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 compound...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 1993, Vol.11 (1), p.49-59
Main Authors: Riley, Christopher M., Ross, Danna L., Velde, David Vander, Takusagawa, Fusao
Format: Article
Language:English
Subjects:
13C-NMR
1H-NMR
aluminum
Anti-Infective Agents - chemistry
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Cations, Divalent - chemistry
complexation
crystal structure, molecular modelling
Fluoroquinolones
magnesium
Magnetic Resonance Spectroscopy
Medical sciences
Metals - chemistry
Molecular Structure
Norfloxacin - chemistry
Pharmacology. Drug treatments
Quinolones - chemistry
X-ray crystallography
X-Ray Diffraction
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Summary: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 timescale. 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.
ISSN:0731-7085
1873-264X
DOI:10.1016/0731-7085(93)80148-T