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The present review summarizes various organic transformations carried out by using sulfonated β-cyclodextrins such as β-cyclodextrin sulfonic acid, β-cyclodextrin propyl sulfonic acid, and β-cyclodextrin butyl sulfonic acid as an efficient, supramolecular reusable catalyst under diverse reaction conditions.

The host-guest chemistry and applications of cyclodextrins in aqueous media is well established. However, a comprehensive study in organic solvents is lacking. Here, we report the design and synthesis of 6-O-tert-butyldimethylsilylated β-cyclodextrin (TBDMS-β-CD) bearing various aromatic substitutions at the 2-O position and their inclusion complex formation with aromatic guests in nonpolar organic solvents. Compared to the parent TBDMS-β-CD, these derivatives exhibit at least a 10-fold increase in inclusion ability toward pyrene through cooperative guest binding with the CD cavity and the aromatic substituents at the 2-O position. The type of the aromatic substituent largely affects the chiral recognition ability of TBDMS-β-CD toward 1-(1-naphthyl)ethylamine in cyclohexane. A TBDMS-β-CD derivative with a p-tolyl substituent has a remarkable chiral selectivity for the (S)-1-(1-naphthyl)ethylamine over the corresponding (R)-isomer (KS /KR =4.1±0.5), whereas a TBDMS-β-CD derivative with a 2-picolyl substituent shows the inverse chiral selectivity (KR /KS =8.7±0.6).

Host-guest supramolecular gels were developed via the self-assembly of inclusion complexes (ICs) of β-cyclodextrins/phenylboronic acid gelator (PBA). Salts and current were involved in the self-assembly to stabilize the host-guest gels. The stability of the gels was greatly improved after salts were added. The stable time of gels was extended from 2.5 h to 120 h with the addition of NH4NO3 at the concentration of 2.5 × 10-2 g/mL. The morphology of the gel was affected by the concentrations of NH4NO3. SEM images revealed that the gels were three-dimensional nanofibrous networks, the sizes of fibers decreased with decreasing NH4NO3 concentrations, which affected the stability of gels, further proved by the rheological properties of gels. More stable gels were obtained with current stimulation, the stable time of the gel was increased from 2.5 h to 55 h with current by adding NaBF4. The current also exhibited significant influence on the aggregation as the voltage varied (0-500 mV) with a constant concentration of salts. The result showed the self-assembly process of host-guest gel could be well controlled via the addition of salts and current to desired morphology and stability.

Partially and exhaustively methylated β-cyclodextrins [(2-methyl)-β-CD (MCD), heptakis-(2,6-di-O-methyl)-β-CD (DIMEB), and heptakis-(2,3,6-tri-O-methyl)-β-CD (TRIMEB)] have been compared in the hydrolysis and enantiodiscrimination of benzodiazepine derivative (R)- or (S)-oxazepam hemisuccinate (OXEMIS), using nuclear magnetic resonance (NMR) spectroscopy as an investigation tool. After 6 h, MCD induced an 11% hydrolysis of OXEMIS, remarkably lower in comparison with underivatized β-CD (48%), whereas no hydrolysis was detected in the presence of DIMEB or TRIMEB after 24 h. DIMEB showed greater ability to differentiate OXEMIS enantiomers in comparison to TRIMEB, by contrast MCD did not produce any splitting of racemic OXEMIS resonances. Both enantiomers of OXEMIS underwent deep inclusion of their phenyl pendant into cyclodextrins cavities from their wider rims, but tighter complexes were formed by DIMEB with respect to TRIMEB.

We discuss the temperature dependence of the 1H and 13C nuclear spin-lattice relaxation rate 1/ T1 and dynamic nuclear polarization (DNP) performance in β-cyclodextrins with deuterated methyl groups. It is shown that 13C DNP-enhanced polarization is raised up to 10%. The temperature dependence of the buildup rate for nuclear spin polarization and of 1/ T1, below 4.2 K, is analyzed in the framework of the thermal mixing regime and the origin of the deviations from the theoretical behavior discussed. 13C 1/ T1 is determined at low temperature by the glassy dynamics and at high temperature by the rotational molecular motions of the deuterated methyl groups. Thanks to deuteration, relaxation times approaching 30 s are achieved at room temperature, making this material interesting for molecular imaging applications. The effect of molecular dynamics on the line width of the NMR spectra is also discussed.

