- Monodisperse nanoparticles from self-assembling amphiphilic cyclodextrins: Modulable tools for the encapsulation and controlled release of pharmaceuticals
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Selective chemical functionalization of cyclodextrins (CDs) is a readily amenable methodology to produce amphiphilic macromolecules endowed with modulable self-organizing capabilities. Herein, the synthesis of well-defined amphiphilic CD derivatives, with a "skirt-type" architecture, that incorporate long-chain fatty esters at the secondary hydroxyl rim and a variety of chemical functionalities (e. g. iodo, bromo, azido, cysteaminyl or isothiocyanato) at the primary hydroxyls rim is reported. Nanoprecipitation of the new CD facial amphiphiles, or binary mixtures of them, resulted in nanoparticles with average hydrodynamic diameters ranging from 100 to 240 nm that were stable in suspension for several months. The precise size, zeta potential and topology of the nanoparticles are intimately dependent on the functionalization pattern at the CD scaffold. Highly efficient molecular encapsulation capabilities of poorly bioavailable drugs such as diazepam (DZ) were demonstrated for certain derivatives, the drug release profile being dependent on the type of formulation (nanospheres or nanocapsules). The efficiency and versatility of the synthetic strategy, together with the possibility of exploiting the reactivity of the functional groups at the nanoparticle surface, offer excellent opportunities to further manipulate the carrier capabilities of this series of amphiphilic CDs from a bottom-up approach.
- Mendez-Ardoy, Alejandro,Gomez-Garcia, Marta,Geze, Annabelle,Putaux, Jean-Luc,Wouessidjewe, Denis,Mellet, Carmen Ortiz,Defaye, Jacques,Fernandez, Jose M. Garcia,Benito, Juan M.
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- A simple synthesis of a highly water soluble symmetrical β-cyclodextrin derivative
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1,3-dipolar cycloaddition between peracetyl-heptakis-6-azido-6-deoxy-β-cyclodextrin and the dimethylester of 2-butyne dicarboxylic acid is a highly efficient route for the introduction of seven 1,2,3-triazole heterocycles and fourteen carboxyl groups on the small rim of the macrocycle.
- Roehri-Stoeckel, Christine,Dangles, Olivier,Brouillard, Raymond
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- Selective binding and controlled release of anticancer drugs by polyanionic cyclodextrins
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The binding stoichiometry, binding constants, and inclusion mode of some water-soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyclodextrin(H1), heptakis-[6-deoxy-6-(2-sulfanylacetic acid)]-β-cyclodextrin(H2), mono-[6-deoxy-6-(3-sulfanylpropanoic acid)]-β-cyclodextrin (H3) and mono-[6-deoxy-6-(2-sulfanylacetic acid)]-β-cyclodextrin (H4), with three anticancer drugs, i.e. irinotecan hydrochloride; topotecan hydrochloride; doxorubicin hydrochloride, were investigated by means of 1H NMR, UV–Vis spectroscopy, mass spectra and 2D NMR. Polyanionic cyclodextrins H1-H2 showed the significantly high binding abilities of up to 2.6 × 104–2.0 × 105 M?1 towards the selected anticancer drugs, which were nearly 50–1000 times higher than the corresponding Ks values of native β-cyclodextrin. In addition, these polyanionic cyclodextrins also showed the pH-controlled release behaviors. That is, the anticancer drugs could be efficiently encapsulated in the cyclodextrin cavity at a pH value similar to that of serum but sufficiently released at an endosomal pH value of a cancer cell, which would make these cyclodextrin derivatives the potential carriers for anticancer drugs.
- Cheng, Jian-Guang,Yu, Hua-Jiang,Chen, Yong,Liu, Yu
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- Mono-benzimidazole functionalized β-cyclodextrins as supramolecular nanovalves for pH-triggered release of p-coumaric acid
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The self-complexation of mono-benzimidazole functionalized β-cyclodextrins was investigated. The unique molecular structure employed as supramolecular nanovalves were installed on the external surface of mesoporous silica to assemble mechanized silica nanoparticles, which showed pH-triggered release property. This journal is
- Wang, Ting,Wang, Mingdong,Ding, Chendi,Fu, Jiajun
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- Sugar-grafted cyclodextrin nanocarrier as a "trojan Horse" for potentiating antibiotic activity
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Purpose: The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated. Methods: Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azide-alkyne click reaction. The sugar molecules serve as a chemoattractant enticing the bacteria to take in higher amounts of the antibiotic, resulting in rapid killing of the bacteria. Results: Three types of hydrophobic antibiotics, erythromycin, rifampicin and ciprofloxacin, are used as model drugs and loaded into the carriers. The minimum inhibitory concentration of the antibiotics in the CD-MAN-antibiotic and CD-GLU-antibiotic complexes for Gram-negative Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii strains, and a number of Gram-positive Staphylococcus aureus strains, including the methicillin-resistant strains (MRSA), are reduced by a factor ranging from 3 to >100. The CD-MAN-antibiotic complex is also able to prolong the stability of the loaded antibiotic and inhibit development of intrinsic antibiotic resistance in the bacteria. Conclusions: These non-cytotoxic sugar-modfied nanocarriers can potentiate the activity of existing antibiotics, especially against multidrug-resistant bacteria, which is highly advantageous in view of the paucity of new antibiotics in the pipeline.
