Β-cyclodextrin Complexes Research Articles

Cardiovascular effects of farnesol and its β-cyclodextrin complex in normotensive and hypertensive rats

Farnesol (FAR) is a sesquiterpene alcohol with a range of reported biological effects including cardioprotective, antioxidant and antiarrhythmic properties. However, due to its volatility, the use of drug incorporation systems, such as cyclodextrins, have been proposed to improve its pharmacological properties. Thus, the aim of this study was to evaluate and characterize the cardiovascular effects of FAR alone, and to investigate the antihypertensive effects of FAR complexed with β-cyclodextrin (βCD) in rats. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after intravenous administration of FAR (0,5; 2,5; 5 and 7,5 mg/kg) in normotensive rats, and after oral acute administration (200 mg/kg) of FAR and FAR/βCD complex in NG-nitro-L-arginine-methyl-ester (L-NAME) hypertensive rats. In normotensive animals, FAR induced dose-dependent hypotension associated with bradycardia. These effects were not affected by pre-treatment with L-NAME or indomethacin (INDO), but were partially attenuated by atropine. Pre-treatment with hexamethonium (HEXA) only affected hypotension. In the hypertensive rats, FAR/βCD potentialized the antihypertensive effect when compared to FAR alone. Molecular docking experiments demonstrated for the first time that FAR has affinity to bind to the M3 and M2 muscarinic, and nicotinic receptors through hydrogen bonds in the same residues as known ligands. In conclusion, our results demonstrated that FAR induced hypotension associated with bradycardia, possibly through the muscarinic and nicotinic receptors. The inclusion complex with βCD improved the antihypertensive effects of FAR, which can be relevant to improve current cardiovascular therapy using volatile natural components.

In Ukrainian

The encapsulation of medicinal substances in various polymers is a common way to increase their thermal, hydrolytic, and chemical stability. However, the bioavailability of the encapsulated drugs decreases. The solution to this important problem can be the preparation of nanocapsules of medicinal substances using complexing agents, for example, cyclodextrins. The purpose of this work is to study the possibility of encapsulation of benzoic, salicylic, and β-resorcylic acids using α- and β-cyclodextrins. The interaction of benzene carboxylic acids with cyclodextrins in aqueous solutions at 20–30 оС has been studied by spectrophotometry. The formation of complexes with a composition of 1:1 in the cyclodextrin – benzene carboxylic acid systems has been proven. The stability constants of the complexes and the main thermodynamic parameters of complex formation have been calculated. It has been shown that the nature of changes in the spectral characteristics of benzene carboxylic acids in the presence of cyclodextrins can be used to predict the possibility of aromatic organic compounds encapsulation. The determining role of the complementarity of geometric parameters of cyclodextrins and benzene carboxylic acids in the preparation of inclusion complexes with features of nanocapsules has been found. The prospects of using β-cyclodextrin for encapsulation of benzene carboxylic acids have been demonstrated. The complexes of β-cyclodextrin with benzene carboxylic acids were synthesized and studied by IR spectroscopy, X-ray analysis and derivatography. The formation of two types of complexes in the β-cyclodextrin – benzene carboxylic acid system was established. The first type of complexes is formed due to nonspecific interactions between the hydrophobic cavity of β-cyclodextrin and the benzene carboxylic acid molecule, the second type is due to specific interactions between the functional groups of molecules. Benzoic and salicylic acids form nanocapsules with β-cyclodextrin, and their hydrolytic and thermal stability increases. Complexes of the second type acquire the properties of a new compound: β-resorcylic acid loses its individuality, forming strong supramolecular structures with β-cyclodextrin.

Evaluation of Enhanced UV Protection Property of Dyed Cotton Fabrics Based on Inclusion Complex of β-cyclodextrin with Natural Coumarin Extracted from Cortex fraxini

Inclusion complex formed between β-cyclodextrin (β-CD) and natural coumarins extracted from Cortex fraxini were utilized to dye and enhancing the UV protection properties of cotton fabric. Natural coumarins were extracted from Cortex fraxini and the total amount of natural coumarins was evaluated. The inclusion complex of natural coumarins with β-CD were formed and analyzed by ultraviolet-visible spectrum, fluorescence spectroscopy, FTIR and TGA. The obtained results showed that a stoichiometry of 1:1 inclusion complex was formed and the fluorescence intensities and ultraviolet absorption of the natural coumarins were both enhanced by incorporating into β-CD. β-CD was grafted onto cotton fabric based on esterification of citric acid with cellulose and cyclodextrin in the presence of sodium hypophosphite. The grafted cotton fabric was then dyed with natural coumarins extraction of Cortex fraxini as natural ultraviolet absorbent to form stable inclusion complex. UV protection factor (UPF), UVA transmittance (TUVA) and UVB transmittance (TUVB), wrinkle recovery and tensile strength of dyed fabrics were evaluated and demonstrated that graft modification of fabrics with β-CD resulted enhancement in UV protection property and durability accompanied with increasing in wrinkle recovery properties and decreasing in tensile strength. Furthermore, apparent morphology, FTIR and TGA analysis of inclusion complexes loaded cotton fabrics and the relationship between structure and properties were investigated.