Natural preservatives for wood protection have gained increasing attention due to their intrinsic antimicrobial properties, renewability, and lower impact on the environment. We report a study on the use of β-cyclodextrin (βCD) derivatives as sustained-release carriers of allyl isothiocyanate (AITC), as a model natural preservative compound. The formation of AITC inclusion complex in βCDs is qualitatively confirmed by FT-IR and the maximum inclusion yield is estimated to be 39%. Impregnation of wood with the water-borne βCD-AITC complexes allows penetration and even distribution of the preservative in the lumen and possibly in the cell walls. The efficacy of the βCD-AITC complexes as wood preservatives of southern yellow pine is examined by the AWPA E10-16 standard. Compared with the water-treated and AITC-treated wood, βCD-AITC-treated wood exhibits decrease in mass loss from 45% to 25% and no visible cell wall damage after exposure to brown and white rot fungi. The results indicate that βCD suppresses the premature leaching of otherwise volatile AITC and suggests a novel approach of application of volatile or water-immiscible natural preservatives for wood protection.

The regioselective difunctionalization of cyclodextrins (CDs) leading to derivatives amenable to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physicochemical properties. The primary-side homo-difunctionalization of β-CD can lead to three regioisomers, while the hetero-difunctionalization can generate three pairs of pseudoenantiomers. Previously, approaches with several synthetic steps, expensive reagents, high purification demands and low yields of the products have been employed. Herein we present direct, short and efficient primary-side difunctionalization strategies featuring reproducibility, ease of product purification, scalability of the reactions and versatility of the substituents introduced. Specifically, the prepared ditosylated β-CDs were separated using preparative reversed-phase column chromatography and their structures were elucidated by NMR experiments. Azidation led to the corresponding pure diazido regioisomers. Direct monotosylation of 6-monoazido-β-CD or monoazidation of the single regioisomers 6A,6X-ditosyl-β-CDs afforded hetero-difunctionalized 6A-monoazido-6X-tosyl-β-CDs in significant yields. Overall, the single regioisomers, 6A,6X-ditosyl-, 6A,6X-diazido- and 6A-monoazido-6X-monotosyl-β-CD were prepared in one or two steps and purified in multigram scale thus opening the way towards further selective and orthogonal functionalizations of β-CD hosts.

In capillary electrophoresis an enantioseparation of daclatasvir (DCV) was observed in case of heptakis(2,6-di-O-methyl)-beta-CD, heptakis(2-O-methyl)-beta-CD and beta-CD, while two peaks with a plateau were noted for heptakis(2,3,6-tri-O-methyl)-beta-CD and heptakis(2,3-di-O-methyl)-beta-CD indicating a slow equilibrium. Heptakis(6-O-methyl)-beta-CD and heptakis(3-O-methyl)-beta-CD yielded broad peaks. Nuclear magnetic resonance experiments including nuclear Overhauser effect-based techniques revealed inclusion complex formation for all CDs with the biphenyl ring of DCV within the cavity and the valine-pyrrolidine moieties protruding from the torus. However, in case of heptakis(2,6-di-O-methyl)-beta-CD, heptakis(2-O-methyl)-beta-CD and beta-CD higher order structures with 1:3 stoichiometry were concluded, where the valine moieties enter additional CD molecules via the secondary side. Heptakis(2,3,6-tri-O-methyl)-beta-CD and heptakis(2,3-di-O-methyl)-beta-CD yielded primarily 1:1 complexes. Higher order complexes between DCV and heptakis(2,6-di-O-methyl)-beta-CD were corroborated by mass spectrometry. Complex stoichiometry was not the reason for the slow equilibrium yielding the plateau observed in capillary electrophoresis, but structural characteristics of the CDs especially complete methylation of the secondary rim.

Gene therapy uses oligonucleotides against genetic disorders to interact with the source of the disease; it can be used to decrease the unwanted side effects of commonly used chemotherapy drugs. Naked oligonucleotides have a short half-life in human plasma (usually less than an hour); therefore, it is essential to choose a suitable carrier platform with excellent biodegradation and tailoring properties. Consequently, non-viral vectors are good candidates to increase the lifetime and improve their therapeutic efficacy. β-Cyclodextrins (CDs) are one of the natural cyclic oligosaccharides that provide the desired goals. Additionally, their appropriate sizes form supramolecular inclusion bodies capable of encapsulating the selected genes. This review focuses on some recent applications of β-CD based nano carriers for gene therapy, specifically the cationic polymers and amphiphilic complexes based on β-CDs used to design the nano systems against different cancer types. Keywords: Cationic polymers, Targeted delivery, Non-viral vector, Amphiphilic CDs, β-cyclodextrin

