Spectroscopic and thermal characterization of the host–guest interactions between α‐, β‐ and γ‐cyclodextrins and vanadocene dichloride

Host–guest interactions between α‐, β‐ and γ‐cyclodextrins and vanadocene dichloride (Cp₂VCl₂) have been investigated by a combination of thermogravimetric analysis, differential scanning calorimetry, powder X‐ray diffraction and solid‐state and solution electron paramagnetic resonance (EPR) spectroscopy. The solid‐state results demonstrated that only β‐ and γ‐cyclodextrins form 1:1 inclusion complexes, while α‐cyclodextrin does not form an inclusion complex with Cp₂VCl₂. The β‐ and γ‐CD–Cp₂VCl₂ inclusion complexes exhibited anisotropic electron‐⁵¹V (I = 7/2) hyperfine coupling constants whereas the α‐CD–Cp₂VCl₂ system showed only an asymmetric peak with no anisotropic hyperfine constant. On the other hand, solution EPR spectroscopy showed that α‐cyclodextrin (α‐CD) may be involved in weak host–guest interactions in equilibrium with free vanadocene species. Copyright © 2008 John Wiley & Sons, Ltd.     

Influence of substituent position and cavity size of the regioisomers of monocarboxymethyl‐α‐, β‐, and γ‐cyclodextrins on the apparent stability constants of their complexes with both enantiomers of Tröger's base

Enantiomers of Tröger's base were separated by capillary electrophoresis using 2^I‐O‐, 3^I‐O‐, and 6^I‐O‐carboxymethyl‐α‐, β‐, and γ‐cyclodextrin and native α‐, β‐, and γ‐cyclodextrin as chiral additives at 0–12 mmol/L for β‐cyclodextrin and its derivatives and 0–50 mmol/L for α‐ and γ‐cyclodextrins and their derivatives in a background electrolyte composed of sodium phosphate buffer at 20 mmol/L concentration and pH 2.5. Apparent stability constants of all cyclodextrin–Tröger's base complexes were calculated based on capillary electrophoresis data. The obtained results showed that the position of the carboxymethyl group as well as the cavity size of the individual cyclodextrin significantly influences the apparent stability constants of cyclodextrin–Tröger's base complexes.     

Formation of a Polypseudorotaxane via Self‐Assembly of γ‐Cyclodextrin with Poly(N‐isopropylacrylamide)

A polypseudorotaxane (PPR) comprising γ‐cyclodextrin (γ‐CD) as host molecules and poly(N‐isopropylacrylamide) (PNIPAM) as a guest polymer is prepared via self‐assembly in aqueous solution. Due to the bulky pendant isopropylamide group, PNIPAM exhibits size‐selectivity toward self‐assembly with α‐, β‐, and γ‐CDs. It can fit into the cavity of γ‐CD to give rise to a PPR, but cannot pass through α‐CD and β‐CD under the same conditions. The ratio of the number of γ‐CD molecules to entrapped NIPAM repeat units is kept at 1:2.2 or 1:2.4, determined by ¹H NMR spectroscopy and TGA analysis, respectively, indicating that there are more than 2 but less than 3 NIPAM repeat units included by one γ‐CD molecule. This finding opens new avenues to PPR‐based supramolecular polymers to be used as solid, stimuli‐responsive materials.     

Molecular Recognition Studies on Modified Cyclodextrins

This account describes our research progress in recent years in the areas of the molecular recognition studies on modified cyclodextrins, including positively charged cyclodextrins, cyclodextrin derivatives with hydrophobic substituent, and dimeric cyclodextrins. Calorimetric titration and various spectrometric techniques were employed to determine the complex stability constants, as well as the thermodynamic parameters, for their inclusion complexation with diverse guest molecules. The results obtained have been discussed from the viewpoint of size/shape‐matching, induced‐fit, geometric compensation, and multiple recognition. Thermodynamically, the compensatory relationship between ΔH and TΔS was found to be exhibited in the inclusion complexation of modified cyclodextrin.     

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.     

