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 JESUS; HIRSCHINGER JEROME; MONTI GUSTAVO

Gotemburgo

Congreso; EUROMAR 2009; 2009

EUROMAR 2009

Dipolar-driven spin diffusion in solid state Nuclear Magnetic Resonance (NMR) is a robust approach for obtaining homonuclear distances. In this work, we applied the centerband-only detection of exchange (CODEX) technique [Wenbin Luo and Mei Hong. J. Am. Chem. Soc. 2006, 128, 7242-7251] on a new pharmaceutical compound, ciprofloxacin saccharinate [Romañuk et al. J. Pharm. Sci. DOI: 10.1002/jps.2168]. This compound exhibits polymorphism, and presents well distinguished solid forms, CIP-SAC (I) and CIP-SAC (II). In particular, CIP-SAC (II) can be obtained as a monocrystal. To carry out the analysis, we use crystallographic data obtained from single crystal X-ray diffraction of CIP-SAC (II), as a starting point to perform the fittings of CODEX data. We calculate the value of Fij(0), the overlap integral describing the probability that single-quantum transitions occur at the same frequency for spins i and j, for CIP-SAC (II). Then, considering this value, we were able to determine distances and molecules per unit cell in CIP-SAC (I). Diffraction data show that CIP-SAC (II) presents two molecules per unit cell (one in the asymmetric unit) with different orientations. From 13C NMR data, CIP-SAC (I) shows at least two molecules per asymmetric unit. Results from CODEX, in addition to 19F spectra, T1F and 13C CP-MAS (cross polarization and magic angle spinning) experiments performed on both solid forms of CIP-SAC,  give us evidence that CIP-SAC (I) is a mixture of two polymorphs, one of them probably CIP-SAC (II). We complemented these experiments with 1H-19F CP-MAS experiments with variable contact time.