Synthesis, characterization, photoluminescence, anti-tumor activity, DFT calculations and molecular docking with proteins of zinc(ii) halogen substituted terpyridine compounds

Abstract

Reactions between halogen substituted terpyridine ligands F- (L¹), Cl- (L²), Br- (L³) and I-4′-phenyl-terpyridine (L⁴) and ZnBr₂ or ZnI₂ led to the formation of complexes [Zn(Br)₂L¹] (1), [Zn(I)₂L¹] (2), [Zn(Br)₂L²] (3), [Zn(I)₂L²] (4), [Zn(Br)₂L³] (5), [Zn(I)₂L³] (6), [Zn(Br)₂L⁴] (7), and [Zn(I)₂L⁴] (8), respectively, which were characterized by elemental analysis, ¹H NMR, IR and single crystal X-ray diffraction. Their photoluminescence properties, solution stabilities, hydrophilicity/lipophilicity properties and anti-proliferative activity against three cancer cell lines as well as structure–function relationships are analyzed. All the complexes, which show high solution stabilities and lipophilicity under determination conditions, reveal much higher antiproliferative activities than cisplatin against the human lung carcinoma cell line (A549), human hepatocellular carcinoma cell line (Bel-7042) and human breast cancer cell line (MCF-7) in vitro. Fluorescence spectroscopy and circular dichroic analysis reveal that the compounds have strong affinity binding with ctDNA and stack onto the base pairs of the ctDNA. The results obtained are further explained in terms of the electronic properties of the compounds by density functional theory (DFT) calculations, and it is found that the halogen anions play critical roles in the antitumor activity of these compounds. Their affinities to HSP90 proteins, ALK, EGFR and HER2 kinases and the binding sites on these proteins have been determined by computational docking analysis, and the results indicate that the only form of their binding is van der Waals forces.