- Preparation, characterization and biological evaluation of β-cyclodextrin-biotin conjugate based podophyllotoxin complex
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Podophyllotoxin is a natural occurring aryltetralin lignin with pronounced cytotoxic activity. However, its clinical application for cancer treatment has been blocked due to its poor water solubility and selectivity. In this work, biotin as a tumor specific ligand was coupled with β-cyclodextrin and the resulting biotin modified β-cyclodextrin was used to complex with podophyllotoxin to improve its aqueous solubility and tumor selectivity. The solubility of β-cyclodextrin was greatly enhanced(>16 times) by conjugating with biotin. podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin inclusion complex was prepared by freeze-drying method and the complex behavior between mono-6-biotin-amino-6-deoxy-β-cyclodextrin and podophyllotoxin was studied by water solubility, phase solubility, Job's plot, UV spectroscopy, Proton Nuclear Magnetic Resonance, Rotating-frame Overhauser Effect Spectroscopy, Powder X-ray diffraction and Scanning electron microscopy. The solubility of podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex was greatly improved(9 times) compared with Podophyllotoxin. The stability constant of podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex (Ks= 415.29 M?1) was 3.2 times that of podophyllotoxin/β-cyclodextrin complex. The possible inclusion mode of podophyllotoxin/mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex was inferred from the Proton Nuclear Magnetic Resonance and Rotating-frame Overhauser Effect Spectroscopy. The cellular uptake study showed that the introduction of biotin increased the cellular uptake of rhodamine-B/mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex. Moreover, cell cytotoxicity study showed that the antitumor activity of podophyllotoxin/ mono-6-biotin-amino-6-deoxy-β-cyclodextrin complex was more potent than podophyllotoxin/β-cyclodextrin complex and free podophyllotoxin. The superior water solubility and enhanced cytotoxicity suggested that the mono-6-biotin-amino-6-deoxy-β-cyclodextrin associated inclusion complex might be a potential and promising delivery system for hydrophobic chemotherapeutics such as podophyllotoxin.
- Zhao, Xiu,Qiu, Neng,Ma, Yingyu,Liu, Junda,An, Lianying,Zhang, Teng,Li, Ziqin,Han, Xu,Chen, Lijuan
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- Aminated β-cyclodextrin-grafted Fe3O4-loaded gambogic acid magnetic nanoparticles: Preparation, characterization, and biological evaluation
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Based on aminated β-cyclodextrin (6-NH2-β-CD)-grafted Fe3O4 and gambogic acid (GA) clathrate complexes, a nanoparticle delivery system was developed with the aim to achieve low irritation, strong targeting, and high bioavailability of a gambogic acid magnetic nanopreparation. 6-NH2-β-CD grafted onto Fe3O4 MNPs was demonstrated by high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential, and magnetic measurements. The average particle size of the Fe3O4?NH2-β-CD MNPs was 147.4 ± 0.28 nm and the PDI was 0.072 ± 0.013. The encapsulation efficiency, drug loading, zeta potential, and magnetic saturation values of the Fe3O4?NH2-β-CD MNPs were 85.71 ± 3.47%, 4.63 ± 0.04%, -29.3 ± 0.42 mV, and 46.68 emu g-1, respectively. Compared with free GA, the in vitro release profile of GA from Fe3O4?NH2-β-CD MNPs was characterized by two phases: an initial fast release and a delayed-release phase. The Fe3O4?NH2-β-CD MNPs displayed continuously increased cytotoxicity against HL-60 and HepG2 cell lines in 24 h, whereas the carrier Fe3O4?NH2-β-CD MNPs showed almost no cytotoxicity, indicating that the release of GA from the nanoparticles had a sustained profile and Fe3O4?NH2-β-CD MNPs as a tumor tissue-targeted drug delivery system have great potential. Besides, blood vessel irritation tests suggested that the vascular irritation could be reduced by the use of Fe3O4?NH2-β-CD MNPs encapsulation for GA. The t1/2 and the AUC of the Fe3O4?NH2-β-CD?GA MNPs were found to be higher than those for the GA solution by approximately 2.71-fold and 2.42-fold in a pharmacokinetic study, respectively. The better biocompatibility and the combined properties of specific targeting and complexation ability with hydrophobic drugs make the Fe3O4?NH2-β-CD MNPs an exciting prospect for the targeted delivery of GA.
- Fang, Wei,Dai, Ya Ji,Wang, Ting,Gao, Hai Tao,Huang, Peng,Yu, Juan,Huang, He Ping,Wang, Dian Lei,Zong, Wei Lu
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- Synthesis, characterization, and in vitro evaluation of artesunate-β-cyclodextrin conjugates as novel anti-cancer prodrugs
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A novel series of artesunate-β-cyclodextrin (ATS-β-CD) conjugates, in which artesunate (ATS) was coupled covalently to one of the primary hydroxyl groups of β-cyclodextrin (β-CD) through amino bond formation, were synthesized and characterized by 1H NMR, HRMS, 2D NMR (ROESY), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results showed that the aqueous solubility of ATS-β-CD conjugates was 26-45 times better than that of free ATS. The cytotoxicity of the ATS-β-CD conjugates was evaluated on human colon cancer cell lines HCT116, LOVO, SW480, and HT-29, and the results indicated that ATS-2NβCD exhibited a very high cytotoxicity against HCT116, LOVO, and HT-29 with IC50 values of 0.58, 1.62, and 5.18 μmol/L, respectively. In addition, the supposition of better cytotoxicity was further supported by the control experiment of fluorescent cyclodextrin.
- Jiang, Rui-Jian,Zhao, Yu-Lin,Chen, Yun-Jian,Xiao, Dan,Wang, Fen,Han, Bin,Yang, Jian,Liao, Xia-Li,Yang, Li-Juan,Gao, Chuan-Zhu,Yang, Bo
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- pH-sensitive β-cyclodextrin derivatives for the controlled release of Podophyllotoxin
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An effective tumor targeting drug delivery systems was designed and synthesized by conjugating pH-sensitive maleamide derivatives to Mono-(6-deoxy-6-amino)-β-CD. Their characteristics and inclusion behaviors with insoluble anticancer drug PPT were investigated in both solution and solid state by means of 1H NMR and 2D-ROESY, XRD, DSC and SEM, which reveal PPT is successfully encapsulated in the cavity of CD derivatives with different stability constants (Ks). Water solubility of PPT are significantly increased to 60.35 and 22.89 mg·mL?1 after formation of inclusion complexes with host-1 and host-2, compared with free PPT (0.12 mg·mL?1). Their acid-controlled release has been studied in vitro by 1H NMR and UV-Vis spectra, living cells incubated with host 1-2 were observed by Inverted fluorescence microscope to confirm pH-response releasing. Moreover, host-1/PPT and host-2/PPT maintain effective cell proliferation inhibition to human cancer, while their cytotoxicity to normal cell is significantly reduced. Our work shows inspiring potential in tumor-targeted delivery and acid-controlled release of PPT both in vitro.
