Effects of amine ligand bulk on the rate of reaction of platinum(II) diamine complexes with guanine and methionine residues.

Becca M. Davis and Kevin M. Williams

NMR spectroscopy was used to observe the effects of amine ligand bulk in the reaction of platinum diamine complexes with DNA and protein residues. Also studied are the effects of bulk in kinetic competition experiments. The reactions of [Pt(en)(D₂O)₂]²⁺ (en = ethylenediamine) 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 utilized. [Pt(en)(D₂O) ₂]²⁺ reacted more quickly with both N-AcMet and 5’-GMP than did the bulky [Pt(Me₄en)(D₂O)]²⁺. The bulk slowed reaction of a second 5’GMP residue even more than reaction with the first; reaction of a second N-AcMet does not occur. In competition studies, [Pt(en)(D₂O)]²⁺ reacted faster with N-AcMet than with 5’-GMP, whereas [Pt(Me₄en)(D₂O)]²⁺ reacted faster with 5’-GMP than with N-AcMet. Thus, the presence of bulk may result in a greater preference for reaction with DNA compared to proteins.