Binuclear Co(II) complexes with macrocycle and carboxylato ligands: structure, cytotoxicity and thermal behavior

Abstract

In vitro cytotoxic evaluation, formation constants and thermal stability of four mixed-ligand Co(II) complexes with tpmc = N,N',N",N'"-tetrakis(2-pyridylmethyl)-1,4,8,11-tetraazacyclotetradecane and carboxylate/dicarboxylate co-ligands of formulas [Co2(benz)2tpmc](ClO4)2•3H2O (1), benz– = benzoate anion; [Co2(L)tpmc](ClO4)2•nH2O, L = pht2– (phthalate dianion), n=2 (2), L = ipht2– (isophthalate dianion), n=4 (3) and L = tpht2–(terephthalate dianion), n=4 (4) are reported. The stoichiometric composition of the compounds in the solution were determined spectrophotometrically using Job's methods. Formation constants, K and Gibbs free energy, ΔG values were calculated. The thermal behavior of the complexes was investigated by simultaneous TG/DSC and TG – MS measurements. The cytotoxic effect of the complexes, the free ligands, the DMSO solvent and cis-platin, as referent cytostatic drug, was evaluated on Human cervix adenocarcinoma (HeLa), human melanoma (Fem-x) and human colon carcinoma (LS174) cell lines. The IC50 values were between 12.7–42.3 μM. The first crystal structure determination of the Co(II) complex [Co2(µ-pht)tpmc](ClO4)2•H2O with boat conformation of tpmc ligand, was also done. The complex crystallizes in monoclinic crystal system, C2/c space group. The geometries around both Co(II) atoms are highly distorted octahedral. The Co(II) ions exhibit CoN4O2 coordination environments with the four nitrogen donor atoms of the tpmc ligand and two oxygen atoms belonging to the one carboxylate group of pht2− ligand. The carboxylate groups of pht2− are coordinated in an endo-bidentate mode. The tpmc ligand adopted a boat conformation in which the two coordinated Co(II) atoms are located on the same side of the ring, with Co•••Co distance amounting 5.4799(5) Å.