A cooperative hydrogen bonding system with a CH⋯O hydrogen bond in ofloxacin

We have investigated a cooperative hydrogen bonding system with a CH⋯O hydrogen bond in ofloxacin by using NMR, UV–Vis spectra together with quantum chemistry calculation. Both pH-dependent NMR experiments and DFT calculation indicate that the intra-molecular CH⋯O hydrogen bond between an aromatic proton and an oxygen atom from the carboxyl group is formed. Notably, the CH⋯O hydrogen bond forms a cooperative hydrogen bonding system with a neighboring OH⋯O hydrogen bond between the carboxyl group and the keto oxygen. The cooperative hydrogen bonding system makes the formation and disruption of the OH⋯O and CH⋯O hydrogen bonds in a synergistic manner. Comparison on the pKa value of the carboxylic group in different fluoroquinolones compounds indicates that the CH⋯O hydrogen bond plays a significant role in stabilizing the OH⋯O hydrogen bond. In addition, the formation and disruption of the cooperative hydrogen bonding system could regulate the conformation of the carboxyl group, which affects the size of the conjugated system and spectral behavior of π–π transition of ofloxacin.

► Intra-molecular CH···O hydrogen bond is formed between an aromatic proton and a carboxyl oxygen in ofloxacin.
► The CH⋯O hydrogen bond forms a cooperative hydrogen bonding system with a neighboring OH⋯O hydrogen bond.
► Formation/disruption of the cooperative hydrogen bonds regulates the conformation and π–π transition of ofloxacin.