NMR and IR characterization of the aluminium complexes of norfloxacin and ciprofloxacin fluoroquinolones

A. K. CHATTAH; Y. GARRO LINCK; G. A. MONTI; P. R. LEVSTEIN; S. BREDA; R. H. MANZO; M. E. OLIVERA

MAGNETIC RESONANCE IN CHEMISTRY

Wiley UK

Año: 2007 vol. 45 p. 850 - 859

0749-1581

A set of new aluminium complexes of norfloxacin (NOR) and ciprofloxacin (CIP) that shows an improvement in their pharmaceutical properties were studied using solution and solid state Nuclear Magnetic Resonance (NMR) and infrared (IR) spectroscopy. The complexes synthesized with two different methods were compared. One of these methods will allow to formulate the compounds at production scale. High resolution 13C spectra were obtained with the cross polarization and magic angle spinning (CP-MAS) experiment. These spectra were assigned by comparing with the solution data of the pure drug and by using a quaternary carbon edition technique. The carbon relaxation times in the rotating frame, T1rC, were measured for all the complexes. A two exponential decay evidences that the complexes are non-homogeneous. The short T1rC values are in the range 320-1100 ms and the long values in the range 1.8-7 ms. 27Al MAS NMR spectra revealed an octahedral coordination between the aluminium ion and oxygens of pure drug, supporting a 3:1 ligand:metal stoichiometry in both CIP and NOR complexes. The stretching and deformation modes of carboxylic acid, carboxylate and keto groups were analyzed by IR. This technique shows that the same modes are present in the aluminiumcomplexes obtained by the two methods and that the coordination of the fluoroquinolone to aluminium occurs through the 4-keto and 3 carboxylic groups.