Molecular Mechanics Predictions, Verifications, and Trends for N-acetylmethionine Reactions with Bulky Platinum Compounds

Donald J. Chapman and Kevin M. Williams

Molecular mechanics calculations can be used to rationalize and to predict favorable and disfavorable products of a reaction. Recent studies involved the reaction of N-acetylmethionine with platinum compounds containing N, N, N’, N’-tetramethylethylenediamine (Me₄en) and N, N–diethylethylenediamine (Et₂en) as carrier ligands. Molecular mechanics calculations rationalized NMR data that showed the products to be sulfur-oxygen chelates with a single methionine. The bulk of the alkyl groups on the diamine nitrogen atoms caused severe steric clashes in structures with two sulfur-coordinated methionine residues, indicating such structures would not form. We have utilized molecular mechanics calculations to study platinum complexes containing a variety of diamine carrier ligands with differing amounts of bulk; the results of calculations on these complexes are compared to results for the previously studied ligands. Our calculations indicate that bulk on just one nitrogen atom is generally sufficient to disfavor coordination of a second methionine.