CHEMISTRY

Effects of Amine Ligand Bulk on the Rate of Reaction with DNA and Protein Residues by Platinum Complexes. BECCA DAVIS*, M. SAMUEL BRADLEY, ALLAN P. LAM, and KEVIN M. WILLIAMS, Department of Chemistry, Western Kentucky University, Bowling Green, KY 42101.

We are studying the competition between protein and DNA adduct formation by analogs of the anticancer drug cisplatin. Specifically, we are utilizing platinum complexes containing diamine ligands with varying amounts of bulk. Two representative complexes, Pt(en)Cl₂ and Pt(Me₄en)Cl₂ (en = ethylenediamine, Me₄en = N,N,N’,N’-tetramethylethylenediamine) have been synthesized. These platinum complexes are then reacted with guanosine 5’-monophosphate (5’-GMP) or N-acetylmethionine (N-AcMet), representative DNA and protein targets, respectively. The reactions are monitored by NMR spectroscopy, and the products are identified by comparison of the NMR data of previously characterized platinum complexes with 5’-GMP and N-AcMet. Results from the NMR studies indicate that the presence of bulk in the diamine ligand affects the relative rates of reaction of 5’-GMP versus N-AcMet. Specifically, the bulk appears to affect the rate of reaction with N-AcMet more than the rate of reaction with 5’-GMP.