Separation ability and stoichiometry of cyclodextrin complexes

Gas-liquid chromatography has been applied to search relations between selectivity towards isomers and stoichiometry of cyclodextrin complexes. The model tested compounds were: dimethylnaphthalenes and alpha- and beta-pinenes as constitutional isomers; cis/trans decalins, anetholes and isosafroles as diastereomers and as enantiomers (+/-)-alpha-pinenes and (+/-)-camphenes. Experimental retention data are used to confirm a simple theoretical model that allows distinguishing formation of G x CD complexes (1:1) and G x CD2 complexes (1:2). Based on the experimental data, stability constants K were evaluated. It has been found that remarkable selectivity factor alpha may appear both within the range of 1:1 stoichiometry (beta-CD complexes of decalins and of alpha- and beta-pinenes) and 1:2 stoichiometry (alpha-CD complexes with (+/-)-alpha-pinenes and (+/-)-camphenes). Occasionally selectivity arises from a different composition, when one isomer forms a 1:1 stoichiometry complex while another forms a 1:2 complex (dimethylnaphthalenes, cis/trans-anetholes and cis/trans-isosafroles).     

Effective staining of tumor cells by coumarin-6 depends on the stoichiometry of cyclodextrin complex formation

In a comprehensive picture of inclusion complex formation of the highly fluorescent dye coumarin-6 (C6) and betacyclodextrin (beta-CD), which was obtained using various fluorescence spectroscopic methods, it was demonstrated that up to three beta-CD rings can thread on the rod like dye molecule. Interaction of coumarins and modified coumarins with cellular organelles or proteins has been reported in several publications. Especially 7-amino-coumarins are characterized by unique properties like high fluorescence quantum yield and are thus already used successfully in different areas, like staining of fluorescent nanoparticles. We could show that Coumarin-6 made soluble by complexation with beta-cyclodextrin is able to stain eukaryotic cells specifically dependent on their origin and cellular behaviour. The staining reaction is independent from pH, is photo stable, and shows no cross talk with proteins in the cytoplasm and other staining procedures or erythrocytes. Staining with coumarin 6/cyclodextrin complexes can thus be used for fast discrimination of different cell types. Importantly, it could be shown that the ideal staining reaction is dependent on the stoichiometry of the complex-formation.     

Short synthesis of skeleton-modified cyclodextrin derivatives with unique inclusion ability

[reaction: see text] Skeleton-modified cyclodextrin (CD) derivatives, in which an alpha-(1,4)-glucosidic bond is converted into a beta-(1,4)-glucosidic bond, were conveniently synthesized by cleavage of a single glucosidic bond in permethylated and 2,6-di-O-methylated alpha- and beta-CDs and subsequent recyclization via the trichloroacetoimidate intermediates. The selective cleavage of an alpha-(1,4)-glucosidic bond of permethylated alpha- and beta-CDs was accomplished by stirring in 30% aq HClO(4) at 25 degrees C to give the corresponding maltohexaose and maltoheptaose derivatives, respectively. The cleavage of a glucosidic bond of hexakis(3-O-benzyl-2,6-di-O-methyl)-alpha-CD was successfully carried out in a mixed 60% aq HClO(4) and 1,4-dioxane solution (1:20). In the case of heptakis(3-O-benzyl-2,6-di-O-methyl)-beta-CD, the solvent-free reaction with p-toluenesulfonic acid was found to be effective for selective cleavage of one glucosidic bond. The permethylated beta-CD derivative with a beta-(1,4)-glucosidic bond (4b) exhibited higher inclusion ability toward sodium m-nitrobenzoate than the parent permethylated beta-CD, while these hosts showed the same inclusion ability toward sodium p-nitrobenzoate. On the other hand, the beta-(1,4)-type permethylated alpha-CD derivative 4a exhibited lower inclusion ability toward sodium p- and m-nitrobenzoates than the parent permethylated alpha-CD. Interestingly, host molecules 4a and 4b showed inclusion selectivity for sodium m-nitrobenzoate as compared with the corresponding para-isomer, in contrast to permethylated CDs which possessed para-isomer selectivity. On the other hand, host molecules 4a and 4b showed para-isomer selectivity toward sodium nitrophenoxide guests, indicating that the inclusion selectivity was remarkably influenced by the guest hydrophilic groups. (1)H NMR studies on complexes of those beta-(1,4)-type CD derivatives with p- and m-nitrobenzoates and p- and m-nitrophenolates were carried out to estimate their structures.     