The aim of this study was to investigate the encapsulation process of R. officinalis (rosemary) essential oil (REO) in beta cyclodextrin (beta-CD), by co-precipitation, using response surface methodology (RSM), specifically the face-centered central composite design (FCCCD). Solid-to-solid (beta-CD/REO) and liquid-to-liquid (ethanol/water) ratios were selected as independent variables and their influence on the dependent variables was assessed. The recovered powder was characterized by different techniques, such as scanning electron microscope (SEM), Fourier Transform-Infrared Spectroscopy (FTIR) and X-Ray Diffractometry (XRD). Moreover, the release of REO from the beta-CD complexes was investigated at different temperatures and pH values. The responses were affected by the concentration of ethanol in the reaction mixture and the amount of REO used. The optimal responses set by the RSM model (p-value < 0.05) were obtained for the optimal parameters ranging from 1.25:1 to 1.7:1 and 16.25:83.75 to 17.5:82.5 for ethanol/water and beta-CD/REO ratios, respectively. The size of the inclusion complexes from the experimental condition 1:1 ethanol/water and 10:90 beta-CD/REO ratios was the highest, with a value of 2.735 +/- 0.192 mu m. Furthermore, the FTIR spectra of inclusion complexes revealed a band downshift relative to the spectrum of beta-CD, attributable to hydrogen bonding between REO components and beta-CD, as well as a new band at 1,747 cm(-1), revealing the presence of oil components, while the XRD patterns of beta-CD recorded before and after the inclusion process indicate a change from a cage-type packing to a channel-type packing of cyclodextrin, which, in turn, indicates a successful inclusion process. Practical applications The encapsulation of EOs into cyclodextrins can enhance their biological properties, which include antioxidant, antimicrobial, anticarcinogenic, anti-inflammatory, and antidepressant activities. Nevertheless, a careful evaluation of the encapsulation conditions should be carried out in order to ensure the highest encapsulation yield without quality loss. In this way, pH and temperature, among other conditions, must be considered for evaluation since food or other matrices may present diverse pH values and be subjected to different temperatures. The present work may contribute to the use of rosemary EOs, with antioxidant and antimicrobial properties, in food and cosmetic industries, avoiding the sometimes-unpleasant flavor and aroma characteristics. info:eu-repo/semantics/publishedVersion

A series of water-soluble encapsulated copper(I), silver(I) or gold(I) complexes based on NHC-capped permethylated cyclodextrins (ICyDMe ) were developed and used as catalysts in pure water for hydration, lactonization, hydroarylation and cycloisomerization reactions. ICyDMe ligands gave cavity-based high regioselectivity in hydroarylations, and high enantioselectivities in gold-catalyzed cycloisomerizations reactions giving up to 98 % ee in water. These ICyDMe are therefore useful ligands for selective catalysis in pure water.

International audience; This work is aimed at developing a new process to separate alpha-cyclodextrin (CD) from binary alpha-CD/beta-CD mixtures. To achieve this objective, a membrane process was designed with water as solvent and using the selective accommodation of a guest Igepal Co-890 (IG) within the beta-CD cavity. In the first part, host-guest inclusion study suggested the formation of IG(2)/beta-CD complex in presence of IG excess. Moreover, increasing IG/CD molar ratio to 1.5 leads to the complete complexation of beta-CD while alpha-CD remains free. The second part was devoted to the separation of alpha- and beta-CD using UF membranes (GH and GK from GE-Osmonics). The influence of parameters including membrane molecular weight cut-off (MWCO), transmembrane pressure (Delta P), IG/beta-CD and alpha-CD/beta-CD molar ratios, was investigated. MWCO, Delta P, IG/beta-CD and alpha-CD/beta-CD molar ratios respectively of 1000 Da, 2 bar, 1.5 and 11:89 are the optimized values to reach an alpha-CD separation factor as high as 38. The experimental data fits very well with predicted values calculated using the parameters found in the complexation study and rejection of single solutions indicating that selectivity predominantly originates from steric exclusion of species by membrane GH.

Cyclodextrins (CDs) are macromolecules with several industrial applications, being particularly used in the food industry as health-promoting compounds protection agents, as flavour stabilizers, or to eliminate undesired tastes and browning reactions, among others. This study shows the effects of α- (10, 30 and 40 mmol L-1 ), β- (3, 6 and 10 mmol L-1 ) and maltosyl-β-CDs (30, 60 and 90 mmol L-1 ) use on the health-promoting glucoraphanin-sulforaphane system of a broccoli juice up to 24 h at 22 °C. Maltosyl-β-CD (90 mmol L-1 ) highly retained glucoraphanin content after 24 h at 22 °C, showing better effectiveness than β-CD (10 mmol L-1 ). Sulforaphane was efficiently encapsulated with β-CD at just 3 mmol L-1 , and the sulforaphane formed was stable during 3 h at 22 °C. On the other hand, 40 mmol L-1 α-CD retained a high glucoraphanin content in broccoli juice. In contrast, glucoraphanin levels in juice without CDs decreased by 71% after 24 h. Consequently, CDs addition may potentially preserve glucoraphanin in this broccoli juice during industrial processing with the possibility to be later transformed by endogenous myrosinase after ingestion to the health-promoting sulforaphane. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

