28 and −7,95 ppm (CH3CO2Na as external standard). These signals correspond to the C2H5N13C bound to the Fe(II) of the different heme units, according to CO exchange experiments. Characteristic resonances can be assigned to C2H5N13C bound to α, β and γ subunits. C2H5N13C appears as a more sensitive probe than 13CO for hemoprotein NMR studies.

Coupure de liaisons silicium—carbone par des complexes du platine(II) : I. Coupure des alkyl- et arylsilanes; nature des complexes reactifs

Abstract The reactivity of a series of monomer and dimer complexes of platinum(II) towards cleavage of the silicon—carbon bond of alkyl- and aryl-silanes has been studied. The only active complexes are those of the type [Pt2Cl4(olefin)2]. An explanation is proposed, based on the nature of the reactive entity.

Coupure du dimere bis(methoxy-2 cyclooctene-5-yl) diiodoplatine par des ligands L. Etude et caracterisation par resonance magnetique nucleaire des isomeres formes

Abstract The bridge splitting reaction of the dimer bis[(2-methoxy-5-cyclooctenyl)-iodoplatinum] (I) by various L ligands leads to an equilibrium mixture of the two stereoisomers [(2-methoxy-5-cyclooctenyl)Pt(L)I] (II and III). 1 H and 13 C NMR data allow an unambiguous identification of the configuration of the isomers. Their ratio in the reaction mixture depends on the nature of the ligand L; the stronger its σ-donor character the higher the proportion of the isomer II having L in a cis position to the Pt C σ-bond.

Carbon-13 NMR studies of C2H5N13C bound to hemoproteins — Evidence for a different distal proteic environment in β-chains either isolated or within human hemoglobin

Abstract The previous assignment of the 13 C resonances of C 2 H 5 N 13 C bound to the α and β subunits of human adult hemoglobin (HbA) is confirmed by the study of Hb-S t Louis β 28 (B 10) Leu →Gln. The large chemical shifts differences between the labelled isocyanide in [Fe(II) (protoporphyrin IX) (RN 13 C) (L)] complexes (L = DMSO or N-methyl-imidazole) and in the hemoglobins complexes, suggest that the heme proteic environment interacts with the bound ligand. For both the α and β chains, there is a significant difference between the chemical shifts of C 2 H 5 N 13 C bound to the subunits in HbA or to the isolated chains, this difference being particularly large for the β-chain. However, for each isolated chain, no difference appears for C 2 H 5 N 13 C bound to either the free sulfhydryl form or the p-hydroxymercuribenzoate derivative. This is the first direct evidence, in the completely liganded state, for a difference between the environments of the ligands bound to the β-chain either free or aggregated within the HbA tetramer. From these results and others obtained with the mutants Hb J Calabria β 64 (E8) Gly → Asp, and Hb I Toulouse β 66 (E 10) Lys → Glu, C 2 H 5 N 13 C appears as a sensitive probe for the modifications of the distal environment of the heme, because of its steric interactions with the aminoacids of the heme pocket.