Isochroman derivatives and their tendency to crystallize in chiral space groups

In methyl [5‐methoxy‐4‐(4‐methoxy­phenyl)­isochroman‐3‐yl]­acetate, C₂₀H₂₂O₅, (I), and methyl [4‐(2,5‐di­methoxy­phenyl)‐8‐methoxy­isochroman‐3‐yl]­acetate, C₂₁H₂₄O₆, (II), the heterocyclic rings adopt half‐chair conformations. The substituents at the 3‐ and 4‐positions are in a trans configuration in both (I) and (II), being in an axial conformation in (I) and in an equatorial conformation in (II). The crystal structure of (I) is stabilized by weak C—H⋯O hydrogen bonding, leading to the formation of an infinite three‐dimensional network. Compound (II) crystallizes in a chiral space group. This feature, which was also found in previously investigated isochroman derivatives, is related to the arrangement of substituents attached to the isochroman moiety.     

Novel coassembly route to Cu-SiO2 MCM-41-like mesoporous materials

A series of mesostructured Cu-SiO2 composites have been synthesized with sodium metasilicate (Na2SiO3) and cuprammonia nitrate (Cu(NH3)4(NO3)2) respectively used as Si and Cu sources. The synthetic procedures were conducted at room temperature, and cetyltrimethylammonia bromide was used as a template. Under our experimental conditions, ordered mesoporous Cu-SiO2 composites could be obtained with a copper content up to 16.8 wt %. Average pore diameters (2.80-3.15 nm), wall thickness (1.30-2.20 nm), and specific surface area (1020-690 m2/g) are found to vary linearly with copper content (0-16.8 wt %). Results of thermal gravimetry-differential thermal analysis reveal the collapse temperature of the order structure starts at approximately 1250 K for mesoporous Cu-SiO2 with 16.8 wt % copper content. As indicated by the outcomes of inductively coupled plasma and X-ray photoelectron spectroscopy studies, copper is mainly incorporated inside the pore wall rather than embedded on the wall surface. Copper species strongly interact with silica, and calcination at high temperatures cannot cause phase separation between silica and copper oxide. Cu status in mesoporous Cu-SiO2 composites is similar to that in copper silicate in neighboring structures. Based on the results, a S+ I- I+ I- mechanism is proposed in which copper entities are surrounded by silicon species during synthesis of the mesostructured composite.     

基于环糊精本征识别能力的手性色谱介质点击制备及应用

目前环糊精（CD）手性固定相（CSP）的研究大多集中于对CD或桥联臂进行功能衍生引入更多作用位点以提升手性拆分能力,鲜有能够反映天然CD本征识别能力的CSP的研究报道,该文通过"巯基-烯"点击化学反应合成了结构明确可控的单（6-巯基-6-去氧）-β -环糊精手性固定相（CSP1）,其最大限度地保留了天然CD的本征结构,且桥联臂无识别作用位点,固体核磁共振（¹³ C SSNMR）和红外光谱（FTIR）的表征结果证明了CSP1的成功制备,元素分析结果表明,与双键功能化硅胶相比,CSP1的C、H、N的百分含量均得到了提高,计算得出CSP1的表面CD固载量为0.82 μmol/m²。采用高效液相色谱反相模式对50多种手性对映体包括异（口恶）唑啉、手性交酯、手性酮、黄烷酮以及丹磺酰氨基酸等进行了手性拆分,充分考察了天然CD的本征手性识别能力,结果表明CD的本征识别能力比较有利于异（口恶）唑啉类样品中含有两个疏水苯环基团Ph-Ph类样品的分离,对于其他几类样品仅利于部分样品的分离。同时与前期制备的功能三唑桥联CD-CSP及咪唑嗡桥联CD-CSP在同一色谱条件下进行了结果比对,结果证明样品的分离过程除了与手性介质的结构有关外,还与样品分子的结构有很大关系,对桥联臂进行功能改性可提升对部分对映体的选择性,但同时会小幅损失CD的本征手性识别能力。对于环糊精本征识别能力易于分离的样品,在设计手性介质时,其桥联臂不需要任何官能团,这为CD固定相结构的设计提供了有益参考。     

Synthesis of novel cyclodextrin derivatives by aromatic spacer insertion and their inclusion ability

Novel cyclic host molecules were synthesized by the insertion of three types of aromatic spacers into the skeleton of permethylated α-cyclodextrin. These host molecules formed a 1:1 complex with sodium 3- and 4-nitrobenzenesulfonates (3- and 4-NBS), and sodium 2,4-dinitrobenzenesulfonate (DNBS) in D₂O/CD₃OD (4:1) solution. The type of spacer inserted remarkably affected the inclusion ability of the hosts toward DNBS. The p-xylylene-inserted CDs showed greater inclusion ability toward DNBS than permethylated α- and β-CDs.     

