Electrochemical Biosensor Utilizing Supramolecular Association of Enzyme on Sol−gel Matrix Embedded Gold Nanoparticles Supported Reduced Graphene Oxide−cyclodextrin Nanocomposite

Herein we present β‐cyclodextrin (CD)‐functionalized reduced graphene oxide (RGO) nanosheets supported on silicate sol‐gel matrix‐embedded gold nanoparticles (Au NPs) modified electrode as a new affinity binding nanocomposite. The modified electrode is fabricated through layer‐by‐layer drop casting followed by immobilization of chemically modified enzyme conjugate (horse radish peroxidase (HRP)?adamantane carboxylic acid (ADA)). This affinity system is based on the supramolecular association between CDs and HRP?ADA and is mimicking the biological avidin?biotin interactions. CDs‐functionalized RGO (RGO?CD) functions as a macrocyclic host to form stable supramolecular inclusion complexes with enzyme conjugate. Besides Au NPs improve the interfacial interaction with RGO?CD nanosheets, and thus exhibit synergistic electrocatalytic effect toward H₂O₂ reduction in the presence of 1 mM hydroquinone.     

环糊精超分子组装体的研究进展

环糊精是由若干个D-吡喃葡萄糖单元通过α-1,4-糖苷键连接而成的环状低聚糖,具有一个亲水性的外表面和一个疏水性的空腔。利用主客体相互作用,环糊精及其衍生物能够选择性地与大小匹配的疏水性客体分子形成各种超分子包合物。本文概述了环糊精的结构与性质,并介绍了近年来国内外以环糊精为基础的纳米粒子、水凝胶等超分子组装体的设计原理、作用机制、刺激响应及应用特点,并对环糊精超分子组装体的前景进行了展望。     

Spectrofluorimetric determination of serotonin and 5-hydroxyindoleacetic acid in urine with different cyclodextrin media

Alternative and sensitive spectrofluorimetric methods for the determination of hydroxyindoles, such as serotonin (5HT) and 5-hydroxyindoleacetic acid (5HIA), were developed on the basis of supramolecular interaction with cyclodextrin (CD) nanocavities (βCD and hydroxypropyl-βCD, HPCD) at different pH values. Both substrates and receptors have acidic protons, therefore the interactions produced in different systems were considered. The effects of neutral CD at pH 2.00 and 6.994, and of anionic CD at pH 13.00 on the specific acid-base species of the compounds at each pH were determined. In all the conditions studied, the fluorescence of the substrates in the presence of CD increased. The association constants (K_A, mol⁻¹ L) between the substrates and CD were determined (30-300) and interpreted. A zero-crossing first-derivative spectrofluorimetric method with and without HPCD was developed for the simultaneous determination of 5HT and 5HIA. The limits of detection (L_D, ng mL⁻¹) for the best conditions were 0.37 for 5HT and 0.50 for 5HIA at pH 2.00 with HPCD. These L_D proved to be better than others reported. The applicability of the direct and derivative spectrofluorimetric methods to urine samples was demonstrated with good recoveries 92-110% and R.S.D. 1-10%.     

Kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides in the presence of supramolecular cyclodextrin nanocapsules

The non-enzymatic kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides was accomplished for the first time by using the selective sequestration of one enantiomer within a supramolecular cyclodextrin (CD) nanocapsule in nonpolar solvents. In addition, the first example of a crystalline structure for an inclusion complex between an acyl chloride and a CD derivative is reported.     

A versatile liposome/cyclodextrin supramolecular carrier for drug delivery through the blood-brain barrier

For many commercial drugs, reaching the central nervous system in large amount without damaging the blood-brain-barrier (BBB) remains a challenging task. We present here a supramolecular strategy aiming at using a well-defined cyclodextrin-coated liposomes as drug carrier and adamantoyl saccharides as BBB-interacting ligands. In this study, the liposome is constituted of n-alkyldimethylammoniumcyclodextrins incorporated in the lipid bilayer of a 3/7 cholesterol/dipalmitoylphosphatidylcholine mixture and the ligand is constituted of an adamantoylglucose molecule whose adamantoyl moiety can be included in the CD cavity. The whole supramolecular assembly has been characterized by light-scattering and ³¹P NMR measurements. Toxicity and permeability studies on an in vitro model of the BBB clearly demonstrated a 5-fold improved ability of the modified liposome to enter the BBB-endothelial cells compared to the non-coated liposome. Fluorescence labelling of these liposomes is also displayed with DiI as a fluorescent probe.     

