Square planar mononuclear Ni(ii) complexes of functionalized 2,2′:6′,2′′-terpyridines: BSA/DNA binding and anticancer activity

Abstract

The nature of heterocyclic ligands and the geometry of coordination complexes play important roles in biological activities. In this regard, a series of functionalized 2,2′:6′,2′′-terpyridine (tpy) ligands (L1–L4) and their respective mononuclear square planar Ni(II) complexes (NiL1–NiL4) were synthesized. The purity of these products was examined using spectroscopic and analytical data. The binding studies of bovine serum albumin (BSA) and DNA with the tpy ligands and their Ni(II) complexes indicated that the Ni(II) complex of tpy-2,6-dimethoxyphenyl 4-methyl-benzenesulfonate exhibited the highest binding affinity (i.e. −9.2 kcal mol⁻¹) among all. Furthermore, cytotoxicity assessments utilizing human hepatocarcinoma (HepG2) and normal Vero cell cultures showcased the potent activity of the NiL1 (L1 = 4-([2,2′:6′,2′′-terpyridin]-4′-yl)-2,6-dimethoxy phenol) complex with an IC₅₀ value of 21.46 ± 3 μM, which was compared with the standard drug cisplatin. In addition, DFT calculations indicated notable variations in the molecular orbital energies (HOMO and LUMO) of the proposed tpy ligands and their respective Ni(II) complexes. Docking simulations demonstrated the competitive binding of these complexes to proteins and DNA. Interactions with BSA and DNA were further examined by employing UV-visible and fluorescence titrations.