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Straightforward Synthesis, Spectroscopic Characterizations, Molecular Docking, Molecular Dynamics Simulations, and Comprehensive DFT Calculations of Novel Tetrazole 1,5 and 2,5-Disubstituted Tetrazole Scaffolds.

Created on 05 Aug 2026

Authors

Riham Sghyar, Ahmed Chelouan, Brahim El Ibrahimi, Olivier Blacque, Basavarajaiah Suliphuldevara Mathada, Prashantha Karunakar, Oussama Moussaoui, Mouad Lahyaoui, Joel T Mague, Ali Aghmiz, Manal El-Gendy, Mohamed Hefnawy, Nada Kheira Sebbar

Published in

ChemistryOpen. Volume 15. Issue 8. Pages e70268.

Abstract

New 1,5- and 2,5-disubstituted tetrazole derivatives were successfully synthesized under phase-transfer catalysis conditions in good to excellent yields (21%-97%). The structures of the obtained compounds were confirmed by 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction analysis. Density functional theory calculations performed at the B3LYP/DNP 3.5 level showed that compound F possesses the smallest HOMO-LUMO energy gap (3.390 eV), suggesting enhanced chemical reactivity. Monte Carlo/SAA simulations demonstrated strong adsorption tendencies on metallic surfaces, particularly for compound 1j on the Fe(110) surface, with an adsorption energy of -229.944 kcal mol-1. Molecular docking investigations against Abl kinase targets demonstrated favorable binding affinities, with docking scores reaching -11.7 and -8.3 kcal mol-1 for the most active derivatives. In addition, 100 ns molecular dynamics simulations confirmed the stability of the 2HZI-3d and 4TWP-2j complexes throughout the simulation period. These findings highlight the potential of the synthesized tetrazole derivatives as promising candidates for further biological and corrosion-related applications.

PMID:
42554420
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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