Study of the inclusion of the (R)- and (S)-camphor enantiomers in a-cyclodextrin by X-ray crystallography and molecular dynamics.

The inclusion of (R)- and (S)-camphor compounds in alpha-cyclodextrin has been studied by X-ray crystallography. The crystal structures of the complexes reveal that one guest molecule is accommodated inside the cavity formed by a head-to-head cyclodextrin dimer. In the crystal lattice, the dimers form layers which are successively shifted by half a dimer. In both (R)- and (S)-cases, the camphor molecule exhibits disorder and occupies three major sites with orientations that can be described as either 'polar' or 'equatorial'. Molecular dynamics simulations performed for the observed complexes indicate that although the carbonyl oxygen of both (R)- and (S)-camphor switches between different hydrogen bonding partners, it maintains the observed mode of 'polar' or 'equatorial' alignment

Enhanced gefitinib cytotoxicity in the presence of cyclodextrins: In-vitro and biophysical studies towards potential therapeutic interventions for cancer

Gefitinib (Iressa®) is an inhibitor of EGFR tyrosine kinase, used in the treatment of lung and other cancers. Its efficient use is severely hampered by very low solubility in water which can be improved by inclusion complexation with cyclodextrins. We have assayed the cytotoxic activity of gefitinib in two pediatric neuroblastoma tumor cell lines expressing EGFR at different levels and found that in the presence of two methylated β-cyclodextrin derivatives (DMβCD, TMβCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) the efficacy of the drug increased significantly. The effects were more pronounced in the presence of HPβCD and, as expected, in the cell line with higher EGFR expression. Biophysical studies were carried out using X-ray crystallography, NMR spectroscopy and molecular dynamics simulations to identify the structure of gefitinib in complex with the above cyclodextrin derivatives. The crystal structure confirms highly dynamic inclusion of gefitinib and the NMR experiments and molecular dynamics simulations show that in solution there is a preference for occupation of the cyclodextrin cavity by the chlorofluorophenol group of gefitinib. © 2017 American Scientific Publishers

Complex Formation between Heptakis(2,6-di-O-methyl)-β-cyclodextrin and Cyclopentadienyl Molybdenum(II) Dicarbonyl Complexes: Structural Studies and Cytotoxicity Evaluations

The inclusion compounds isolated from nonaqueous solutions of heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) and the complexes [CpMoL2(CO)2](BF4) (L = MeCN, L2 = 2,2′-biimidazole) were characterized in the solid state by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), 13C{1H} CP/MAS NMR, and FTIR spectroscopy. Powder XRD showed that the compound with [CpMo(MeCN)2(CO)2](BF4) was amorphous, while that with [CpMo(H2biim)(CO)2](BF4) was microcrystalline. The powder XRD pattern of the microcrystalline product could be satisfactorily indexed in the orthorhombic crystal system with space group P212121 and final unit cell parameters of a = 28.489(3) Å, b = 19.198(2) Å, and c = 16.042(2) Å. A hypothetical structural model for the crystal packing was obtained through Monte Carlo optimizations using fixed DIMEB, [CpMo(H2biim)(CO)2]+, and BF4− geometries. In the final model the BF4− anions are housed inside the toroidal cavity of DIMEB and the organometallic complex cations are regularly distributed in between the DIMEB-tetrafluoroborate complexes, occupying the intermolecular void spaces. The cytotoxicity of the free complexes and the corresponding DIMEB adducts was tested against K1735-M2 mouse melanoma cells and H9c2 rat myoblast cells in aqueous solution. The MeCN complex and its corresponding DIMEB adduct showed no significant activity for use as chemotherapeutic agents. In contrast, the biimidazole complex exhibited significant cytotoxicity against K1735-M2 cells, especially for concentrations above 50 μM, and the cytotoxicity was even higher when the DIMEB adduct was used. Epifluorescence microscopy indicated that mitochondrial alterations took place at an earlier time point than major changes in cell morphology

A Hybrid Mechanism in Chiral Discrimination Induced by Crystallization of Supramolecular Compounds

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