Synthesis, characterization and biological activity of two new polymeric copper(II) complexes with α-ketoglutaric acid thiosemicarbazone

In this paper we describe the synthesis of new copper complexes with alpha-ketoglutaric acid thiosemicarbazone. The crystal structures of the two compounds: [Cu(H(2)ct)Cl](n) [{Cu(H(2)ct)Cl}(2)] (1) and [Cu(Hct)](n).3nH(2)O (2) (H(3)ct = alpha-ketoglutaric acid thiosemicarbazone) have been determined by X-ray and spectroscopic methods. In I two independent copper atoms are present. Cu(I), in a nitrogen- and oxygen-bridged polymer, is a six-coordinated (4+2). Cu(2), five coordinated (4+1), is a chlorine-bridged dimer. In 2 the copper atom presents a penta-coordination, polymeric chains form layers and the -CH2CH2COO- groups bridge copper atoms. In 1 a monodentate and in 2 a syn-anti bidentate bridging carboxylate are present. The biological properties of I and 2 and also of the free ligand (H(3)ct) were tested in vitro and compared on Friend erythroleukemia cells (FLC) and on human leukemia cell lines K562 and U937. On the FLC cells the free ligand does not inhibit cell growth. but increases the DNA synthesise complex I inhibits cell proliferation and increases the DNA synthesis; complex 2 inhibits cell growth, but induces a decrement of DNA synthesis and increases the reverse transcriptase activity. Regarding the human cell lines, both complexes show proliferation inhibition through an apoptosis mechanism on cell line U937. while they have no effects on the K562 line. (C) 2002 Elsevier Science Inc. All rights reserved.