The first successful investigation into a cyclodextrin-based enzyme model as an efficient catalyst for luminol chemiluminescent reaction

The chemiluminescence of the luminol-H2O2 system is found for the first time to be remarkably enhanced by the Ce(IV) complexes of cyclodextrin dimers.     

Crystal Structures of β‐Cyclodextrin Inclusion Complexes with 7‐Hydroxycoumarin and 4‐Hydroxycoumarin and Substituent Effects on Inclusion Geometry

Two inclusion complexes of β‐cyclodextrin‐7‐hydroxycoumarin ( 1 ) and β‐cyclodextrin‐4‐hydroxycoumarin ( 2 ) were prepared and their crystal structures were investigated by single crystal X‐ray crystallography under cryogenic condition. Both structures consist of stacks of face‐to‐face cyclodextrin dimers arranged in brickwork‐like pattern along the crystallographic a‐axis. For complex 1 , each of the two dimeric β‐cyclodextrins includes one 7‐hydroxycoumarin molecule that penetrates deeply into the cyclodextrin dimer and locates its lactonering at the center of the dimer cavity. For complex 2 , each cyclodextrin dimer accommodates three 4‐hydroxycoumarin molecules. One of them is sandwiched between two units of the cyclodextrin dimer, the other two are shallowly included in the cavities of the dimeric cyclodextrins respectively and protrude their lactone rings from the primary end of the cyclodextrin. The substituent effects of guest molecules on inclusion geometry of various coumarin molecules in β‐cyclodextrin were examined.     

Ruthenium and Osmium Podate Cyclodextrins with Dual-function Recognition Sites for Luminescent Sensing

A multifunctionalised podand cyclodextrin ligand, β-CD-(urebpy)⁷, with urea--bipyridine binding sites leads to ruthenium and osmium, {Ru[β-CD-(urebpy)⁷]}[PF⁶]² {Os[β-CD-(urebpy)⁷]}[PF⁶]², cyclodextrins. The bipyridine ligands are preorganised by the cyclodextrin cavity encapsulating the ruthenium and osmium core to give photoactive metallocyclodextrins. The podate cyclodextrin complexes show characteristic ruthenium and osmium tri-bipyridine luminescence. It is demonstrated that the ruthenium cyclodextrins participate in sensing schemes through both the cyclodextrin cavity and the urea cage at the bottom of the cyclodextrin rim. Luminescence quenching of the ruthenium emission is observed by addition of anthraquinone guests in the cyclodextrin cavity or addition of dihydrogen phosphate anion.     

Synthesis and inclusion properties study of some mono 6-amino ??-cyclodextrin dimers bridged by N,N-succinyldiamide linkers

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).     

Adduct Formation Between γ-Cyclodextrin and the Bifluorophore 1,3-Bis(1-pyrenyl)propane

The complexation of the bifluorophore 1,3-bis(pyrenyl)propane with γ-cyclodextrin in water has been studied by means of steady state and time-resolved fluorescence spectroscopy. It was found that in the association with γ-cyclodextrin the propane chain of 1,3-bis(pyrenyl)propane folds and the two pyrene units enter the same cyclodextrin cavity where they form weakly bound ground state dimers, which upon excitation emit excimer fluorescence. In addition to this 1:1 excimer emitting complex, two more complexes were detected, which emit monomer pyrene fluorescence. One has 1:1 stoichiometry, i.e. isomeric to the previous complex, and the other, with 2:1 stoichiometry, is comprised of two γ-cyclodextrin units and one 1,3-bis(pyrenyl)propane.     

Inclusion compounds of plant growth regulators in cyclodextrins, part VII: study of the crystal structures of 2-naphthylacetic acid encapsulated in β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin complexes by X-ray crystallography

The crystal structures of the β-naphthylacetic acid (2NAA)/β-cyclodextrin (β-CD) and the 2NAA/heptakis(2,3,6-tri-O-methyl)-β-CD (TMβCD) complexes are reported. The 2NAA/β-CD complex crystallizes in the triclinic system forming a dimer inside the cavity of which two 2NAA molecules disordered over two sites are located. The dimers are stacked along the c axis according to the channel packing mode forming a nanotube which resembles a wireway as it contains guest molecules linked by π–π interactions inside each dimeric cavity and by H-bonds between the adjacent dimers. The 2NAA/TMβCD complex crystallizes in the orthorhombic space group P2₁2₁2₁. Its asymmetric unit contains one host, one guest distributed over two sites and one water molecule having a low occupancy factor. The complexes are packed in a head-to-tail mode forming a screw channel along the b axis. The carboxyl group of the guest protrudes towards the “free” space between the complexes and is H-bonded to the water molecule which in turn is H-bonded to the O5n atom of the host of the subsequent complex. The orientation of the guest molecule in the 2NAA/β-CD complex has been found opposite to that of the guest in the 2NAA/TMβCD complex probably due to the formation of dimers and the π–π interactions between the naphthalene moieties of the encapsulated molecules inside the dimeric cavity.     