Remarkable Stabilization of the α‐Helix Structure by an Intramolecular Host‐Guest Bridge in a Cyclodextrin‐Peptide Hybrid

A cyclodextrin‐peptide hybrid (CD‐peptide) bearing three units of γ‐cyclodextrin, cholic acid, and a dansyl fluorophore in the side chain has been prepared. In this novel CD‐peptide, the cholic acid unit acts as an internal guest and forms an intramolecular inclusion complex with γ‐cyclodextrin in the CD‐peptide. This intramolecular complex works as a host‐guest bridge in the CD‐peptide and remarkably stabilizes the α‐helix structure of the CD‐peptide.     

Selective Autonomous Molecular Transport and Collection by Hydrogel‐Embedded Supramolecular Chemical Gradients

Selective transport and concentration of molecules to specified regions on a substrate both enhances the potential to detect such molecules and provides a path to spatially localize such molecules prior to initiation of subsequent chemical reactions. Here, we first embed radially symmetric α‐, β‐, and γ‐cyclodextrin gradients in a hydrogel matrix. Driven by host‐guest interactions between the cyclodextrins and the target molecule, we observe these gradients can serve to direct 2D molecular transport. Using xanthene dyes and organophosphates as target molecules, we found the transport metrics, e.g., selectivity, rate, and concentration limits, are strongly dependent on the specific cyclodextrin forming the gradient. In all cases, as the concentrating power of the gradient increased, the rate of target concentration slowed, which we hypothesize is because stronger interactions between the target and the cyclodextrin decrease the rate of target diffusion. The concentration enhancement for the nerve agent simulant 4‐methylumbelliferyl phosphate (15.8) is the greatest when the gradient is formed using β‐cyclodextrin while directed concentration of cyanomethyl phosphonate, a smaller non‐aromatic organophosphate, is observed only for the smaller α‐CD. To provide a near real‐time read‐out of the concentration of the analyte, we used an array of IR resonant metallic nanoantennas tuned to a specific IR absorption band of the analyte to enhance the IR signal generated by the analyte.     

Guest Binding with Sulfated Cyclodextrins: Does the Size of Cavity Matter?

Sulfated cyclodextrins have recently emerged as potential candidates for producing host–induced guest aggregation with properties better than p-sulfonatocalixarenes that have previously shown numerous applications involving the phenomena of host-induced guest aggregation. In the class of sulfated cyclodextrins (SCD), sulfated β-cyclodextrin (β-SCD) remains the most extensively investigated host molecule. Although it is assumed that the host-induced guest aggregation is predominantly an outcome of interaction of the guest molecule with the charges on the exterior of SCD cavity, it has not been deciphered whether the variation in the cavity size will make a difference in the efficiency of host-induced guest-aggregation process. In this investigation, we present a systematic study of host–induced guest aggregation of a cationic molecular rotor dye, Thioflavin T (ThT) with three different sulfated cyclodextrin molecules, α-SCD, β-SCD and γ-SCD, which differ in their cavity size, using steady-state emission, ground-state absorption and time-resolved emission measurements. The obtained photophysical properties of ThT, upon interaction with different SCD molecules, indicate that the binding strength of ThT with different SCD molecules correlate with the cavity size of the host molecule, giving rise to the strongest complexation of ThT with the largest host molecule (γ-SCD). The binding affinity of ThT towards different host molecules has been supported by molecular docking calculations. The results obtained are further supported with the temperature and ionic strength dependent studies performed on the host-guest complex. Our results indicate that for host–induced guest aggregation, involving oppositely charged molecules, the size of the cavity also plays a crucial role beside the charge density on the exterior of host cavity.     

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。     

Complex formation of cyclodextrins with poly(propylene glycol) derivatives

The complex formation between cyclodextrins (CDs) and poly(propylene glycol) (PPG) derivatives is described. β‐CD and γ‐CD formed complexes with PPG derivatives such as 1‐naphthyl (1NA), 2‐naphthyl (2NA), 3,5‐dinitrobenzoyl, and 2,4‐dinitrophenyl PPG. α‐CD did not form complexes with these PPG derivatives. Although γ‐CD gave complexes with 9‐anthryl PPG (PPG9An), β‐CD did not efficiently form complexes with PPG9An. β‐CD did not form complexes with trityl PPG, demonstrating that trityl groups were too bulky to thread a β‐CD cavity. The emission spectra of the complexes showed that β‐CD bound a single 2NA moiety in its cavity and that γ‐CD included two 2NA moieties. In contrast, γ‐CD bound a single 1NA moiety in the cavity. X‐ray diffraction studies and ¹H NMR analysis showed that the CD molecules were stacked along a PPG chain to form a channel structure. The inclusion modes are discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4839–4849, 2000     