- Li, Min,Neoh, Koon Gee,Xu, Liqun,Yuan, Liang,Leong, David Tai,Kang, En-Tang,Chua, Kim Lee,Hsu, Li Yang
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- Entirely oligosaccharide-based supramolecular amphiphiles constructed: Via host-guest interactions as efficient drug delivery platforms
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Entirely oligosaccharide-based supramolecular amphiphiles were constructed via host-guest interactions between ferrocene-terminated acetylated-maltoheptaose (Fc-AcMH) and β-cyclodextrin-terminated four-arm star maltoheptaose (MH4-β-CD). The amphiphiles could self-assemble to form spherical supramolecular nanoparticles to provide efficient drug delivery platforms. The combination of a pH-sensitive covalent acetal group and the oxidation-sensitive noncovalent host-guest interaction of β-CD and ferrocene provided the obtained fully oligosaccharide-based supramolecular amphiphiles. The structures of these amphiphiles could respond to the intracellular microenvironment.
- Shi, Yuting,Li, Hongping,Cheng, Ju,Luan, Tingting,Liu, Di,Cao, Yufei,Zhang, Xiangdong,Wei, Hua,Liu, Yali,Zhao, Guanghui
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- Improved cyclodextrin-based receptors for camptothecin by inverse virtual screening
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We report the computeraided optimization of a synthetic receptor for a given guest molecule, based on inverse virtual screening of receptor libraries. As an example, a virtual set of β-cyclodextrin (β-CD) derivatives was generated as receptor candidates for the anticancer drug camptothecin. We applied the two docking tools AutoDock and GlamDock to generate camptothecin complexes of every candidate receptor. Scoring functions were used to rank all generated complexes. From the 10% top-ranking candidates nine were selected for experimental alidation. They were synthesized by reaction of heptakis-[6-deoxy-6-iodo]-β-CD with a thiol compound to form the hepta-substituted β-CDs. The stabilities of the camptothecin complexes obtained from solubility measurements of five of the nine CD derivatives were significantly higher than for any other CD derivative known from literature. The remaining four CD derivatives were insoluble in water. In addition, corresponding mono-substituted CD derivatives were synthesized that also showed improved binding constants. Among them the 9-H-purine derivative was the best, being comparable to the investigated hepta-substituted β-CDs. Since the measured binding free energies correlated satisfactorily with the calculated scores, the applied scoring functions appeared to be appropriate for the selection of promising candidates for receptor synthesis.
- Steffen, Andreas,Thiele, Carolin,Tietze, Simon,Strassnig, Christian,Kaemper, Andreas,Lengauer, Thomas,Wenz, Gerhard,Apostolakis, Joannis
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- Multicharge β-cyclodextrin supramolecular assembly for ATP capture and drug release
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A hyaluronidase-responsive polysaccharide supramolecular assembly was constructed from an amphiphilic β-cyclodextrin bearing seven hexylimidazolium units (AMCD), adamantyl-grafted hyaluronic acid, and chlorambucil, which showed specific cancer cell targeting and controlled drug release abilities. Interestingly, ternary supramolecular assembly can disassemble in the presence of hyaluronidase, and the released AMCD can assemble with ATP to form a stable 1?:?1 complex, which enhanced the efficacy of chlorambucil on cancer chemotherapy by inhibiting ATP hydrolysis.
- Chen, Changhui,Chen, Yong,Dai, Xianyin,Li, Jingjing,Jia, Shanshan,Wang, Shuaipeng,Liu, Yu
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- Synthesis of the dendritic type β-cyclodextrin on primary face via click reaction applicable as drug nanocarrier
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Abstract The objective of this study was the syntheses of well-defined glycodendrimer with entrapment efficiency by click reactions, with β-cyclodextrins (β-CDs) moiety to keep the biocompatibility properties, besides especially increase their capacity to
- Toomari, Yousef,Namazi, Hassan,Akbar, Entezami Ali
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- Probing carbohydrate-carbohydrate interactions by photoswitchable supramolecular glycoclusters
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The synthesis of photo-switchable glycoclusters with distinct sugar arrangements is described and the use of these clusters to study carbohydrate-carbohydrate interactions (CCIs) is demonstrated.
- Bavireddi, Harikrishna,Bharate, Priya,Kikkeri, Raghavendra
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- Synergistic inhibition of aggressive breast cancer cell migration and invasion by cytoplasmic delivery of anti-RhoC silencing RNA and presentation of EPPT1 peptide on “smart” particles
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Overexpression of RhoC protein in breast cancer patients has been linked to increased cancer cell invasion, migration, and metastases. Suppressing RhoC expression in aggressive breast cancer cells using silencing RNA (siRNA) molecules is a viable strategy to inhibit the metastatic spread of breast cancer. In this report, we describe the synthesis of a series of asymmetric pH-sensitive, membrane-destabilizing polymers engineered to complex anti-RhoC siRNA molecules forming “smart” nanoparticles. Using β-CD as the particle core, polyethylene glycol (PEG) chains were conjugated to the primary face via non-cleavable bonds and amphiphilic polymers incorporating hydrophobic and cationic monomers were grafted to the secondary face via acid-labile linkages. We investigated the effect of PEG molecular weight (2 & 5 kDa) on transfection capacity and serum stability of the formed particles. We evaluated the efficacy of EPPT1 peptides presented on the free tips of the PEG brush to function as a targeting ligand against underglycosylated MUC1 (uMUC1) receptors overexpressed on the surface of metastatic breast cancer cells. Results show that “smart” nanoparticles successfully delivered anti-RhoC siRNA into the cytoplasm of aggressive SUM149 and MDA-MB-231 breast cancer cells, which resulted in a dose-dependent inhibition of cell migration and invasion. Further, EPPT1-targeted nanoparticles demonstrate a synergistic inhibition of cell migration and invasion imparted via RhoC knockdown and EPPT1-mediated signaling via the uMUC1 receptor.
