Organometallic complexes with biological molecules: XII. Solid-state and solution studies on dialkyltin(IV)- and trialkyltin(IV)-thiaminepyrophosphate derivatives

Abstract

Dialkyltin(IV) and trialkyltin(IV) derivatives of the coenzyme thiaminepyrophosphate (H2TPP) have been synthesized with general formula R2Sn(HTPP)2·nH2O (Alk = Me, n = 2; Alk = Bu, n = 4) and R3SnHTPP·nH2O (R=Me, n = 2; R = Bu, n = 1), respectively. The solid-state structure of the complexes has been investigated through infrared and Mossbauer spectroscopy. The infrared data suggest the involvement of only phosphate oxygen atoms in the coordination of both dialkyl- and trialkyl-tin(IV) moieties, with phosphate anions behaving as monoanionic bidentate bridging or chelating groups, with the tin(IV) involved in six- and five-fold coordination geometries, respectively, in R2Sn(HTPP)2·nH2O (R = Me, n = 2; R = Bu, n = 4) and R3SnHTPP·nH2O (R = Me, n = 2; R = Bu, n = 1). The 119Sn Mossbauer data, and in particular rationalization of the experimental nuclear quadrupole splittings, Δ, through the point-charge model formalism, suggests the occurrence of an octahedral trans-R2 structure in R2Sn(HTPP)2·nH2O (R = Me, n = 2; R = Bu, n = 4) and a trigonal-bipyramidal structure in R3SnHTPP·nH2O (R = Me, n = 2; R = Bu, n = 1). 1H and 13C NMR spectra, in D2O, suggested that the soluble derivatives, at room temperature, in solution, maintained the solid-state structure. The interactions of dibutyltin(IV)–thiaminepyrophosphate (DBTPP) and tributyltin(IV)–thiaminepyrophosphate (TBTPP) complexes with Bluescript KS(+) plasmid and immortalized 3T3 fibroblasts were studied. Both compounds have a clear inhibitory effect on the growth of immortalized mouse embryonal fibroblasts (NIH-3T3), TBTPP being the much more active. No evidence was found, however, for DNA cleavage by the compounds at molar ratios as high as 1:10 (DBTPP, TBTPP/DNA base pairs). According to our observations, the cytotoxicity of TBTPP does not seem to be based on direct interaction with DNA, but in the presence of TBTPP (1:10, TBTPP/DNA bp), plasmid DNA seems to be more susceptible to cleavage by UV. Copyright © 1999 John Wiley & Sons, Ltd.