- Gao, Chuanzhu,Li, Fanjie,Liao, Xiali,Yang, Bo,Yang, Jing,Yang, Lei,Yang, Waixiang,Zhao, Yulin
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- Fuel-Driven and Enzyme-Regulated Redox-Responsive Supramolecular Hydrogels
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Chemical reaction networks (CRN) embedded in hydrogels can transform responsive materials into complex self-regulating materials that generate feedback to counter the effect of external stimuli. This study presents hydrogels containing the β-cyclodextrin (CD) and ferrocene (Fc) host–guest pair as supramolecular crosslinks where redox-responsive behavior is driven by the enzyme–fuel couples horse radish peroxidase (HRP)–H2O2 and glucose oxidase (GOx)–d-glucose. The hydrogel can be tuned from a responsive to a self-regulating supramolecular system by varying the concentration of added reduction fuel d-glucose. The onset of self-regulating behavior is due to formation of oxidation fuel in the hydrogel by a cofactor intermediate GOx[FADH2]. UV/Vis spectroscopy, rheology, and kinetic modeling were employed to understand the emergence of out-of-equilibrium behavior and reveal the programmable negative feedback response of the hydrogel, including the adaptation of its elastic modulus and its potential as a glucose sensor.
- Jain, Mehak,Ravoo, Bart Jan
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- Fluorescent sensors of molecular recognition. Modified cyclodextrins capable of exhibiting guest-responsive twisted intramolecular charge transfer fluorescence
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α-, β-, and γ-cyclodextrin derivatives bearing a p-(dimethylamino)benzoyl (DMAB) moiety (DMAB-αCyD, DMAB-βCyD, and DMAB-γCyD, respectively) have been synthesized as fluorescent sensors of molecular recognition. These compounds show dual fluorescence emission arising from normal planar (NP) and twisted intramolecular charge transfer (TICT) exited states, and among them strong TICT emission was observed for DMAB-βCyD. The induced circular dichroism spectra of the derivatives suggest that only DMAB-βCyD among other derivatives binds the DMAB moiety into its own cavity, forming an intramolecular inclusion complex. This conformation was confirmed by the analysis of its 1H-NMR data and was related to its strong TICT emission. The intensity of the TICT emission of DMAB-βCyD decreased markedly with increasing the concentration of cyclic alchols, monoterpenes, or steroids. This observation was explained by the guest-induced location change of the DMAB moiety from inside to outside of the cavity. Since the TICT emission intensity depended on the size, shape, and polarity of the guest molecules, DMAB-βCyD was useful as a fluorescent chemosensor of molecular recognition.
- Hamasaki, Keita,Ikeda, Hiroshi,Nakamura, Asao,Ueno, Akihiko,Toda, Fujio,Suzuki, Iwao,Osa, Tetsuo
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- Homodimerization and heteroassociation of 6-O-(2-sulfonato-6-naphthyl)-γ-cyclodextrin and 6-deoxy-(pyrene-1-carboxamido)-β-cyclodextrin
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6-O-(2-Sulfonato-6-naphthyl)-γ-cyclodextrin (1) and 6-deoxy-(pyrene-1-carboxamido)-β-cyclodextrin (2) were prepared. Homodimerizations of 1 and 2 and heteroassociation between 1 and 2 were investigated by 1H NMR, circular dichroism, and fluorescence spectroscopic methods. The compounds 1 and 2 form head-to-head dimers with dimerization constants of 140 ± 50 and 270 ± 70 M-1, respectively. We also determined the association constants of 1 with β-CD as 270 ± 20 M-1 and 2 with γ-CD as 100 ± 30 M-1 from fluorescence and circular dichroism titration data, respectively. The heteroassociation between 1 and 2 was manifested in increased circular dichroism ellipticities of 2, downfield shift of the H-2 proton of the pyrene group of 2, and upfield shift of the H-5 proton of the naphthyl group of 1 upon mixing 1 and 2. The analysis of circular dichroism titration data of 2 with 1 gave the association constant as 9300 ± 1600 M-1. The NMR and circular dichroism spectra suggested that the naphthyl group of 1 is deeply included into the β-CD cavity of 2, while the pyrene group of 2 is partially inserted in the γ-CD cavity of 1 in the complex. The energy-minimized structure from molecular modeling of the complex supports this. We believe that the facile heteroassociation of two cyclodextrin derivatives having different sizes of cavity and pendant group could be utilized as a useful strategy for assembling functionalized CDs for various applications.
- Park, Joon Woo,Song, Hee Eun,Lee, Soo Yeon
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- Insight into the Excitation-Dependent Fluorescence of Carbon Dots
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High quantum yield, photoluminescence tunability, and sensitivity to the environment are a few distinct trademarks that make carbon nanodots (CDs) interesting for fundamental research, with potential to replace the prevalent inorganic semiconductor quantum dots. Currently, application and fundamental understanding of CDs are constrained because it is difficult to make a quantitative comparison among different types of CDs simply because their photoluminescence properties are directly linked to their size distribution, the surface functionalization, the carbon core structures (graphitic or amorphous) and the number of defects. Herein, we report a facile one-step synthesis of mono-dispersed and highly fluorescent nanometre size CDs from a ‘family’ of glucose-based sugars. These CDs are stable in aqueous solutions with photoluminescence in the visible range. Our results show several common features in the family of CDs synthesized in that the fluorescence, in the visible region, is due to a weak absorption in the 300–400 nm from a heterogeneous population of fluorophores. Fluorescence quenching experiments suggest the existence of not only surface-exposed fluorophores but more importantly solvent inaccessible fluorophores present within the core of CDs. Interestingly, time-resolved fluorescence anisotropy experiments directly suggest that a fast exchange of excitation energy occurs that results in a homo-FRET based depolarization within 150 ps of excitation.
- Divya, Sasi,Narayan, Satya,Ainavarapu, Sri Rama Koti,Khushalani, Deepa
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- β-Cyclodextrin-Modified Magnetic Nanoparticles Immobilized on Sepharose Surface Provide an Effective Matrix for Protein Refolding
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In this article, we propose an impressive and facile strategy to improve protein refolding using solid phase artificial molecular chaperones consisting of the surface-functionalized magnetic nanoparticles. Specifically, monotosyl-β-cyclodextrin connected to the surface of 3-aminopropyltriethoxysilane (APES)-modified magnetic nanoparticles is immobilized on the sepharose surface to promote interaction with exposed hydrophobic surfaces of partially folded (intermediates) and unfolded states of proteins. Their efficiencies were investigated by circular dichroism spectroscopy and photoluminescence spectroscopy of the protein. Although the mechanism of this method is based on principles of hydrophobic chromatography, this system is not only purging the native protein from inactive inclusion bodies but also improving the protein refolding process. We chose β-cyclodextrin (β-CD) considering multiple reports in the literature about its efficiency in protein refolding and its biocompatibility. To increase the surface area/volume ratio of the sepharose surface by nanoparticles, more β-CD molecules are connected to the sepharose surface to make a better interaction with proteins. We suppose that proteins are isolated in the nanospace created by bound cyclodextrins on the resin surface so intermolecular interactions are reduced. The architecture of nanoparticles was characterized by Fourier transform infrared spectra, X-ray diffraction, scanning electron microscopy images, energy dispersive X-ray spectroscopy, nuclear magnetic resonance (1H NMR and 13C NMR), and dynamic light scattering.
- Ghaeidamini, Marziyeh,Kharat, Ali N.,Haertlé, Thomas,Ahmad, Faizan,Saboury, Ali A.
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- Supramolecular self-assembled aggregates formed by pentacosa-10,12-diynyl amidomethyl-β-cyclodextrin
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Mono[6-deoxy-6-(pentacosa-10,12-diynyl amidomethyl)]-β-cyclodextrin was successfully synthesized by reacting mono-6-amino-6-deoxy-β- cyclodextrin with N-hydroxysuccinimide ester of 10,12-pentacosadiynoic acid in DMF. The modified β-cyclodextrin self-assembled and aggregated to form a worm-like supramolecular structure, and the novel supramolecular aggregates were studied using 2D nuclear magnetic resonance spectroscopy, X-ray powder diffraction, thermogravimetry, and electron microscopy. Interestingly, the synthesized pentacosa-10,12-diynyl amidomethyl-β-cyclodextrin formed columnar type self-aggregates and it was clearly differentiated from cage-like structure of native β-cyclodextrin.
