Study the Structure and Dynamics of Antifungal Agent Ketoconazole by CSA and Site-Specific Spin-Lattice Relaxation Time Measurements

The study investigated the structure and dynamics of the antifungal agent ketoconazole using chemical shift anisotropy (CSA) tensor and site-specific spin-lattice relaxation time measurements. It found that the spin-lattice relaxation rate was generally slow across most carbon nuclei sites, except for those on the piperazine ring and methyl group, indicating a close-pack arrangement due to π-π stacking interactions. The molecular correlation time varied significantly, with carbon atoms on the benzene, 1,3-dioxolane, imidazole, and 2,4-dichlorobenzene rings having longer correlation times compared to those on the piperazine ring. The study highlighted the correlation between ketoconazole's structure and dynamics, providing insights that could aid in developing advanced antifungal drugs and offering valuable CSA data for NMR crystallography.