Kinds Of Cyclodextrins Research Articles

Enzymatic cyclodextrin synthesis-tributyrin inclusion complex: Properties, structural characterization and release behaviors in vitro

Tributyrin, a good butyric acid donor, has the potential to prevent colon cancer. The cyclodextrin-tributyrin inclusion complexes synthesized by enzymatic methods have the advantages of low costs and simple technology. However, the structure as well as compositions of the inclusion complexes and release behaviors of inclusion guest molecules have not been elucidated. We evaluated the properties and structure of the enzymatic cyclodextrin synthesis-tributyrin inclusion complex (ECT). In vitro release behaviors of inclusion complexes were investigated and kinetic simulation performed. The ECT exhibited a double-layer encapsulation structure while the carrier was mainly composed of three kinds of cyclodextrins and macrodextrins, among which the levels of β-CD were higher. The storage experiment revealed that the encapsulation complex had a good stability. Kinetic simulation showed that ECT release in vitro conforms to the Hixson-Crowell model. These findings imply that ECT could effectively pass through the stomach and tributyrin release mainly occurred in the large intestines. Therefore, ECT can effectively improve tributyrin bioavailability, which provides a basis for in vivo ECT applications.

NMR Investigation of the Supramolecular Complex Formed by a Phenylboronic Acid-Ferrocene Electroactive Probe and Native or Derivatized β-Cyclodextrin.

Specifically designed electrochemical sensors are standing out as alternatives to enzyme-based biosensors for the sensing of metabolites. In our previous works, we developed a new electrochemical assay based on cyclodextrin supramolecular complexes. A ferrocene moiety (Fc) was chemically modified by phenylboronic acid (4-Fc-PB) and combined with two different kinds of cyclodextrins (CDs): β-CD and β-CD modified by a dipicolylamine group (dpa-p-HB-β-CDs) for the sensing of fructose and adenosine-triphosphate (ATP), respectively. The aim of the present work is to better comprehend the features underlining the aforementioned complex formation. For the first time, a study about inclusion phenomena between the 4-Fc-PB electroactive probe with β-CD and with dpa-p-HB-β-CD was performed by using nuclear magnetic resonance (NMR) analysis. In particular, we focused on providing insights on the interaction involved and on the calculation of the binding constant of 4-Fc-PB/β-CD supramolecular complex, and elucidation about a drift in the time observed during the control experiments of the electrochemical measurements for the 4-Fc-PB/dpa-p-HB-β-CD supramolecular complex. In this sense, this paper represents a step further in the explanation of the electrochemical results obtained, pointing out the nature of the interactions present both in the formation of the inclusions and in the sensing with the analytes.

Preparation and Properties of Cyclodextrin Inclusion Complexes of Hyperoside.

In order to improve the aqueous solubility and enhance the bioavailability of Hyperoside (Hyp), three inclusion complexes (ICs) of Hyp with 2-hydroxypropyl-β-cyclodextrin (2H-β-CD), β-cyclodextrin (β-CD), and methyl-β-cyclodextrin (M-β-CD) were prepared using the ultrasonic method. The characterization of the inclusion complexes (ICs) was achieved using Fourier-transform infrared spectroscopy (FTIR), scanning electronic microscopy (SEM), X-ray powder diffraction (XRPD), thin-layer chromatography (TLC), and 1H nuclear magnetic resonance (1H NMR). The effects of the ICs on the solubility and antioxidant activity of Hyp were investigated. A Job’s plot revealed that the Hyp formed ICs with three kinds of cyclodextrin (CD), all at a 1:1 stoichiometric ratio. The FTIR, SEM, XRPD, TLC, and 1H NMR results confirmed the formation of inclusion complexes. The water solubility of the IC of Hyp with 2-hydroxypropyl-β-cyclodextrin was enhanced 9-fold compared to the solubility of the original Hyp. The antioxidant activity tests showed that the inclusion complexes had higher antioxidant activities compared to free Hyp in vitro and the H2O2–RAW264.7 cell model. Therefore, encapsulation with CDs can not only improve Hyp’s water solubility but can also enhance its biological activity, which provides useful information for the potential application of complexation with Hyp in a clinical context.

Computational Insights Into the Influence of Substitution Groups on the Inclusion Complexation of β-Cyclodextrin.