The strange case of achiral compounds which were reported to always crystallize in the same chiral group

Structural Chemistry - In the present review, one of the mysteries of chemistry, the non-stochastic preference for one enantiomer during crystallization processes, is discussed with some examples...     

Ability of the acetotoluides to form cyclodextrin inclusion complexes

Conclusion These series of experiments have shown that the -CD cavity was too small to allow stable inclusion complex formation. p-ACT is the isomer within this series that is best able to form inclusion complexes with -CD, then m-ACT and finally o-ACT. This would seem to indicate that the benzene ring of the molecule is the part of the structure most likely to penetrate the cavity since (a) -CD could not form stable complexes with any of the guest molecules and (b) less effective entry into the -CD cavity is the results of the acetamido group moving from p^–m^–o^– positions. Benzene ring penetration of the CD cavity is therefore required for stable inclusion complex formations in this group of compounds.     

Synergism by coassembly at the origin of ion selectivity in liquid-liquid extraction

In liquid-liquid extraction, synergism emerges when for a defined formulation of the solvent phase, there is an increase of distribution coefficients for some cations in a mixture. To characterize the synergistic mechanisms, we determine the free energy of mixed coassembly in aggregates. Aggregation in any point of a phase diagram can be followed not only structurally by SANS, SAXS, and SLS, but also thermodynamically by determining the concentration of monomers coexisting with reverse aggregates. Using the industrially used couple HDEHP/TOPO forming mixed reverse aggregates, and the representative couple U/Fe, we show that there is no peculiarity in the aggregates microstructure at the maximum of synergism. Nevertheless, the free energy of aggregation necessary to form mixed aggregates containing extracted ions in their polar core is comparable to the transfer free energy difference between target and nontarget ions, as deduced from the synergistic selectivity peak.     

The use of naphthalene fluorescence probes to study the binding sites on cyclodextrin polymers formed from reaction of cyclodextrin monomers with epichlorohydrin

Three naphthalene-based fluorescence probes were used as guest molecules to study host/guest binding with cyclodextrin (CD) polymer hosts prepared by treating -,-, or -cyclodextrin monomers with epichlorohydrin. The fluorescence data indicate that the binding interaction is much stronger for the probes with the CD polymers than with the CD monomers. Moreover, the fluorophore binding site on the CD polymers is also more hydrophobic than that on the CD monomers. Fluorescence lifetime data from one of the bound probes (2-(N-methylanilino) naphthalene-6-sulfonic acid) suggest that more than one type of binding site may exist on the CD polymers with this probe. A comparison of fluorescence data using different molecular weight ranges of the CD polymers appear to rule out the possibility of a 12 host/guest complex, where the two CD units come from the same polymer chain.     

Synthesis of stimuli-responsive cyclodextrin derivatives and their inclusion ability control by ring opening and closing reactions

Novel stimuli-responsive cyclodextrins (CDs), in which a disulfide unit was inserted into the rings of permethylated alpha- and beta-CDs, were synthesized. Their inclusion ability was controlled by the opening and closing of the ring based on dithiol-disulfide interconversions.     

Facile and versatile strategy to prepare magnetic molecularly imprinted particles based on the coassembly of magnetic nanoparticles and amphiphilic random copolymers

Magnetic molecularly imprinted polymer nanoparticles for bisphenol A were prepared by coassembling magnetic nanoparticles and amphiphilic random copolymers. Under optimized conditions, bisphenol A as template molecules, magnetic molecularly imprinted polymer particles with regular morphology, small size, good monodispersity, and high content of OA‐Fe₃O₄ were prepared by the coassembly method using P(MMA‐co‐MAA) with monomer ratio of 9:1. These magnetic molecularly imprinted polymer particles could be rapidly collected by an external magnet within 1 min. The saturated adsorption capacity of the magnetic molecularly imprinted polymer for bisphenol A was 201.5 mg/g, and the imprinting factor was 2.5. The separation factors for bisphenol A to β‐estradiol, estriol, and diethylstilbestrol was 3.1, 2.9, and 3.7, respectively. Unlike assembling amphiphilic copolymer in the selective solvent, the coassembly process was simple and rapid. Therefore, the present work provided a facile and versatile approach to construct magnetic molecularly imprinted polymer nanoparticles under mild conditions.     

