Packing Interactions in Hydrated and Anhydrous Forms of the Antibiotic Ciprofloxacin: a Solid-State NMR, X-ray Diffraction, and Computer Simulation Study

We present an experimental NMR, X-ray diffraction (XRD),
and computational
study of the supramolecular assemblies of two crystalline forms of
Ciprofloxacin: one anhydrate and one hydrate forming water wormholes.
The resonance assignment of up to 51 and 54 distinct 13C and 1H resonances for the hydrate is reported. The effect
of crystal packing, identified by XRD, on the 1H and 13C chemical shifts including weak interionic H-bonds, is quantified; 1H chemical shift changes up to ∼−3.5 ppm for
CH···π contacts and ∼+2 ppm (CH···O(−)); ∼+4.7 ppm ((+)NH···O(−)) for H-bonds. Water intake induces chemical shift
changes up to 2 and 5 ppm for 1H and 13C nuclei,
respectively. Such chemical shifts are found to be sensitive detectors
of hydration/dehydration in highly insoluble hydrates.