International audience; The initial synthesis of two β-cyclodextrin derivatives bearing seven carboxylate ligands was optimized in order to improve the production of contrast agents. A speciation study using potentiometric analysis was performed on a gadolinium(III) complex. The in vivo myocardic activity was evaluated on mice. This study highlights the best efficiency for the cyclodextrin derivative having free hydroxyl groups and validated the biomedical potential of the flexible cyclodextrin scaffold as a cardiac MRI probe.

The formation of host–guest inclusion complexes (ICs) by an ionic liquid (IL) 1-butyl-3-methylimidazolium octylsulphate [Bmim][OS] within α- and β-cyclodextrins (CDs) has been explored by 1H NMR, 13C NMR and 2D 1H–1H COSY methods. The mechanism of the CD–[Bmim][OS] host:guest complex formation is systematically presented. The structural effect and various types of interactions, such as, H-bonding, electrostatic force and hydrophobic interactions that are responsible for the inclusion of the IL [Bmim][OS] into the cavity of CDs have been critically discussed with the help of NMR methods. It is observed that the hydrophobic effect plays a crucial role in supporting the formation of CD–[Bmim][OS] ICs. Furthermore, the spectral results obtained from 2D 1H–1H COSY NMR suggest that both H-bonding and electrostatic interactions also make a significant contribution to the stability of the IL–CD ICs.

The aim of the present study was the encapsulation of Rosmarinus officinalis essential oil (REO) in β-cyclοdextrin (β-CD) and two chemically modified β-CD matrices and the evaluation of the antibacterial activity of the prepared inclusion complexes against Staphylococcus aureus. The inclusion complexes possessed nanoscale size ranging from 395.7 ± 13.7 to 594.9 ± 18.8 nm, good size dispersion (0.366 ± 0.009 to 0.482 ± 0.043) and satisfactory stability in suspension (ζ-potential, −24.3 ± 4.2 to −31.5 ± 4.9 mV), while the inclusion efficiency ranged from 65% to 78%. The in vitro release profiles of the inclusion complexes revealed an initial burst effect, with the release kinetics being better fitted on the Higuchi model following quasi-Fickian diffusion. The antibacterial activity of the inclusion complexes of REO in β-CD, HP-β-CD and Me-β-CD against S. aureus was evaluated for 3 days and it was observed that both β-CD and HP-β-CD exhibited prolonged activity in comparison to the pure REO.

Synthetic assembly of two β-cyclodextrins (CDs) was efficiently accomplished using a 6,6′-di-iodotrehalose derivative as a unique linker by means of a one-pot reaction in liquid ammonia for Birch reduction and subsequent SN2 replacement. The unique sulfide-linked CD dimer displayed a wider hydrophobic region due to the cavity of the CDs and a part of similar structure of a trehalose linker. An inclusion property of the CD dimer was tentatively examined using TNS (2-p-toluidinylnaphthalene-6-sulfonate) as a model guest compound.

The potential applications of catechin in food products are limited by its astringent taste, sparing solubility in water and sensitivity to oxygen, light and pH. A finishing formulation that is capable of protecting catechin is needed to deliver this antioxidant to its physiological targets with minimal loss of bioactivity. The aims of this study were to optimize the yield, microencapsulation efficiency and antioxidant properties of the inclusion complex (IC) and to determine the physicochemical properties and stability of β-CD-, HPβ-CD and Mβ-CD-complexed-catechin for potential functional food and health supplement applications. An inclusion complex prepared from 0.006 mol/L catechin and β-cyclodextrin (β-CD) with a 1:1 core to wall ratio showed the highest yield, encapsulation efficiency and antioxidant activity. Catechin complexed with β-CD more efficiently than with hydroxypropyl- β-cyclodextrin (HPβ-CD) or methyl- β-cyclodextrin (Mβ-CD). Encapsulation with β-CD was observed to double the water solubility of catechin. Particles of complexes ranging from 5 to 100 μm with spherical morphology were produced. 1 H NMR spectroscopy and DSC confirmed the host – guest complexation of catechin in the β-CD cavity. The current study shows that encapsulation of catechin with β-CD provides protection against temperature, light and oxygen. These inclusion complexes have potential applications as functional foods and health supplements.

