SYNTHESIS OF FUNCTIONALIZED PLATINUM COMPLEXES CONTAINING DIMETHYLSULFOXIDE AS LEAVING GROUP - OBSERVATION OF NOVEL STERIC CONTROL OF INTRASTRAND VERSUS INTERSTRAND CROSS-LINKING BY USE OF BULKY LIGANDS

Dinuclear bis(platinum) cations, containing as potential leaving group dimethylsulfoxide (Me,SO), were prepared. The general formula is [{tr ans-Pt(Me(2)SO)(NH3)(2)}2NH2(CH2)(n)NH2](4+). These complexes were fou nd to induce the Z form of poly(dG-dC).poly(dG-dC). The complexes also appear to bind to DNA forming interstrand cross-links by displacement of Me,SO. In aqueous solution, rapid hydrolysis occurs to free diamin e and the trans-[Pt(H2O)(Me(2)SO)(NH3)(2)](2+) cation. In a surprising finding, this monomeric species (as the chloride trans-[PtCl(Me(2)SO) (NH3)(2)](+)) was found to be a much more efficient interstrand cross- linking agent than the parent trans-[PtCl2(NH3)(2)]. Thus, steric cont rol by bulky ligands such as Me(2)SO may be used to affect relative te ndencies to inter- or intrastrand cross-link formation in platinum com plexes.