A 500, 400 and 300 MHz proton NMR study of the reaction product of cis-Pt(NH3)2Cl2 or cis-[Pt(NH3)2 (H2O)2] (NO3)2 with the deoxydinucleotide d(GpG): cis-[Pt(NH3)2 d(GpG)] was carried out. Complete assignment of the proton resonances by decoupling experiments and computer simulation of the high field part of the spectrum yield proton-proton and proton-phosphorus coupling constants of high precision. Analysis of these coupling constants reveal a 100% N (C3'-endo) conformation for the deoxyribose ring at the 5'-terminal part of the chelated d(GpG) moiety. In contrast, the 3'-terminal -pG part of the molecule displays the normal behaviour for deoxyriboses: the sugar ring prefers to adopt an S (C2'-endo) conformation (about 70%). Extrapolating from this model compound, it is suggested that Pt chelation by a -dGpdG- sequence of DNA would require a S to N conformational change of one deoxyribose moiety as the main conformational alteration and lead to a kink in one strand of the double-helical structure of DNA.

A conformational study of the double‐stranded decanucleotide d(GCCG*G*ATCGC) · d(GCGATCCGGC), with the G* guanines chelating a cis‐Pt(NH3)2 moiety, has been accomplished using 1H and 31P NMR, and molecular mechanics. Correlation of the NMR data with molecular models has disclosed an equilibrium between several kinked conformations and has ruled out an unkinked structure. The deformation is localized at the CG*G*· CCG trinucleotide where the helix is kinked by approximately 60° towards the major groove and unwound by 12–19°. The models revealed an unexpected mobility of the cytosine complementary to the 5′‐G*. This cytosine can stack on either branch of the kinked complementary strand. The energy barrier between the two positions has been calculated to be ≤ 12 kJ/mol. The NMR data are in support of rapid flip‐flopping of this cytosine. An explanation for the strong downfield shift observed in the 31P resonance of the G*pG* phosphate is given.

Direct evidence for the involvement of thiophene S-oxide as a key primary reactive intermediate in the metabolism of thiophene (1) in rats was obtained from the isolation of two diastereoisomeric thiophene S-oxide dimers, 4a and 4b, both in vitro (oxidation of thiophene with rat liver microsomes) and in vivo (isolation of 4a from rat urine). The structure of these dimers was established after an original preparation of identical samples by oxidation of thiophene with H2O2 and CF3COOH. In fact, the H2O2/CF3COOH system appeared to be the best oxidizing agent for the selective transformation of thiophene to its S-oxide. The complete determination of the structures of 4a and 4b was carried out for the first time by X-ray diffraction for the former and by a sequence of chemical reactions for the latter. The reported results indicate two fates for thiophene S-oxide in vivo: (i) its dimerization via a Diels−Alder reaction and (ii) its reaction with nucleophiles such as glutathione leading eventually to mercapturates. These results together with recent literature data on thiophene derivatives suggest that thiophene S-oxides, a class of reactive intermediates whose chemistry is still not well-known, could play a central role in the metabolism and toxic effects of thiophenes in mammals. This situation would be different from that observed in the metabolism of other aromatic compounds, such as benzene or furan, in which arene oxides are predominant intermediates.