Diorganotin(IV) N-acetyl-L-cysteinate complexes: Synthesis, solid state, solution phase, DFT and biological investigations.

Abstract

Diorganotin(IV) complexes of N-acetyl-L-cysteine (H2NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have been synthesized and their solid and solution-phase structural configurations investigated by FTIR, Mössbauer, 1H, 13C and 119Sn NMR spectroscopy. FTIR results suggested that in R2Sn(IV)NAC (R=Me, Bu, Ph) complexes NAC2− behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through estertype carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From 119Sn Mössbauer spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R2Sn(IV) trigonal bipyramidal configuration. In DMSO-d6 solution, NMR spectroscopic data showed the coordination of one solvent molecule to tin atom, while the coordination mode of the ligand through the ester-type carboxylate and the deprotonated thiolate group was retained in solution. DFT (Density Functional Theory) study confirmed the proposed structures in solution phase as well as the determination of the most probable stable ring conformation. Biological investigations showed that Bu2SnCl2 and NAC2 induce loss of viability in HCC cells and only moderate effects in non-tumor Chang liver cells. NAC2 showed lower cytotoxic activity than Bu2SnCl2, suggesting that the binding with NAC2− modulates the marked cytotoxic activity exerted by Bu2SnCl2. Therefore, these novel butyl derivatives could represent a new class of anticancer drugs.