Molecular encapsulation is extremely important in pharmaceutical and drug delivery science. In this article, one of the most important sulfa drugs, namely, sulfacetamide sodium, has been probed in the solution and solid phases for encapsulation within the cavities of α- and β-cyclodextrins. Various physicochemical techniques were employed to establish the outcome of the work. The isothermal titration calorimetric method was used to evaluate the stoichiometry, association constant, and thermodynamic parameters with high accuracy. The solid inclusion complexes were analyzed by spectroscopic techniques to ascertain the encapsulation of the investigated drug within the cavities of α- and β-cyclodextrins. This phenomenon of drug inclusion is exceedingly significant for its stabilization against external hazards, such as oxidation, sensitization, and photolytic cleavage, for the proficient and accurate regulatory release of an essential amount of drug at the targeted site for a period of time and for the preven...

The present work focuses on the mechanochemical preparation of industrially important β-cyclodextrin (CD) derivatives. Activated CDs have been reacted with nitrogen and sulfur nucleophiles using a planetary mill equipped with stainless steel, zirconia and glass milling tools of different sizes. It is shown that the milling frequency and the number as well as the size of the milling balls have an effect on the nucleophilic reaction.

We report new 3D fragment descriptors to model parameters and properties of stereoisomeric molecules and conformers. New 3D fragment descriptors have been applied to discriminate between stereoisomers in predictive QSPR modeling of the standard free energy (∆G°) for the 1:1 inclusion complexation of 76 chiral guests with β-cyclodextrin (β-CD) and 40 chiral guests with 6-amino-6-deoxy-β-cyclodextrin (am-β-CD) in water at 298 K. The in-house software, mfSpace (Molecular Fragments Space), was used for QSPR modeling, generation and coding of the 3D fragment descriptors. The program implements the Singular Value Decomposition for Multiple Linear Regression analysis as machine learning method. We used ensemble modeling techniques which include the generation of many individual models, the selection of the most relevant ones and followed by their joint application to test compounds, i.e., applying a consensus model for average predictions. The models based on 2D and 3D fragment descriptors provide the best predictions in external fivefold cross-validation: root mean squared error RMSE = 1.1 kJ/mol and determination coefficient $$R_{{det}}^{2}$$ = 0.918 (β-CD), RMSE = 0.89 kJ/mol and $$R_{{det}}^{2}$$ = 0.910 (am-β-CD).

An in-depth theoretical analysis of two monosubstituted cyclodextrins (CDs) has been performed in order to find the appropriate level of theory capable of the correct qualitative description of their experimentally evidenced self-inclusion phenomenon. The correct increased stability of conformations with substituents included into the cavity (‘IN’ conformations) compared with those in which substituents point outside the cavity (‘OUT’ conformations) is qualitatively predicted by molecular mechanics, the dispersion-corrected self-consistent-charge density-functional tight-binding (SCC-DFTB-D), dispersion-corrected density-functional theory (DFT-D), single-point second-order Moller–Plesset (MP2), and domain based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) computations. The latter four approaches provide also quantitative insights into the relative stability of the ‘IN’ and ‘OUT’ conformations. The method of choice for the fast evaluation of the stability order of the CD conformations is the SCC-DFTB-D that yields relative energies with nearly DFT-D and MP2 accuracy.

To improve the water solubility of daidzein, solid inclusion complexes of daidzein with two amino-modified β-cyclodextrins (ACDs), i.e., mono-6-amino-6-deoxy-β-cyclodextrin (NCD) and mono-6-ethylenediamino-6-deoxy-β-cyclodextrin (ENCD), were prepared by the saturated solution method in water with yields of 83% and 67%, respectively, under the optimized conditions including the ratio of daidzein/ACD of 3:1 and the stirring time of 72 h. The formation of the two inclusion complexes was confirmed by X-ray diffractometry (XRD) and thermo gravimetric (TG) analysis. The inclusion stoichiometry of the inclusion complexes was 1:1 from the Job plot and their complexation stability constants (KS) were 899.2 and 203.8 M−1 from fluorescence titration, respectively. After formation of inclusion complexes with NCD and ENCD, the water solubility of daidzein was dramatically raised to 15.2 and 13.2 mg mL−1 at 25 °C, increasing by 1800 and 1500-fold compared to native daidzein (8.31 μg mL−1).

The interactions between bile salts and modified cyclodextrins (CD) have aroused intensive interest because of their influence on the in vivo drug release within the small intestine. We use a recently proposed molecular dynamics/quantum mechanics/continuum solvent model (Ye et al. in Chem Phys Lett 648:170, 2016) to investigate the microscopic binding mechanisms of the natural, dimethylated (M200), randomly methylated (M214), and trimethylated (M300) $$\beta$$ -CDs, with glycocholate (GC). The computed binding free energies of the four CDs with GC decrease in the following order: natural $$\beta$$ -CD > M200 > M214 > M300, which is in accord with the experimental data. As suggested by the computed thermodynamic quantities, the relative stabilities of the four CD/GC complexes are determined by both the host–guest interactions (enthalpy plus entropy) and the solvent effects. Moreover, the former favors M200, while the latter favors natural $$\beta$$ -CD. For M300, both factors are in disadvantage.