- Cho, Eunae,Kim, Hwanhee,Yang, Jee Eun,Jun, Bong-Hyun,Paik, Seung R.,Jung, Seunho
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- 1,3-Dipolar cycloaddition reaction of bipyridinium ylides with the propynamido-β-cyclodextrin. A regiospecific synthesis of a new class of fluorescent β-cyclodextrins
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The 1,3-dipolar cycloaddition reaction of bipyridinium ylides with the electron deficient propynamido-β-cyclodextrin was studied. This reaction resulted in the regiospecific formation of a new class of fluorescent β-cyclodextrins. The new fluorophore systems were characterized spectroscopically by their absorption and emission maxima and their quantum yields.
- Delattre, Fran?ois,Woisel, Patrice,Surpateanu, Gheorghe,Bria, Marc,Cazier, Francine,Decock, Patrick
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- Synthesis of lipophosphoramidyl-cyclodextrins and their supramolecular properties
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The synthesis of lipophosphoramidyl-β-CD was obtained by an Atherton-Todd (AT) reaction that involved dioleylphosphite and either functionalized permethylated or native β-cyclodextrin. This AT reaction that produced dioleylphosphoramide by making use of the amino group grafted on cyclodextrin, was optimized for these cyclic oligosaccharides. These new amphiphilic compounds were fully characterized, and their self-assembling properties were investigated: the mean size diameter and polydispersity measured by Dynamic Light Scattering (DLS) were affected by the nature of the aqueous media and the temperature of storage. The encapsulation properties of these nanoparticles have been evaluated using carboxyfluorescein and scopolamine derivatives as model of guests.
- Gervaise, Cédric,Bonnet, Véronique,Wattraint, Olivier,Aubry, Fréderic,Sarazin, Catherine,Jaffrès, Paul-Alain,Djeda?ni-Pilard, Florence
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- Self-assembled supramolecular bidentate ligands for aqueous organometallic catalysis
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(Chemical Equation Presented) Sugar snap P: An N,P heterobidentate supramolecular ligand was synthesized in water by mixing a monoamino-β- cyclodextrin with an appropriate phosphane. The resultant assembly was used with a platinum(II) salt in aqueous medium to catalyze the hydrogenation of an allylic alcohol (see picture).
- Machut, Cecile,Patrigeon, Julien,Tilloy, Sebastien,Bricout, Herve,Hapiot, Frederic,Monflier, Eric
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- Synthesis and immunostimulatory activity of sugar-conjugated TLR7 ligands
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Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), which are activated by recognizing pathogen-associated molecular patterns (PAMPs). The activation of TLRs initiates innate immune responses and subsequently leads to adaptive immune responses. TLR agonists are effective immuomodulators in vaccine adjuvants for infectious diseases and cancer immunotherapy. In exploring hydrophilic small molecules of TLR7 ligands using the cell-targeted property of a vaccine adjuvant, we conjugated 1V209, a small TLR7 ligand molecule, with various low or middle molecular weight sugar molecules that work as carriers. The sugar-conjugated 1V209 derivatives showed increased water solubility and higher immunostimulatory activity in both mouse and human cells compared to unmodified 1V209. The improved immunostimulatory potency of sugar-conjugates was attenuated by an inhibitor of endocytic process, cytochalasin D, suggesting that conjugation of sugar moieties may enhance the uptake of TLR7 ligand into the endosomal compartment. Collectively our results support that sugar-conjugated TLR7 ligands are applicable to novel drugs for cancer and vaccine therapy.
- Baba, Akihito,Wakao, Masahiro,Shinchi, Hiroyuki,Chan, Michael,Hayashi, Tomoko,Yao, Shiyin,Cottam, Howard B.,Carson, Dennis A.,Suda, Yasuo
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- Supramolecular Photochirogenesis Driven by Higher-Order Complexation: Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate to Slipped Cyclodimers via a 2:2 Complex with β-Cyclodextrin
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Chiral slipped 5,8:9′,10′-cyclodimers were preferentially produced over classical 9,10:9′,10′-cyclodimers upon supramolecular photocyclodimerization of 2-anthracenecarboxylate (AC) mediated by β-cyclodextrin (β-CD). This photochirogenic route to the slipped cyclodimers, exclusively head-to-tail (HT) and highly enantioselective, has long been overlooked in foregoing studies but is dominant in reality and is absolutely supramolecularly activated by 2:2 complexation of AC with β-CD. The intricate structural and photophysical aspects of this higher-order complexation-triggered process have been comprehensively elucidated, while the absolute configurations of the slipped cyclodimers have been unambiguously assigned by comparing the experimental and theoretical circular dichroism spectra. In the 2:2 complex, two ACs packed in a dual β-CD capsule are not fully overlapped with each other but are only partially stacked in a slipped anti- or syn-HT manner. Hence, they do not spontaneously cyclodimerize upon photoexcitation but instead emit long-lived excimer fluorescence at wavelengths slightly longer than the monomer fluorescence, indicating that the slipped excimer is neither extremely reactive nor completely relaxed in conformation and energy. Because of the slipped conformation of the AC pair in the soft capsule, the subsequent photocyclodimerization becomes manipulable by various internal or external factors, such as temperature, pressure, added salt, and host modification, enabling us to exclusively obtain the slipped cyclodimers with high regio- and enantioselectivities. In this supramolecularly driven photochirogenesis, the dual β-CD capsule functions as a chiral organophotocatalyst to trigger and accelerate the nonclassical photochirogenic route to slipped cyclodimers by preorganizing the conformation of the encapsulated AC pair, formally mimicking a catalytic antibody.
- Wei, Xueqin,Wu, Wanhua,Matsushita, Ryohei,Yan, Zhiqiang,Zhou, Dayang,Chruma, Jason J.,Nishijima, Masaki,Fukuhara, Gaku,Mori, Tadashi,Inoue, Yoshihisa,Yang, Cheng
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- Synthesis, characterization and biological activity of Rhein-cyclodextrin conjugate
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Cyclodextrin conjugate complexation is a useful method to enhance the solubility and absorption of poorly soluble drugs. A series of new Rhein-β-cyclodextrin conjugates (Rh-CD conjugates) have been synthesized and examined. Rhein is covalently linked with the β-CD by amido linkage in a 1:1 molar ratio. The conjugates were characterized by 1H NMR, 13C NMR, HRMS, powder X-ray diffraction (powder XRD) as well as thermogravimetric analysis (TGA). The results reveal that incorporation of β-CD could improve the aqueous solubility of Rhein and the cytotoxicity against hepatocellular carcinoma (HepG2) cell line as well as antibacterial activity against three organisms. The improved biological activity and the satisfactory water solubility of the conjugates will be potentially useful for developing novel drug-cyclodextrin conjugates, such as herbal medicine.
