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-RuIICl2(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.