- Kaushal, Neha,Tiruchinapally, Gopinath,Durmaz, Yasemin Yuksel,Bao, LiWei,Gilani, Rabia,Merajver, Sofia D.,ElSayed, Mohamed E.H.
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- Biomimetic artificial ion channels based on beta-cyclodextrin
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Star polymers based on β-cyclodextrin were synthesized by a "click-chemistry" process and characterized by NMR, SEC and BLM. The resulting triazole functional groups create, at a specific pH range, electrostatic hindrance between pores inserted in lipid bilayers, preventing their aggregation, allowing formation of well-defined isolated unitary pores and mimicking biological natural channels.
- El Ghoul, Yassine,Renia, Ruddy,Faye, Ibrahima,Rassou, Soumassoudrane,Badi, Nezha,Bennevault-Celton, Veronique,Huin, Cecile,Guegan, Philippe
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- Synthesis of poly(2-methyl-2-oxazoline) star polymers with a β-cyclodextrin core
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Synthesis of star polymers with a-cyclodextrin (CD) core was undertaken using the arm-first, then the core-first strategy. Cationic ring opening polymerisation (CROP) of 2-methyl-2-oxazoline (MeOx) was first initiated by allyl bromide, and then quenched with heptakis(6-deoxy-6-amino)-CD in order to get a 7-arm star polymer. Then heptakis(6-deoxy-6-iodo-2,3-di-O-acetyl)-CD was synthesised in order to get an initiator for the CROP of MeOx. Initiation and propagation kinetic measurements were undertaken and the ratio kp/ki was found to be too high to provide a controlled polymerisation. Using iodine as co-initiator allowed a decrease of the kp/ki ratio that gave better control of the polymerisation. DOSY NMR and viscosity characterisations were undertaken, and both techniques lead to the demonstration of a lower hydrodynamic volume of the star polymers versus the linear counterparts, for compounds of the same molecular weight.
- Pereira, Guillaume,Huin, Ccile,Morariu, Simona,Bennevault-Celton, Vronique,Gugan, Philippe
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- Synthesis of an MUC1 Glycopeptide Dendrimer Based on β-Cyclodextrin by Click Chemistry
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Glycopeptide dendrimers are attractive candidates for biomedical applications. Here, an efficient method for preparing multivalent MUC1 glycopeptide dendrimers based on β-cyclodextrin is described. By using copper(I) bromide and thioanisole as a catalyst system, precisely defined heptavalent conjugates were efficiently obtained. Using this heptavalent glycopeptide dendrimer, we observed multivalent effects in recognition and association processes in antibody and epitope interactions, which might have biomedical applications..
- Chen, Pu-Guang,Huang, Zhi-Hua,Sun, Zhan-Yi,Li, Qian-Qian,Chen, Yong-Xiang,Zhao, Yu-Fen,Li, Yan-Mei
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- Facial Synthesis and Bioevaluation of Well‐Defined OEGylated Betulinic Acid‐Cyclodextrin Conjugates for Inhibition of Influenza Infection
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Betulinic acid (BA) and its derivatives exhibit a variety of biological activities, especially their anti‐HIV‐1 activity, but generally have only modest inhibitory potency against influenza virus. The entry of influenza virus into host cells can be competitively inhibited by multivalent derivatives targeting hemagglutinin. In this study, a series of hexa‐, hepta‐ and octavalent BA derivatives based on α-, β-and γ-cyclodextrin scaffolds, respectively, with varying lengths of flexible oligo(ethylene glycol) linkers was designed and synthesized using a microwave‐assisted copper‐catalyzed 1,3‐di-polar cycloaddition reaction. The generated BA‐cyclodextrin conjugates were tested for their in vitro activity against influenza A/WSN/33 (H1N1) virus and cytotoxicity. Among the tested com-pounds, 58, 80 and 82 showed slight cytotoxicity to Madin‐Darby canine kidney cells with viabilities ranging from 64 to 68% at a high concentration of 100 μM. Four conjugates 51 and 69–71 showed significant inhibitory effects on influenza infection with half maximal inhibitory concentration val-ues of 5.20, 9.82, 7.48 and 7.59 μM, respectively. The structure‐activity relationships of multivalent BA‐cyclodextrin conjugates were discussed, highlighting that multivalent BA derivatives may be potential antiviral agents against influenza infection.