- Liu, Manshuo,Lv, Pin,Liao, Rongqiang,Zhao, Yulin,Yang, Bo
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- Facile preparation and characterization of novel oleanane-type triterpene functionalized β-cyclodextrin conjugates
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Oleanolic acid (OA) and echinocystic acid (EA), two naturally occurring pentacyclic oleanane triterpenes, are gaining increasing attention due to their promising pharmacological activities. Conjugation with amphiphilic α(β)-cyclodextrin (CD) via “click chemistry” can improve their solubility and anti-HCV entry potency. In the present work, four water-soluble β-CD-pentacyclic triterpene conjugates were designed and synthesized, in which OA and EA was coupled to one of the primary hydroxyl groups of β-CD via ester and amide bonds. The structures of the conjugates were unambiguously determined by 1H NMR, 13C NMR and HRMS or MALDI-TOF-MS. All the conjugates showed lower hydrophobicity (AlogP) than their parent compounds and no significant cytotoxicity was found to HL-60, A549, Hela and Bel-7402 cells at concentrations up to 10 μmol/L. Further anti-HCV entry activity and mechanism studies are under way in our laboratory.
- Jiao, Pingxuan,Wang, Shouxin,Liang, Shuobin,Li, Man,Gao, Qianqian,Ji, Dezhong,Chen, Yingying,Li, Haiwei,Ran, Fuxiang,Zhang, Yongmin,Zhang, Lihe,Zhou, Demin,Xiao, Sulong
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- Synthesis and inclusion properties study of some mono 6-amino β-cyclodextrin dimers bridged by N,N-succinyldiamide linkers
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Methylated and partially methylated cyclodextrin homo- and heterodimers linked by diamidosuccinic bridges were synthesised and their inclusion properties were evaluated using NMR and isothermic microcalorimetric measurements ITC. The selective binding of ligands, such as bisadamantyl derivatives, to the cavities of unprotected cyclodextrin dimers showed the equimolar formation of bidendate inclusion complexes (2:2, two ligand guest to two cavities host).
- Hocquelet, Celine,Jankowski, Christopher K.,Pelletier, Andre Lucien,Tabet, Jean-Claude,Lamouroux, Christine,Berthault, Patrick
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- Synthesis of bifunctional peptide derivatives based on a β-cyclodextrin core with drug delivery potential
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A selective, versatile, robust methodology for bifunctionalization of β-cyclodextrin is achieved allowing the attachment of peptides in varying C- and/or N-terminal combinations on resin using Fmoc SPPS. Two linkers are attached to cyclodextrin enabling selective binding to the resin (or a peptide attached to the resin). Continuation of peptide growth and/or cleavage from the resin follows, thus various combinations of peptide-cyclodextrin species are achieved. A model peptide (Gly-Ala) is used in this study to illustrate the potential of this system for attaching one or more bioactive peptides for drug transport and release purposes.
- White, Rachel J.,Plieger, Paul G.,Harding, David R.K.
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- Self-assembly PEGylation retaining activity (SPRA) technology via a host-guest interaction surpassing conventional PEGylation methods of proteins
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Polyethylene glycol (PEG) modification (PEGylation) is one of the best approaches to improve the stabilities and blood half-lives of protein drugs; however, PEGylation dramatically reduces the bioactivities of protein drugs. Here, we present "self-assembly PEGylation retaining activity" (SPRA) technology via a host-guest interaction between PEGylated β-cyclodextrin (PEG-β-CyD) and adamantane-appended (Ad) proteins. PEG-β-CyD formed stable complexes with Ad-insulin and Ad-lysozyme to yield SPRAinsulin and SPRA-lysozyme, respectively. Both SPRA-proteins showed high stability against heat and trypsin digest, comparable with that of covalently PEGylated protein equivalents. Importantly, the SPRA-lysozyme possessed ca. 100% lytic activity, whereas the activity of the covalently PEGylated lysozyme was ca. 23%. Additionally, SPRA-insulin provided a prolonged and peakless blood glucose profile when compared with insulin glargine. It also showed no loss of activity. In contrast, the covalently PEGylated insulin showed a negligible hypoglycemic effect. These findings indicate that SPRA technology has potential as a generic method, surpassing conventional PEGylation methods for proteins.
- Hirotsu, Tatsunori,Higashi, Taishi,Hashim, Irhan Ibrahim Abu,Misumi, Shogo,Wada, Koki,Motoyama, Keiichi,Arima, Hidetoshi
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- Self-inclusion behavior and circular dichroism of aliphatic chain-linked β-cyclodextrin-viologen compounds and their reduced forms depending on the side of modification
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The self-inclusion behavior and induced circular dichroism (ICD) characteristics of two β-cyclodextrin (β-CD) derivatives, in which a 1-methyl-4,4′-bipyridinium (viologen) group is connected by an octamethylene chain to either the primary (22+) or secondary (3 2+) side of β-CD, and of their reduced forms, are investigated. 1H NMR studies showed that 22+ forms an intramolecular self-inclusion complex with Kin = 3.1 ± 0.4, whereas 3 2+ forms a head-to-head type of dimer with KD = 65 ± 10 M-1 at 25 °C. 22+ and 32+ form [2]pseudorotaxanes with α-CD, with the secondary side of the α-CD facing the viologen moiety. The ICD characteristics of mono-6-[4-(1-methyl-4- pyridinio)-1-pyridinio]-β-CD (12+), 22+, 3 2+, and methyloctyl viologen-β-CD complexes were obtained for the oxidized and reduced states of the viologen units. The results indicated dimer formation for 1°, and intramolecular complexation for 2.+ and 2° in which the reduced viologen units are outside the β-CD cavity. The results also indicated intramolecular complexation for 3.+ and 3°, but with reduced viologen units inside the cavity. This work provides unequivocal evidence of the preference of the secondary side of cyclodextrins for viologen groups, regardless of their oxidation states, and the dependence of ICD of the viologen chromophores on their location with respect to the CD cavity.
- Park, Joon Woo,Lee, Soo Yeon,Song, Hyun Jung,Park, Kwanghee Koh
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- Effects of temperature and host concentration on the supramolecular enantiodifferentiating [4 + 4] photodimerization of 2-anthracenecarboxylate through triplet-triplet annihilation catalyzed by Pt-modified cyclodextrins
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Visible-light-driven photocatalytic supramolecular enantiodifferentiating dimerization of 2-anthracenecarboxylic acid (AC) through triplet-triplet annihilation (TTA), mediated by the Schiff base Pt(II) complex (Pt-1, Pt-2, and Pt-3) was studied. The host concentration and the temperature effects on the stereoselectivity were comprehensively investigated. Increasing the concentration of sensitizers/hosts significantly enhanced the conversion of the photoreaction but led to reduced enantioselectivities of the chiral photodimers 2 and 3 when the photoreaction was triggered by a 532 nm laser, which was in contrast with the results obtained by direct irradiation of AC with a 365 nm light-emitting diode (LED) lamp, due to the aggregation of the sensitizer/host in water. The cyclization of AC through triplet-triplet annihilation displayed significant temperature dependency when Pt-3 was employed as the sensitizer/host. Increasing the temperature from 0 ?C to 30 ?C with 5% equiv. of Pt-3 led to a great increase of the ee of 2 from 2.1% to 31.6%. However, hardly any temperature dependency was observed when the photodimerization was mediated by other sensitizers and/or hosts, or the photoreaction was triggered directly with a 365 nm LED lamp.
