Zinc complexes with cyclic derivatives of alpha-ketoglutaric acid thiosemicarbazone: synthesis, X-ray structures and DNA interactions

Abstract Six new cyclic ligands derived from a-ketoglutaric acid thiosemicarbazone (H3ct) and their zinc complexes have been synthesized and characterized by analytical and spectroscopic (IR and NMR) studies. The X-ray structures of ligands Me-H2ctC (1), Allyl-H2ctc (3) and of complex [Zn(Me-HctC)2(OH2)2] Æ 2H2O (7) have been determined. In complex (7) the zinc atom lies on a twofold axis and is surrounded in a tetrahedral coordination by two water molecules and two carboxylic oxygen donor atoms from the ligand. DNA titration in the UV–visible region and thermal denaturation have been employed to determine the details of DNA binding for the studied compounds. Studies of nuclease activity have also been performed with all our compounds through a gel electrophoresis experiment using plasmid pBR322 showing that no DNA breakings take place. Tests in vitro on human leukemia cell line U937 have been carried out on cell growth inhibition where solubility of the compounds allowed the experiments.