engleski

NMR and theoretical investigations of norfloxacin

Fluoroquinolones are widely used for treatments of different infectious diseases: urinary, respiratory and bones infections. They are characterized by a broad antibacterial spectrum, good oral absorption and tissue distribution. However, fluoroquinolones show some adverse effects, e.g. complexation with metal cations such as calcium, magnesium, bismuth and aluminium ions, commonly present in antacid and multivitamin preparations. In connection with these the structure of fluoroquinolones at different pH values and the pattern of their complexation is important in studying of drug interactions. We investigated norfloxacin (Figure), orally active fluoroquinolone antimicrobial structurally related to nalidixic acid. The structure of norfloxacin (NF), were investigated by one- and two-dimensional homo- and heteronuclear 1H and 13C NMR spectroscopy and by semi-empirical theoretical calculations. The nuclear shieldings (chemical shifts) were calculated with GIAO/DFT theoretical method. The two-dimensional NMR techniques: COSY, COSYLR, NOESY, ROESY, HMQC and HMBC were used for structural and conformational determination. Complexes with the following metal ions were prepared: Ca2+, Mg2+, Fe2+, Fe3+, Cu2+, Zn2+, Al3+ and the complexation was studied by IR spectra as well. The study revealed fold-in orientation of the side-chain CH3 group and pyperazine ring and the complexation with metal ions at the oxygen atoms of carboxyl and carbonyl groups of NF.

fluoroquinolone antibiotics; norfloxacin; metal ion complexes; semi-empirical theoretical calculations; 1D- and 2D NMR; homo- and hetero-nuclear 1H and 13 C NMR spectroscopy

Rezultati istraživanja objavljeni u radu rezultat su dugogodišnje suradnje Farmaceutsko-biokemijskog fakulteta i NMR centra Instituta Ruđer Bošković, u polju primjene suvremenih spektroskopskih metoda u strukturnoj analizi lijekova i njihovih metabolita, te drugih biološki aktivnih spojeva.