1H-driven 19F spin diffusion and cross polarization measurements for distance and structure determination in ciprofloxacin derivatives

GARRO LINCK YAMILA; CHATTAH ANA KARINA; ROMAÑUK CAROLINA BEATRIZ; OLIVERA MARÍA EUGENIA; BAGGIO ROBERTO; GARLAND MARÍA TERESA; CUFFINI SILVIA LUCIA; MANZO RUBEN HILARIO; RAYA JESÚS; HIRSCHINGER JEROME; MONTI GUSTAVO ALBERTO

Gotemburgo

Congreso; EUROMAR 2009; 2009

European Magnetic Resonance Meeting

INTRODUCTION: Ciprofloxacin (CIP) is a widely prescribed broad-spectrum oral antibiotic. New pharmaceutical derivatives of fluoroquinolones with saccharine (SAC) having sweet taste, have been recently reported1. In particular CIP saccharinate (CIP-SAC) exhibits polymorphism and presents well distinguished solid forms, CIP-SAC (I) and CIP-SAC (II). Single Crystal X Ray Diffraction was performed in CIP-SAC (II) which can be obtained as a monocrystal. In this work, we applied the centerband-only detection of exchange (CODEX) technique to determine distances and molecules per unit cell in CIP-SAC (I). Conclusions ? CIP-SAC (II) was studied and compared with CIP-SAC (I) previously reported. The solid state techniques used in this work allow the successful characterization of polymorphic forms of pharmaceutically relevant compounds in solid state. ? Both polymorphs are crystalline solids and they are not the physical mixtures of the precursors. ? Changes in hydrogen bonds interactions were observed ? All resonances belonging to CIP-SAC (II) can be seen in the CIP-SAC (I) spectrum. ? The general features and resonance shifts, observed in CIP-SAC (I) can also be observed in CIP-SAC (II). For example the shifts in C(3), C(10), C(28), C(29). Then the interactions found for CIP SAC(II) with the combination of RX and NMR data, could in principle, be extrapolated to CIP-SAC(I). ? We could determine intermolecular distances between fluorine nuclei (r). ? In CIP-SAC (I) we could observe two different distances between 19F one of 7.9 A and another of 12.4 A. ? In CIP SAC (I) two different numbers of molecules per unit cell are observed. ? CODEX experiment and 13C CP-MAS spectra allow us to conclude that CIP-SAC (I) is a mix of two structures: some molecules in the unit cell present similar orientation than CIP-SAC (II).