- Rao, Ming,Wu, Wanhua,Yang, Cheng
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- The complexes of cannabidiol mediated by bridged cyclodextrins dimers with high solubilization, in vitro antioxidant activity and cytotoxicity
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The poor water-solubility of Cannabidiol (CBD) seriously hinders its pharmacological activities such as anti-anxiety, anti-epilepsy, anti-oxidation and anti-cancer, etc. In this paper, we successfully designed and synthesized two bridged cyclodextrins (CDs) dimers with different length of bridged chains (succinic acid (SACDD) and 3,3′-thiodipropionic acid (TPACDD)) to encapsulate CBD, a reported DMCD (2,6-Di-O-methyl-β-cyclodextrin) with single cavity was used as a control complex. Their characteristics and inclusion complexation behaviors were investigated via XRD, SEM, NMR and TGA, the obtained data suggests CBD is successfully encapsulated into two cavity of bridged CD dimers with stronger stability constants, compared with DMCD. Water solubility of CBD is significantly promoted by 6.76 × 105 and 4.52 × 105 folds after formation of inclusion complexes, as well as the antioxidant activity in vitro (5.26-fold enhanced). MTT assays shows they remained effective anti-tumor activity, while they barely show cytotoxicity to normal cell. Our work might provide a strategy for development and application of water-solubility CBD.
- Chen, Liyuan,Yang, Waixiang,Gao, Chuanzhu,Liao, Xiali,Yang, Jing,Yang, Bo
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- A cyclodextrin-capped histone deacetylase inhibitor
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We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap". HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity.
- Amin, Jahangir,Puglisi, Antonino,Clarke, James,Milton, John,Wang, Minghua,Paranal, Ronald M.,Bradner, James E.,Spencer, John
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Read Online
- Electrochemical impedance determination of polychlorinated biphenyl using a pyrenecyclodextrin-decorated single-walled carbon nanotube hybrid
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This work reports the first detailed study on an electrochemical impedance sensor for determination of polychlorinated biphenyl (PCB), such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77), based on a single-walled carbon nanotube/pyrenecyclodextrin (SWCNT/PyCD) hybrid.
- Wei, Yan,Kong, Ling-Tao,Yang, Ran,Wang, Lun,Liu, Jin-Huai,Huang, Xing-Jiu
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Read Online
- β-Biguanidinium-cyclodextrin: A supramolecular mimic of mitochondrial ADP/ATP carrier protein
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We reported a novel mono-β-cyclodextrin derivative, mono-6-deoxy-6-biguanidino-β-cyclodextrin (β-biGCD), which was investigated as a mimic of ADP/ATP carrier (AAC). Its affinity toward AMP, ADP, and ATP was evaluated by means of isothermal titration calorimetry (ITC). The association constants (Ka) of β-biGCD binding to AMP, ADP, and ATP were determined to be (1.07±0.04)×106, (5.86±0.02)×106, and (4.33±0.06)×10 6 L mol-1, respectively, which were 100-fold higher than mono-guanidino-β-cyclodextrin (ca. 104 L mol-1). UV spectroscopic titrations further confirmed the above results. The interaction between β-biGCD and nucleotides was probed by docking simulation. These results reveal that the biguanidinium moiety mimics the arginine residues of mitochondrial AAC protein.
- Chen, Huo-Yan,Zhao, Meng,Tan, Jia-Heng,Huang, Zhi-Shu,Liu, Gao-Feng,Ji, Liang-Nian,Mao, Zong-Wan
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Read Online
- New amphiphilic biodegradable β-cyclodextrin/poly(l-leucine) copolymers: Synthesis, characterization, and micellization
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A new amphiphilic biodegradable β-cyclodextrin/poly(l-leucine) (β-CD-PLLA) copolymer was synthesized by ring-opening polymerization of N-carboxy-l-alanine anhydride (LL-NCA) in N,N-dimethylformamide (DMF) initiated by mono-6-amino-β-cyclodextrin (H2N-β-CD). The structures of the copolymers were determined by IR, 1H NMR and GPC. The fluorescence technique was used to determine the critical micelle concentrations (CMC) of copolymer micelle solution. The diameter and distribution of micelles were characterized by dynamic light scattering (DLS) and its shape was observed by transmission electron microscopy (TEM). The results showed that LL-NCA could be initiated by H2N-β-CD to produce the copolymer. These copolymers could self-assemble into nano-micelles in water. The CMC of copolymer solution and the size of micelle reduced with increasing proportion of the hydrophobic part. TEM images demonstrated the micelles are all spherical. Such block copolymers could be expected to find applications in drug delivery systems and other biomedical fields.
- Zhang, Guolin,Liang, Fang,Song, Ximing,Liu, Daliang,Li, Mengjiang,Wu, Qiuhua
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- 6A-O-[(4-biphenylyl)acetyl]-alpha-, -beta-, and -gamma-cyclodextrins and 6A-deoxy-6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and -gamma-cyclodextrins: potential prodrugs for colon-specific delivery.
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Cyclodextrins (CyDs) are known to be fermented to small saccharides by colonic microflora, whereas they are only slightly hydrolyzable and thus are not easily absorbed in the stomach and small intestine. This property of CyDs is particularly useful for colon-specific delivery of drugs. In this study, an antiinflammatory 4-biphenylylacetic acid (BPAA) was selectively conjugated onto one of the primary hydroxyl groups of alpha-, beta-, and gamma-CyDs through an ester or amide linkage, 6A-O-[(4-biphenylyl)acetyl[-alpha-, -beta-, and -gamma-CyDs (1-3) and 6A-deoxy-6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and -gamma-CyDs (4-6). In rat cecal and colonic contents (10%, w/v), 1 and 3 released more than 95% of BPAA within 1-2 h, and 2 released about 50% of the drug within 12 h. The amide prodrugs, 4-6, did not release BPAA in the cecal contents, but gave BPAA/maltose or BPAA/triose conjugates linked through an amide bond. On the other hand, these prodrugs were found to be stable in the contents of rat stomachs and small intestines, in intestinal or liver homogenates, and in rat blood. The serum levels of BPAA increased about 3 h after oral administration of 1 and 3 to rats, accompanying a marked increase in the serum levels, whereas 2 and 4-6 resulted in little increase of the serum levels. These facts suggest that BPAA is released after the ring opening of CyDs followed by the ester hydrolysis, and the BPAA activation takes place site-specifically in the cecum and colon. Therefore, the present CyD prodrug approach provides a versatile means of constructing a novel colon-specific drug delivery system.
- Uekama,Minami,Hirayama
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Read Online
- Functionalization using biocompatible carboxylated cyclodextrins of iron-based nanoMIL-100
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Here we report the first example of nanoMIL-100 particles modified with monomeric cyclodextrin derivatives of different length by exploiting strong interactions between non-saturated iron trimers at the external surface and carboxylate functionalities located at the end of biocompatible and flexible linkers of cyclodextrins. The main results revealed that, after the functionalization, the cyclodextrins are selectively located at the external surfaces covering the nanoparticles. Z potential measurements show that this functionalization induced changes respect to the bare nanoMIL-100 particles, however, the presence of the cyclodextrins does not modify the size neither porosity of the nanoparticles. The amount of cyclodextrins attached, investigated by thermogravimetry, increases with the length of the linker between CD cavity and nanoparticle surface, reaching up a 9 % wt. Auger spectroscopy suggested a clear predominant sp3 character after the functionalizations (vs. sp2 predominance in the unmodified nanoMIL-100). This study supposes the creation of an alternative family of hybrids based on carboxylated monomeric cyclodextrins.
