Ni(ii)/Cu(ii)/Zn(ii) 5,5-diethylbarbiturate complexes with 1,10-phenanthroline and 2,2′-dipyridylamine: synthesis, structures, DNA/BSA binding, nuclease activity, molecular docking, cellular uptake, cytotoxicity and the mode of cell death

Abstract

New 5,5-diethylbarbiturate (barb) complexes of Ni(II), Cu(II) and Zn(II) with 1,10-phenanthroline (phen) and 2,2′-dipyridylamine (dpya), namely [Ni(phen-κN,N′)₃]Cl(barb)·7H₂O (1), [Cu(barb-κN)(barb-κ²N,O)(phen-κN,N′)]·H₂O (2), [Cu(barb-κN)₂(phen-κN,N′)] (2a), [Zn(barb-κN)₂(phen-κN,N′)]·H₂O (3), [Ni(barb-κ²N,O)(dpya-κN,N′)₂]Cl·2H₂O (4), [Cu(barb-κ²N,O)₂(dpya-κN,N′)]·2H₂O (5) and [Zn(barb-κN)₂(dpya-κN,N′)] (6), were synthesized and characterized by elemental analysis, UV-vis, FT-IR and ESI-MS. The structures of the complexes were determined by X-ray crystallography. Notably, 3 and 6 were fluorescent in MeOH : H₂O at rt. The interaction of the complexes with fish sperm (FS) DNA and bovine serum albumin (BSA) was investigated in detail by various techniques. The complexes exhibited groove binding along with a partial intercalative interaction with DNA, while the hydrogen bonding and hydrophobic interactions played a major role in binding to BSA. It is noteworthy that 2 exhibited the highest affinity towards DNA and BSA. Enzyme inhibition assay showed that 1–4 show a preference for both A/T and G/C rich sequences in pUC19 DNA, while 5 and 6 display a binding specificity to the G/C and A/T rich regions, respectively. These findings were further supported by molecular docking. The cellular uptake studies suggested that 2 was deposited mostly in the membrane fraction of the cells. Among the present complexes, 2 exhibited a very strong cytotoxic effect on A549, MCF-7, HT-29 and DU-145 cancer cells, being more potent than cisplatin. Moreover, 2 induces cell death through the apoptotic mode obtained by flow cytometry.