- Chen, Yingying,Gao, Qianqian,Liang, Shuobin,Ma, Xinyuan,Tretyakova, Elena V.,Wang, Xinchen,Xiao, Sulong,Zhang, Yongmin,Zhou, Demin
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- Method for synthesizing beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in water phase
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The invention discloses a method for synthesizing a beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in a water phase. The method comprises the following steps: in the water phase, catalyzing ketone and aldehyde with equal molar weig
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Paragraph 0032-0033
(2021/01/28)
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- The uncommon strong inhibition of α-glucosidase by multivalent glycoclusters based on cyclodextrin scaffolds
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The homeostasis disruption of d-glucose causes diabetes, a dramatic chronic disease worldwide. Type 1 diabetes is a successfully treatable form, where blood d-glucose is regulated by insulin treatment. In contrast type 2 diabetes, the non-insulin dependent kind, is problematic. The control of the d-glucose blood level via intestinal α-d-glucosidase inactivation can be achieved by using competitive inhibitors, such as iminosugars (e.g. acarbose) or sulfonium sugar derivatives (e.g. salacinol). Recently, an unprecedented result showed that multivalent diamond nanoparticles grafted with unmodified sugars displayed α-glucosidase inhibition at low micromolar concentrations. Herein we describe the synthesis of multivalent glycoclusters using cyclodextrins (CDs) as scaffolds and an assessment of their role as inhibitors of α-d-glucosidase. The glycoclusters were efficiently obtained from per-azido α, β and γ-CD derivatives and propargyl glycosides using click-chemistry under microwave irradiation. The methodology was successfully applied to various protected and non-protected propargylated monosaccharides, including both O- and S-glycosides, giving clear evidence of its versatility. The targeted 6-per-glycosylated CDs were isolated in moderate to excellent yields (30-90%) by silica gel chromatography. The results showed inhibition of α-glucosidase from Saccharomyces cerevisiae with IC50 values in the 32-132 μM range, lower than that of acarbose (IC50 = ~250 μM), a well-known competitive inhibitor used in the clinical treatment of type 2 diabetes. Preliminary experiments suggest a mixed-type non-competitive inhibition mode for these new glycoclusters.
- Alali, Urjwan,Vallin, Aurélie,Bil, Abed,Khanchouche, Takwa,Mathiron, David,Przybylski, Cédric,Beaulieu, Rémi,Kovensky, José,Benazza, Mohammed,Bonnet, Véronique
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p. 7228 - 7237
(2019/08/07)
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- Amphipathic β-cyclodextrin nanocarriers serve as intelligent delivery platform for anticancer drug
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A novel glutathione-responsive (GSH-responsive)star-like amphiphilic polymer (C12H25)14-β-CD-(S-S-mPEG)7 (denoted as CCSP)was designed for efficient antitumor drug delivery. The amphiphilic β-cyclodextrin (β-CD)self-polymerize in water to form a sphere with a diameter of 40–50 nm. The secondary hydroxyl groups of β-CD were modified by dodecyl to form a hydrophobic core and the primary hydroxyl groups of β-CD were decorated with PEG through disulfide bond to form a hydrophilic shell. Since the hydrophobic cavity of β-CD was maintained, the hydrophobic core formed by dodecyl as well as cavity of β-CD provided CCSP with a loading content as high as 39.6 wt%. Importantly, DOX@CCSP exhibited low drug leakage and negligible cytotoxicity in non-reductive physiological environment, while it showed rapid release and high cytotoxicity in reductive tumorous environment via the breakage of disulfide bond. In view of the above-mentioned advantages of DOX@CCSP nanocarriers such as high loading content, proper size, favorable stimulus-response release performance and low leakage, it is believed that CCSP may offer great potential to be used as an intelligent nanocarrier for anticancer drug delivery.
- Liu, Hui,Chen, Jian,Li, Xiufang,Deng, Zhiwei,Gao, Peiru,Li, Jianbin,Ren, Tao,Huang, Ling,Yang, Yanjing,Zhong, Shian
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p. 429 - 440
(2019/05/15)
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- Micelles via self-assembly of amphiphilic beta-cyclodextrin block copolymers as drug carrier for cancer therapy
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We developed intelligent, star-shaped amphiphilic β-cyclodextrin (β-CD) co-polymer nanocarriers to circumvent the poor drug loading and water-solubility of β-CD. The secondary hydroxyl groups of β-CD were methylated to improve solubility, and the primary hydroxyl groups were conjugated with mPEG-b-PCL-SH through disulfide linkage to amplify the hydrophobic cavity and enhance the stability of the nanocarrier. A series of amphiphilic β-CD block copolymers (CCPPs) differing in molecular weights were synthesized that could self-assemble into core-shell nanospheres measuring 50–70 nm in water. The different CCPP carriers were screened for their drug loading, encapsulation and release efficiencies, and CCPP-2 showed the highest drug loading capacity of 31.9% by weight. These nanocarriers accumulated at the tumor site through the EPR effect and released the drug in a controlled manner in the reductive tumor microenvironment, with negligible premature leakage and side effects. Therefore, CCPP-2 shows significant potential as a smart and efficient nanovehicle for anticancer drug delivery.