Cyclodextrins (CDs) and their derivatives have good prospects in soil remediation application due to their ability to enhance the stability and solubility of low water-soluble compounds by inclusion performance. To investigate the effect of different structural properties of cyclodextrin and its derivatives on the inclusion complexation, molecular dynamic (MD) simulations were performed on the inclusion complexes formed by three kinds of CDs with polycyclic aromatic hydrocarbons (PAHs). Based on neutral β-CD, the other two CDs were modified by introducing substitutional groups, including 2-hydroxypropyl and sulfonated butyl (SBE) functional groups in the ring structure, called HP-CD and SBE-CD. MD results show that PAH can merely enter into the cavity of SBE–β-CD from its wide rim. The substitutional groups significantly affect the structure of CDs, which may also cause the flipping of the glucose units. However, the substitutional groups can also enlarge the volume of the hydrophobic cavity, resulting in a tight combination with the guest molecules.

The photochemical effects of visible light on K2[PtCl4] hydrolysis and the synthesis of Pt nano catalysts

The hydrolysis of K2[PtCl4] under visible light, the equilibrium, morphology, and size of Pt NPs combined with CDs, the valence states of Pt element and the bonding of Pt NPs with CDs, the influence of different kinds of cyclodextrin (α, β, γ-CDs), the acidity of the solution, and the visible light color on the catalytic ability of Pt NPs were all researched by typical approaches. All results prove visible light irradiation is effectively playing a key role in the reaction process to form Pt NPs in a very narrow size distribution. pH = 9, β-CDs, and purple visible light are the optimized reaction conditions. The Pt-CDs present a high rate constant of 0.88 min−1 in the catalytic reduction of 4-NP. This research is beneficial for expanding photochemical approaches from ultraviolet light to visible light, which is more of green chemistry, low cost, and facile.

New Enhanced Method for Determination of Trace Sulfamethodxazole Based on the Fluorescence Behaviors of Cyclodextrins in Water Solutions.

The widespread occurrence of sulfonamides (SAs) in the environment water has rasied great concerns about their potential to antibiotics resistance. In this study, the fluorescence behaviors of sulfamethoxazole (SMZ) representing certain properties of the SAs mixed with three different kinds of cyclodextrins (CDs) in water solutions were investigated, respectively. The result reported that the shapes of the fluorescence peak and its position for the SMZ that were mixed with the CDs were almost the same as those of the standard SMZ, respectively. In addition, compared with the identical control sample the fluorescence of SMZ mixed with each of the CD was greatly enhanced. Therefore, a new simple, and sensitive spectrofluorimetric method for the determination of SMZ was established in water solutions. and the dynamic linear ranges varied from 0.01 to 0.7mg/L with the detection limit of 7.1ng/L. And the correlation coefficient was more than 99.9%. Significantly, this new method was successfully applied to direct determination of SMZ in pharmaceutical compounds. Moreover, the results showed that the SMZ could separately form the 1:1 supramolecular compound with each of the CD.

A Theoretical Basis for the Enhancement of Seebeck Coefficients in Supramolecular Thermocells

Abstract Seebeck coefficients (Se) of supramolecular thermocells harnessing four kinds of cyclodextrins as host molecules were investigated. Theoretical analysis revealed that association enthalpy between the hosts and triiodide has a major influence on the Seebeck coefficients of the thermocells. Thermodynamic parameters of host–guest associations were evaluated by isothermal titration calorimetry, which is in good agreement with the theoretically estimated values from thermocell measurements. This result provides a guideline to estimate Seebeck coefficient of supramolecular thermocells and to determine the thermodynamic parameters.

Effects of cyclodextrin on the stereoselectivity inhibition of acetylcholinesterase by isomalathion

ABSTRACTIn attempt to evaluate the effects of cyclodextrins (CDs) on enantioselectivity of chiral pesticides toxicity, this study investigated effects of three kinds of cyclodextrins including α-CD, β-CD and randomly methylated β-CD (RAMEB) on toxicity of four enantiomers of isomalathion including (1R, 3R)-isomalathion, (1S, 3S)-isomalathion, (1S, 3R)-isomalathion and (1R, 3S)-isomalathion. Generally, the addition of α-CD and RAMEB (1.5 g/L to 3.5 g/L concentration) could lead to reduction of isomalathion toxicity in most cases, while the presence of β-CD (0.3 g/L to 1.5 g/L concentration) enhanced the toxicity of isomalathion. It was speculated that higher electronic cloud density and lower water solubility of β-CD than α-CD and RAMEB might favor to combination between acetylcholinesterase (AChE) and isomalathion included by β-CD. With respect for α-CD and RAMEB, isomalathion included by them could be easily dissolved in water because of high water solubility of the two CDs. Therefore, α-CD and RAMEB can be used as remediation regent for the pollution of isomalathion, and β-CD can act as an additive in improving bioactivity of such pesticides. In addition, the presence of CDs can alter enantioselectivity of chiral pesticides. The differences on the extent of enantioselectivity variation of isomalathion induced by α-CD, RAMEB and β-CD might be ascribe to the different cavity, electron cloud density and solubility among the three CDs. In conclusion, the above results gave researchers a possibility to change enantioselectivity of chiral pesticides from undesirable outcomes to desirable ones.

