Macromolecular Insights Into Benzimidazole Derivatives: A Density Functional Theory Evaluation Linking Electronic Descriptors to Drug Development

A series of benzimidazole macromolecules ( F1–F4 ) was synthesized through stepwise chemical transformations and structurally characterized using FT‐IR and 1 H‐NMR spectroscopic techniques. To complement the experimental investigation, density functional theory calculations were performed at the B3LYP/6‐31G(d,p) level to evaluate the electronic structure and reactivity behavior of the studied compounds. Frontier molecular orbital analysis and global reactivity descriptors were employed to assess electronic stability, charge‐transfer capability, and interaction potential relevant to biologically active heterocycles. The calculated HOMO–LUMO energies and derived parameters, including energy gap (Δ E ), chemical hardness ( η ), softness ( δ ), electronegativity ( χ ), electrophilicity index ( ω ), and chemical potential ( μ ), revealed significant variation among the investigated derivatives. Compound F3 exhibited the smallest Δ E , lowest hardness, highest softness, and enhanced electrophilicity, indicating superior electronic flexibility and a strong tendency for charge‐transfer interactions. Compound F4 showed balanced electronic characteristics suitable for further structural optimization, whereas F1 and F2 demonstrated higher electronic stability but comparatively lower reactivity. From a research management perspective, integrating experimental synthesis with computational evaluation provides a decision‐support framework for prioritizing high‐potential candidates early in the process, thereby reducing unnecessary experimental effort, optimizing resource utilization, and enhancing the economic efficiency of the drug discovery process.