Antiproliferative evaluation and supramolecular association involving electrostatically enhanced π-π interaction in isostructural coordination solids of Mn(II), Co(II) and Zn(II) chlorobenzoates: Experimental and theoretical studies

Three new isostructural coordination solids viz. [Co(3-CNpy)(2)(2-ClBz)(2)(H2O)(2)] (1), [Mn(3-CNpy)2(2-ClBz)(2)(H2O)(2)] (2) and [Zn(3-CNpy)(2)(2-ClBz)(2)(H2O)(2)] (3) (3-CNpy=3-cyanopyridine, 2-ClBz=2-chlorobenzoate) have been synthesized from purely aqueous media and characterized by X-ray crystal structure analysis, FT-IR, electronic spectra and TGA. Several non-covalent hydrogen bonding interactions of the types O-H center dot center dot center dot O, C-H center dot center dot center dot O, C-H center dot center dot center dot N, C-H center dot center dot center dot Cl and pi-pi stacking contacts build up the supramolecular networks in the crystal structures. Electrostatically enhanced p-p interactions are observed in 1-3 between the phenyl rings of 2-ClBz and pyridine ring of 3-CNpy of the monomeric units of the complexes. We have used the molecular DFT calculations to evaluate energetically the strength of these contacts and also to analyze the effect of the metal on the interaction energies. The energetic features of the H-bonding and pi-stacking interactions for 1-3 reveal that the H-bonded assembly is more favorable than the pi-stacked contacts. The electrostatically enhanced energy of the pi-stacking interactions is stronger than that usually observed for pi-stacking interactions involving arenes. The cytostatic potential of all complexes have been studied in Dalton's lymphoma (DL) cell line by MTT assay, apoptosis assay and further corroborated with molecular docking simulation. The complexes exhibit cytotoxicity (similar to 25-30%) through apoptotic cell death with negligible cytotoxicity (similar to 5-10%) in normal PBMC cells. In silico-docking techniques have been performed with apoptosis regulator protein BCL-2 for the identification of critical amino acids and their possible binding affinity with the synthesized complexes. The pharmacophore features based on structure activity relationship (SAR) of the complexes have been identified and the study reveal that the features viz., hydrophobic, aromatic, positive ionizable, negative ionizable, H-bond donor and acceptor and halogen bond donor properties play important role for the biological activities of the complexes.