Comprehensive study of 1,2,4-triazolo[1,5]benzodiazepine derivatives: Synthesis, characterization, X-ray diffraction, DFT calculations, Hirshfeld surface analysis, ADMET properties, and molecular docking

In this research, the synthesis of triazolobenzodiazepine derivatives was achieved through a [3 + 2] cycloaddition reaction between N-(4-bromophenyl)-C-ethoxycarbonylnitrilimine and benzodiazepine 1. The structures of the products, denoted as 3 and 4, were determined using NMR spectroscopy (1H and 13C). However, only one single crystal, corresponding to compound 4, was successfully obtained. Single-crystal X-ray diffraction analysis of compound 4 confirms the proposed structure and accurately determines the stereochemistry, indicating that the styryl group at position 3a and the phenyl group at position 5 are on opposite sides. We compared the spectral data obtained from theoretical calculations with the experimental data. and found high correlation coefficients, indicating a satisfactory reproducibility of both the geometrical parameters and chemical shifts by the computational method used. Additionally, we used Hirshfeld surface analysis to explore the intermolecular interactions within the crystal lattice, providing further understanding of the molecular packing. Additionally, an ADMET study was performed to estimate its toxicity, excretion, metabolism, distribution, and absorption.