Water soluble fluorescent Ag clusters trapped in the cavity of β-cyclodextrin (β-CD) was synthesized by a facile one-pot procedure at room temperature. It’s demonstrated that the glutathione bound to Ag cores penetrates through the cavity of β-CDs, which acted as the templates and restricted the size of clusters. Fluorescence enhancement was observed in Ag clusters when Al3+ was added. The fluorescence enhancement mechanism was studied. Comparing to interaction between shell ligands and Al3+, it’s likely the interaction between Ag cores and Al3+ plays dominant role in this process.

Compared with polypseudorotaxanes (PPRs) formed from the self-assembly of β-cyclodextrins (β-CDs) with poly(propylene glycol) (PPG) and γ-CDs with poly( N-isopropylacrylamide) (PNIPAAm), the ratio of the inner cavity size of β-CD to the cross-sectional area of PNIPAAm appears not appropriate for their self-assembly. For a better understanding of the possibility of β-CDs including PNIPAAm and the crystal structure of PPRs formed therefrom, the PNIPAAm homo- and copolymers were subjected to self-assembly with β-CDs in an aqueous solution at room temperature. The results revealed that when β-CDs meet thicker PNIPAAms, the self-assembly takes place, not only giving rise to PPRs by a manner of main-chain inclusion complexation but also presenting the PPRs a matched over-fit crystal structure different from those of either a matched tight-fit β-CD-PPG PPR or a mismatched over-fit γ-CD-PNIPAAm PPR. This is most likely due to the thicker PNIPAAm adapting its unfavorable main-chain cross-sectional area to fit into the cavity of β-CDs by changing the side-chain conformations. Based on the X-ray diffraction patterns, a monoclinic crystal system was created from these PPRs and the unit cell parameters calculated were as follows: a = 15.3 Å, b = 10.3 Å, and c = 21.2 Å; β = 110.3°; and space group P2. It suggested that this matched over-fit crystal structure would possess a Mosaic crystal structure rather than a typical channel-like one.

7 pags., 10 figs. -- Open Access funded by Creative Commons Atribution Licence 4.0, In the present work, the application of the amine electrooxidation method to achieve the grafting of amino β-cyclodextrins (CD-amines) on glassy carbon electrodes (GCE) in aqueous media has been investigated. The results indicate that the electrooxidation procedure of CD-amines on GCE effects their covalent immobilization without the need of additional linkers or intermediates. Cyclic voltammograms of ferricyanide proved that the immobilized CDs cover at a large extent the GCE surface. This immobilization is due to real grafting and not the result of a weak physisorption interaction. Indeed, the presence of contributions characteristic of amide groups and the absence of peaks typical of amine groups in the XPS N 1s spectra of the modified GCE, support the evidence of the covalent bonding of the CDs to the glassy carbon surface through amide bond formation. Electrochemical experiments demonstrated that ferrocenemethanol and bentazon can be encapsulated within the cavity of the CDs immobilized on GCEs via the formation of inclusion compounds. Overall, the results of the present work show that this simple amine-electrooxidation strategy is suitable to immobilize CDs on glassy carbon surfaces while maintaining their inclusion abilities and, therefore, open the door to design cheap and simple electrochemical sensors for environmental applications., The authors acknowledge financial support from FONDECYT (Grant. N. 1151329) and MINECO, Spain (Project MAT2015-64110- C2-1-P).

The chiral separation ability of the full library of methylated-β-cyclodextrins towards pharmacologically significant racemic drugs including basic compounds was studied by chiral CE. The syntheses of all the methylated, single isomer β-cyclodextrins were revised and optimized and the aqueous solubility of the derivatives was unambiguously established. The three most relevant commercially available methylated isomeric mixtures were also included in the screening, so a total of ten various methylated CDs were investigated. The effects of the selector concentration on the enantiorecognition properties at acidic pH were investigated. Among the dimethylated β-cyclodextrins, the heptakis (2,6-di-O-methyl)-β-cyclodextrin isomer (2,6-DIMEB) resulted to be the most versatile chiral selector. Terbutaline was selected as a model compound for the in-depth investigation of host-guest enantiodiscrimination ability. The association constants between the two terbutaline enantiomers and 2,6-DIMEB were determined in order to support that the enantioseparation is driven by differences is host-guest binding. The migration order of the enantiomers was confirmed by performing spiking experiments with the pure enantiomers. 1D and 2D NMR spectroscopy was applied to the 2,3-, and 2,6-DIMEB/terbutaline systems to rationalize at molecular level the different enantioseparation ability of the dimethylated β-cyclodextrin selectors.