Binding behaviors of scutellarin with α-, β-, γ-cyclodextrins and their derivatives

A series of cyclodextrin/scutellarin inclusion complexes were prepared from α-cyclodextrin, β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin with scutellarin (SCU), and their inclusion complexation behaviors, such as stoichiometry, complex stability constants and inclusion mode, were investigated by means of UV/Vis spectroscopy, ¹H NMR and 2D NMR. The results showed that the SCU could be efficiently encapsulated in the cyclodextrin cavity in aqueous solution to produce complexes that were more soluble than free SCU. The enhanced binding ability of cyclodextrins towards SCU was discussed from the viewpoint of the size/shape-fit and multiple recognition mechanism between host and guest.     

Complexation of cyclodextrins with flavines in aqueous solutions

Data on the binding mode and thermodynamics of complex formation for various cyclodextrins (CDs) with flavines are summarized. It is shown that the governing factors of complexation are the size, degree of hydration, and hydrophobicity of the guest molecule. It is found that the presence of small hydrophobic substituents in a flavine’s structure increases their affinity toward cyclodextrin cavities, raising the stability of a complex. In contrast, the presence of bulky and polar side groups in a flavine’s structure prevents its inclusion in a macrocyclic cavity and weakens complexation. The size of a CD cavity plays a minor role in the interaction between CDs and flavines, since the inclusion of a guest molecule is only partial.     

Electrospray ionization mass spectrometry studies of cyclodextrin‐carboxylate ion inclusion complexes

Aqueous solutions containing simple model aliphatic and alicyclic carboxylic acids (surrogates 1–4) were studied using negative ion electrospray mass spectrometry (ESI‐MS) in the presence and absence of α‐, β‐, and γ‐cyclodextrin. Molecular ions were detected corresponding to the parent carboxylic acids and complexed forms of the carboxylic acids; the latter corresponding to non‐covalent inclusion complexes formed between carboxylic acid and cyclodextrin compounds (e.g., β‐CD, α‐CD, and γ‐CD). The formation of 1:1 non‐covalent inclusion cyclodextrin‐carboxylic complexes and non‐inclusion forms of the cellobiose‐carboxylic acid compounds was also observed. Aqueous solutions of Syncrude‐derived mixtures of aliphatic and alicyclic carboxylic acids (i.e. naphthenic acids; NAs) were similarly studied using ESI‐MS, as outlined above. Molecular ions corresponding to the formation of CD‐NAs inclusion complexes were observed whereas 1:1 non‐inclusion forms of the cellobiose‐NAs complexes were not detected. The ESI‐MS results provide evidence for some measure of inclusion selectivity according to the 'size‐fit' of the host and guest molecules (according to carbon number) and the hydrogen deficiency (z‐series) of the naphthenic acid compounds. The relative abundances of the molecular ions of the CD‐carboxylate anion adducts provide strong support for differing complex stability in aqueous solution. In general, the 1:1 complex stability according to hydrogen deficiency (z‐series) of naphthenic acids may be attributed to the nature of the cavity size of the cyclodextrin host compounds and the relative lipophilicity of the guest. Copyright © 2009 John Wiley & Sons, Ltd.     

Solubilization of Polycyclic Aromatics in Water by γ‐Cyclodextrin Derivatives

A series of hydrophilic per‐6‐thio‐6‐deoxy‐γ‐cyclodextrins (CDs) were synthesized from per‐6‐iodo‐6‐deoxy‐γ‐CD. These new hosts are able to solubilize polycyclic aromatic guests in aqueous solution to much higher extents than native CDs. Phase‐solubility diagrams were mostly linear in accordance with both 1:1 and 1:2 CD–guest complexes in aqueous solution. The stoichiometry of the inclusion complexes was further investigated by fluorescence spectroscopy, which revealed very pronounced Stokes shifts typical for 1:2 complexes. This finding was further consolidated by quantum mechanical calculations of dimer formation of the guests and space‐filling considerations by using the cross‐sectional areas of the CDs and guests. The calculated dimerization energies correlated well with the binding free energies measured for the 1:2 complexes, and provided the main contribution to the driving force of complexation in the γ‐CD cavity.     

