CHEMISTRY

Molecular mechanics analysis of bulky platinum complexes with DNA and protein residues. DONALD J. CHAPMAN*, CARRIE ROWAN, and KEVIN M. WILLIAMS, Department of Chemistry, Western Kentucky University, Bowling Green, KY 42101.

It has been found that certain platinum containing compounds act as anticancer drugs or as agents to cleave proteins. In order to find new compounds that can be able to perform the functions of known platinum compounds, molecular mechanics calculations are performed. This modeling helps us pinpoint compounds in order to conserve time and resources that would be spent doing laboratory studies as well as acting as a confirmation for data found in the laboratory. For our modeling we have modified the AMBER force field and tested how our platinum compounds would interact with proteins and DNA. Molecular mechanics analysis of Pt(Me₄en)(methionine)₂ complexes (Me₄en = N,N,N',N'-tetramethylethylenediamine), in which the methionine residues are coordinated via the sulfur atom, revealed significant steric clashes; experimental studies confirmed that such a complex did not form. The non-C₂-symmetrical Et₂en ligand (Et₂en = N,N-diethylenediamine) has bulk on only one of the two amine nitrogens. As a result, conformations of Pt(Et₂en)(methionine)₂ in which the bulk of the methionine ligands is oriented away from the N,N-diethyl side of the Et₂en ligand have relatively few steric clashes. Chelates in which a single methionine residue coordinates to the platinum via the sulfur atom and either a nitrogen or an oxygen atom may have less steric hindrance than the complexes with two methionine residues.