- Li, Xiufang,Liu, Hui,Li, Jianbing,Deng, Zhiwei,Li, Lingjun,Liu, Junjun,Yuan, Jing,Gao,Yang, Yanjing,Zhong
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- β-Cyclodextrin Covalent Organic Framework for Selective Molecular Adsorption
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Covalent organic frameworks (COF) are complex functional systems constructed with atomic precision by linking well-defined building blocks through robust covalent bonds. β-cyclodextrin (β-CD) is a most employed supramolecule which bears a hydrophobic cavity guiding molecular specific recognitions. Building COF with asymmetric β-CD linkers is challenging and has never been reported. Here, β-CD COF is grown with heptakis(6-amino-6-deoxy)-β-CD and terephthalaldehyde in green solvents of water and ethanol at room temperature. The COF is characterized by powder X-ray diffraction, which matches well with the simulated crystal structure. Weaving β-CD into a framework through reticular chemistry allows the integration of a large amount of β-CD units (50 mol %), much higher than β-CD polymers. The β-CD COF has larger surface area, more uniform pore size, and higher thermal stability than the non-crystalline β-CD polymer produced by the same reagents. Finally, the β-CD COF holds abundant specific interaction sites enabling selective molecular adsorption.
- Wang, Ren-Qi,Wei, Xue-Bing,Feng, Yu-Qi
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supporting information
p. 10979 - 10983
(2018/07/31)
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- VIRUCIDAL COMPOUNDS AND USES THEREOF
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The invention relates to virucidal compounds, virucidal compositions comprising thereof and uses thereof in treatment of viral infections, for sterilizations and for disinfections. The compounds are sulfonylalkylcyclodextrins.
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Page/Page column 18
(2018/02/23)
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- A new sugar nano micelle and its preparation method and application
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The invention discloses a novel saccharide nano micelle and a preparation method and application thereof and in particular relates to a saccharide nano micelle with a tumor cell targeting property, belonging to the field of medicines and pharmacy. According to the invention, cyclodextrin with rich sources is used as a self-assembly construction unit, cyclodextrin molecules are designed and modified to prepare amphipathic molecules, the primary hydroxyl surface of cyclodextrin is modified by monosaccharide molecules and oligosaccharide molecules with the targeting property and good hydrophilicity, such as mannitose and galactose, and the secondary hydroxyl surface of cyclodextrin is modified by aliphatic chains so as to be used as a hydrophobic part. By virtue of the hydrophilic/hydrophobic action principle of the amphipathic molecules, the regulation and control on assembly of the amphipathic molecules can be realized to a certain degree, thereby obtaining a saccharide nano material. The nano micelle prepared from the nano material not only has low toxicity but also can deliver anti-cancer drugs targeting tumor cells, so that the nano micelle can be used as a delivery carrier for all kinds of anti-cancer drugs.
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Paragraph 0038; 0039
(2019/01/05)
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- Enhanced photocatalytic activity of gold nanoparticles driven by supramolecular host-guest chemistry
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Functionalization of gold nanoparticles with supramolecular hosts allows their plasmon-based photocatalytic activity to be enhanced. This is mainly ascribed to the formation of labile host-guest complexes with the reagent molecules on the metal surface, thus promoting nanoparticle-substrate approximation without interfering with the light-induced catalytic process.
- Padilla, Marc,Peccati, Francesca,Bourdelande, José Luis,Solans-Monfort, Xavier,Guirado, Gonzalo,Sodupe, Mariona,Hernando, Jordi
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supporting information
p. 2126 - 2129
(2017/02/19)
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- Inhibition of influenza virus infection by multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin conjugates
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Multivalent ligands that exhibit high binding affinity to influenza hemagglutinin (HA) trimer can block the interaction of HA with its sialic acid receptor. In this study, a series of multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin (CD) derivatives were designed and synthesized using 1, 3-dipolar cycloaddition click reaction. A cell-based assay showed that three compounds (25, 28 and 31) exhibited strong inhibitory activity against influenza A/WSN/33 (H1N1) virus. Compound 28 showed the most potent anti-influenza activity with IC50 of 4.7?μM. The time-of-addition assay indicated that compound 28 inhibited the entry of influenza virus into host cell. Further hemagglutination inhibition (HI) and surface plasmon resonance (SPR) assays indicated that compound 28 tightly bound to influenza HA protein with a dissociation constant (KD) of 4.0?μM. Our results demonstrated a strategy of using per-O-methylated β-CD as a scaffold for designing multivalent compounds to disrupt influenza HA protein-host receptor protein interaction and thus block influenza virus entry into host cells.
- Tian, Zhenyu,Si, Longlong,Meng, Kun,Zhou, Xiaoshu,Zhang, Yongmin,Zhou, Demin,Xiao, Sulong
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p. 133 - 139
(2017/04/14)
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- Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins
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A number of per-6-substituted cyclodextrin derivative syntheses have been effectively carried out in a planetary ball mill under solvent-free conditions. The preparation of Bridion and important per-6-amino/thiocyclodextrin intermediates without polar aprotic solvents, a source of byproducts and persistent impurities, could be performed. Isolation and purification processes could also be simplified. Considerably lower alkylthiol/halide ratio were necessary to reach the complete reaction in comparison with thiourea or azide reactions. While the presented mechanochemical syntheses were carried out on the millimolar scale, they are easily scalable.