An efficient methodology to study cyclodextrin clusters: application to α-CD hydrated monomer, dimer, trimer and tetramer

The hydrated α-cyclodextrin (α-CD) clusters resulting from the following process: nα-CD + n(H₂O)₆ → α-CD_n · 6nH₂O, with n = 1, 2, 3, 4, have been investigated using semiempirical (PM3), ab initio Hartree-Fock and Density Functional Theory (BLYP functional) levels of theory. The largest structure containing 576 atoms and 5,760 contracted basis functions (6-31G(d,p) basis set) poses as a considerable hard task for quantum chemical calculations. As the number of basis function increases rapidly with the cluster size, an alternative procedure to make the calculations feasible is certainly welcome, in order to perform BLYP calculations with an adequate basis set. Through the aid of a computer program that we developed, it became of practical use the selection of atom by atom basis sets, using the common chemical sense, enabling quantum mechanical calculations to be performed for very large molecular interacting systems (inclusion complexes), at an affordable computational cost. In this article we show how an appropriate selection of basis functions, leaving the CH_n groups with a minimal basis set and the oxygen atoms (and OH groups) with a better quality basis set, lower considerably the computational cost with no significant loss in the calculated interaction energies. A regular pattern is observed for α-CD hydrated monomer, dimer, trimer and tetramer, therefore adding support to the use of this procedure when studying larger hydrogen bonded clusters where electron correlation effects are important. We show that the procedure reported here enables DFT calculations for hydrated cyclodextrin using basis set up to the 6-311++G(3df,3pd) triple zeta quality .     

Immobilization of Xanthine Oxidase on Carbon Nanotubes Through Double Supramolecular Junctions for Biosensor Construction

A novel approach for the noncovalent functionalization of single‐walled carbon nanotubes with enzymes, using a β‐cyclodextrin‐modified pyrene derivative, mono‐6‐ethylenediamino‐(2‐pyrene carboxamido)‐6‐deoxy‐β‐cyclodextrin (Pyr‐βCD), as a molecular bridge for the construction of a supramolecular assembly between the nanotube surface and an adamantane‐modified enzyme, is reported. The Pyr‐βCD derivative was synthesized and its stacking to SWNT through π–π interactions accomplished. The functionalized nanotubes showed low capacity for the nonspecific adsorption of proteins, but were able to immobilize adamantane‐modified xanthine oxidase via host‐guest associations. This double supramolecular junctions‐based approach was employed to modify a glassy carbon electrode with the enzyme/nanotubes complex for designing a biosensor device toward xanthine. The biosensor showed fast electroanalytical response (10 s), high sensitivity (5.9 mA/M cm²) low detection limit (2 µM) and high stability.     

Supramolecular assembly system depended on guest species based on bis-naphthane modified β-cyclodextrin dimer

The supramolecular assembly system based on bis naphtahlene modified β-cyclodextrin dimer linked with ethylenediamine unit was studied. The synthesis of the titled compound (β-1) was succeeded in a 7% synthetic yield. It was observed that β-1 showed monomer emission, which was decreased concurrently with appearance of excimer emission in an addition of guest species such as 1-adamantanol or ursodeoxycholic acid. When γ-CyD was added to the system, two types of fluorescent spectra were obtained, which was depended on guest species. It was indicated that both of naphthalene units of β-1 were included in the γ-CyD cavity in the presence of 1-adamantanol in a fashion of 2:1 complex. On the other hand, an addition of ursodeoxycholic acid gave disappearance of the excimer emission as well as increase of monomer emission. In the system, each of the appended units was trapped by the each of two γ-CyDs, which is 2:2 complex formation.     

