DIORGANOTIN(IV) ANTITUMOR AGENT - (C2H5)(2)SNCL2(PHEN) NUCLEOTIDES AQUEOUS AND SOLID-STATE COORDINATION CHEMISTRY AND ITS DNA-BINDING STUDIES/

This contribution reports a solution and solid-state study of the aque ous nucleotide coordination chemistry of the diethyltin(IV) antitumor agent, (C2H5)(2)SnCl2(phen), [trans-en(2)Os(eta-H-2)] (CF3SO3)(2), a v ersatile H-1 NMR probe for biomolecules, is first used to investigate the interaction of (C2H5)(2)SnCl2(phen) with DGMP in neutral aqueous s olution, and then the synthesis of mixed-ligands complexes formulated as (C2H5)(2)SnCl(phen)(Nu) (Nu is nucleotide) by reactions of (C2H5)(2 )SnCl2(phen) with equimolar nucleotides under biologically relevant co nditions is described. The new complexes were characterized by 500 MHz H-1, P-31 NMR spectra; these spectroscopic data suggest that one of c is-chloro atoms in (C2H5)(2)SnCl2(phen) is substituted by nucleotide, and that Sn(IV) is directly coordinated to the phosphate group of the nucleotide. No evidence was found for the coordination via donor atoms of the base. On the basis of the above model studies, absorbance, flu orescence and cyclic voltammetric methods, viscosity determination, as well as agrose gel electrophoresis of superhelical pBR(322) plasmid D NA were used to study the interaction of (C2H5)(2)SnCl2(phen) with DNA . The results indicate that (C2H5)(2)SnCl2(phen) binds to DNA by doubl e modes. The drug first reacts electrostatically with the sugar-phosph ate backbone of DNA; this results in changes of DNA conformation, and then phen ligand can intercalate into double-helix DNA and cause unwin ding of the DNA.