Experimental and theoretical investigation of a benzazole-2-carboxamide derivative: Crystal structure, spectroscopic characterization, antiproliferative evaluation, and molecular docking studies

In this study, the structural, spectroscopic, and biological properties of a benzazole-2-carboxamide derivatives, N-(1H-benzo[d]imidazole-2-yl)-4-chlorobenzamide, were comprehensively investigated through both experimental and theoretical approaches. First, the crystal structure of the compound was revealed with the help of single-crystal X-ray diffraction (XRD). Subsequently, density functional theory (DFT) calculations were performed using Gaussian 09 W to optimize the molecular geometry, simulate vibrational spectra, predict nuclear magnetic resonance (NMR) parameters, analyze frontier molecular orbitals HOMO (Highest Occupied Molecular Orbital) - LUMO (Lowest Unoccupied Molecular Orbital), and generate molecular electrostatic potential (MEP) surface maps. To enhance the accuracy of vibrational assignments, potential energy distribution (PED) analysis was conducted via the VEDA4 software. Furthermore, theoretical infrared (IR) and NMR data were compared with experimental results, with results from FT-IR, ¹H-NMR, and ¹³CNMR spectra demonstrating strong agreement and validating the computational models. In addition to spectroscopic characterization, the antiproliferative activity of the synthesized compound against human breast cancer cell line MCF7 and a normal mouse fibroblast cell line (L929) was evaluated. Among the tested compounds, those exhibiting the highest inhibitory activity against MCF7 cells were selected for further analysis. In order to explain the underlying molecular interactions, molecular placement studies were carried out with the help of the Schrödinger Maestro software program, which targets the basic protein binding sites to predict binding affinity and interaction patterns. Collectively, this integrated study provides valuable insights into the structural, spectroscopic, and biological behavior of benzazole-based derivatives, highlighting the synergy between experimental techniques and computational modeling in modern drug discovery research. © 2025 Elsevier B.V.