- Ca?ón-Mancisidor, Walter,Carmona, Thais,Giménez-Marqués, Mónica,Gutiérrez-Cuti?o, Marlen,Hermosilla-Ibá?ez, Patricio,Mínguez Espallargas, Guillermo,Marco, José F.,Pérez, Edwin G.,Venegas-Yazigi, Diego
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- Biodegradable supramolecular micellesviahost-guest interaction of cyclodextrin-terminated polypeptides and adamantane-terminated polycaprolactones
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Biodegradable supramolecular micelles were prepared exploiting the host-guest interaction of cyclodextrin and adamantane. Cyclodextrin-initiated polypeptides acted as the hydrophilic corona, whereas adamantane-terminated polycaprolactones served as the hydrophobic core.
- Pottanam Chali, Sharafudheen,Azhdari, Suna,Galstyan, Anzhela,Gr?schel, André H.,Ravoo, Bart Jan
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supporting information
p. 9446 - 9449
(2021/09/22)
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- Visible light-activatable cyclodextrin-conjugates for the efficient delivery of nitric oxide with fluorescent reporter and their inclusion complexes with betaxolol
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This contribution reports the design, synthesis, photochemical properties and drug inclusion capability of two novel β-cyclodextrin (βCD) conjugates, βCD-NBFNO1 and βCD-NBFNO2, covalently integrating an N-nitroso amino-nitro-benzofurazan in the primary and secondary hydroxyl rims of the βCD scaffold, respectively through flexible spacers of different length. Both βCD conjugates are water-soluble and release nitric oxide (NO) under the input of either blue or green light, with quantum yields ΦNO (blue) = 0.13, 0.31 and ΦNO (green) = 0.007, 0.013 respectively, the former representing the largest values ever reported for nonmetal-containing NO donors activatable by visible light. The good contrast between the fluorescence green emission of the chromogenic moiety after and before the NO release permits the easy and in real-time quantification of the amount of NO generated, without the addition of external fluorescent agents. Despite the presence of the appendages, these βCD derivatives are also able to complex betaxolol, a β-blocker drug widely used for the reduction of the intraocular pressure, with binding constants Kb = 500 ± 50 and 1100 ± 100 M-1, respectively, without affecting the photochemical performances. In view of the well-known vasodilator properties of NO, the present βCD derivatives represent intriguing candidates for biopharmaceutical research studies addressed to combined therapeutic ocular applications.
- Seggio, Mimimorena,Payamifar, Sara,Fraix, Aurore,Kalydi, Eszter,Kasal, Petr,Catanzano, Ovidio,Conte, Claudia,Quaglia, Fabiana,Sortino, Salvatore
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supporting information
p. 8449 - 8455
(2021/05/26)
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- Functional carrier based on alkylamino cyclodextrin in entrapment of ferulic acid
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The invention discloses application of a functional carrier based on alkylamino cyclodextrin in entrapment of ferulic acid. On the one hand, alkylamino-modified beta-cyclodextrin is designed as a mainbody to prepare a ferulic acid clathrate compound; and on the other hand, an alkylamino cyclodextrin high-molecular polymer connected with linear polymer molecules is designed to load ferulic acid. Compared with the ferulic acid monomer, the ferulic acid entrapped by the carrier has advantages that the water solubility is obviously improved and the thermal stability is also enhanced; and a certain theoretical reference is provided for developing a novel water-soluble ferulic acid material and expanding the application of ferulic acid in the field of food and medicine.
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Paragraph 0039; 0041-0042; 0044
(2020/04/02)
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- Water soluble homogeneous catalysts that are recoverable by phase selectivity and host-guest interactions
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A chemical reaction is catalyzed in an organic solvent using a water soluble N-heterocyclic carbene homogeneous catalyst to form a reaction mixture. An aqueous phase in the reaction mixture. A solvent in which the catalyst is insoluble is added to the reaction mixture, causing the catalyst to migrate to the aqueous phase to form a catalyst-laden aqueous phase. The catalyst is extracted from the catalyst-laden aqueous phase.
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Page/Page column 9
(2020/08/30)
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- MICROSPHERES CONTAINING THERAPEUTIC AGENTS AND RELATED METHODS OF USE
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Microspheres, compositions including the microspheres, and methods of using the microspheres are disclosed herein. The microspheres can be substantially spherical and can include a copolymer of a monomer (such as an acrylic monomer) and a cyclodextrin or a derivative thereof. The microspheres can also include a therapeutic agent, such as a platinum-based drug.
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Paragraph 00134; 00135
(2019/03/05)
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- Picolinamide modified β-cyclodextrin/Pd (II) complex: Asupramolecular catalyst for Suzuki-Miyaura coupling of aryl, benzyl and allyl halides with arylboronic acids in water
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Novel supramolecular catalysts for Suzuki-Miyaura coupling were prepared and characterized by NMR, FT-IR, TEM, XRD, TGA, and XPS. The resulting picolinamide-modified β-cyclodextrin/Pd(II) complex (Pd(II)@PCA-β-CD) showed very efficient catalytic activity for Suzuki-Miyaura coupling of aryl, benzyl, and allyl halides with arylboronic acids in an environmentally benign aqueous solution. Various organic halides including chlorides can produce good to excellent yields with phenyl-boronic acid and a catalytic amount of Pd(II)@PCA-β-CD. This hydro-soluble catalyst was capable of being reused for at least eight runs with only a slight loss of catalytic activity. A putative mechanism of the Pd(II)/Pd(IV) catalytic cycle was also explored and calculated by ab initio QM/MM methods.
- Luo, Kaixiu,Zhang, Lu,Yang, Rui,Jin, Yi,Lin, Jun
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p. 200 - 210
(2018/08/09)
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- Removable Water-Soluble Olefin Metathesis Catalyst via Host-Guest Interaction
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A highly removable N-heterocyclic carbene ligand for a transition-metal catalyst in aqueous media via host-guest interactions has been developed. Water-soluble adamantyl tethered ethylene glycol in the ligand leads a hydrophobic inclusion into the cavity of β-cyclodextrin. Ruthenium (Ru) olefin metathesis catalyst with this ligand demonstrated excellent performance in various metathesis reactions in water as well as in CH2Cl2, and removal of residual Ru was performed via filtration utilizing a host-guest interaction and extraction.
- Kim, Cheoljae,Ondrusek, Brian A.,Chung, Hoyong
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supporting information
p. 736 - 739
(2018/02/09)
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- Synthetic β-Cyclodextrin Dimers for Squaraine Binding: Effect of Host Architecture on Photophysical Properties, Aggregate Formation and Chemical Reactivity
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Reported herein is the synthesis and application of three novel β-cyclodextrin dimer hosts for the complexation of near infrared (NIR) squaraine dyes in aqueous solution. A series of eight different N-substituted N-methyl anilino squaraine dyes with variable terminal groups are investigated, with an optimal n-hexyl-substituted squaraine guest demonstrating binding constants orders of magnitude higher than the other squaraine–host combinations and comparable to literature-reported systems. Moreover, hydrophobic complexation of the squaraine dyes with the β-cyclodextrin dimer hosts causes drastic changes in the squaraine's photophysical properties, propensity for aggregation and susceptibility to hydrolytic decay.
- Chaudhuri, Sauradip,Verderame, Molly,Mako, Teresa L.,Bandara, Y. M. Nuwan D. Y.,Fernando, Ashvin I.,Levine, Mindy
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supporting information
p. 1964 - 1974
(2018/05/15)
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- A oleanolic acid with amine cyclodextrin clathrate
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The invention discloses a clathrate compound of pentacyclic triterpene oleanolic acid and amine cyclodextrin, the amine cyclodextrin is amino-substituted beta-cyclodextrin, The clathrate compound is prepared by employing a solvent method or an ultrasonic method; after oleanolic acid and amine cyclodextrin form the clathrate, the solubility of clathrate in water can be greatly increased, stability is increased, and bioavailability is increased. The antitumor in-vitro experiment shows that the clathrate has good antitumor in-vitro activity; the preparation method has the advantages of simple process, easy operation and mild reaction condition, and can be used for development of new oleanolic acid preparation.