- Jicsinszky, Laszlo,Caporaso, Marina,Martina, Katia,Gaudino, Emanuela Calcio,Cravotto, Giancarlo
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supporting information
p. 2364 - 2371
(2016/12/07)
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- Electrochemical control of a non-covalent binding between ferrocene and beta-cyclodextrin
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The forces required for the detachment of ferrocene (Fc) from β-cyclodextrin (βCD) in a single host (βCD)-guest (Fc) complex were investigated using force spectroscopy under electrochemical conditions. The redox state of the guest Fc moiety as well as the structure of the supporting matrix was found to decisively affect the nanomechanical properties of the complex. This journal is
- Kolivo?ka,Mohos,Pobelov,Rohrbach,Yoshida,Hong,Fu,Moreno-García,Mészáros,Broekmann,Hromadová,Sokolová,Valá?ek,Wandlowski, Th.
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supporting information
p. 11757 - 11759
(2015/05/20)
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- Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers
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A novel electronic nose system comprising functionalized β-cyclodextrin wrapped reduced graphene oxide (RGO) sensors with distinct ability of discrimination of a set of volatile organic compounds has been developed. Non-covalent modification of chemically functionalized cyclodextrin with RGO is carried out by using pyrene adamantane as a linker wherever necessary, in order to construct a supramolecular assembly. The chemical functionality on cyclodextrin is varied utilising the principle of selective chemical modification of cyclodextrin. In the present study, the combined benefits of the host-guest inclusion complex formation ability and tunable chemical functionality of cyclodextrin, as well as the high surface area and electrical conductivity of graphene, are utilized for the development of a set of highly selective quantum resistive chemical vapour sensors (QRS), which can be assembled in an electronic nose.
- Nag, Sananda,Duarte, Lisday,Bertrand, Emilie,Celton, Véronique,Castro, Micka?l,Choudhary, Veena,Guegan, Philippe,Feller, Jean-Fran?ois
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supporting information
p. 6571 - 6579
(2015/03/13)
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- Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers
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A novel electronic nose system comprising functionalized β-cyclodextrin wrapped reduced graphene oxide (RGO) sensors with distinct ability of discrimination of a set of volatile organic compounds has been developed. Non-covalent modification of chemically functionalized cyclodextrin with RGO is carried out by using pyrene adamantane as a linker wherever necessary, in order to construct a supramolecular assembly. The chemical functionality on cyclodextrin is varied utilising the principle of selective chemical modification of cyclodextrin. In the present study, the combined benefits of the host-guest inclusion complex formation ability and tunable chemical functionality of cyclodextrin, as well as the high surface area and electrical conductivity of graphene, are utilized for the development of a set of highly selective quantum resistive chemical vapour sensors (QRS), which can be assembled in an electronic nose.
- Nag, Sananda,Duarte, Lisday,Bertrand, Emilie,Celton, Vronique,Castro, Mickal,Choudhary, Veena,Guegan, Philippe,Feller, Jean-Franois
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supporting information
p. 6571 - 6579
(2015/05/20)
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- A convenient procedure for the formation of per(6-deoxy-6-halo) cyclodextrins using the combination of tetraethylammonium halide with [Et 2NSF2]BF4
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A convenient and efficient procedure for the regioselective halogenation of the primary alcohols of cyclodextrins using the reagent combination of tetraethylammonium halide with [Et2NSF2]BF4 is described. Georg Thieme Verlag Stuttgart New York.
- Liu, Xiaofeng,Cheng, Sen,Wang, Xiaolei,Xue, Weihua
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p. 3103 - 3105
(2013/12/04)
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- Efficient microwave-assisted synthetic protocols and in silico behaviour prediction of per-substituted β-cyclodextrins
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Selective per-substituted cyclodextrin design enables the carrier's physicochemical and binding properties to be tailored and can even modify some biological native structure effects. We herein report a number of highly efficient microwave-assisted synthe
- Martina,Cravotto,Caporaso,Rinaldi,Villalonga-Barber,Ermondi
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p. 5521 - 5527
(2013/09/02)
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- Cyclodextrin-centred star polymers synthesized via a combination of thiol-ene click and ring opening polymerization
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The synthesis of cyclodextrin-centred star polymers via thiol-ene addition of per-6-thio-β-cyclodextrin (CD-(SH)7) with vinyl terminated polymers is described. The obtained thiol-ene product was employed as an initiator for ring opening polymerization (ROP) of ε-caprolactone (ε-CL).
- Zhang, Qiang,Li, Guang-Zhao,Becer, C. Remzi,Haddleton, David M.