Comprehensive evaluation of solubilization of flavonoids by various cyclodextrins using high performance liquid chromatography and chemometry

Flavonoids have many pharmacological activities, but the water solubility is poor, Cyclodextrin (CD) can be used to increase the solubility of flavonoids through making flavonoids into their cavities. While various CDs have different solubilization effects on flavonoids. Therefore, the purpose of this study was to evaluate the solubilization of flavonoids by three classes of cyclodextrins by Chemometrics (I native CDs: alpha-cyclodextrin (α-CD), beta-cyclodextrin (β-CD) and gamma-cyclodextrin (γ-CD); II hydrophilic CD derivatives: methyl-β-cyclodextrin (Me-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD); III ionic CD derivative: sulfobutyl ether β-cyclodextrin (SBE-β-CD)). All selected CDs had significant solubilization effects (P < 0.01). The solubilization coefficients of six kinds of CDs on flavonoids were α-CD: 41.77, γ-CD: 61.81, β-CD: 143.45, HP-β-CD: 415.43, Me-β-CD: 558.53, SBE-β-CD: 709.56, respectively. Phase solubility study indicated that six kinds of CDs and kaempferide can form inclusion complexes with 1:1 M ratio, association constants (Ka) of inclusion compounds were kaempferide-α-CD: 808 L/mol, kaempferide-β-CD: 1541 L/mol, kaempferide-γ-CD: 1191 L/mol, kaempferide-HP-β-CD: 9335 L/mol, kaempferide-Me-β-CD: 10,421 L/mol, kaempferide-SBE-β-CD: 12,502 L/mol, respectively. The study showed that SBE-β-CD has the best solubilization effect on flavonoids, therefore, SBE-β-CD may be widely used as a solubilizing agent for flavonoids.

Studies on the Inclusion Complexes of Daidzein with β-Cyclodextrin and Derivatives.

The inclusion complexes between daidzein and three cyclodextrins (CDs), namely β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD, DS = 12.5) and (2-hydroxy)propyl-β-cyclodextrin (HP-β-CD, DS = 4.2) were prepared. The effects of the inclusion behavior of daidzein with three kinds of cyclodextrins were investigated in both solution and solid state by methods of phase-solubility, XRD, DSC, SEM, 1H-NMR and 2D ROESY methods. Furthermore, the antioxidant activities of daidzein and daidzein-CDs inclusion complexes were determined by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method. The results showed that daidzein formed a 1:1 stoichiometric inclusion complex with β-CD, Me-β-CD and HP-β-CD. The results also showed that the solubility of daidzein was improved after encapsulating by CDs. 1H-NMR and 2D ROESY analyses show that the B ring of daidzein was the part of the molecule that was most likely inserted into the cavity of CDs, thus forming an inclusion complex. Antioxidant activity studies showed that the antioxidant performance of the inclusion complexes was enhanced in comparison to the native daidzein. It could be a potentially promising way to develop a new formulation of daidzein for herbal medicine or healthcare products.

Cyclodextrin glycosyltransferase variants experience different modes of product inhibition

Cyclodextrin glycosyltransferase (CGTase) can be used for the industrial production of cyclodextrins. However, product inhibition by cyclodextrins largely restrains the cyclization activities of CGTase and severely limits the application of cyclodextrins. In this paper, the kinetic mechanisms of the three kinds of cyclization reaction were studied, and the product inhibition modes of two CGTases from different sources were compared. The results confirm that the synthesis of each cyclodextrin is substantially inhibited by the corresponding cyclodextrin. Meanwhile, product inhibition studies indicate competitive inhibition for α-CGTase and a mixed pattern for β-CGTase. This demonstrates that the inhibition type is not decided by the kinds of cyclodextrins or the varieties of cyclization reactions, but by the structure of the CGTase.

Inhibition of cyclodextrins on α-galactosidase

This work successfully investigated the effects of different influential factors and hydrophobic cavities of cyclodextrins (CDs) on α-galactosidase (α-Gal) by detecting α-Gal activity. The highest inhibitory concentration of three kinds of CDs (α-, β-, and γ-CD) on α-Gal was 10mM. Moreover, the highest inhibition of α-Gal was obtained under the following conditions: reaction time of 90min, temperature of 30°C, and pH 6.0. Compared with other CDs, β-CD showed more ability to interact with α-Gal due to its appropriate cavity geometric dimensions. From circular dichroism and nuclear magnetic resonance it was observed that β-CD changed the secondary structure of α-Gal and formed a hydrogen bond with this enzyme.