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Paragraph 0045-0046
(2017/12/02)
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- MICROSPHERES CONTAINING THERAPEUTIC AGENTS AND RELATED METHODS OF USE
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Microspheres, compositions including the microspheres, and methods of using the microspheres are disclosed herein. The microspheres can be substantially spherical and can include a copolymer of a monomer (such as an acrylic monomer) and a cyclodextrin or a derivative thereof. The microspheres can also include a therapeutic agent, such as a platinum-based drug.
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Paragraph 0120
(2017/09/02)
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- Merging supramolecular catalysis and aminocatalysis: Amino-appended β-cyclodextrins (ACDs) as efficient and recyclable supramolecular catalysts for the synthesis of tetraketones
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Well-designed amino-appended β-cyclodextrins (ACDs) with an amino side chain of different lengths at the primary face of β-CD were synthesized and employed in the catalytic synthesis of a series of tetraketones as supramolecular catalysts in water for the first time. Yields of 58-97% were obtained with up to 30 examples of substrate. The catalyst could be recycled easily, while a 92% yield and 84% rate of catalyst recovery could be achieved after 8 cycles of catalyst recycling. Moreover, a catalytic mechanism merging supramolecular catalysis and aminocatalysis could be proposed through detailed 1D and 2D NMR, ESI-MS and Job plot analyses. This protocol retained the promising characteristics of ambient temperature, green medium, simple operation, broad substrate scope, excellent yields, superb catalyst recycling performance and unique catalytic mechanism.
- Ren, Yufeng,Yang, Bo,Liao, Xiali
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p. 22034 - 22042
(2016/03/08)
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- The amino side chains do matter: Chemoselectivity in the one-pot three-component synthesis of 2-amino-4: H -chromenes by supramolecular catalysis with amino-appended β-cyclodextrins (ACDs) in water
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In this study, the one-pot three-component synthesis of 2-amino-4H-chromenes was accomplished by supramolecular catalysis using a series of well-designed amino-appended β-cyclodextrins (ACDs) in water. The catalytic mechanism was elucidated in detail with 1D and 2D NMR and ESI-MS analyses, while the key roles of amino side chains of ACDs in the reaction chemoselectivity were addressed for the first time.
- Ren, Yufeng,Yang, Bo,Liao, Xiali
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p. 4283 - 4293
(2016/07/06)
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- Enantiomeric recognition of amino acid ester salts by β-cyclodextrin derivatives: An experimental and computational study
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β-cyclodextrin derivatives bearing benzoyl (β-CD-1) and naphthoyl (β-CD-2) moieties have been synthesized from salicylic acid and 3-hydroxy-2-naphthoic acid by a convenient method in 60% and 58% yields, respectively, and were tested for enantiomeric recognition of amino acid ester derivatives. Their ability to discriminate between various L-/D-amino acid methyl ester hydrochloride salts was examined using the 1H NMR titration method in DMSO-d6 at 25 °C. β-CD-2 produced a fairly good discrimination of tryptophan ester salts with a binding constant of 4041 M-1 for L-salt compared with 2864 M-1 for D-salt, which corresponds to a difference of-0.21 kcal mol-1 in binding free energies. The binding free energies obtained from molecular dynamic calculation by MM/PB(GB)SA are consistent with those obtained from the experimental results.
- Rezanka, Michal,Stibor, Ivan,Azizoglu, Murat,Turgut, Yilmaz,Pirinccioglu, Necmettin
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p. 249 - 267
(2016/10/22)
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- SELF-ASSEMBLED TARGETED INCLUSION COMPLEXES FOR DRUG DELIVERY
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Inclusion complexes are provided containing a targeted carrier non-covalently associated with an active agent. The targeted carrier includes an inclusion host that binds the active agent or a binding partner attached to the active agent. The targeted carrier includes a targeting moiety attached to the inclusion host or to a polymer or linker attached thereto. Pharmaceutical formulations of the inclusion complexes are provided. Methods of making the inclusion complexes and formulations thereof are provided. Methods of using the inclusion complexes and formulations are provided. In some embodiments the inclusion complex includes a progesterone or estrogen targeting moiety that targets the inclusion complex to cancer cells. The targeting can cause internalization of the active agent in the target cells. In some embodiments the active agent is an anthracycline such as doxorubicin and the target cells are cancer cells.
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Page/Page column 29
(2016/09/22)
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- ORGANIC-INORGANIC HYBRID SOLID HAVING A MODIFIED OUTER SURFACE
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The present invention concerns metal-organic hybrid solids having a modified outer surface. These solids can be used, for example, for the storage and vectoring of molecules of interest such as pharmaceutically active ingredients, compounds of interest in cosmetics and markers, for example contrast agents. These solids have good results in terms of active drug loading capacities, biocompatibility, stability and controlling the release of the active ingredients encapsulated.
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Paragraph 0464; 0465; 0466; 0467; 0468
(2015/06/10)
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- NUCLEIC ACID COMPLEXES
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The invention relates to nucleic acid complexes, methods of preparation thereof, and uses thereof for delivering a nucleic acid into a cell.
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Paragraph 0114
(2015/07/27)
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- ADSORBENT FOR ORGANIC FLUORO-COMPOUND COMPRISING CYCLODEXTRIN-SUPPORTED POLYMER
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The present invention is to provide a material that is capable of selectively adsorbing organic fluoro-compounds such as perfluorooctane sulfonic acid, allows the adsorbed organic fluoro-compounds to be recovered, and is reusable as an adsorbent, specifically to provide a polymer in which cyclodextrin is supported on the surface of a water-insoluble polymer, and an adsorbent containing the same, and a method of use of the same as a selective adsorbent of, in particular, an organic fluoro-compound.
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- Supramolecular self-assembled nanoparticles for chemo-photodynamic dual therapy against cisplatin resistant cancer cells
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Supramolecular self-assembled nanoparticles that can overcome cisplatin resistance were constructed by utilizing a platinum(iv) prodrug bridged β-cyclodextrin dimer and adamantyl group modified porphyrin as the host and guest molecules, respectively.
- Zhang, Wei,Li, Yi,Sun, Jing-Hua,Tan, Cai-Ping,Ji, Liang-Nian,Mao, Zong-Wan
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supporting information
p. 1807 - 1810
(2015/01/30)
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- Conductive Elastomers with Autonomic Self-Healing Properties
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Healable, electrically conductive materials are highly desirable and valuable for the development of various modern electronics. But the preparation of a material combining good mechanical elasticity, functional properties, and intrinsic self-healing ability remains a great challenge. Here, we design composites by connecting a polymer network and single-walled carbon nanotubes (SWCNTs) through host-guest interactions. The resulting materials show bulk electrical conductivity, proximity sensitivity, humidity sensitivity and are able to self-heal without external stimulus under ambient conditions rapidly. Furthermore, they also possess elasticity comparable to commercial rubbers.