The Effect of Cyclodextrins on the Luminol-Hydrogen Peroxide Chemiluminescence

The action of different molar ratios of α, β, γ-cyclodextrin upon the chemiluminescence of the luminol-H₂O₂ in alkaline buffer Tris-HCl, pH=8.5 has been evidenced. It was found out that α, β, γ- cyclodextrin have an antioxidant capacity, probably due to the free radicals (that are generate in the system) encapsulation in the their cavity. This behaviour depends on α, β, γ-cyclodextrin molar ratio; α-cyclodextrin and γ-cyclodextrin protects more efficiently against free radicals than β-cyclodextrin. These findings could be very important regarding the oxidative stress process.     

Binding Affinity of Novel Cyclodextrin Dimers to Ethyl Orange

The interaction between ethyl orange (Eto, guest) and β-cyclodextrin dimers (1a～d, host) bridged with 2-t-butoxycarbonyl(Boc)-amino diacid was investigated. A remarkable synergic complexation of two cavities in host molecule was observed.     

Mesoporous silica and chitosan based pH-sensitive smart nanoparticles for tumor targeted drug delivery

This study investigated inclusion formation and the physicochemical properties of naringin/cyclodextrin through a combined computational and experimental approach. Molecular dynamics simulations were applied to investigate the thermodynamics and geometry of naringin/cyclodextrin cavity docking. The complexes were investigated by UV, FT-IR, DSC, XRD, SEM, 2D-NOSEY and ¹H-NMR analyses. Clearly visible protons belonging to naringin and chemical shift displacements of the H3 and H5 protons in cyclodextrin were anticipated in the formation of an inclusion complex. Naringin solubility increased linearly with increasing cyclodextrin concentration (displaying an A_L profile). The simulations indicated that the phenyl group of naringin was located deep within the cyclodextrin cavity, while the glycoside group of naringin was on the plane of the wider rim of cyclodextrin. The simulation and molecular modeling results indicate that (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) provided the more stable inclusion complex. This result was also in good concordance with the stability constants that had been determined by the phase solubility method. The consistency of the computational and experimental results indicates their reliability.     

Changing mechanisms in the beta-cyclodextrin-mediated hydrolysis of phenyl esters of perfluoroalkanoic acids

The rate of hydrolysis of esters CF(3)(CF(2))(n)COOPh (1 (n = 1), 2 (n = 2), and 3 (n = 6)) was measured at pH 6.00 and at pH higher than 9.00 in the presence of beta-cyclodextrin (beta-CD). For compounds 1 and 2 the reaction rate decreases as the beta-CD concentration increases, and they show saturation effects at all pH. It is suggested that the substrate forms an inclusion complex with cyclodextrin. Analysis of the rate data allows calculation of the association equilibrium constant, K(CD), the rate constant for the reaction of the included compound, k(c), and K(TS) which is the hypothetical association equilibrium constant for the transition state of the cyclodextrin-mediated reaction. The dependence of log K(CD) and log K(TS) with the number of atoms in the chain is different. We suggest that the reactions of 1 and 2 take place with the perfluorinated alkyl chain included in the cavity, whereas the transition state for the reaction of phenyl trifluoroacetate involves a complex with the aryl ring inside the cavity. At low pH the inhibition comes from the protection of the carbonyl group toward nucleophilic attack by water. In basic pH the reaction of HO(-) as an external nucleophile is also inhibited. The cyclodextrin-mediated reaction involves the ionized OH group at the rim of the cyclodextrin cavity with poor efficiency due to an unfavorable orientation of the substrate in the complex. On the other hand, the reaction of compound 3 is strongly accelerated by cyclodextrin because the association of the substrate with cyclodextrin competes with the monomer-aggregate equilibrium and at high enough cyclodextrin concentration the main species present in solution is the complex between 3 and cyclodextrin.     

超分子体系中的分子识别桥──连环糊精对模型底物的键合能力及分子选择性

综述了近年来桥连双环糊精分子识别的研究进展,主要从疏水相互作用、多重识别、尺寸和构型匹配、热力学性质以及环糊精二聚体分子识别的一些应用等方面对研究结果进行了评述.     

