Synthetic endeavors on cadmium species bearing glycolate and aromatic chelators with structure-specific biotoxic correlations in vitro

Abstract

Cadmium is a well-known metallotoxin widespread in the environment and easily reaching cellular targets in lower and higher organisms, including humans. The form(s) of that metal ion through which it interacts with biomolecular targets in a cellular milieu are critical in cell survival. Poised to investigate the structure-specific activity of Cd(II) in a cellular environment and delve into the associated biotoxic processes, binary and ternary systems of that metal ion in the presence of the physiological α-hydroxycarboxylic acid glycolic acid and aromatic (N,N′)-binders 2,2′-bipyridine (2,2′-bipy) and 4,4′-bipyridine (4,4′-bipy) were examined synthetically in aqueous media and a pH-specific fashion. The arising new materials [Cd(C2H3O3)2]n (1), [Cd(C2H3O3)(C10H8N2)(NO3)]n·nH2O (2), and {[Cd(C2H3O3)(C10H8N2)(H2O)](NO3)}n·2nH2O (3) project coordination polymers, which were physicochemically characterized through elemental analysis, FT-IR, NMR, luminescence and X-ray crystallography. The distinct spectroscopic features of 1–3, with luminescence exemplifying distinct behavior (2,3), further corroborated by crystallographic analysis, lend credence to a structure-specific selection of species employed in ensuing in vitro biological studies. The emerging results in two different cell lines (3T3-L1, Saos-2) reveal a concentration-dependent, structure-specific and cell line-specific toxicity profile of Cd(II), reflecting its coordination composition and formulation, rendering it soluble and bioavailable (1,2). Mechanistic information riding on caspase-dependent investigation unravels that metal ion's specific behavior compromising cell survival and integrity. Employment of ethylenediamine tetraacetic acid (EDTA) a) shows efficient sequestration of Cd(II) away from its toxic reactivity denoting the strength of interactions involved, and b) lends credence to further development of appropriately configured organic binders, selectively providing molecular protection from Cd(II) toxicity.