Per(5-N-carboxamide-5-dehydroxylmethyl)-β-cyclodextrin derivatives with seven equivalent amide groups directly attached to each pyranose ring were synthesized. The amide cyclodextrins show unique recognition properties toward hydrogen phosphonate anions. An X-ray crystallographic analysis revealed its recognition mode in which unsymmetrically arranged amide groups play distinctive roles both as a hydrogen bond donor and acceptor.

A novel supramolecular assembly was constructed by the noncovalent complexation of hexa-cata-hexabenzocoronene modified permethyl-β-cyclodextrins with tetrasodium tetraphenylporphyrintetrasulfonate in water, exhibiting highly efficient excited energy transfer behaviors and a promising DNA photocleavage ability.

Encapsulation of caffeic acid (CAA), ferulic acid (FEA) and sinapic acid (SIA) molecules with α-CD and β-CD was studied by UV-visible, fluorescence, time-resolved fluorescence and molecular modelling techniques. This analysis reports the probing of cyclodextrin (CD) cavities with the help of dual emission properties of the above hydroxycinnamic acids (HCAs) in aqueous solution. The normal Stokes shifted bands originated from the locally excited state and the large Stokes shifted bands due to the emission from an intramolecular charge transfer (ICT) state were observed. The ratio of the TICT emission to the normal emission increased with α-CD and β-CD concentration. CD studies indicates (i) HCAs forms 1:1 inclusion complex and (ii) acrylic group present in the interior part of the CD cavity and OH/OCH3 groups present in the upper part of the CD cavity. pH studies suggest proton transfer reactions follow the same trend in these molecules. A mechanism is proposed to explain the inclusion process. PM3 optimizations were also carried out to assign the encapsulation of the HCA molecules.

A method was built to separate three kinds of enantiomers of non-natural carboxyl amino acid with CE while CM-β-CDacted as chiral selective reagent. Several different β-CD derivatives were used as the chiral separation agent, and it was proved that CM-β-CDhad the advantage of chiral selectivity for carboxyl amino acids. Three kinds of enantiomers of carboxyl amino acids were separated by CE in a 50 μm i.d.×60 cm (effective length 45 cm) fused-silica capillary at 20 kV voltages and 10 mM NaH2PO4 solution served as running buffer solution with 10 mM CM-β-CDserving as selective reagent. The optimum detection wavelength was 214nm.

Structure and stability of an eventual inclusion complex formed by Lidocaine and two cyclodextrins (α- and β-CD) were investigated using molecular mechanics and quantum-chemical methods in the gas phase and in water. The molecular docking and quantum chemical calculations results show that no inclusion complex is formed between α-CD and Lidocaine molecule, while the conformational research allowed observing two minimum-energy structures between this molecule and β-CD. From a potential energy scan, a partial inclusion of the two ends of Lidocaine by the secondary face of the cavity of β-CD is observed with a better stability for the complex including the ((-N(C2H5)2) group in it. The minimum energy conformers, obtained by semi empirical method (PM3), have been exposed to fully geometry optimization employing ONIOM2 calculations by combining PM3 method with B3LYP, M06-HF and WB97XD functionals at 6-311G (d,p) basis set. The results show that complexation reactions are thermodynamically favored (Gand#176; ˂ 0) and the inclusion complexes are energetically stables and well structured (Sand#176; ˂ 0). According to the analysis of natural bond orbitals, the Van der Waals interactions are the sole driving forces that ensure the stability of the formed complexes.

This project aimed to explore the inclusion mechanism and structure of azo dye ethyl red (ER) included into cyclodextrins (CDs) through experiments and computer simulation. Molecular docking and dynamic simulations presented a stable 1:1 inclusion complex and the visual structure model that the ethyl end of ER was enclosed into the cavity of CDs, which were consistent with the results of Job plots, 1H NMR and 2D-ROESY. The inclusion process driven mainly by entropy with the binding constant following the order of DM (dimethyl)-β-CD > HP (hydroxypropyl)-β-CD. The aqueous solubility of ER was significantly improved by the inclusion of CDs.

