cis-[PtA2(nucleotide)2] complexes (A2 stands for two amines or a diamine) have been extensively investigated as model compounds for key cisplatin-DNA adducts. All cis-[metal(nucleotide/nucleoside)2] complexes with guanine and related purines characterized in the solid state thus far have the ΔHT conformation (head-to-tail orientation of the two bases and righthanded chirality). In sharp contrast, the ΛHT conformation (left-handed chirality) dominates in acidic and neutral aqueous solutions of cis-[PtA2(5′-GMP)2] complexes. Molecular models and solution experiments indicate that the ΛHT conformer is stabilized by 5′phosphate/N1H hydrogen-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-[PtA2(nucleotide)2] solid-state structures: a ΛHT conformation, very strong hydrogen-bond interactions between the phosphate and N1H 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 ΛHT conformer, global forces rather than local interactions account for the predominance of the ΔHT conformer over the ΛHT conformer in the solid state and in both inter- and intrastrand HT crosslinks of oligonucleotides and DNA.
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