A study on interwoven hydrogen bonding interactions in new zidovudine-picric acid (1:1) cocrystal through single crystal XRD, spectral and computational methods

High throughput of cocrystals furnishes information on the proximity of an Active Pharmaceutical Ingredient (API) and coformer. In this paper, the mechanochemical synthesis of 1:1 cocrystal of anti-HIV drug Zidovudine (AZT), with Picric acid (PA) is presented. The single-crystal X-ray diffraction confirms that cocrystal is crystallized in the monoclinic crystal system (space group P21 ) with one molecule of AZT and a molecule of PA in the asymmetric unit. The molecular interactions in the crystal structure were analyzed by considering short contacts and intermolecular contacts using quantum topological atoms in molecules (QTAIM) and Hirshfeld surface methods. In the crystal structure of AZT-PA, intermolecular hydrogen bonds (N-H center dot center dot center dot O, O-H center dot center dot center dot O, C-H center dot center dot center dot O, and C-H center dot center dot center dot N) and intermolecular interactions (C-O center dot center dot center dot pi, N-O center dot center dot center dot pi and C-H center dot center dot center dot pi) were involved in the formation of supramolecular assembly. The major inter contacts O center dot center dot center dot H and N center dot center dot center dot H contribute 38.4% and 11.1% respectively as resulted from Hirshfeld Surfaces. The cocrystal models were illustrated using density functional theory and the quantum topology. The experimental and theoretical FTIR spectrum of the cocrystal was compared and analyzed. Also, the crystal packing was analyzed using molecular dynamics (supercell model). Additionally, Thermoanalytical methods (DSC/TGA) indicated that the crystallinity of AZT-PA was preserved up to 129 degrees C. (C) 2020 Elsevier B.V. All rights reserved.