CHIRAL SPECIFICITY OF NOVEL PLATINUM COMPLEXES IN THEIR CROSS-MEMBRANE TRANSPORT AND DNA MOLECULAR RECOGNITION

A series of new chiral Pt-complexes has been designed and synthesised. The effects of the chiral features and stereochemistry of newly-synth esised complexes on their anticancer activity, cross-membrane transpor t and DNA molecular recognition have been studied. The effects of chir al specificity on the cross-membrane transport of Pt-complexes were mo nitored by measuring the platinum concentration in the cytosol as a fu nction of time. Specific interaction of DNA with three different chira l complexes were investigated by biomicrocalorimetric and CD technique s, and DNA T-m measurements. R,R-Pt was found to be the most active in its cross-membrane transport and its interaction with DNA, which agre ed with results in the anticancer tests in vitro. Direct evidence for molecular mechanism of DNA specificity of chiral Pt-complexes was foun d by HPLC elucidated by molecular modelling studies.