Phenanthroline-based Ni(II) coordination compounds involving unconventional discrete fumarate-water-nitrate clusters and energetically significant cooperative ternary π-stacked assemblies: Antiproliferative evaluation and theoretical studies

• Published in: Journal of molecular structure 2022-01, Vol.1248, p.131424, Article 131424
• Main Authors: Nath, Hiren, Sharma, Pranay, Frontera, Antonio, Barcelo-Oliver, Miquel, Verma, Akalesh K., Das, Jumi, Bhattacharyya, Manjit K.
• Format: Article
• Language: English
• Subjects: Cooperative ternary π-stacked assemblies; Cytotoxicity; Fumarate-water-nitrate cluster; Infinite cluster; SAR features
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131424

•Phenanthroline-based coordination compounds of Ni(II).•Energetically significant cooperative π-stacked assemblies.•Unconventional fumarate-water-nitrate and infinite nitrate water clusters.•DFT calculations and Structure Activity Relationship.•Apoptosis assay in Dalton's Lymphoma cancer cell lines. Two new Ni(II) coordination complexes involving fumarate and 1,10-phenathroline viz.; [Ni2(phen)2(µ-fum)(H2O)6](fum)·6H2O (1) and [Ni(phen)2(H2O)2](0.5 fum)(NO3)·4H2O (2) (fum = fumarate, phen = 1,10-phenanthroline) have been isolated in aqueous medium at room temperature. Crystal structure analyses of the compounds reveal the presence of cooperative (π–π)2/(π–π)1/(π–π)2 stacked ternary assemblies which provide stabilities to the layered architectures. The lattice water and the large counter anions in the lattice of the compounds are involved in the formation of unconventional discrete cyclic fumarate-water, fumarate-water-nitrate clusters and infinite nitrate-water 1D chains that are very scarcely reported in the literature. The energetically significant π-stacked dimers observed in the biologically relevant ternary assemblies of the crystal structures are further studied theoretically using DFT calculations and NCI plot index computational tools. DFT calculations reveal that the cooperative (π–π)2 binding mode of compound 1 is energetically more significant than (π–π)1 Moreover, the study also reveals that for the equivalent cooperative (π–π)1 stacking interactions in both the structures, the energy is unexpectedly higher for compound 2 than that observed for compound 1. Both the compounds induce significant cytotoxicity in Dalton's lymphoma (DL) cancer cells by inducing apoptotic cell death with negligible cytotoxicity in normal cells. Decrease in the mitochondrial membrane potential (MMP) of DL cells after treatment with the compounds also corroborates the apoptotic cell death. The molecular docking and pharmacophore features reveal that the compounds interact and accommodated well with the active sites of anti-apoptotic proteins. Phenanthroline-based Ni(II) compounds involving unconventional discrete fumarate-water clusters and infinite nitrate-water chains with energetically significant and biologically relevant cooperative (π-π)2/(π-π)1/(π-π)2 ternary assemblies. [Display omitted]