Nanodimer cyclodextrin ligands with high affinity to steroids

Molecular-imprinting by cross-linking of ligands of ??-cyclodextrin (CD) complex with steroids has been developed for the synthesis of tailor-made CD dimer. Steroids of androstane (9??-hydroxy-androst-4-en-3,17-dione, androst-4-en-3,17-dione, androsta-1,4-dien-3,17-dione (ADD)) and pregnane (hydrocortisone, 6-methyl-hydrocortisone, 20-hydroxymethylpregna-1,4-diene-3-one (HMPD)) series were used as template molecules. For imprinting procedure, crystalline ??-CD complexes of exact stoichiometry (??-CD:steroid template = 2:1) were synthesized following by toluene 2,4-diisocyanate (TDI) cross-linking. The attempts to produce CD dimer for steroid without hydrophobic side chain failed, while tailor-made CD dimer has been obtained using HMPD as a template. The dimer was characterized by ¹H NMR and mass-spectrometry. The complex stability constant (K_S) towards HMPD template exceeded 10⁷ M^?1. The K_S of CD dimer with ADD exceeded the corresponded value of TDI-modified CD monomer by more than an order of magnitude. The dimer was applied for quantitative extraction of ADD from aqueous solution using dialysis membranes impermeable for CD. The value of K_S for ADD estimated from balanced concentrations of dialysis data corresponded to that calculated by nonlinear spectrometric method.     

Multivalent binding of galactosylated cyclodextrin vesicles to lectin

Amphiphilic beta-cyclodextrins with alkylthio chains at the primary-hydroxyl side and galactosylthio-oligo-(ethylene glycol) units at the secondary-hydroxyl side, which form nanoparticles and vesicles, show multivalent effects in their binding to lectin.     

2,4-Dichlorophenol sorption on cyclodextrin polymers

The sorption of β-cyclodextrin polymer (β-CDP) and γ-cyclodextrin polymer (γ-CDP) toward 2,4-dichlorophenol (2,4-DCP) in aqueous solutions was investigated. The influence of sorption conditions including initial 2,4-DCP concentration, contact time and pH on sorption capability were discussed. Their sorption behaviors for 2,4-DCP were conducted and it was found the sorption kinetics followed the Ho and McKay equation and the film diffusion was the rate-determined step. The sorption isotherm can be correlated to Freundlich model and the sorption capacity on β-CDP was much larger than that on γ-CDP. The maximum sorption capacity of 2,4-DCP for β-CDP was measured to be 0.16 mmol/g with the initial concentration at 0.67 mmol/L at 288 K. The CDPs were easily recovered by ethanol as washing solvent and they could be used as a kind of recyclable sorbents.     

环糊精在金属酶模拟中的应用

非共价作用（如氢键、静电和疏水作用）普遍存在于天然金属酶中,对酶活化或底物催化过程有重要的协同作用.近年来基于超分子化学理论的金属酶模拟研究不断向酶的活性中心亚稳态和次层结构的生物功能模拟方向发展.本文将根据报道的文献并结合本课题组的研究工作,对环糊精（一种重要的超分子主体）构建金属酶模型的研究进行综述.     

Interaction between block copolymer micelles and azobenzene-containing surfactants: from coassembly in water to layer-by-layer assembly at the interface

In this paper, we describe the use of block copolymer micelles to incorporate Azo-AOT, an azobenzene-containing amphiphile having a structure suitable for reverse micelle formation and the fabrication of polyelectrolyte/micelle multilayer films. Interestingly, it is found that the PS21-PAA157 micelles can incorporate more Azo-AOT molecules than the PS115-PAA15 micelles, which is different from the case of incorporation of noncharged hydrophobic molecules. Moreover, Azo-AOT incorporated into the PS21-PAA157 micelles undergoes a faster photoisomerization than in the PS115-PAA15 micelles, which seems to be related to different aggregation states of Azo-AOT in the two micelles. From the data of UV-vis spectra, we can infer that Azo-AOT adopts a reverse micelle-like aggregation state in the PS115-PAA15 micelles and disperses in the interface between the core and corona of PS21-PAA157 micelles. These polyelectrolyte/micelle films incorporating functional amphiphiles have great potential in the field of functional thin films.     

Solubilizing mutations used to crystallize one CFTR domain attenuate the trafficking and channel defects caused by the major cystic fibrosis mutation

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) Cl(-) channel. F508del, the most frequent CF-causing mutation, disrupts both the processing and function of CFTR. Recently, the crystal structure of the first nucleotide-binding domain of CFTR bearing F508del (F508del-NBD1) was elucidated. Although F508del-NBD1 shows only minor conformational changes relative to that of wild-type NBD1, additional mutations (F494N/Q637R or F429S/F494N/Q637R) were required for domain solubility and crystallization. Here we show that these solubilizing mutations in cis with F508del partially rescue the trafficking defect of full-length F508del-CFTR and attenuate its gating defect. We interpret these data to suggest that the solubilizing mutations utilized to facilitate F508del-NBD1 production also assist folding of full-length F508del-CFTR protein. Thus, the available crystal structure of F508del-NBD1 might correspond to a partially corrected conformation of this domain.