- Guo, Kun,Zhang, Da-Li,Zhang, Xiao-Mei,Zhang, Jian,Ding, Li-Sheng,Li, Bang-Jing,Zhang, Sheng
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supporting information
p. 12127 - 12133
(2015/10/12)
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- An efficient multiple healing conductive composite via host- Guest inclusion
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A self-healable conductive composite is developed by combining the small molecules and nanotubes through host-guest interactions. This material shows uniform conductivity, microwave absorption and humidity sensing properties, and can be rapidly healed to over 90% electrical and mechanical properties with the aid of water multiple times. In addition, the produced material is also remouldable and recyclable.
- Zhang, Da-Li,Ju, Xin,Li, Luo-Hao,Kang, Yang,Gong, Xiao-Lei,Li, Bang-Jing,Zhang, Sheng
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supporting information
p. 6377 - 6380
(2015/04/14)
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- Nucleic acid complexes
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The invention relates to nucleic acid complexes, methods of preparation thereof, and uses thereof for delivering a nucleic acid into a cell.
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(2015/01/07)
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- Scutellarin-cyclodextrin conjugates: Synthesis, characterization and anticancer activity
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A series of scutellarin-cyclodextrin conjugates (SCU-CD conjugates), in which scutellarin was covalently bound to one of the primary hydroxyl groups of β-CD, were prepared, and their structures were determined using NMR and MS. These conjugates were further characterized by XRD and TG. The results showed that the aqueous solubility of the conjugates was much higher than that of scutellarin, and the conjugates could hardly be hydrolyzed to scutellarin in aqueous solutions. The cytotoxicity of SCU-CD conjugates on human colon cancer cell lines HT-29, SW480, Lovo and HTC116 indicated that the antitumor activities of the conjugates were better than that of scutellarin. This high antitumor activity, along with the satisfactory aqueous solubility and high stability of the conjugates, will be potentially useful for their application on human colon cancer chemotherapies.
- Yang, Bo,Zhao, Yu-Lin,Yang, Xia,Liao, Xia-Li,Yang, Jian,Zhang, Ji-Hong,Gao, Chuan-Zhu
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p. 1308 - 1314
(2013/08/24)
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- Pendant polymer:Amino-β-cyclodextrin:siRNA guest:Host nanoparticles as efficient vectors for gene silencing
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A novel siRNA delivery vector has been developed, based on the self-assembly of monosubstituted cationic β-CD derivatives with a poly(vinyl alcohol)MW27kD (PVA) main-chain polymer bearing poly(ethylene glycol)MW2000 (PEG) and acid-labile cholesterol-modified (Chol) grafts through an acid-sensitive benzylidene acetal linkage. These components were investigated for their ability to form nanoparticles with siRNA using two different assembly schemes, involving either precomplexation of the pendant Chol-PVA-PEG polymer with the cationic β-CD derivatives before siRNA condensation or siRNA condensation with the cationic β-CD derivatives prior to addition of Chol-PVA-PEG to engage host:guest complexation. The pendant polymer:amino- β-CD:siRNA complexes were shown to form nanoparticles in the size range of 120-170 nm, with a slightly negative zeta potential. Cell viability studies in CHO-GFP cells shows that these materials have 103-fold lower cytotoxicities than 25 kD bPEI, while maintaining gene-silencing efficiencies that are comparable to those of benchmark transfection reagents such as bPEI and Lipofectamine 2000. These results suggest that the degradable Chol-PVA-PEG polymer is able to self-assemble in the presence of siRNA and cationic-β-CD to form nanoparticles that are an effective and low-toxicity vehicle for delivering siRNA cargo to target cells.
- Kulkarni, Aditya,Defrees, Kyle,Hyun, Seok-Hee,Thompson, David H.
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supporting information; experimental part
p. 7596 - 7599
(2012/06/30)
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- Microwave-assisted synthesis of 6-amino-β-cyclodextrins
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A general microwave-assisted procedure for the synthesis of 6-amino-β-cyclodextrins is reported. Mono-tosyl-β-cyclodextrin was used as the starting material in a one-pot route employing a solvent-free microwave-assisted reaction with a liquid amine. Shorter reaction times were observed for the formation of 6-amino-β-cyclodextrins using this novel microwave approach compared to the thermal procedure.
- Puglisi, Antonino,Spencer, John,Clarke, James,Milton, John
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body text
p. 475 - 478
(2012/08/28)
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- Ester catalytic hydrolysis by a tridentate N,N′,N″-copper bridged cyclodextrin dimer
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A new pyridine bridged cyclodextrin dimer mono-copper complex (CuL) was synthesized and characterized. The hydrolysis of carboxylic acid esters, bis(4-nitrophenyl)carbonate (BNPC) and 4-nitrophenyl acetate (NA), and phosphate ester, a DNA model bis(4-nitrophenyl)phosphate (BNPP), promoted by CuL has been investigated. The resulting hydrolysis rate constants showed that CuL had a very high rate of catalysis for BNPC hydrolysis, yielding a 2.73 × 10 3-fold rate enhancement over uncatalyzed hydrolysis at pH 7.00, compared to only a 78.2-fold rate enhancement for NA hydrolysis. The initial first-order rate constant of catalytic hydrolysis for BNPP was 1.01 × 10-7 s-1 at pH 8.5, 35 °C and 0.1 mM catalyst concentration, about 1260-fold acceleration over uncatalyzed hydrolysis. The second rate constant kBNPP of BNPP hydrolysis promoted by CuL was found to be 5.94 × 10-4 M-1 s-1.
- Tang, Si-Ping,Chen, Sha,Wu, Guang-Fei,Chen, Huo-Yan,Mao, Zong-Wan,Ji, Liang-Nian
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scheme or table
p. 184 - 188
(2011/04/22)
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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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experimental part
p. 809 - 821
(2010/05/02)
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- Cyclodextrin supramolecular complex as a water-soluble ratiometric sensor for ferric ion sensing
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Heightened concern for human health and environmental protection has stimulated active research on the potential impact of transition-metal ions and their toxic effects, thus it is very demanding to design transition-metal ion detection methods that are cost-effective, rapid, facile, and applicable to the environmental and biological milieus. In this study, we demonstrated an alternative strategy for constructing a water-soluble FRET-based ratiometric sensor for ferric ion detection by forming a supramolecular β-cyclodextrin/ dye complex. This water-soluble FRET system consists of a dansyl-linked β-cyclodextrin (β-CD-DNS) and a spirolactam rhodamine-linked adamantane (AD-SRhB). The dansyl moiety serves as the donor, and the spirolactam-rhodamine B derivative (SRhB) was chosen as a sensitive, selective chemosensor for Fe(III) ions and a very efficient ring-opening reaction induced by Fe(III) generates the long-wavelength rhodamine B fluorophore that can act as the energy acceptor. Moreover, the adamantyl (AD) group, which is known for its capability to form stable host-guest inclusion complexes with β-CD derivatives, was covalently linked to the spirolactam rhodamine, thus the adamantyl moiety of the ion-recognition element can be anchored inside theCDcavity. In this way, the donor-acceptor separation can be kept within the critical Foerster distance; accordingly, energy transfer can take place from the donor (dansyl) to the acceptor (rhodamine derivative/Fe(III) complex), and thus ratiometric detection for Fe(III) in an aqueous medium can be fulfilled. This FRET-based supramolecular sensor can be readily formed via an inclusion process using the donor part and the acceptor part, hence this strategy could afford a robust approach for constructing a wide range of FRET-based water-soluble sensing systems simply by assembling a specifically predesigned donor-linked CD and acceptor-linked adamantane.
- Xu, Meiyun,Wu, Shuizhu,Zeng, Fang,Yu, Changmin
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experimental part
p. 4529 - 4534
(2011/10/19)
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