Energetically significant unconventional π-π contacts involving fumarate in a novel coordination polymer of Zn(II): In-vitro anticancer evaluation and theoretical studies

A new fumarato bridged Zn(II) coordination polymer viz. catena[mu-fumaratobis(3,5-dimethylpyrazole)zinc(II) trihydrate],{[Zn-2(mu-fum)(2)(Hdmpz)(4)]center dot 3H(2)O}(n) (1) (where, fum = fumarate, Hdmpz = 3,5-dimethylpyrazole) has been synthesized in purely aqueous medium at room temperature. The compound is structurally characterized by single crystal X-ray diffraction, FT-IR, electronic spectroscopy, PXRD and TGA. The zig-zag polymeric chain of 1 self assembles into a 2D supramolecular network via C-H center dot center dot center dot pi, C-H center dot center dot center dot C, N-H-center dot center dot center dot O and C-H center dot center dot center dot O interactions. Particularly relevant in 1, since in addition to the aforementioned non-covalent interactions, the electron rich pi-system of fumarate is involved in energetically significant unconventional pi-pi contacts with the electron poor pi-cloud of Hdmpz, which have been analyzed by DFT calculations and characterized using the non-covalent interaction (NCI) plot index. The strong H-bond agrees well with the MEP analysis since it is established between the H-bond donor involving NH group of Hdmpz and the H-bond acceptor involving O-atom of carboxylate moiety. The compound has been investigated for anticancer activities considering cell cytotoxicity, apoptosis and molecular docking as parameters in Dalton's lymphoma (DL) malignant cancer cell line and results were compared with cisplatin (reference drug) under the same experimental conditions. Interestingly, negligible cytotoxic effect was observed against normal cells (PBMC) in comparison to the cancer cells (DL). The treatment of the compound caused appearance of apoptotic cells as evident by fluorescence based nuclear morphology study. The in silica study reveals that the compound interacts with the antiapoptotic proteins such as bcl-2, bcl-XL and Mcl-1 which may lead to apoptotic cell death.