The use of co-solvents to increase drug solubility is limited mainly due to their toxicity. Many solvents are not biodegradable and have significant environmental impact. Furthermore, uncontrolled precipitation of the compound may arise when solvent-based formulation is introduced into an aqueous medium. Cyclodextrins (CD) can form inclusion complexes resulting in an increase in the guest's solubility. Herein, we evaluated the effect of dimethylsulfoxide (DMSO), ethanol (EtOH), CD, and their association, on the solubility of two natural anti-oxidants, trans-anethole (AN) and caffeic acid (CA). The findings revealed that co-solvents or CD enhanced the solubility of these compounds. Nonetheless, if the concomitant presence of co-solvent and CD induced a loss of the solubilizing efficiency of CD it allowed lowering the quantity of solvent needed to achieve the same solubility. Consequently, the concentration of CD and co-solvent in the complexation media should be optimized to solubilize the required amount of the guest.

As commonly-used cyclic oligomers, cyclodextrins are usually composed of 6 and 7 glucopyranose units (α-cyclodextrin and β-cyclodextrin). The binding constant is a significant parameter to estimate the association stability of inclusion complexes and evaluate the influence of cyclodextrins on guest compounds. In order to cover the shortage of experimental methods, we intended to predict the binding constants and interaction forces of cyclodextrin inclusion complexes by developing consensus models and calculating energy changes. 418 cyclodextrin inclusion complexes were collected with their experimental binding constants. By combining 6 description methods and 5 machine learning methods, we built 60 single models, which were selected to develop 104 consensus models. The coefficients of determination of the test sets in the best α-cyclodextrin consensus model and the best β-cyclodextrin consensus model were 0.84 and 0.89, respectively. The applicability domains of models were defined. After performing molecular docking and calculating energy changes, we could observe the binding poses, identify the interaction forces, and select the dominant forces. The consensus models and the calculation of energy changes can be applied to explore the binding capacity and interaction forces of inclusion complexes.

Host-guest interactions are widely employed in constructing responsive materials, although less is known to manipulate the chiral property of materials using such host-guest dynamics. With the supramolecular self-assembly based on β-cyclodextrin (β-CD) and alkyl amines (CH3(CH2)n-1NH2), we report that faster host-guest dynamics induces a dipole located above the cavity of β-CD, whereas slower dynamics create in-cavity dipole. These two scenarios correspond to negative and positive chiral signals, respectively. Considering that a larger fraction of amines facilitates faster exchange between the threaded and unthreaded amines, the chiral signal for the right-handed helical ribbons can be manipulated simply by alternatively increasing the fraction of amines and β-CD. Excitingly, enzyme responsive supramolecular chirality is obtained as a result of shifting the molar ratio by enzyme triggered hydrolysis of β-CD. We expect that this strategy may open up an area of rationally designed chiral supramolecular materials based on host-guest chemistry.

The strong binding of the adamantyl moiety to the cavity of β-cyclodextrin makes it a common binding motif in supramolecular chemistry and a common model system. Despite the attention, there are still unresolved questions regarding the orientation of the adamantane derivatives in the inclusion complexes—do they protrude from the wide or narrow opening of the cyclodextrin hosts? A combined analysis of ROESY NMR and molecular dynamics simulations allows the conclusion that positively charged adamantane derivatives are oriented with the hydrophilic group protruding from the wider opening of the cyclodextrin, while negatively charged adamantane derivatives form two coexisting types of complexes where the hydrophilic group respectively protrudes from the wide and narrow opening. Interestingly, structural modifications of the cyclodextrin host only have a slight impact on the guest orientation.

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.

The inclusion complexation behavior of 2,5-Bis(5-tert-butyl-benzoxazol-2yl)-thiophene (UVOB) with native β-cyclodextrin (βCD) and βCD-monochlorotriazinyl (βCD-MCT) was evaluated by fluorescence spectroscopy. The association constant (Ks), stoichiometry, , and were evaluated at 25℃ ± 0.1℃ in phosphate buffer solution (pH = 10.5, 0.1 mo•dm–3) in order to find out the complex formation ability and stability. Fluorescence enhancement for UVOB and UVBNB with both CDs has been observed as a result of the complex formation. A stoichiometry 1:1 for UVOB in both CDs was observed; a stoichiometry 3:1 for UVBNB in both CDs has been observed. The Ksvalues for UVOB were 4916 ± 137 M–1 and 655 ± 19 M–1 (acetone: water 90/10, v/v) with βCD and βCD-MCT, respectively. The value obtained indicates a spontaneous and stable complex formation, but the complex βCD-UVOB showed high Ks value as an indicative of a high concentration of complex formed. Additionally, Ks and thermodynamic parameters and were evaluated in a commercial product UVBNB (UVOB, 13%, v/v). In aqueous solution, the values obtained were 2552 ± 115 and 1787 ± 75 M–1 respectively. Complexation of UVOB with CDs is an interesting approach for utilization of UVOB in aqueous systems without the need of solvents and or surfactants used in commercial product (UVBNB).