Formation of cyclodextrin nanotube induced by POPOP molecule

The interaction between 2,2′-p-phenylenebis (5-phenyloxazol) (POPOP) and cyclodextrins (CDs) was investigated using UV-Vis absorption, steady-state fluorescence, and dynamic light scattering (DLS). The results indicated that POPOP could form the 1:2 (guest:host) inclusion complex with β-CD at lower concentrations, which could further form the extended nanotube at higher concentrations. POPOP could also induce the formation of the nanotube of γ-CD. The fluorescence emission of POPOP in aqueous solution of γ-CD showed obvious red shift accompanied by the disappearance of fine structure compared with that in aqueous solution of β-CD, which could be attributed to the formation of the excimer of POPOP in the larger cavity of γ-CD. It was found that at pH greater than 12, the hydrogen bond between the neighboring CDs was destroyed, which led to the collapse of the nanotubular structure. The results also showed that the nanotube structure was not stable at temperatures above 331 K.     

Studies of cyclodextrin effect for glycosylation by galactosyltransferase

Cyclodextrins (CDs) do not disturb HPLC purification and do not form lather, which makes them superior to commonly used surfactants. In this paper, the authors describe the utility of CDs, specifically α-CD, β-CD, and γ-CD, for the synthesis of neoglycolipids from insoluble peptide-linked substrates. γ-CD was found to be well matched to the bulky benzyl group and accelerated the reaction for the substrate having Phe (F), while β-CD was well matched to the methyl group and accelerated the reaction for the substrate having Ala (A). Galactosylation to water-insoluble peptide-linked glucosaminide substrate by galactosyltransferase proceeded 63% at the most, but using either β-CD or γ-CD gave quantitative yield within 10 h.     

Redox-responsive supramolecular nanoparticles based on amphiphilic sulfonatocalixarene and selenocystamine dihydrochloride

A supramolecular nanoparticle was fabricated based on the aggregation of amphiphilic p-sulfonatocalixarene induced by selenocystamine dihydrochloride (Se-Cys). Owing to the property of Se-Cys, the nanoparticles showed the redox-responsive disassembly behaviors with the addition of H2O2 and GSH     

Computational study on the molecular inclusion of andrographolide by cyclodextrin

Due to the poor water solubility of andrographolide (andro), an inclusion technique has been developed to modify its physical and chemical properties so as to improve its bioavailability. In contrast with the immense experimental studies on the inclusion complexes of andro:cyclodextrin, no computational study has so far been carried out on this system. In this work, preliminary docking experiments with AutoDock were performed. Density Functional Theory (DFT) and Austin Model 1 (AM1) calculations upon the docking instances were applied to investigate the two possible modes of molecular inclusions between andro and x-cyclodextrin (xCD, where x is alpha, beta or gamma). Atoms-in-Molecules (AIM) analysis based on the B3LYP/cc-pVDZ wavefunction was applied to verify the existence of the intermolecular hydrogen bonds. It was found that the most stable complex among the six possible inclusion complexes was the one formed between andro and betaCD with andro's decalin ring moiety wrapped by CD at a ratio of 1:1. The hydrogen bonds between andro and CD were responsible for the stability of the inclusion complexes. The calculated data were found to be consistent with the experimental results. Thus, the results of this study can aid new drug design processes.     

Esterase activity of cyclodextrin dithiocarbamates

The catalytic activity of dithiocarbamate appended α- and β-cyclodextrins in the hydrolysis of p-nitrophenyl acetate (PNPA) was studied at alkaline pH. The values of k_cat/k_uncat for the hydrolysis of PNPA ranged from 8 to 165 in the presence of the catalyst and are pH independent in the range 7.5-9.0. Addition of Cu(II) increases the activity by factors of 75-515 and k_cat values increase with increasing pH in the same range. The differences in the obtained kinetic parameters are interpreted on the basis of two different mechanisms.     

多酸-环糊精超分子体系的研究进展

综合评述了近些年来基于环糊精的多金属氧簇超分子体系的代表性工作, 以参与构建的多酸-环糊精超分子复合物中不同多酸的结构类型为分类依据进行了相应的归纳概述. 希望本文可以引起读者对于多金属氧簇-环糊精超分子体系的研究兴趣, 并为研究者提供一些新的思路和启发.     