荧光标识的环糊精二聚体与小肽衍生物之间的包合行为研究

报道了利用荧光偏振方法研究导硫氰酸盐荧光素（FITC）标识,并由天冬氨酸 、谷氨酸、(1R, 3R)-1-氨基-1,3-二羟基环丁烷和（1R, 3R）-1-氨基-1,3-二 羟基环戊烷衍生物桥联的环糊精二聚体（1～4,作为主体）,在pH = 7.4的水溶液 中与几个低分子量的多肽衍生物:Adm-Lys(Adm)-Arg-Arg 5; Adm-Lys(Adm)-D-Arg- D-Arg 6; Adm-Cha-Arg-Arg 7; Adm-Cha-D-Arg-D-Arg 8（作为客体,其中Arg, Lys, Cha和Adm分别为精氨酸,赖氨酸,β-环已烷丙氨酸和1-羟基金刚烷）之间 的键合常数（K_b)和包合反应的热力学参数（△G°,△H°,△S°）。从主-客体 键合常数的比较、客体嵌入基团的结构与周边环境的考察发现,主、客体之间的键 合能力因客体非进入基团（Arg)空间构型上的变化而有所不同。通过比较主体包结 一对手性异构体的自由能变化增量（-△△G_(DL)°）以及一对手性异构体（L-与 D-）与同一主体的键合常数之比（K_L/K_D),讨论了环糊精二聚体对D-型或L-型多 肽衍生物的手性识别能力。根据各体系T△S°与△H°之间较好的线性关系,探讨 了环糊精二聚体与多肽衍生物之间相互作用的焓-熵补偿行为。     

Homodimerization and heteroassociation of 6-O-(2-sulfonato-6-naphthyl)-gamma-cyclodextrin and 6-deoxy-(pyrene-1-carboxamido)-beta-cyclodextrin

6-O-(2-sulfonato-6-naphthyl)-gamma-cyclodextrin (1) and 6-deoxy-(pyrene-1-carboxamido)-beta-cyclodextrin (2) were prepared. Homodimerizations of 1 and 2 and heteroassociation between 1 and 2 were investigated by (1)H 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 beta-CD as 270 +/- 20 M(-)(1) and 2 with gamma-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 beta-CD cavity of 2, while the pyrene group of 2 is partially inserted in the gamma-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.     

Synthesis and characterization of an amphiphilic cyclodextrin, a micelle with two recognition sites

A cyclodextrin derivative (Mod-CD) was synthesized through the monoesterification of beta-cyclodextrin (beta-CD) with 3-((E)-dec-2-enyl)-dihydrofuran-2,5-dione. The compound is an interesting surfactant that can form large aggregates not only through the interaction of the hydrophobic tails as in common amphiphilic compounds but also through the inclusion of the alkenyl chain into the cavity of another Mod-CD molecule. The self-inclusion of the chain in the cavity of cyclodextrin as well as the intermolecular inclusion was demonstrated by 1H NMR measurements that were able to detect methyl groups in three different environments. Besides, in the aggregates of Mod-CD, the cavity is available to interact with external guests such as phenolphthalein, 1-amino adamantane, and Prodan. Phenolphthalein has the same binding constant with Mod-CD and beta-CD, but the equilibrium constant for the interaction with Prodan is about 2 times larger for Mod-CD than for beta-CD. The latter result is attributed to the fact that this probe interacts with the micelle in two binding sites: the cavity of the cyclodextrin and the apolar heart of the micelle as evidenced by the spectrofluorimetric behavior of Prodan in solutions containing different concentrations of Mod-CD.     

Cyclodextrin phosphanes as first and second coordination sphere cavitands

The binding properties of two alpha-cyclodextrins, each containing two C(5)-linked "CH(2)PPh(2)" units, L 1 (A,D-substituted) and L 2 (A,C-substituted), have been investigated. Both ligands readily form transition-metal chelate complexes in which the metal centres are immobilised at the cavity entrance. Although diphosphane L 1 displays a marked tendency to behave only as a trans-spanning ligand, the ligand possesses a certain degree of flexibility, for example, allowing the stabilisation of a trigonal silver(I) complex in which the bite angle drops to 143 degrees. Another feature of L 1 concerns its ability to function as an hemilabile ligand. Together with four methoxy groups anchored onto the primary face, the two P(III) centres of L 1 form a circularly arranged P(2)O(4) 12-electron donor set able to complex an Ag(+) ion in a dynamic way, each of the four oxygen atoms coordinating successively to the silver ion. Furthermore, the particular structures of L 1 and L 2, characterised by the presence of P(III) units lying close to the cavity entrance, lead upon complexation to complexes whereby the first coordination sphere is partly entrapped in the cyclodextrin. Thus, when treated with metal chlorides, both ligands systematically produce complexes in which the Mbond;Cl unit is maintained inside the cyclodextrin through weak Cl.H-5 interactions. The chelate complex [Ag(L 1)]BF(4) reacts with acetonitrile in excess to afford a mixture of two equilibrating complexes, [Ag(acetonitrile)(L 1)]BF(4) and [Ag(acetonitrile)(2)(L 1)]BF(4), whose coordinated nitriles lie inside the cyclodextrin cavity. The inner-cavity ligands can be substituted by a benzonitrile molecule. The present study provides the first identification of an [Ag(acetonitrile)(2)(phosphane)(2)](+) ion. The unexpected stabilisation of this species probably rests on a cavity effect, the cyclodextrin walls favouring recombination of the complex after facile dissociation of the nitrile ligands.     