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supporting information; experimental part
p. 8063 - 8065
(2012/09/07)
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- A mixed cyclodextrin-biphenyl thermotropic liquid crystal: Synthesis, liquid-crystalline properties, and supramolecular organization
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A well-defined structure liquid crystal heptakis [6deoxy-6-(1-H-1,2,3- triazol-4-yl)(methyl)6-(4-methoxybiphenyl4'-yloxy) hexanoyl]-β-cyclodextrin (H6B-β-CD) was synthesized from propargyl 6-(4-methoxybiphenyl-4′- yloxy) hexanoate (P6B) and heptakis (6-deoxy-6-azido)-β-cyclodextrin ((N3)7-β-CD) by click reaction. The chemical structure of H6B-β-CD was confirmed by 1H NMR, FTIR, and MALDI-TOF MS. The thermal stability of the compound was investigated by thermogravimetric analysis (TGA). The liquid crystalline behavior was studied by differential scanning calorimetry (DSC), polarizing optical microcopy (POM), and wide-angle X-ray diffraction (WAXD) measurement. These investigations have shown that the supramolecular structure of H6B-β-CD are consisted of a large scale ordered lamellar structure and a small scale ordered structure (SmE) at low temperature region. As the temperature increases, the small scale structure becomes disordered relatively in the first instance, from smectic E to smectic A. Then, the lamellar structure collapses and nematic phase and isotropic phase are observed in sequence.
- Chen, Li,Hu, Tian-Hui,Xie, He-Lou,Zhang, Hai-Liang
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experimental part
p. 2838 - 2845
(2011/03/19)
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- Click synthesis of estradiol-cyclodextrin conjugates as cell compartment selective estrogens
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Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E2) was explored extensively using a number of different click chemistries and the cell membrane permeability of synthetic CD-E2 conjugate was explored by cell reporter assays and confocal fluorescence microscopy. In simile with reported dendrimer-E2 conjugates, CD-E2 was found to be a stable, extranuclear receptor selective estrogen that penetrated into the cytoplasm.
- Kim, Hye-Yeong,Sohn, Johann,Wijewickrama, Gihani T.,Edirisinghe, Praneeth,Gherezghiher, Teshome,Hemachandra, Madhubani,Lu, Pei-Yi,Chandrasena, R. Esala,Molloy, Mary Ellen,Tonetti, Debra A.,Thatcher, Gregory R.J.
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scheme or table
p. 809 - 821
(2010/05/02)
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- CYCLODEXTRIN DERIVATIVES AS POTENTIATORS FOR ANTIBIOTICS
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The invention provides a new class of antibiotics that are derivatives of cyclodextrin, which is a cyclic molecule comprising D-glucose units. In addition, the invention provides a method for potentiating the activity of antibiotic to inhibit the growth o
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Page/Page column 57-58
(2009/06/27)
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- Multiresponsive supramolecular nanogated ensembles
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(Figure Presented) A new multiresponsive supramolecular nanogated ensemble has been developed by introducing β-cyclodextrin (β-CD) into polymer-grafted mesoporous silica. The crosslinked polymer produced by host-guest interaction between β-CD and diazo-li
- Liu, Rui,Zhang, Ying,Feng, Pingyun
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supporting information; experimental part
p. 15128 - 15129
(2010/01/30)
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- Polycationic β-cyclodextrin "click clusters": Monodisperse and versatile scaffolds for nucleic acid delivery
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Herein, a novel series of multivalent polycationic β-cyclodextrin "click clusters" with discrete molecular weight have been synthesized, characterized, and examined as therapeutic pDNA carriers. The materials were creatively designed based on a β-cyclodextrin core to impart a biocompatible multivalent architecture and oligoethyleneamine arms to facilitate pDNA binding, encapsulation, and cellular uptake. An acetylated-per-azido- β-cyclodextrin (4) was reacted with series of alkyne dendrons (7a-e) (containing one to five ethyleneamine units) using copper-catalyzed 1,3-dipolar cycloaddition, to form a series of click clusters (9a-e) bearing 1,2,3-triazole linkers. Gel electrophoresis experiments, dynamic light scattering, and transmission electron microscopy revealed that the macromolecules bind and compact pDNA into spherical nanoparticles in the size range of 80-130 nm. The polycations protect pDNA against nuclease degradation, where structures 9c, 9d, and 9e did not allow pDNA degradation in the presence of serum for up to 48 h. The cellular uptake profiles were evaluated in Opti-MEM and demonstrate that all the click clusters efficiently deliver Cy5-labeled pDNA into HeLa and H9c2 (2-1) cells, and compounds 9d and 9e yielded efficacy similar to that of the positive controls, Jet-PEI and Superfect. Furthermore, the luciferase gene delivery experiments revealed that the level of reporter gene expression increased with an increase in oligoethyleneamine number within the cluster arms. The cytotoxicity profiles of these materials were evaluated by protein, MTT, and LDH assays, which demonstrate that all the click clusters remain nontoxic within the expected dosage range while the positive controls, Jet PEI and Superfect, were highly cytotoxic. In particular, 9d and 9e were the most effective and promising polycationic vehicles to be further optimized for future systemic delivery experiments.
- Srinivasachari, Sathya,Fichter, Katye M.,Reineke, Theresa M.
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p. 4618 - 4627
(2008/09/21)
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- Recognition of ionic guests by ionic β-cyclodextrin derivatives
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Inclusion compounds of cationic, anionic, and neutral p-substituted derivatives of feri-butylbenzene complexed in β-cyclodextrin and its ionic 6-mono and 6-hepta derivatives were systematically investigated by isothermal titration calorimetry (ITC). All inclusion compounds showed 1:1 stoichiometry with binding constants ranging from 10 to 3 × 106 M -1. The binding free energies could be subdivided into apolar and electrostatic contributions. The electrostatic interactions could be quantitatively described by Coulomb's law by taking into account the degree of protonation of hosts and guests, the orientations of the guests within the hosts, and ion shielding as described by the Debye-Hueckel-Onsager theory. The orientations of the guests within the cyclodextrin cavities were determined by ROESY NMR spectroscopy.
