Abstract
Organic crystals hold a significant importance in pharmaceuticals, biological systems and functional materials. In the present study, a tricyclic aromatic structure, tetrahydrocarbazole (THC), incorporating a nitrile functionality was synthesized via the Fischer indolization of 4-hydroxycyclohexanone with 4hydrazinobenzonitrile hydrochloride in 70% yield. The detailed description of noncovalent interactions of various types and strengths in the crystal structure of tetrahydrocarbazole-carbonitrile was investigated using a combination of experimental and theoretical methods. The supramolecular assembly of THC involved the extensive network of N -H...O and O -H...N hydrogen bonds, and weaker 2r...2r and C -H...2r contacts. The nature of noncovalent interactions was visualized using molecular electrostatic potential whereas QTAIM and NCIPlot methods revealed the energetic features of 2r-stacking and H-bonding in the supramolecular assemblies of tetrahydrocarbazole-carbonitrile. In vitro evaluation of urease inhibitory potential of target compound revealed a 4-fold strong inhibition (IC 50 = 5.26 +/- 0.10 mu M) compared to standard drug (thiourea; IC 50 = 22.3 +/- 1.06 mu M). Finally, molecular docking analysis showed significant interactions of target compound with various active site amino acids of Jack bean urease. (c) 2023 Elsevier B.V. All rights reserved.