Interaction of Some Non-Platinum Metal Anticancer Complexes With Nucleotides and DNA and The Two-Pole Complementary Principle (TPCP) Arising Therefrom

Abstract

The binding modes of some non-platinum metal anticancer complexes, Cp₂TiCl₂, Cp₂ZrCl₂, (CH₃)₂SnCl₂, (C₂H₅)₂SnCl₂, (C₂H₅)₂SnCl₂(phen) (phen=Phenanthroline) and cis-Ru^IICl₂(DMSO)₃ (DMSO) (cis-RDT) with nucleotides and DNA in aqueous solution at physiological pH values were investigated by various modern techniques. 5'-dGMP with Cp₂TiCl₂ or cis-RDT forms chelate complexes in which both N₇ and phosphate of dGMP bind to the metal center. Whereas Cp₂ZrCl₂ and all the diorganotin compounds can bind dGMP only via the phosphate group. The investigations of the interactions between Cp₂TiCl₂ or (C₂H₅)₂SnCl₂ and DNA indicate that there are two types of binding sites on DNA for Cp₂TiCl₂, i.e., the base nitrogen rings and the phosphate group, while (C₂H₅)₂SnCl₂ can bind to DNA only via the phosphate group. At last, by carefully comparing and analysing the binding modes-activity relationships of the above anticancer complexes and other non-platinum and platinum anticancer complexes, a hypothesis named “Two-Pole Complementary Principle” was put forward.

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