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

Y. GARRO LINCK; A.K. CHATTAH; C. ROMAÑUK; M.E. OLIVERA; R. BAGGIO; M.T. GARLAND; S.L. CUFFINI; R.H. MANZO; J. RAYA; J. HIRSCHINGER; G.A. MONTI

Gotemburg, Suecia

Congreso; EUROMAR Magnetic Resonance Conference; 2009

EUROMAR

Dipolar-driven spin diffusion in solid state Nuclear Magnetic Resonance (NMR) is a robust approach for obtaining semi-quantitative homonuclear distances. In this work, we applied the centerband-only detection of exchange (CODEX) technique [REF codex] on a new pharmaceutical compound, ciprofloxacin saccharinate[ref: JPS], This compound exhibits polymorphism, and presents well distinguished solid forms I and II. In particular,  form II could be obtained as a monocrystal. For the analysis, we used crystallographic data obtained from single crystal diffraction of form II, as a starting point to perform the fittings of CODEX data. Taking into account the value of F(0) (the overlap integral) obtained for form II, we were able to determine distances and molecules per unit cell in the form I. We could conclude that form II presents two molecules per unit cell (one in the assymetric unit) with different orientations. On the other hand, form I shows at least two molecules per asymmetric unit. Results from CODEX,  in addition to 19F spectra and T1F experiments performed on both solid forms of CIP-SAC,  gave us evidence that form I can be a mixture of two polymorphs, one of them probably the form II. We complemented this experiments with 1H-19F CP-MAS (cross polarization and magic angle spinning) experiments with variable contact time to determine internuclear distances 1H-19F.