PREPARATION, CHARACTERIZATION, DNA-BINDING, AND IN-VITRO CYTOTOXICITYOF THE ENANTIOMERS OF THE PLATINUM(II) COMPLEXES L-(R)-3-AMINOHEXAHYDROAZEPINEDICHLOROPLATINUM(II), YL-(R)-3-AMINOHEXAHYDROAZEPINEDICHLOROPLATINUM(II) AND YL-(R)-3-AMINOHEXAHYDROAZEPINEDICHLOROPLATINUM(II) ANDL-(S)-3-AMINOHEXAHYDROAZEPINEDICHLOROPLATINUM(II), YL-(S)-3-AMINOHEXAHYDROAZEPINEDICHLOROPLATINUM(II)

A series of chiral diaminedichloroplatinum(II) complexes derived from [Pt(ahaz)Cl-2] (ahaz = 3-aminohexahydroazepine) have been synthesized and tested for cytotoxic activity. Novel synthetic pathways were devel oped to produce the structural derivatives of the ahaz ligand, with al kyl substituents on the exocyclic nitrogen atom. The platinum(II) comp lexes of these ligands were synthesized and characterized by NMR and C D spectroscopy, confirming isomeric and enantiomeric purity. The cryst al structures of three of these complexes, [Pt(S-meahaz)-Cl-2], [Pt(R- etahaz)Cl-2], and [Pt(S-dimeahaz)Cl-2] (meahaz = N-methylahaz, etahaz = N-ethylahaz, dimeahaz = N,N-dimethylahaz), have been determined to e stablish the orientation of the protons and alkyl substituents on the nitrogen donor atoms. In vitro assays of the cytotoxic activity of the complexes have revealed a significant and reproducible enantioselecti ve trend with the R-enantiomers more active than the S-enantiomers in all cell lines. Increasing the steric bulk on the amine groups was fou nd to have only a modest effect on activity. No enantioselectivity was observed in the binding of R- and S-[Pt(etahaz)Cl-2] to calf-thymus D NA.