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

Abstract

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.