Synthetic exploration of the binary cadmium-quinic acid system linked to in vitro cytotoxicity and chelation cytoprotection investigation

Abstract

In order to investigate the structure-specific bioactivity of Cd(II) in a cellular environment and delve into the associated biomolecular interactions, binary systems of that metal ion in the presence of the physiological naturally-occurring α-hydroxycarboxylic acid quinic acid were examined synthetically in a pH-specific mode. Two discrete polymeric compounds [Cd(C7H11O6)2]n·n/2H2O (1) and [Cd(C7H11O6)2]n·nH2O (2) were isolated and characterized through elemental analysis, FT-IR, NMR, TGA, and X-ray crystallography. Despite their discrete solid state metal-binding ligand coordination modes and lattice architecture, ESI-MS studies on 1 and 2 showed that both give rise to the same species upon dissolution in water. In vitro biological investigation of the toxicity profile of 2 in two cell lines, 3 T3-L1 and Saos-2, point out the influence of the coordination environment of Cd(II) on cell survival, migration and cellular morphology. The in vitro cytotoxic work showed a concentration- and tissue-specific pattern for the Cd-quinate system. Finally, the cytoprotective role of the chelator agent EDTA was investigated in these cell lines at various concentrations of 2, thereby providing insight into Cd(II) interactions with cellular targets compromising cellular integrity. The collective results, signify the a) importance of the aqueous chemistry of Cd(II) with biologically significant substrates, leading to discrete and isolable architectures reflecting binary Cd(II)-quinate composition, b) formulation of the cytotoxicity profile, based on well-defined Cd(II) species, and c) selection and use of appropriately configured organic chelators into future research linked to the development of preventive and/or therapeutic approaches pertaining to Cd(II) (de)toxification processes.