Conformational analysis of arbidol in supercritical carbon Dioxide: Insights into 'opened' and 'closed' conformer groups

Arbidol is a pharmaceutical compound of significant importance due to its versatile applications in antiviral and Immunomodulatory therapies. The present study reports on the identification of multiple arbidol conformers in a supercritical carbon dioxide solution. The conformers were characterized based on various dihedral angles and the analysis of NOESY spectra. The study reveals distinct conformer groups, namely the "opened" and "closed" conformations, based on the angle τ2 that governs the alignment of the phenyl ring around the indole moiety of the compound. The analysis of the chemical shifts in the 1H NMR spectra of ARB in different solvents (supercritical carbon dioxide, deuterochloroform, and hexadeutero-dimethyl sulfoxide) reveals variations in the proton signals, indicating changes in the conformation of arbidol molecules and the impact of ring currents from the phenyl fragment. The nuclear Overhauser effect spectroscopy analysis of arbidol in supercritical carbon dioxide confirms the presence of distinct conformer groups and their internuclear distances. The distances H22-H25/29 and H22-H10 are found to be indicative of the "closed" conformer group, with values consistent with previous studies. The proportions of "opened" and "closed" conformer groups in supercritical carbon dioxide are calculated using the experimental distances and compared with theoretical calculations. The preference of the conformer group in supercritical carbon dioxide is found to be the "closed" group, similar to previous studies on arbidol forms. Overall, this study provides insights into the conformational behavior of arbidol in supercritical carbon dioxide and highlights the potential of supercritical carbon dioxide as a promising medium for developing new arbidol forms.