Ternary Pt(II)-amino acid-nucleotide complexes: kinetics of formation

Ternary complexes of Pt(II) with the nucleotides 5′-GMP, 3′-GMP and 5′-dGMP (GMP=guanosinemonophosphate), and with the amino acids N_α-BOCL-histidine, N_α-BOC-L-methionine and 1-methylimidazole (1-MeIm) were studied as models for Pt mediated DNA-protein crosslinks. The triamine complexes [PtAm₂(L)Cl]⁺ (where Am₂=cis- or trans-(NH₃)₂ or ethylenediamine and L=1-MeIm or N_α-BOC-L-his-N3) react readily with the mononucleotides 5′-GMP, 3′-GMP and 5′-dGMP to form the ternary crosslinked complexes PtAm₂(L)(nucleotide). The 5′-nucleotides react faster than their 3′ counterparts towards either triamine complex. Kinetic studies by ¹H NMR show that cis-[PtAm₂(1-MeIm-N3)Cl]⁺ reacts with 5′-GMP faster than the trans isomer (second order rate constants k₂=0.756 and 0.358 M^-1 s^-1, respectively) and that the ethylenediamine complex is faster than both (k₂=1.09 M^-1 s^-1).