Insight into structural topology and supramolecular assembly of tetrahydrocarbazole-carbonitrile: On the importance of noncovalent interactions and urease inhibitory profile

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 4-hydrazinobenzonitrile 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 NH…O and OH…N hydrogen bonds, and weaker π…π and CH…π contacts. The nature of noncovalent interactions was visualized using molecular electrostatic potential whereas QTAIM and NCIPlot methods revealed the energetic features of π-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 (IC50 = 5.26 ± 0.10 µM) compared to standard drug (thiourea; IC50 = 22.3 ± 1.06 µM). Finally, molecular docking analysis showed significant interactions of target compound with various active site amino acids of Jack bean urease.