Synthesis, molecular structure, solution equilibrium, and antiproliferative activity of thioxotriazoline and thioxotriazole complexes of copper(II) and palladium(II)

Preparations of copper(II) and palladium(II) complexes of 4-amino-5-methylthio-3-(2-pyridyl)-1,2,4-triazole (C) and the copper(II) complex of 1,4-dihydro-4-amino-3-(2-pyridyl)-5-thioxo-1,2,4-triazole (HL) are described. These complexes have been characterized by means of spectroscopy and microanalysis. Molecular structures of HL (1), [CuCl2(H2L)]Cl-2H(2)O (2a), cis-[CuCl2(L-1)] (3), and cis-[PdCl2(L-1)] (4) have been determined by single-crystal X-ray diffraction. The HL ligand acts as a N,S bidentate through the thioxo moiety and the exo-amino group whilst the ligand L-1 forms N,N coordination complexes through the pyridine and triazole nitrogen atoms. Speciation in solution of the systems Cu/HL and Cu/L-1 have been determined by means of potentiometry and spectrophotometry as well as for the Cu/L-1/A (HA = glycine) system in order to determine species present at physiological pH. Antiproliferative activity of these complexes and their ligands was evaluated, using the AlamarBlue(TM) Assay, on normal human fibroblasts (HF) and human fibrosarcoma tumor (HT1080) cells. The copper compounds cis-[CuCl2(H2L)]Cl and cis-[CuCl2(L-1)] exerted significant antiproliferative activity of both normal and neoplastic cells; although dose-response experiments revealed that the HT1080 cell line was more sensitive to the tested drugs than normal fibroblasts. (C) 2002 Elsevier Science Inc. All rights reserved.