Characterization of the complexation of fluoroquinolone antimicrobials with metal ions by nuclear magnetic resonance spectroscopy.
The complexation of the fluoroquinolone antimicrobials is important because it has been implicated in reduced oral bioavailability and reduced antimicrobial activity when the drugs are co-administered with antacids or multi-vitamin preparations containing iron. The complexation of two model compounds, lomefloxacin and norflaxacin was studied using NMR. With aluminum ions, exchange between free and bound drug molecules was slow on the NMR time-scale. Two complexes, proposed to have stoichiometries of 2:1 and 3:1 (drug:metal) based on peak widths and variable temperature studies, were observed. The crystal structure of lomefloxacin, which shows intermolecular self association previously reported to be crucial to the drug's mode of action, is also reported. Because the metal ion complexes could not be crystallized, the crystal structure of uncomplexed lomefloxacin together with the NMR data on the aluminum complexes were used in the molecular modelling of the lomefloxacin-aluminum complexes.
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
C M
CM
Riley
D L
DL
Ross
D
D
Vander Velde
F
F
Takusagawa
D000890:Anti-Infective Agents / Q000737:chemistry*; D002413:Cations, Divalent / Q000737:chemistry; D024841:Fluoroquinolones; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D009643:Norfloxacin / Q000737:chemistry*; D015363:Quinolones / Q000737:chemistry*; D014961:X-Ray Diffraction
D000890:Anti-Infective Agents; D002413:Cations, Divalent; D024841:Fluoroquinolones; D008670:Metals; D015363:Quinolones; C053091:lomefloxacin; D009643:Norfloxacin