Influence of carrier ligand NH hydrogen bonding to the O6 and phosphate group of guanine nucleotides in platinum complexes with a single guanine ligand

Coordinated N,N',N"-trimethyldiethylenetriamine (Me(3)dien) has several pos sible configurations: two have mirror symmetry (R,S configurations at the t erminal nitrogens) and the terminal N-Me's anti or syn with respect to the central N-Me (anti-(R,S) and syn-(R,S) isomers, respectively), and two are nonsymmetrical (R,R and S,S configurations at terminal nitrogens, rac denot es a 1:1 mixture of the two isomers). For each configuration, two,Me(3)dien PtG atropisomers can be formed (anti or syn orientation of central N-Me and G O6, G = guanine derivative), and these can be observed since the termina l N-Me's decrease the rate of G rotation about the Pt-N7 bond. In symmetric al syn-(R,S)-Me(3)dienPtG derivatives with G = 9-EtG and 3'-GMP, the anti r otamer, which can form O6-NH H-bonds, was slightly favored over the syn rot amer but never more than 2:1. This anti rotamer is also favored by lower st eric repulsion between the terminal N-Me's and G O6; thus, the contribution of O6-NH H-bonding to the stability of the anti rotamer could be rather sm all. With G = 5'-GMP, an O6-NH H-bond in the anti rotamer and a phosphate-N H H-bond in the syn rotamer can form, Only the syn rotamer was detected in solution, indicating that NH H-bonds to 5'-phosphate are far more important than to O6, particularly since steric factors favor the anti rotamer. Inte rconversion between rotamers was faster for syn-(R,S) than for rac-Me(3)die n derivatives. This appears to be determined by a smaller steric impediment to G rotation of two "quasi equatorial" N-Me's, both on one side of the pl atinum coordination plane (syn-(R,S) isomer), than one "quasi equatorial" a nd one "quasi axial" N-Me on either side of the coordination plane (me isom er).