CHEMISTRY

Factors affecting the rate of reaction of platinum(II) complexes with DNA and protein targets. BECCA M. SANDLIN*, and KEVIN M. WILLIAMS, Department of Chemistry, Western Kentucky University, Bowling Green, KY 42101-1079.

NMR spectroscopy has been used to observe the effects of amine ligand bulk and hydrogen bonding on the rates of reaction of platinum diamine complexes with DNA and protein residues. The reactions of [Pt(dien)(D₂O)]²⁺ (dien = diethylenetriamine) or [Pt(Me₄en)(D₂O)₂]²⁺ (Me4en = N, N, N’,N’-tetramethylethylenediamine) with 5’GMP (guanosine 5’ monophosphate, a DNA nucleotide) and/or N-AcMet (N-acetylmethionine, an amino acid derivative) have been monitored by NMR spectroscopy. We have utilized kinetic competition experiments in which a platinum complex has been added to a mixture of 5'-GMP and N-AcMet; we have also determined rate constants for the individual reactions. As expected, the bulky [Pt(Me₄en)(D₂O)₂]²⁺ complex reacted slower with both 5'-GMP and N-AcMet than the less bulky [Pt(dien)(D₂O)]²⁺ complex. The bulk of the Me₄en ligand slowed reaction of a second 5’GMP residue more than it slowed reaction with the first; reaction of a second N-AcMet did not occur. In competition studies, it was observed that [Pt(dien)(D₂O)]²⁺ reacted faster with N-AcMet than with 5’-GMP, whereas [Pt(Me₄en)(D₂O)₂]²⁺ had a tendency to react faster with 5’-GMP than with N-AcMet. We are now studying [Pt(en)(D₂O)₂]²⁺ reactivity to determine whether the preference for 5'-GMP is related to amine ligand bulk or to hydrogen bonding.