- Wenz, Gerhard,Strassnig, Christian,Thiele, Carolin,Engelke, Annegret,Morgenstern, Bernd,Hegetschweiler, Kaspar
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scheme or table
p. 7202 - 7211
(2009/08/14)
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- β-Cyclodextrin derivatives that inhibit anthrax lethal toxin
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Recently, we demonstrated that simultaneous blocking of bacterial growth by antibiotics and inhibition of anthrax toxin action with antibodies against protective antigen were beneficial for the treatment of anthrax. The present study examined the hypothesis that blocking the pore formed by protective antigen can inhibit the action of anthrax toxin. The potential inhibitors were chosen by a structure-based design using β-cyclodextrin as the starting molecule. Several β-cyclodextrin derivatives were evaluated for their ability to protect RAW 264.7 cells from the action of anthrax lethal toxin. Per-substituted aminoalkyl derivatives displayed inhibitory activity and were protective against anthrax lethal toxin action at low micromolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates for anthrax treatment.
- Karginov, Vladimir A.,Yohannes, Adiamseged,Robinson, Tanisha M.,Fahmi, Nour Eddine,Alibek, Kenneth,Hecht, Sidney M.
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- A highly active anion-selective aminocyclodextrin ion channel
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Negative beats positive: A channel composed of oligoether chains attached by amine groups to β-cyclodextrin mediates the transport of halides across a phospholipid bilayer (see scheme) at faster rates than those observed for monovalent cations. Protonatio
- Madhavan, Nandita,Robert, Erin C.,Gin, Mary S.
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p. 7584 - 7587
(2007/10/03)
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- Novel fluorinated amphiphilic cyclodextrin derivatives: Synthesis of mono-, di- and heptakis-(6-deoxy-6-perfluoroalkylthio)-β-cyclodextrins
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A new series of fluorinated amphiphilic β-cyclodextrin derivatives has been synthesized. The strategy is based on the modification of the C-6 position of the mono-6-deoxy-6A-para-tolylsulfonyl, di-6A, 6D-deoxy-6A, 6D-(para-tolylsulfonyl) and heptakis-(6-deoxy-6-iodo)-β-cyclodextrin precursors. The synthesis lead to mono-perfluoroalkylthio-, di-perfluoroalkylthio- and heptakis-perfluoroalkylthio-β-cyclodextrin in excellent yields (90-99%).
- Peroche, Sandrine,Parrot-Lopez, Hélène
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p. 241 - 245
(2007/10/03)
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- Amino acid derivatives of β-cyclodextrin
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The syntheses of the heptaamino acid-substituted β-cyclodextrins per-6-[(phenylalanyl)amino]-β-cyclodextrin (6), per-6-cysteinyl-β-cyclodextrin (7), as well as the per-2,3-dimethyl-per-6-cysteinyl-β-cyclodextrin (12) are described. The amino acids were coupled to the primary face of the β-cyclodextrin torus using the backbone carboxylic acid functionality of phenylalanine and the side chain thiol group of cysteine. In the case of the heptacysteinyl derivatives, polyzwitterionic compounds were obtained and shown to be highly water soluble.
- Ashton, Peter R.,Koeniger, Rainer,Stoddart, J. Fraser,Alker, David,Harding, Valerie D.
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p. 903 - 908
(2007/10/03)
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- Improved preparation of hexakis(6-deoxy)cyclomaltohexaose and heptakis(6-deoxy)cyclomaltoheptaose
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Hexakis(6-deoxy)cyclomalto-hexaose and hexakis(6-deoxy)cyclomalto-hexaose were prepared by direct halogenation of cyclodextrins, with high yields. Direct bromination of cyclomaltohexaose for 15 hours gave a 93% yield.
- Baer,Vargas Berenguel,Shu,Defaye,Gadelle,Santoyo Gonzalez
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p. 307 - 314
(2007/10/02)
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- An improved method of synthesis of per-6-deoxy-6-iodo-β-cyclodextrin
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Summary: A number of per-6-substituted-6-deoxy-β-cyclodextrin derivatives have been synthesized for many years, of them, per-6-deoxy-6-iodo-β-cyclodextrin is of great importance in supramolecular chemistry. By reviewing all published papers related to synthesis of per-6-deoxy-6-iodo-β-cyclodextrin and combining with our experimental verification, this work has reported an improved method of synthesis of per-6-deoxy-6-iodo-β-cyclodextrin. The approach mainly uses adding a certain amount of methanol instead of removing DMF before adjusting pH. We think this project is simple, efficient, high repeatable and suitable for large-scale preparation, superior even to all the previously reported methods. The synthesis of bromo, chloro substituted -per-6-β-CD may also refer to this improved method. At the same time, the detailed introduction of operation process and precautions will serve as a reference and guidance to the beginner who will engage in the study on the chemical synthesis reaction of sugar and cyclodextrin.
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