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 N[sbnd]H…O and O[sbnd]H…N hydrogen bonds, and weaker π…π and C[sbnd]H…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.