Energetically significant antiparallel π-stacking contacts in Co(II), Ni(II) and Cu(II) coordination compounds of pyridine-2,6-dicarboxylates: Antiproliferative evaluation and theoretical studies

• Published in: Inorganica Chimica Acta 2020-02, Vol.501, p.119233, Article 119233
• Main Authors: Bhattacharyya, Manjit K., Dutta, Debajit, Nashre-ul-Islam, Swah Mohd, Frontera, Antonio, Sharma, Pranay, Verma, Akalesh K., Das, Amal
• Format: Article
• Language: English
• Subjects: Antiproliferative; Antiproliferatives; Apoptosis; Aqueous solutions; Cell death; Chemical analysis; Chemical synthesis; Coordination compounds; Copper; Crystal structure; Cytotoxicity; Dimers; Docking; Hydrogen bonding; Infrared analysis; Nickel; Organic chemistry; Pharmacology; Pyridine dicarboxylate; Single crystals; Stacking; Synthesis; Toxicity; Water chemistry
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2019.119233

Antiparallel π-stacking interactions observed in the solid state structures of three new complexes have been analyzed by DFT calculations, molecular electrostatic potential (MEP) surface and non-covalent interaction (NCI plot) index computational tools. All the compounds interact with anti-apoptotic cancer target proteins and the results are comparable with respective reference inhibitors. [Display omitted] •Supramolecular association in Co(II), Ni(II) and Cu(II) coordination compounds.•Energetically significant antiparallel π-stacking contacts.•DFT calculations and NCI plot analyses.•Anti-proliferative potential and in silico docking simulation.•Pharmacophore and ADMET features based on structure activity relationship (SAR). Three new coordination compounds of types [Co(py)(2,6-PDC)(H2O)2].H2O (1), [Ni(py)(2,6-PDC)(H2O)2].H2O (2) and [Cu(py)(2,6-PDC)(H2O)].2H2O (3) (py = pyridine, 2,6-PDC = Pyridine-2,6-dicarboxylate) have been synthesized from purely aqueous media and characterized using elemental analysis, spectroscopic (IR and electronic) and single crystal X-ray diffraction techniques. Several supramolecular contacts of types OH⋯O, CH⋯O, CH⋯π, CH⋯C and π–π stacking stabilize the crystal structures. The layers in the crystal structures stack in perpendicular direction resulting in 1D channel with enclathrated water molecules. The strength of the antiparallel π-stacking interactions involving the pyridine rings in the supramolecular dimer of the compounds have been evaluated using DFT calculations and the influence of the pyridine coordination to the strength of the stacking assembly have been confirmed. The anti-proliferative potential of the compounds has been studied in Dalton’s lymphoma (DL) cell line by using MTT cell viability assay and apoptosis assay. All the three complexes exhibit short term (24 h) cytotoxicity (∼20–30%) through apoptotic cell death with negligible cytotoxicity (∼5–10%) in normal cells. In silico docking simulation has been performed with apoptosis regulator protein BCL-2 for the identification of possible molecular mode of action of the synthesized complexes. The pharmacophore features based on structure activity relationship (SAR) of the complexes have been identified. The SAR results reveal that the molecular features such as, hydrophobic, aromatic, positive ionizable, negative ionizable, H-bond donor and acceptor and halogen bond donor associated with the structures of the compounds play important role in the biological ac