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 C-13 and H-1 resonances for the hydrate is reported. The effect of crystal packing, identified by XRD, on the H-1 and C-13 chemical shifts including weak interionic H-bonds, is quantified; H-1 chemical shift changes up to similar to-3.5 ppm for CH center dot center dot center dot pi contacts and similar to+2 ppm (CH center dot center dot center dot O(-)); similar to+4.7 ppm ((+)NH center dot center dot center dot O(-)) for H-bonds. Water intake induces chemical shift changes up to 2 and 5 ppm for H-1 and C-13 nuclei, respectively. Such chemical shifts are found to be sensitive detectors of hydration/dehydration in highly insoluble hydrates.