Synthesis of amphiphilic polymer networks with guest‐host properties

A modular assembly procedure for producing amphiphilic polymer networks containing specific linker lengths between cyclodextrin (CD) cross‐link sites is described. The linker type and length can be selected to tune the relative hydrophilicity/hydrophobicity of the network, and the size of the guest‐host binding site can be varied by using either α‐, β‐, or γ‐CD as the node. The two‐step, one‐pot reaction sequence produces well‐defined networks with stable ether linkages that can be purified by simple washing and filtration steps. Short ethylene glycol versus long polyethylene oxide linkers result in networks that are generally insoluble in common organic solvents, but which swell to varying degrees in polar protic, polar aprotic, and chlorinated solvents such as water, methanol, ethanol, dimethylsulfoxide, dimethylformamide, methylene chloride, and chloroform. All networks swell in water and present a hydrophobic CD cavity that is available for binding nonpolar molecules. The networks should be applicable to the removal of hydrophobic contaminants, for example, pharmaceutical molecules, from water or wastewater streams. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1824–1831     

基于环糊精包结络合作用的大分子自组装*

本文综述了基于环糊精包结络合作用的大分子自组装的研究进展,包括：（1) 线型、梳型、多臂星型或超支化聚合物与环糊精或其二聚体自组装形成多聚轮烷（分子项链）、多聚准轮烷、双多聚（准）轮烷、分子管、双分子管、超分子凝胶及其应用;（2）桥联环糊精与桥联客体分子自组装制备线型或超支化超分子聚合物;（3）温度、pH值、光及客体分子刺激响应智能体系; （4) 通过亲水性的环糊精线型均聚物与含金刚烷的疏水性聚合物之间的包结络合作用来制备高分子胶束及其空心球等。     

Modulation of the Thermoresponsive Behavior of Poly(N,N‐diethylacrylamide) via Cyclodextrin Host/Guest Interactions

The modulation of the cloud point of aqueous poly(N,N‐diethylacrylamide) solutions via the formation of supramolecular cyclodextrin complexes with hydrophobic end groups, namely adamantyl, tert‐butyl phenyl and azobenzene, synthesized via RAFT polymerization is described. The dependence of the apparent cloud points after cyclodextrin complexation is investigated with respect to the type and quantity of the guest end group, the polymer chain length and the cyclodextrin/end group ratio. Furthermore, the effect is reversed via the addition of guest molecules or via biocompatible enzymatic degradation of the cyclodextrins entire.

     

Inhibition of acid‐induced decomposition of diphenyltriazenes by complexation with cyclodextrins

Acid‐promoted N? N bond cleavage in 1,3‐diphenyltriazenes (X‐Ph‐N=N‐NH‐Ph‐X; X = H, 4‐OCH₃), leading to formation of diazonium ions and anilines, is strongly inhibited in aqueous solutions in the presence of cyclodextrins (CDs). The inhibition is ascribed to the formation of inclusion complexes that render the guest diphenyltriazene significantly less basic as a result of the less polar nature of the CD cavity (a microsolvent effect). Association equilibrium constants for 1:1 host–guest complexes increase in the order α‐CD <β‐CD ～ permethyl‐β‐CD < hydroxypropyl‐β‐CD, with values for X = 4‐OCH₃ being larger than those for X = H. In the case of α‐CD, formation of 2:1 host–guest complexes is also involved. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 567–574, 2010     

Reversible Phase Transition of Robust Luminescent Hybrid Hydrogels

We report herein on remote control over a reversible phase transition of robust luminescent hybrid hydrogels as enabled by the rational selection and incorporation of photoswitches. Azobenzene units functionalized with a guanidinium group were utilized as the photoswitches and incorporated through a host–guest inclusion method involving α‐cyclodextrins functionalized with 2,6‐pyridinedicarboxylic acid (PDA) groups. While the guanidinium functional groups bind to the negatively charged Laponite matrix surface to connect organic and inorganic components, the PDA groups enable simultaneous coordination with different lanthanide metal ions, thus rendering the hydrogel broadly luminescent. Owing to its conformation‐dependent binding behavior with α‐cyclodextrin, the isomerization of azobenzene induced association or dissociation of the inclusion complexes and thus lead to a reversible photocontrolled sol?gel phase transition of the luminescent hybrid hydrogels.