Diorganotin(IV) antitumor agent. (C2H5)2SnCl2 (phen)/nucleotides aqueous and solid-state coordination chemistry and its DNA binding studies
Published on Nov 1, 1996in Journal of Inorganic Biochemistry 3.06
· DOI :10.1016/0162-0134(96)00039-6
Abstract This contribution reports a solution and solid-state study of the aqueous nucleotide coordination chemistry of the dieihyltin(IV) antitumor agent, (C 2 H 5 )2SnC1 2 (phen). [trans-en 2 OS(η-H 2 ] (CF 3 SO 3 ) 2 , a versatile 1 H NMR probe for biomolecules, is first used to investigate the interaction of (C 2 H 5 ) 2 SnC1 2 (phen) with DGMP in neutral aqueous solution, and then the synthesis of mixed-ligands complexes formulated as (C 2 Hn5) S nC1(phenXNu) (Nu is nucleotide) by reactions of (C 2 H 5 ) 2 SnC1 2 (phen) with equimolar nucleotides under biologically relevant conditions is described. The new complexes were characterized by 500 MHz 1H, 31 P NMR spectra; these spectroscopic data suggest that one of cis-chloro atoms in (C 2 H 5 ) 2 SnC1 2 (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, fluorescence and cyclic voltammetric methods, viscosity determination, as well as agrose gel electrophoresis of superhelical pBR322 plasmid DNA were used to study the interaction of (C 2 H 5 ) 2 SnCl 2 (phen) with DNA. The results indicate that (C 2 H 5 ) 2 SnCl 2 (phen) binds to DNA by double modes. The drug first reacts electrostatically with the sugar-phosphate backbone of DNA; this results in changes of DNA conformation, and then phen ligand can intercalate into double-helix DNA and cause unwinding of the DNA.