Platinum Complexes with NH Groups on the Carrier Ligand and with Only One Guanine or Hypoxanthine Derivative. Informative Models for Assessing Relative Nucleobase and Nucleotide Hydrogen-Bond Interactions with Amine Ligands in Solution

Abstract

Complexes of the type syn-(R,S)-Me(3)dienPtL (Me(3)dien = N,N',N' '-trimethyldiethylenetriamine; L = guanine or hypoxanthine derivative) have two rotamers, a feature useful for assessing hydrogen-bond interactions between a Me(3)dien NH group and either the O6 or the phosphate group of the coordinated L. The two rotamers are defined as endo and exo for the rotamer with the six-membered ring of the purine on the same side and on the opposite side, respectively, of the coordination plane as the N-Me's. For L = 5'-GMP and 5'-IMP the endo rotamer is the exclusive form (at neutral and basic pH) or is present at 90% and more (low pH where 5'-phosphate group is protonated). A 5'-phosphate group can be positioned to form a direct H-bond with a Me(3)dien NH group only in the endo form; such an H-bond explains this high endo preference. Such a direct phosphate-NH H-bond is not possible for other complexes used in this study because either L has no phosphate group (9-EtG, Guo) or the phosphate is at the 3'-position (3'-GMP and 3'-IMP), too far for H-bonding. Nevertheless, a preference for the endo rotamer was observed for these L also. This result is opposite to that expected both from potential steric repulsion of the L O6 with the N-Me groups and also from the lack of a potential favorable H-bond interaction between L O6 and a Me(3)dien NH. For the 9-EtG adduct, the temperature dependence of the endo/exo equilibrium and the activation parameters for endo/exo interconversion suggest that the preference for the endo rotamer arises from the hydration of the Me(3)dien NH groups; such hydration is favorable in the endo rotamer. At basic pH, N1H deprotonation increases the H-bond capacity of O6, and the exo rotamer increases in stability, becoming the dominant rotamer for the 9-EtG and Guo adducts. For L = 3'-GMP and 3'-IMP, stabilization of the endo form upon phosphate deprotonation at neutral pH was observed. This result is attributed to an H-bonding network involving water, the 3'-phosphate, and the Me(3)dien NH groups.