Platinum interactions with nucleic acids: insights from model compounds

Abstract

A systematic review of the molecular structures of a large number of platinum(II) complexes with purine and pyrimidine bases and their nucleosides and nucleotides is presented. From these studies it is evident that the endocyclic nitrogen donor atoms of the heterocyclic purine and pyrimidine bases are dominant metal binding sites for Pt(II). Secondary interactions involving the exocyclic functional groups of the bases and the phosphate moiety of nucleotides are also noted. For Pt(II) complexes containing two adjacent (cis) bases, it is further indicated that intracomplex and intercomplex base-base interactions are of particular importance, giving rise in some cases to discontinuous helical arrays of Pt(II) complexes. These helical arrays may provide some insights into platinized-DNA polymers. Attention is also given to polynuclear species which are models for the family of mixed-valent platinum-pyrimidine blues. Finally, an attempt is made to extend the results of small molecule studies to give insights into the general area of Pt(II)-DNA chemistry and, in particular, the mode of action of the active anti-neoplastic agent cisPt.