Effect of terminal N-substitution in 2-oxo-1,2-dihydroquinoline-3-carbaldehyde thiosemicarbazones on the mode of coordination, structure, interaction with protein, radical scavenging and cytotoxic activity of copper(ii) complexes

Abstract

Four 2-oxo-1,2-dihydroquinoline-3-carbaldehyde N-substituted thiosemicarbazone ligands (H₂-OQtsc-R, where R = H, Me, Et or Ph) and their corresponding new copper(II) complexes [CuCl₂(H₂-OQtsc-H)]·2H₂O (1), [CuCl₂(H₂-OQtsc-Me)]·2H₂O (2), [CuCl₂(H₂-OQtsc-Et)(CH₃OH)]Cl (3) and [CuCl(H-OQtsc-Ph)]·CH₃OH (4) have been synthesized in order to correlate the effect of terminal N-substitution on coordination behaviour, structure and biological activity. Single crystal X-ray diffraction studies revealed that the complexes 1, 2 and 3 have square pyramidal geometry around the central metal ion. In the complexes 1 and 2, the copper ion is coordinated by the ligand with ONS donor atoms, one chloride ion in apical position and the other chloride in the basal plane. Complex 3 consists of [CuCl₂(H₂-OQtsc-Et)(CH₃OH)]⁺ cation and a chloride as counter ion. The copper ion is coordinated by the ligand with ONS donor atoms and by one chloride ion in the basal plane. One methanol molecule is bonded through its neutral oxygen in the apical position. Complex 4 is square planar with the ligand coordinating through uni-negative tridentate ONS⁻ and by one chloride ion in the basal plane. The binding of complexes with lysozyme protein was carried out by fluorescence spectroscopy. Investigations of antioxidation properties showed that all the copper(II) complexes have strong radical scavenging properties. The cytotoxicity of the complexes 3 and 4 against NIH 3T3 and HeLa cell lines showed that synergy between the metal and ligands results in a significant enhancement in the cell death with IC₅₀ of ∼10–40 μM. A size dependence of substitution at terminal N in the thiosemicarbazones on the biological activities of the complexes has been observed.