The first pure Lambda HT rotamer of a complex with a cis-[metal (nucleotide)(2)] unit: A cis-[Pt(amine)(2)(nucleotide)(2)] Lambda HT rotamer with unique molecular structural features

摘要

cis-[PtA(2)(nucl eotide)21 complexes (A(2) stands for two amines or a diamine) have been extensively investigated as model compounds for key cisplatin-DNA adducts. All cis-[metal(nucleotideucleoside)(2)] complexes with guanine and related purines characterized in the solid state thus far have the Delta HT conformation (head-to-tail orientation of the two bases and righthanded chirality). in sharp contrast, the Lambda HT conformation (left-handed chirality) dominates in acidic and neutral aqueous solutions of cis-[PtA(2)(5'GMP)(2)] complexes. Molecular models and solution experiments indicate that the Lambda HT conformer is stabilized by 5'-phosphate/N1H hydfogen-bond interactions between cis nucleotides with the normal anti conformation. However, this evidence, while compelling, is indirect. At last, conditions have been defined to allow crystallization of this elusive conformer. The structure obtained reveals three unique features not present in all other cis[PtA(2)(nucleotide)(2)] solid-state structures: a Lambda HT conformation, very strong hydrogen-bond interactions between the phosphate and NIH of cis nucleotides, and a very small dihedral angle between the planes of the two guanines lying nearly perpendicular to the coordination plane. These new results indicate that, because there are no local base-base repulsions precluding the Lambda HT conformer, global forces rather than local interactions account for the predominance of the Delta HT conformer over the Lambda HT conformer in the solid state and in both inter- and intrastrand HT crosslinks of oligonucleotides and DNA.