Energetically significant cooperative π-stacked ternary assemblies in Ni(II) phenanthroline compounds involving discrete water clusters: Anticancer activities and theoretical studies

Two new coordination compounds viz. [Ni(phen)(2)(NO3)](NO3)center dot 4H(2)O (1) and [Ni(phen)(2)(H2O)Cl]Cl center dot 4H(2)O (2) (phen = 1,10-phenanthroline) have been synthesized and characterized using elemental analysis, TGA, PXRD, electronic, FT-IR spectroscopy and single crystal X-ray diffraction techniques. Crystal structure analysis reveals the formation of discrete water and anion-water clusters that contribute to the layered assemblies of the compounds. Moreover, the enclathration of (H2O)(4) cluster in the layered assembly of 2 also provides rigidity to the crystal structure. Unconventional anion-n - interaction is also observed in compound 1 involving the n-system of the chelate ring of coordinated phen. Detailed structural investigation reveals the presence of biologically relevant cooperative pi-stacked (pi-pi)(1)/(pi-pi)(2)/(pi-pi)(1) ternary assemblies in both the compounds. Interestingly, DFT calculations reveal that (pi-pi)(2) binding mode in 2 is energetically significant than in compound 1 which is further analyzed by NCI plot index computational tool. The compounds have been screened for anticancer activities considering cell cytotoxicity and apoptosis in Dalton's lymphoma (DL) malignant cancer cell line. The complexes significantly inhibit cell viability by inducing apoptotic cell death in cancer cell lines with negligible cytotoxicity in normal cells. DNA ladder assay results in the degradation of genomic DNA into small inter-nucleosomal fragments (damage DNA) which is a biochemical hallmark of DL cells undergoing apoptosis. Lactate dehydrogenase (LDH) leakage assay also reveals the release of the intracellular enzyme LDH from DL cells indicating the irreversible cell death involving cell membrane damage. The molecular docking simulations reveal that the compounds interact and accommodated well with the active site of anti-apoptotic BCL proteins. Structure activity relationship (SAR) analysis based on pharmacophore modelling reveal that the molecular features of the compounds play important roles in the biological activities. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Two new coordination compounds were synthesized and characterized, showing different water and anion-water clusters formation in the crystal structures with biological active pi-stacked ternary assemblies. These compounds exhibit anticancer activity against DL malignant cancer cell line by inducing apoptotic cell death.