Intermolecular interactions, disorder and twinning in ciprofloxacin-2,2-difluoroethanol (2/3) and ciprofloxacin-water (3/14.5)
The antibiotic ciprofloxacin [systematic name: 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-4-ium-1-yl)-1,4-dihydroquinoline-3-carboxylate], has been crystallized as a 2:3 solvate with 2,2-difluoroethanol, 2C(17)H(18)FN(3)O(3)·3C(2)H(4)O(2), (I), and as a 3:14.5 hydrate, 3C(17)H(18)FN(3)O(3)·14.5H(2)O, (II). The structure of (I) was determined using synchrotron X-ray diffraction data and refined as a two-component nonmerohedral twin. Both structures contain several independent molecules in the asymmetric unit: (I) contains two zwitterionic ciprofloxacin molecules and three difluoroethanol solvent molecules, while (II) contains three zwitterionic ciprofloxacin molecules and a mixture of ordered and disordered water molecules. The intermolecular interactions were analysed using fingerprint plots derived from Hirshfeld surfaces, providing a detailed description of the unique environment of each independent ciprofloxacin molecule.
- [Show abstract] [Hide abstract] ABSTRACT: The interaction in the solid state between ciprofloxacin (CIP) and norfloxacin (NOR) was investigated and a new multicomponent molecular complex (COP) was obtained and characterized. It is composed of equimolar quantities of both compounds, according to TLC and 1H NMR data. As single-crystal X-ray analysis showed, COP crystallizes in the triclinic system, space group P(1̅). The asymmetric unit comprises three independent zwitterions (A, B, and C) with contributions of both CIP and NOR, as well as 14.6 water molecules. At the zwitterion A site, the occurrence is about 37% (CIP), 63% (NOR); at the B site, there is predominantly CIP (70%); and at the C site the occurrence is about 43% (CIP) and 57% (NOR), yielding an overall 1:1 CIP-NOR ratio in the crystal. TG data evidenced a one-step loss of solvent (about 18% per COP zwitterion) below 110 °C, confirming the presence of water molecules. The propensity for heteroassociation between CIP and NOR, under the conditions described herein, originated a co-crystal reported for the first time between FQs, and became one of the most interesting aspects of this research.
- [Show abstract] [Hide abstract] ABSTRACT: In the title salts, C12H14N2(2+)·2ClO4(-), (I), and C12H14N2(2+)·S2O8(2-), (II), the dication is organized around an inversion centre located at the centre of the -CH2CH2- bridge and the two pyridine segments are anti with respect to one another. The peroxodisulfate anion in (II) also exhibits inversion symmetry. Hirshfeld surface analysis shows closely similar Hirshfeld surface shapes for the dications in the two salts, reflecting similar intermolecular contacts and similar conformations. The two-dimensional fingerprint plots (FPs) are quite asymmetric, due to the presence of more than one component (cation and anion). The most striking of the complementary features for each of the FPs of the dications is the broad green spike in the region de > di, without the presence of a corresponding spike in the region de < di, reflecting the absence of O...H contacts. Moreover, H...O interactions (51% in the dications of both salts) outnumber other contacts in both crystal structures.
- [Show abstract] [Hide abstract] ABSTRACT: Two salt forms of fluoroquinolone antibacterial drug, ciprofloxacin (CIP) with non-steroidal anti-inflammatory drugs, diflunisal (CIP/DIF) and indoprofen (CIP/INDP/H2O) are synthesized and characterized by PXRD, FTIR, DSC and TGA. Crystal structure determination allowed us to study the drug-drug interactions and the piperazine based synthon (protonated piperazine-carboxylate) in the two forms, which is potentially useful for the crystal engineering of new salt forms of many piperazine based drugs.