Energetically significant nitrile•••nitrile and unconventional C-H•••π(nitrile) interactions in pyridine based Ni(II) and Zn(II) coordination compounds: Antiproliferative evaluation and theoretical studies

Two new coordination compounds viz. [Ni(2,6-PDC)(Hdmpz)(H2O)(2)]center dot H2O (1) and [Zn(3-CNpy)(2)Cl-2] (2) (2,6-PDC = 2,6-pyridinedicarboxylate, Hdmpz = 3,5-dimethylpyrazole, 3-CNpy = 3-cyanopyridine) have been synthesized and characterized using elemental analysis, thermogravimetric analysis, electronic, infrared spectroscopy and single crystal X-ray diffraction techniques. Crystal structure analyses reveal the presence of supramolecular assemblies involving interesting dimers with unconventional contacts in the compounds. DFT (Density Functional Theory) calculations on the supramolecular dimers in the crystal structure of 1 reveal that the sum of contributions of anion-pi, pi-pi and other long range interactions due to the approximation of the bulk monomers is energetically significant. Molecular Electrostatic Potential (MEP) surface and Quantum Theory of Atoms in Molecules (QTAIM) analyses on the interesting supramolecular dimers of the crystal structures of 2 reveal the presence of unconventional anion center dot center dot center dot pi contacts involving coordinated chlorido ligands and C-H center dot center dot center dot pi(nitrile) interactions involving the pi-system of the nitrile moiety of 3-cyanopyridine. Remarkably, Atoms in Molecules analysis also confirms the existence of energetically significant unconventional anti-parallel nitrile center dot center dot center dot nitrile interaction in the crystal structure of 2. Cell cytotoxicity of the compounds performed in Dalton's lymphoma (DL) malignant cancer cell line showed effective potency with negligible cytotoxicity in normal cells (similar to 12%). It is interesting that compound 1has excellent cytotoxic potency with IC50 closer to cisplatin and can bind different biological targets with similar signalling pathways. Structure activity relationship (SAR) analyses of 1 and 2 based on pharmacophore modelling reveal that the molecular features associated with the structures of the compounds play important role in the biological activities. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Two new coordination compounds have been synthesized and characterized, showing interesting supramolecular properties with unconventional contacts and good cytotoxic potency. One of the compounds demonstrates cytotoxic potency similar to cisplatin, and may target different biological pathways, with molecular features playing a key role in biological activities.