Chemical and in vitro study of the potential of 3-(aryl)-2-sulfanylpropenoic acids and their Zn(II) complexes as protective agents against cadmium toxicity

The free H2xspa ligands [xspa = pspa, Clpspa, tspa or fspa where p = 3-(phenyl), Clp = 3-(2-chlorophenyl), t = 3-(2-thienyl), f = 3-(2-furyl) and spa = 2-sulfanylpropenoato], their Zn(II) complexes of formula [HQ]2[Zn(xspa)2] (HQ = diisopropylammonium) and the Cd(II) equivalents were prepared and characterized by elemental analysis and by IR, Raman and NMR (1H, 13C) spectroscopy. X-Ray studies of the crystal structures of [HQ]2[Zn(pspa)2], [HQ]2[Zn(Clpspa)2], [HQ]2[Zn(tspa)2] and [HQ]2[Zn(fspa)2] show that the zinc atom is coordinated to two O atoms and two S atoms of the ligands in a distorted tetrahedral ZnO2S2 environment. In the structures of [HQ]2[Cd(pspa)2] and [HQ]2[Cd(Clpspa)2] the cadmium atom is coordinated to three S atoms and two carboxylato O atoms of the ligands in a distorted trigonal bipyramidal environment. The interchange of ligands between Zn(II) and Cd(II) was studied by 113Cd NMR spectroscopy. The in vitro protective effect of H2xspa and their Zn(II) complexes against Cd toxicity was investigated using the human hepatocarcinoma HepG2 cell line and the pig renal proximal tubule LLC-PK1 cell line. The incorporation of Zn(II) was found to be relevant in the case of H2pspa, with an increase observed in the cell viability of the LCC-PK1 cells with respect to the value for the free ligand.