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NMR Spectroscopic and Theoretical Investigations of Fluoroquinolone Norfloxacin

The fluoroquinolones are characterized by a broad antibacterial spectrum, good oral absorption and tissue distribution and they are widely used for treatments of different urinary, respiratory and bones infections. Although fluoroquinolones show low frequency of adverse effec ts, a number of them have been observed, e.g. inhibition of metabolism of methylxanthines-theophylline, coffeine), complexation with metal cations such as calcium, magnesium, bismuth and aluminium ions, commonly present in multivitamin and antacid preparations, etc. Therefore, the structure of fluoroquinolones at different pH values and the pattern of their complexation is important in studying of drug interactions. We investigated here norfloxacin (Figure), orally active fluoroquinolone antimicrobial structurally related to nalidixic acid, by one- and two-dimensional homo-and heteronuclear 1H and 13C NMR spectroscopy and by semi-empirical and DFT theoretical calculations. The two-dimensional NMR techniques: COSY, COSYLR, NOESY, ROESY, HMQC and HMBC were used for structural and conformational determination. The nuclear shieldings (chemical shifts) were calculated with GIAO/DFT theoretical method. Complexes with the following metal ions were prepared: Ca2+, Mg2+, Fe2+, Fe3+, Cu2+, Zn2+, Al3+ and the complexation was studied by, UV, IR and NMR spectroscopy, as well. The study has revealed the fold-in orientation of the side-chain CH3group and pyperazine ring and the complexation with metal ions at the oxygen atoms of carboxyl and carbonyl groups of norfloxacin.

Fluoroquinolone antibiotics; Norfloxacin; Complexation; 1H and 13C NMR one- and two-dimensional spectra; Semi-empirical and DFT theoretical calculations

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