Integrated spectroscopic, DFT, and molecular docking investigation of dorzolamide hydrochloride as a potential anti-glaucoma agent

Dorzolamide Hydrochloride (DHC) is a clinically important carbonic anhydrase inhibitor widely used in the treatment of glaucoma through the reduction of intraocular pressure. In this work, a comprehensive experimental and computational investigation of DHC was carried out to elucidate its structural, electronic, spectroscopic, and biological properties. The molecular geometry and vibrational behavior were analyzed using spectral analysis in combinational DFT calculations. Optimized geometry showed good agreement with experimental observations, while vibrational assignments supported by potential energy distribution analysis enabled reliable interpretation of the recorded spectra. FMOs revealed an energy gap of 4.335 eV, indicating moderate stability with favorable charge-transfer characteristics relevant to bioactivity. Natural bond orbital analysis confirmed significant intra molecular charge delocalization and stabilization interactions. Molecular electrostatic potential, Fukui function, ELF, LOL, RDG, and ALIE analyses identified the chemically reactive regions and highlighted the role of non-covalent interactions in molecular stability and reactivity. TD-DFT calculations supported the observed electronic absorption behavior and suggested notable light-harvesting and radiative transition characteristics. Drug-likeness, ADMET, and toxicity predictions indicated generally acceptable pharmaceutical features with moderate toxicity concerns. Molecular docking against glaucoma-related protein targets demonstrated favorable binding affinities, supporting the biological relevance of DHC as an anti-glaucoma compound. Overall, this integrated study provides a detailed understanding of the molecular behavior of DHC and reinforces its therapeutic potential in ocular disease management.