The enhancement of fluorescence quantum yields of anilino naphthalene sulfonic acids by inclusion of various cyclodextrins and cucurbit[7]uril

The association constants (K) for the inclusion complexation of four kinds of cyclodextrins (CDs (β- and γ-), 2,6-di-O-methylated β-CD, and 2,3,6-tri-O-methylated β-CD) and cucurbit[7]uril (CB[7]) with 1,8- and 2,6-anilinonaphthalene sulfonic acids (ANSs) were determined from fluorescence spectra enhanced by inclusion. Various CDs and CB[7] form stable 1:1 inclusion complexes with 1,8- and 2,6-ANSs: K=80–11700M−1 for 2,6-ANS and 50–195M−1 for 1,8-ANS. The high stability of the inclusion complexes of 2,6-ANS with CB[7] and 2,6-di-O-methylated β-CD is shown. Further, we determined the fluorescence quantum yields (Φ values) for the inclusion complexes of ANSs by using a fluorescence spectrophotometer equipped with a half-moon unit. The Φ values of 1,8- and 2,6-ANSs were largely enhanced by the inclusion of methylated β-CDs and did not correlate with the degree of stability (K) of the inclusion complexes. We characterized the structures of the inclusion complexes by 2D ROESY-NMR measurements. In addition, the microenvironmental polarity inside the hydrophobic CD and CB[7] cavities was evaluated using the fluorescence probe 2,6-ANS. Based on the emission mechanism and the aspect of inclusion in a hydrophobic cavity, we have suggested that the microenvironmental polarity and viscosity for the excited state of ANS plays an important role for the Φ values of inclusion complexes.

Homotropic cooperativity of cyclodextrin dimer as an artificial hydrolase

Three kinds of cyclodextrin (CD) dimer (one homo-dimer of β-CD and two types of hetero-dimer of α-CD and β-CD) were synthesized as artificial hydrolases. The initial rates of the cleavage reaction of p-nitrophenyl methoxyethoxyethoxyacetate ( 8) by each of the three dimers were measured under the condition of excess of substrate at 25 °C in a pH 7.4 phosphate buffer solution. In a plot of initial rate against concentration of the substrate, the reaction with the homo-dimer ( βCβH 5) gave a sigmoidal curve, whereas the reaction with either of the hetero-dimers gave a simple hyperbolic curve. Only βCβH 5 showed homotropic cooperativity, with a Hill constant of 1.8.

Development of a new delivery system consisting in ‘drug–in cyclodextrin–in PLGA nanoparticles’

A combined approach based on drug cyclodextrin (CD) complexation and loading into PLGA nanoparticles (NP) has been developed to improve oxaprozin therapeutic efficiency. This strategy exploits the solubilizing and stabilizing properties of CDs and the prolonged-release and targeting properties of PLGA NPs. Drug-loaded NPs, prepared by double-emulsion, were examined for dimensions, zeta-potential and entrapment efficiency. Solid-state studies demonstrated the absence of drug–polymer interactions and assessed the amorphous state of the drug-CD complex loaded into NPs. Drug release rate from NPs was strongly influenced by the presence and kind of CD used. The percentage released at 24 h varied from 16% (plain drug-loaded NPs) to 50% (drug-βCD-loaded NPs) up to 100% (drug-methylβCD-loaded NPs). This result suggests the possibility of using CD complexation not only to promote, but also to regulate drug release rate from NPs, by selecting the proper type of CD or CD combination.

Host–guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Nitroheterocyclic compounds (NC) were candidate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydroxymethylnitrofurazone (NFOH), a potential antichagasic compound, with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), Hydroxypropyl-β-cyclodextrin (HP-β-CD), Dimethyl-β-cyclodextrin (DM-β-CD) and γ-cyclodextrin (γ-CD) by fluorescence spectroscopy and molecular modeling studies. Hildebrand–Benesi equation was used to calculate the formation constants of NFOH with cyclodextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-β-CD > β-CD > α-CD > HP-β-CD > γ-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as therapeutic options for the oral treatment of Chagas disease.

