Supramolecular assemblies involving unconventional non-covalent contacts in pyrazole-based coordination compounds of Co(II) and Cu(II) pyridinedicarboxylates: Antiproliferative evaluation and theoretical studies

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In vitro antiproliferative activities have been explored in pyrazole-based Co(II) and Cu(II) compounds involving unusual double anion–π, C H⋯π( chelate ) and C H⋯π( carbonyl ) contacts. Two coordination compounds of Co(II) and Cu(II) viz. [Co(2,6-PDC)(Hdmpz) 3 ]·H 2 O ( 1 ) and [Cu(2,6-PDC)(Hdmpz) 2 ] ( 2 ) (2,6-PDC = 2,6-pyridinedicarboxylate, Hdmpz = 3,5-dimethylpyrazole) have been synthesized and characterized using single crystal XRD, elemental analysis, TGA, electronic, FT-IR and 1 H NMR spectroscopy. Crystal structure analysis of 1 and 2 reveals the presence of supramolecular assemblies involving various non-covalent interactions. The crystal structure of 1 is stabilized by a structure guiding hydrogen bonded synthon involving the lattice water molecules and unusual double anion–π interactions involving the carboxylate moieties of 2,6-PDC . Unconventional C H⋯π( carbonyl ) and C H⋯π( chelate ) contacts involving carbonyl moiety and the chelate ring of 2,6-PDC observed in the crystal structure of 2 also provide rigidity to the layered assemblies. Such unconventional C H⋯π contacts involving carbonyl moiety and chelate ring of 2,6-PDC are scarcely explored. DFT calculations in combination with QTAIM and NCI Plot analyses have been performed on supramolecular dimers of the compounds to explore the energetic features of the self-assembled dimers. The large dimerization energies of the dimers indicate the significance of these non-covalent interactions in governing solid state stabilities of the compounds. Antiproliferative evaluation of the compounds considering cell cytotoxicity and apoptosis assays revealed that the compounds induced significant concentration dependent cytotoxicity in Dalton’s lymphoma (DL) cancer cells with nominal effects on normal PBMC cells. Molecular docking and pharmacophore modelling studies of the compounds have been further carried out to establish the structure activity relationship (SAR).