Cytotoxic trans-oriented platinum complexes only form adducts with single-stranded oligodeoxynucleotides.

The reactions of the anticancer complex trans-[PtCl(2)[(E)-HN==C(OMe)Me](2)] (trans-EE) with both single-stranded and double-stranded deoxyribonucleotides have been studied by HPLC and 2D [(1)H,(15)N] HMQC NMR spectroscopy and compared with those of cis-[PtCl(2)(NH(3))(2)] (cis-DDP). Reactions of trans-EE with the single-stranded oligonucleotides d(CCTCGCTCTC) and d(CCTGGTCC) proceed rapidly through solvolysis of the starting substrate and subsequent formation of G-N7/monochloro trans-EE adducts. The rate of reaction is comparable to that of formation of an adduct from trans-EE and the dinuclotide d(ApG). Quite unexpectedly, the double-helical duplexes, d(TATGGTACCATA)(2) and d(TATGGCCATA)(2), with no terminal G residues, are practically inert towards trans-EE, and only minor species (< 5 % as estimated from HPLC traces) appear during 24 h reaction time. However, the duplexes d[(CCTCGCTCTC). (GAGAGCGAGG)] and d(GATAGGCCTATC)(2), which contain both terminal and central G residues, undergo platination only at the terminal, solvent-exposed, G residues, thereby confirming that the interior of the duplex is not accessible to trans-EE due to steric hindrance. In contrast, cis-DDP was found to bind exclusively to the central GG pair in d(GATAGGCCTATC)(2).