Study of the complexation of resveratrol with cyclodextrins by spectroscopy and molecular modeling

In present work the complexation of Res with two kinds of cyclodextrins (CDs), native β-cyclodextrin (β-CD) and modified hydroxypropyl-β-cyclodextrin (HP-CD), have been investigated by fluorescence spectroscopy, 1H-NMR spectroscopy and molecular modeling methods. The stoichiometric ratios, inclusion constants and thermodynamic parameters have been determined by the fluorescence data. In all cases 1:1 inclusion complexes are formed. The inclusion ability of HP-CD is larger than that of β-CD. Both inclusion processes have negative ∆G, negative ∆H and positive ∆S. Thermodynamic analysis suggests that Van der Waals force of guest-host interactions and the release of high-enthalpy water molecules from the cavity of CDs play important roles in driving complex formation. The study of molecular modeling shows that part of the A-ring and the B-ring of Res are placed in the cavity of β-CD, and the hydroxyl groups are projected outside. As for Res in HP-CD, the B-ring of Res is included in the cavity of HP-CD, and part of the A-ring is pointed outside. 1H-NMR spectroscopy results show that H2, H3, H4 and H5 protons of Res are more affected by the complexatin, indicating that they are located inside the torus of CDs, which are in agreement with the result of the molecular modeling.

Study on Supramolecular Systems of Mg-meso-Tetrakis(2-thienyl)Porphyrin with Cyclodextrins by Spectroscopy Method

In phosphate buffer solution of pH 5.4, the formation of supramolecular systems of Mg-meso-tetrakis(2-thienyl)porphyrin(Mg-TTP) with β-CD, carboxymethyl-β-CD (CM-β-CD), heptakis(2,6-di-O-methyl)-β-CD (DM-β-CD), heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD) and sulfurbutylether-β-CD (SBE-β-CD) has been studied by means of UV–vis, fluorescence and NMR spectroscopy, respectively. And the Mg-TTP can form 1:1 host-guest inclusion complexes with five cyclodextrins. In this paper, the inclusive capability of different kinds of cyclodextrins is compared. The inclusion ability of modified β-CD with Mg-TTP is stronger than the native β-CD. And the inclusion ability of TM-β-CD with Mg-TTP is the strongest among five CDs, which indicates that the hydrophobic effect plays a crucial role in the inclusion procedure except for the capacity matching. In addition, 1H-NMR data and 2D-ROESY NMR spectra support the inclusion conformation of the TM-β-CD-Mg-TTP supramolecular system, indicating the interaction mechanism of inclusion processes.

Effect of Cyclodextrins on Saccharide Sensing Function of a Fluorescent Phenylboronic Acid in Water

An inclusion complex consisting of a fluorescent phenylboronic acid (C1-APB) and beta-cyclodextrin (beta-CD) acts as a supramolecular saccharide sensor whose response mechanism is based on photoinduced electron transfer (PET). This study evaluated four kinds of cyclodextrins (alpha-CD, beta-CD, gamma-CD, and NH(2)-beta-CD) by comparing their pH profiles, and confirmed that beta-CD was the best host for C1-APB because the C1-APB/beta-CD complex exhibited high affinity for saccharides as well as high fluorescent recovery upon saccharide binding. An investigation of the beta-CD concentration effect revealed the formation of a 1:1 inclusion complex of C1-APB with beta-CD. The observed saccharide selectivity of the C1-APB/beta-CD complex is in the following order: D-fructose (4039 +/- 69 M(-1)) > D-ribose (1083 +/- 26 M(-1)) > L-arabinose (474 +/- 11 M(-1)) > D-galactose (318 +/- 3 M(-1)) > maltotoriose (135 +/- 5 M(-1)) > D-glucose (114 +/- 2 M(-1)) > maltose (81 +/- 2 M(-1)). In addition to monomer emission, dimer emission from pyrene dimers was observed in the spectra for the C1-APB/gamma-CD complex, which allowed a ratiometric analysis. This study shows that the combination of a simple fluorescent probe, C1-APB, with various CDs diversifies the response systems for saccharide recognition.

Complexation of morin with three kinds of cyclodextrin: A thermodynamic and reactivity study

Properties of inclusion complexes between morin (M) and β-cyclodextrin (βCD), 2-hydroxypropyl-β-cyclodextrin (HPβCD) and Heptakis (2,6- O-di methyl) β-cyclodextrin (DMβCD) such as aqueous solubility and the association constants of this complex have been determined. The water solubility of morin was increased by inclusion with cyclodextrins. The phase-solubility diagrams drawn from UV spectral measurements are of the A L-type. Also ORAC FL studies were done. An increase in the antioxidant reactivity is observed when morin form inclusion complex with the three cyclodextrin studied. Finally, thermodynamics studies of cyclodextrin complexes indicated that for DMβCD the inclusion is primarily enthalpy-driven process meanwhile βCD and HPβCD are entropy-driven processes. This is corroborated by the different inclusion geometries obtained by 2D-NMR.