Atomic-Scale Resolution Insights into Structural and Dynamic Differences between Ofloxacin and Levofloxacin

Area of Science:

• Solid-state Nuclear Magnetic Resonance (NMR) Spectroscopy
• Crystallography
• Medicinal Chemistry

Background:

• Ofloxacin and levofloxacin are enantiomers, with levofloxacin exhibiting superior antibiotic activity.
• Understanding the atomic-level differences between enantiomers is critical for drug development.
• Solid-state NMR provides insights into molecular structure and dynamics.

Purpose of the Study:

• To investigate the atomic-level structure and dynamics of ofloxacin and levofloxacin using advanced solid-state NMR.
• To elucidate differences in the local electronic environment and nuclear spin dynamics between the two enantiomers.
• To correlate these molecular differences with observed variations in antibiotic efficacy.

Main Methods:

• Solid-state NMR spectroscopy
• Chemical Shift Anisotropy (CSA) tensor analysis
• ¹³C spin-lattice relaxation time measurements
• ¹H-¹³C Frequency-Switched Lee-Goldburg Heteronuclear Correlation (FSLGHETCOR) experiments

Main Results:

• Significant differences in CSA parameters and ¹³C spin-lattice relaxation times were observed between ofloxacin and levofloxacin.
• These differences indicate distinct local electronic configurations and nuclear spin dynamics.
• FSLGHETCOR experiments identified specific heteronuclear correlations (C15-H7, C13-H12) in ofloxacin, absent in levofloxacin.

Conclusions:

• The study demonstrates significant structural and dynamic differences between ofloxacin and levofloxacin at the atomic level.
• NMR crystallography reveals how variations in electronic configuration and nuclear spin dynamics impact drug properties.
• These findings underscore the importance of NMR approaches in understanding enantiomeric differences and advancing drug design.