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

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.

Automated summary

In this study, a tricyclic aromatic structure, tetrahydrocarbazole (THC), with a nitrile functionality was synthesized, and the noncovalent interactions in the crystal structure of THC were investigated using experimental and theoretical methods. The results showed the presence of extensive N-H...O and O-H...N hydrogen bonds as well as weaker 2r...2r and C-H...2r contacts in the supramolecular assembly of THC. Furthermore, THC exhibited strong inhibitory potential against urease activity. Rating: 8 points.