Comparison of the complexation of fluoroquinolone antimicrobials with metal ions by nuclear magnetic resonance spectroscopy

Masahiro Sakai, Akihiro Hara, Saeko Anjo, Mikio Nakamura

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Abstract

The complexation of fluoroquinolone antimicrobials with various metal ions have been studied in aqueous solution (pD 2.5, 37°C) by 1H and 13C-NMR spectroscopy. The compounds examined are levofloxacin, ciprofloxacin and lomefloxacin. In each drug, new signals have appeared by the addition of Al3+, suggesting that the complexes are formed between the drug and Al3+ and that the ligand exchange is slow on the NMR time scale. Solution structure of the major species in the presence of 2.0 mol equiv of Al3+ has been proposed based on the large downfield shifts of some specific protons. Signals of both the coordinated and free drugs have shown slight broadening at 90°C due to the enhanced rate in ligand dissociation process, though the coalescence phenomena are not observed even at this temperature. Thus, the complexes are supposed to be stable at the physiological condition. Titration experiments have revealed that the binding ability of levofloxacin toward Al3+ is much stronger than that of ciprofloxacin and lomefloxacin at pD 2.5. In contrast to the complexation with Al3+, the binding of these drugs with other metal ions such as Ca2+ and Mg2+ is much weaker; NMR signals have shown no appreciable downfield shift by the addition of Ca2+ and Mg2+. Based on these results, it is concluded that the fluoroquinolone antimicrobials examined in the present study at pD 2.5 exist as stable complexes in the presence of Al3+ and the absorptivity of the drugs on oral administration could be affected by Al3+. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)1057-1067
Number of pages11
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume18
Issue number6
DOIs
Publication statusPublished - 1999 Jan 1

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Keywords

  • C-NMR
  • Complexation
  • H-NMR
  • Metal ions
  • Quinolone antimicrobials

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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