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 geometry of coordination complexes play an important role in the 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, and the purity of these products was examined by 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 tpy-2,6-dimethoxyphenyl 4-methylbenzenesulfonate Ni(II) complex exhibited the highest binding ability (i.e. -9.2 kcal/ mol) among all. Furthermore, the cytotoxicity assessments utilizing human hepatocarcinoma (HepG2) and plain Vero cell cultures showcased potent activity of the complex NiL1 (L1 = 4-([2,2':6',2''-terpyridin]-4'-yl)-2,6-dimethoxyphenol) with an IC50 value of 21.46 ± 3 μM. and were compared with the standard drug cisplatin and normal cell line (Vero). In addition, the DFT calculations indicated notable variations in the molecular orbital energies (HOMO & LUMO) of the proposed tpy ligands and their respective Ni(II) complexes. Docking simulations demonstrated the competitive binding of these complexes to both protein and DNA. Interactions with BSA and DNA were further examined by employing UV-visible and fluorescence titrations.