Organometallic Complexes with Biological Molecules: VII. Dialkyl- and Trialkyl-tin (IV)[meso-tetra(4-carboxyphenyl)porphinate] Derivatives: Solid-state, Solution-phase Structural Aspects andIn Vivo Effects

Abstract

The synthesis, the structural features and the in vivo biological activity of diorganotin(IV) and triorganotin(IV) derivatives of [meso-tetra(4-carboxyphenyl)porphine] (H4TPPC) are reported. Derivatives with general formula (R2Sn)2TPPC and (R3Sn)4TPPC (R=Me, Bu, and Ph) were obtained, and the main information extracted from the infrared and Mössbauer spectral data, in the solid state, was in favor of the occurrence of five-coordinated tin(IV) atoms, in a polymeric trigonal-bipyramidal configuration, attained through two differently coordinated, ester-type and chelating respectively, carboxylate anions in [R2Sn]2TPPC, while in [Alk3Sn]4TPPC five-coordination of the tin(IV) atom is reached through bridging carboxylate groups. 1H and 13C NMR spectra, in DMSO-d6 or CDCl3 suggested that the soluble derivatives, at room temperature or at 342 K, were present in solution as simple monomers. The interactions of (trimethyltin)4[meso-tetra(4-carboxyphenyl)porphinate] (TMTPPC) and (tributyltin)4[meso-tetra(4-carboxyphenyl)porphinate] (TBTPPC) with Bluescript KS(+) plasmid and cultured 3T3 fibroblasts were studied. Both compounds have a clear inhibitory effect on the growth of cultured mouse embryonal fibroblasts (NIH-3T3), TBTPPC being much more active. No evidence was found, however, for DNA cleavage by the compounds at molar ratios as high as 1:10 (TMTPPC, TBTPPC/DNA base pairs). According to our observations, the cytotoxicity of TBTPPC and TMTPPC does not seem to be based on direct interaction with DNA. © 1997 John Wiley & Sons, Ltd.