Analyzing atomic scale structural details and nuclear spin dynamics of four macrolide antibiotics: erythromycin, clarithromycin, azithromycin, and roxithromycin.

The current investigation centers on elucidating the intricate molecular architecture and dynamic behavior of four macrolide antibiotics, specifically erythromycin, clarithromycin, azithromycin, and roxithromycin, through the application of sophisticated solid-state nuclear magnetic resonance (SSNMR) methodologies. We have measured the principal components of chemical shift anisotropy (CSA) parameters, and the site-specific spin-lattice relaxation time at carbon nuclei sites. To extract the principal components of CSA parameters, we have employed 13 C 2DPASS CP-MAS SSNMR experiments at two different values of magic angle spinning (MAS) frequencies, namely 2 kHz and 600 Hz. Additionally, the spatial correlation between 13 C and 1 H nuclei has been investigated using 1 H- 13 C frequency switched Lee-Goldburg heteronuclear correlation (FSLGHETCOR) experiment at a MAS frequency of 24 kHz. Our findings demonstrate that the incorporation of diverse functional groups, such as the ketone group and oxime group with the lactone ring, exerts notable influences on the structure and dynamics of the macrolide antibiotic. In particular, we have observed a significant decrease in the spin-lattice relaxation time of carbon nuclei residing on the lactone ring, desosamine, and cladinose in roxithromycin, compared to erythromycin. Overall, our findings provide detailed insight into the relationship between the structure and dynamics of macrolide antibiotics, which is eventually correlated with their biological activity. This knowledge can be utilized to develop new and more effective drugs by providing a rational basis for drug discovery and design.