Combined Experimental and Computational Studies of N-Phenyl Spectroscopy, DFT Calculations, and Druggability Analysis

Abstract

In this study, spectroscopic analyses and density functional theory (DFT) calculations have been used to characterize the N-phenyl-o-benzenedisulfonimide as a disulfonimide. Vibrational analysis using normal coordinate treatment revealed vibrational modes in the mid-IR and far-IR ranges, with an RMS error of 11.8 cm- 1. Diagnostic sulfonyl stretching vibrations were observed at 1345 cm- 1 and 1325 cm- 1 for the asymmetric modes, and at 1180, 1146 (s), and 1113 cm-1 in the IR spectrum. The 13C and 1HNMR spectra were recorded in DMSO, and chemical shifts were calculated at different levels of theories with the CPCM solvation model. It was found that the B3LYP/cc-pVTZ level of theory provided the best agreement between experimental and theoretical chemical shifts for both 13C and 1HNMR spectra in DMSO. X-ray crystallography revealed four intermolecular C-H center dot center dot center dot O hydrogen bonds in the crystal structure, which was further refined with the NoSpherA2 quantum chemistry method for enhanced accuracy. UV-Vis's analyses in both DMSO and chloroform solvents indicated predominant pi ->pi* transitions between benzene rings, which was further supported by the significant electron delocalization energies (10-30 kcal/mol) observed in the NBO analyses. Druggability analysis, including target prediction, molecular docking, MD simulations, and ADMET analysis, also identified the binding potential, stability, and pharmacokinetic properties of the title molecule. Notably, docking and MD simulations demonstrated selective inhibition of the CA XII enzyme, highlighting its potential as a promising candidate for developing new cancer therapies. Theoretical insights into local reactivity descriptors revealed the critical role of electronic properties in modulating enzyme-ligand interactions and the compound's inhibitory activity.