Self-assembled Cu(ii) and Ni(ii) metallamacrocycles formed from 3,3,3′,3′-tetrabenzyl-1,1′-aroylbis(thiourea) ligands: DNA and protein binding studies, and cytotoxicity of trinuclear complexes

Abstract

Self-assembled metallamacrocyclic Cu(II) and Ni(II) complexes of the types [Cu(L1-O,S)]₃ (1), [Ni(L1-O,S)]₃ (2), [Cu(L2-O,S)]₂ (3) and [Ni(L2-O,S)]₂ (4) [H₂L1 = 3,3,3′,3′-tetrabenzyl-1,1′-terephthaloylbis(thiourea) and H₂L2 = 3,3,3′,3′-tetrabenzyl-1,1′-isophthaloylbis(thiourea)] were synthesized and characterized by analytical, spectroscopic (UV-Vis, FT-IR, mass, ¹H & ¹³C NMR and EPR) and single crystal X-ray diffraction techniques. The crystal structures of [Ni(L1-O,S)]₃ and [Cu(L2-O,S)(Py)]₂ showed the formation of self-assembled 3 : 3 and 2 : 2 metallamacrocyclic Cu(II) and Ni(II) complexes respectively. The binding affinity and binding mode of the trinuclear complexes toward CT DNA were determined by UV-Vis spectrophotometric titrations and the fluorescent indicator displacement (FID) assay. The interaction of the ligand (H₂L1) and the complexes (1 and 2) with BSA was investigated using UV-Vis and fluorescence spectroscopic methods. Absorption and emission spectral studies indicate that the complexes 1 and 2 interact with CT DNA and BSA protein more strongly than their parent ligand. Both the complexes (1 and 2) cleaved the pBR 322 plasmid DNA in the absence of an external agent. Complex 1 [IC₅₀ = 22.36 (A549) and 10 μM (MCF7)] exhibited higher cytotoxicity than cyclophosphamide against A549 and MCF7 cancer cell lines. The IC₅₀ value of 2 (29.24) is lower in the A549 cell line and slightly higher (18.04) in the MCF7 cell line than that of cyclophosphamide [IC₅₀ = 41.84 (A549) and 11.89 μM (MCF7)].