The Construction and Transition of Supramolecular Hydrogels Induced by Cyclodextrin Inclusion

Soft hydrogel nano‐ and micro‐structures have great potential applications in the field of tissue engineering and chemical sensors. In this paper, a supramolecular hydrogel was constructed by combining a triblock copolymer poly(ethylene oxide)₁₀₀‐(propyleneoxide)₇₀‐(ethyleneoxide)₁₀₀ (PEO₁₀₀‐PPO₇₀‐PEO₁₀₀ ) (Pluronic F127), mono‐6‐thio‐β‐cyclodextrins (SH‐β‐CDs), and silver nanoparticles. Here, SH‐β‐CDs couple to the silver nanoparticles via thio groups and include PPO blocks of F127 using the hydrophobic cavity to form pseudo‐polyrotaxanes. Moreover, the hydrogel can be transformed to a homogenous solution by the addition of hydrochloride powder. These results are important for research related to the construction of soft hydrogel materials and control their mechanical properties.     

Regioselective photoamination of 4-nitroveratrole upon cyclodextrin complexation

Photoamination of 4-nitroveratrole in cyclodextrins with the nucleophiles ammonia, methylamine and hexylamine provides a new route to regioselectivity. This method gives a displaced product para to the nitro group as the predominant product, in contrast to the solution reaction wherein the meta-displaced product predominates. This is due to the change in the mechanistic shift fromS _N2Ar*, wherein the nitro group is meta-directing, to a mechanism involving electron transfer from the nucleophile to the excited aromatic substrate(S _N (ET)Ar*) to give the para-displaced product     

Laterally non-symmetric aza cryptand molecules stitched by water

Crystal structure of the compound L·4H₂O (L = aza cryptand) and its supramolecular assembly via H-bonding through water molecules are described here. The compound crystallizes in the cubic space group Pa3 (no. 205) with the following lattice parameters: a=b=c=19.023(2) Å, V=6883.9(4) Å³, Z=8, R ₁=0.0592, wR ₂ = 0.1572, S=0.964.     

Enantiomer separation by gas chromatography on cyclodextrin chiral stationary phases

Fused silica capillary columns coated with several alkyl or acyl cyclodextrin derivatives, especially those of α- and β-cyclodextrins, are suitable for the enantiomer separation of a wide variety of volatile compounds of different molecular size and functionality. Positional isomers and more than 250 pairs of optical isomers have been resolved, including chiral hydrocarbons, acetals, ethers, epoxides, carbonates, lactones, esters, acids, ketones, aldehydes, alcohols, halocarbons, and also nitrogen-and sulfur-containing compounds. The physical properties of the cyclodextrin derivatives, even those obtained as viscous fluids, could be improved by dissolving them in polysiloxane liquid phases commonly used for GLC.     

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

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

Study on the Supramolecular System of TAPP and Cyclodextrins by Spectroscopy

The ability of β-cyclodextrin (β-CD), γ-CD, hydroxypropyl-β-CD (HP-β-CD), trimethyl-β-CD (TM-β-CD), sulfurbutylether-β-CD (SBE-β-CD) and carboxymethyl-β-cyclodextrin (CM-β-CD) to break the aggregate of the meso-tetrakis(4-N-trimethylaminobenzyl)porphyrin (TAPP) and to form 2:1 inclusion complexes has been studied by absorption and fluorescence spectroscopy. The formation constants are calculated, respectively, by fluorimetry, from which the inclusion capacity of different CDs is compared and the inclusion mechanism of charged-β-CD (SBE-β-CD and CM-β-CD) is quite different from that of the parent β-CD. At lower pH, the complexation between TM-β-CD and H²TAPP²⁺ (the form of the diprotonated TAPP) hampers the continuous protonation of the pyrrole nitrogen of TAPP and the hydrophobic cavity may prefer to bind an apolar neutral porphyrin molecule. ¹HNMR data support the inclusion conformation of the porphyrin–cyclodextrin supramolecular system, indicating the interaction of the meso-phenyl groups of TAPP with the cavity of CDs. For this host–guest inclusion model, cyclodextrin being regarded as the protein component, which acts as a carrier enveloping the active site of heme prosthetic group within its hydrophobic environment, provides a protective sheath for the porphyrin, creating artificial analogues of heme-containing proteins. However, for TAPP, encapsulated within this saccharide-coated barrier, its photophysical and photochemical properties changed strongly.