Abstract:
Complexes of iron(II), cobalt(III) and nickel(II) with 4-(4-methoxyphenyl)-2-(2-(1-(pyrazin- 2yl)ethylidene)hydrazinyl)thiazole (PyztH) have been synthesized and characterized by elemental analyses, spectroscopic methods, CV measurements and a DFT study. The crystal and molecular structures were
determined by the X-ray diffraction method. The complexes have the compositions [Fe(Pyzt)2]Br2 (1), [Co(Pyzt)2]PF6 (2) and [Ni(Pyzt)(PyztH)]ClO4 (3), with an approximate octahedral environment around the metal centre with NNN donor atoms from the two coordinating ligands. The complexes belong to the triclinic crystal system and crystallize in the space group P-1. Complex 1 is stabilized by strong hydrogen bonds, whereas the stability of complexes 2 and 3 is associated to p–p stacking interactions. The chemical reactivity, frontier orbital picture and energies of the HOMO and LUMO of the complexes have
been estimated by a DFT study. The complexes are redox active species and respond with a quasi-reversible redox process. The cytotoxicity of the complexes was tested against U-937 human monocytic cells
and shows IC50 values of 132 (for 1), 45 (for 2) and 162 mM (for 3). A LDH release assay indicates that 2
and 3 show apoptosis in the tumour cell. Complex 2 induces apoptosis by disrupting the mitochondrial
membrane potential and homeostasis leading to cytotoxicity, as envisaged by PARP cleavage. Complexes
1, 2 and 3 show high binding constants (2.01 106 M1 for 1, 1.18 107 M1 for 2 and 2.90 107 M1 for
3) with CTDNA which attest the groove binding nature of the complexes with DNA. The compounds also exhibit a remarkable zone of inhibition against specific tested bacterial and fungal strains. Based on the results, the cobalt complex (2) shows the best antitumor and antimicrobial activity among the complexes under investigation.