β-Cyclodextrin dimers linked through their secondary faces with rigid spacer arms as hosts for bile salts

A convenient synthesis of β-cyclodextrin dimers in which the two cyclodextrin units are linked by rigid tethers of relatively short length through their secondary sides is reported. Compounds hexa-2,4-diynediyl- and 1,4-phenylenediethyne-briged β-cyclodextrin dimers are obtained in good yields from mono-2-O-propargyl-β-cyclodextrin through Pd-mediated oxidative homo- and heterocoupling reactions. Isothermal titration calorimetry and NMR spectroscopy (PGSE and 2D-ROESY) are used to determine the thermodynamic parameters (K, ΔH, and TΔS°) for the complexation of such β-cyclodextrin dimers with sodium cholate, deoxycholate, and chenodeoxycholate as well as to estimate the size of the supramolecular structures. The binding of bile salts is enhanced relative to that of native β-cyclodextrin. Although chenodeoxycholate salt binds in a 1:1 fashion, cholate and deoxycholate salts bind in a 1:2 sequential mode.     

Synthesis and self-inclusion of bipyridine-spaced cyclodextrin dimers

The synthesis and conformational behavior of two cyclodextrin dimers containing aromatic bipyridine spacers is presented. The proton NMR spectra of these dimers in aqueous solution show a doubling of signals in the aromatic region due to complete or partial self-inclusion of the spacer. The degree and the strength of self-inclusion is dependent on the substitution pattern of the bipyridine unit. This unexpected difference in the self-inclusion behavior is revealed by 2D NOESY and circular dichroism spectra.     

水溶液中的氨基酸桥联环糊精二聚体的分子识别

采用荧光偏光方法研究了用2-氨基-L-1,5-戊二酸衍生物和(1R,3R)-1-氨基-1,3-二羧基环戊烷衍生物桥联的环糊精二聚体1和2(主体),在298K、pH=7.4时,与四个低分子量的多肽(客体,H-Trp-Trp-Arg-Arg-NH23;Adm-Trp-Arg-Arg-NH24;Adm-D-Trp-Arg-Arg-NH25;H-Trp-Trp-Trp-Trp-Arg-Arg-NH26)之间的相互作用。研究结果表明,二聚体环糊精对于多肽的分子识别作用,就主体而言,即便是主体作用位点以外部分基团结构的改变,对主-客体之间的分子识别也有重要影响,并且两个空腔在组装客体过程中相互之间产生协同作用,就客体而言,多肽分子的链长、疏水性及其嵌入基团的极性、大小、形状等对包合物的形成与稳定均起重要作用。主-客体组装过程中产生负的焓变和正的熵变,表明范德华-伦敦色散力、氢键和疏水相互作用是本文研究体系的主要包合驱动力。     

The solvolysis of benzoyl halides as a chemical probe determining the polarity of the cavity of dimethyl-β-cyclodextrin

The solvolysis of benzoyl halides (BzX) in the presence of dimethyl-β-cyclodextrin (DM-β-CD) was studied. Methylation or hydroxyalkylation of the hydroxyl groups in β-cyclodextrin increases their solubility and the highest possible concentration of DM-β-CD that can be dissolved in water is 0.2 M. The ability to use more readily soluble CDs may allow one to determine the stoichiometry of their complexes and the properties of water held in their cavity with increased precision. Based on the experimental results, this cyclodextrin forms host-guest complexes of variable stoichiometry where two reaction pathways are considered: in water and in the internal cavity of the cyclodextrin. We determined the rate constants for the halides in their reaction inside the internal cavity. This allowed the influence of the substituent and leaving group on the reactions in the bulk water and the internal cavity of DM-β-CD to be compared. Depending on whether the solvolysis reaction is preferentially associative or dissociative, the presence of the cyclodextrin has a catalytic or inhibitory effect, respectively.     

Complexation and (templated) synthesis of rhenium complexes with cyclodextrins and cyclodextrin dimers in water

Several small, lipophilic rhenium complexes form inclusion complexes with native beta-cyclodextrin (beta-CD) and beta-CD dimers. Association constants larger than 10(9)M(-1) were obtained using dimers. The use of beta-CD also enabled the synthesis of these rhenium complexes in water, in excellent yields, through complexation of the otherwise insoluble corresponding ligands. The influence of the reaction time and temperature on the configuration of the reaction products has been investigated in depth for one of these complexes. Using a beta-CD dimer, it proved possible to specifically template the formation of one configuration. The strength of the complexes of the rhenium complexes in cyclodextrin dimers may allow radiolabeling of biomolecules.