Supramolecular assemblies involving energetically significant unconventional p(CN)-p and anion-p (nitrile) contacts in Zn(II) coordination compounds: Antiproliferative evaluation and theoretical studies

Two new coordination compounds of Zn(II) involving cyanopyridine ligands viz . [Zn(2,6-PDC) (3-CNpy)(H2O)(2)] (1) and [Zn(4-CNpy)(2)Cl-2] (2) (2,6-PDC = 2,6-pyridinedicarboxylate, 3-CNpy = 3-cyanopyridine, 4-CNpy = 4-cyanopyridine) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (FT-IR, electronic and 1H-NMR) techniques and single crystal XRD. Crystal structure analyses of 1 and 2 unfold the presence of unusual pi(CN)-pi interactions which provide stability to the layered assemblies of the compounds. Anion -n with parallel nitrile-nitrile interactions in 1 and unconventional anion-n(nitrile) with antiparallel nitrile-nitrile interactions in 2 also contribute to the stability of the crystal structures. Antiparallel CO-CO interactions give additional reinforcement to the crystal structure of 1. DFT calculations in combination with MEP surface and NCI plot/QTAIM analyses on different self-assembled supramolecular dimers of the compounds revealed that the unusual CN middotmiddotmiddotn interactions in 1 and Chlorine-n(nitrile) in 2 are energetically significant. The studies also reveal that both H-bonding and n-stacking interactions are energetically important for the stability of the compounds. Compounds 1 and 2 mediated anticancer evaluation on Dalton's lymphoma (DL) cancer cells has been explored considering cytotoxicity and apoptosis assays. The compounds induce significant concentration dependent cytotoxicity in DL cells with negligible effects on normal PBMC cells. Molecular docking studies reveal that the compounds effectively interact with the active sites of antiapoptotic proteins which are actively involved in cancer progression. Pharmacophore features of the structures of the compounds have been finally identified to establish the structure activity relationships (SAR). (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

Two new coordination compounds of Zn(II) with cyanopyridine ligands have been synthesized and characterized. Unusual pi(CN)-pi interactions and anion-n interactions contribute to the stability of the crystal structures. The compounds exhibit significant cytotoxicity and interact effectively with antiapoptotic proteins.