2D homonuclear and heteronuclear correlation NMR experiments in solid state applied to a new pharmaceutical compound

GARRO LINCK YAMILA; CHATTAH ANA KARINA; ROMAÑUK CAROLINA BEATRIZ; OLIVERA MARÍA EUGENIA; MANZO RUBEN HILARIO; CUFFINI SILVIA LUCIA; GRAF ROBERT; MONTI GUSTAVO ALBERTO; SPIESS HANS

Gotemburgo

Congreso; EUROMAR 2009; 2009

European Magnetic Resonance Meeting

INTRODUCTION: Ciprofloxacin (CIP) is a widely prescribed broad-spectrum oral fluoroquinolone antibiotic. Low solubility and bitter taste are unfavorable properties associated with most fluoroquinolones that limit their formulation. Saccharine (SAC) derivatives, either as salts or co-crystals, show an improved solubility behavior and better taste. Advanced solid state nuclear magnetic resonance (NMR) techniques have been used to study a new pharmaceutical compound, the ciprofloxacin saccharinate, CIP-SAC. This compound has been previously reported and fully characterized with a variety of solid state techniques (IR, DSC, XRD and 13C CP-MAS NMR)1. This saccharinate evidences polymorphism presenting two well distinguished solid forms, CIP-SAC (I) and (II). In this work we performed 2D 13C-1H heteronuclear correlation experiments (REPT-HSQC2 and HETCOR3). These data were complemented with double quantum MAS experiments (BABA pulse sequence4) to identify 1H-1H connectivities, hydrogen bonds and dipolar proximities. Conclusions ? 2D Heteronuclear and Homonuclear spectra allow us to identify intra and intermolecular interactions for the three compounds. ? Differences and similarities in the structures of the different solid forms have also been established and supported with single crystal XR diffraction data obtained for CIP-SAC (II). ? 2D Heteronuclear correlation experiments allow us to assign 1H spectra and to identify hydrogen bonding interactions between O (18) and O (19) through C(4) and C(3a) resonances. ? Changes in the chemical shift of H (2), H(5) and H(8) indicate p-p interactions. ? Ionic interactions can be identified due to shifts in the protons belonging to the piperazine group. ? 2D 1H-1H spectra are similar for CIP-SAC (I) and CIP-SAC (II) this lead us to the conclusion that most of the interactions are intramolecular. ? Comparing 1H spectra obtained at 60 kHz with 1H spectra in solution we can conclude that new hydrogen bondings interactions are present in the solid state.