A cooperative hydrogen bonding system with a CHO hydrogen bond in ofloxacin

We have investigated a cooperative hydrogen bonding system with a CHO 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 CHO hydrogen bond between an aromatic proton and an oxygen atom from the carboxyl group is formed. Notably, the CHO hydrogen bond forms a cooperative hydrogen bonding system with a neighboring OHO hydrogen bond between the carboxyl group and the keto oxygen. The cooperative hydrogen bonding system makes the formation and disruption of the OHO and CHO hydrogen bonds in a synergistic manner. Comparison on the pKa value of the carboxylic group in different fluoroquinolones compounds indicates that the CHO hydrogen bond plays a significant role in stabilizing the OHO 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 ??-?? transition of ofloxacin. ? 2013 Elsevier B.V. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000318961000017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701SCI(E)EI3122-128104