Modes of Micromolar Host-Guest Binding of β-Cyclodextrin Complexes Revealed by NMR Spectroscopy in Salt Water.

Multitopic supramolecular guests with finely tuned affinities toward widely explored cucurbit[n]urils (CBs) and cyclodextrins (CDs) have been recently designed and tested as functional components of advanced supramolecular systems. We employed various spacers between the adamantane cage and a cationic moiety as a tool for tuning the binding strength toward CB7 to prepare a set of model guests with KCB7 and Kβ-CD values of (0.6-5.0) × 1010 M-1 and (0.6-2.6) × 106 M-1, respectively. These accessible adamantylphenyl-based binding motifs open a way toward supramolecular components with an outstanding affinity toward β-cyclodextrin. 1H NMR experiments performed in 30% CaCl2/D2O at 273 K along with molecular dynamics simulations allowed us to identify two arrangements of the guest@β-CD complexes. The approach, joining experimental and theoretical methods, provided a better understanding of the structure of cyclodextrin complexes and related molecular recognition, which is highly important for the rational design of drug delivery systems, molecular sensors and switches.

Assessing collision cross section calculations using MobCal-MPI with a variety of commonly used computational methods

Structural studies with ion mobility require an accurate methodology to bridge theoretical modelling of chemical structure with experimental determination of an ion’s collision cross section (CCS). The parallelized MobCal-MPI package enables rapid and accurate evaluation of CCSs that are applicable to several chemical classes, but was only assessed for accuracy using a single model chemistry: B3LYP-D3/6-31++G(d,p). In this work, the performance of MobCal-MPI was validated across 25 different model chemistries, which encompassed PM7, Hartree-Fock, and three common DFT functionals (B3LYP-D3, ωB97X-D, and M06-2X-D3) using six different basis sets (6-31 G, 6-31 G(d,p), 6-31++G(d,p), def2-SVP, def2-TZVP, and def2-TZVPP). Performance assessment was accomplished using geometries generated from a set of 50 structurally diverse molecules at each level of theory. MobCal-MPI calculates CCSs that correlate well with experimental values for all model chemistries explored (< 2.5% RMSD) with the exception of PM7 (3.0 % RMSD) and methods that employ basis sets lacking polarization functions (e.g., 6-31G; < 4% RMSD). While any of the 25 model chemistries can be used with MobCal-MPI with reasonable accuracy, caution should be exercised when coupling CCS calculations with PM7 or basis sets that lack polarization functions. Following benchmarking, MobCal-MPI was used to calculate the CCS of a macromolecular construct consisting of atropine and β-cyclodextrin. The CCSs calculated for the β-cyclodextrin complex using either the PM7 or B3LYP-D3 model chemistries agree with experimental values within the expected error of the method (< 2.5 %).

The relationship between solvatochromic properties and in silico ADME parameters of new chloroethylnitrosourea derivatives with potential anticancer activity and their β-Cyclodextrin complexes

In view of the anticancer effect of nitrosoureas a set of four new N-(2-chloroethyl)-N-nitrosourea (CENU) derivatives was synthesized. An in silico absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) prediction study revealed that the CENU derivatives satisfied all the required criteria for oral administration and introduced them as remarkable anticancer candidates in the central nervous system (CNS). A comparative solvatochromic study including the Kamlet-Taft, Catalán and Laurence models indicated that the solvatochromic behavior of the CENUs depended on both, unspecific and specific solvent–solute interactions. In detail, the solvatochromic effect of the solvent polarity on the absorption and emission maxima was significant for all CENUs, whereas the solvatochromic effect of the solvent’s ability to donate or accept hydrogen bonds on the absorption and emission maxima was critically dependent on the electron density of the N’-aryl group. From the solvatochromic comparison method, excellent correlations (r ≥ 0.890) were obtained between the ADME parameters and the solvatochromic regression coefficients obtained by the Catalán model. As potential stabilizers, inclusion complexes of the investigated CENU derivatives with β-cyclodextrin (β-CD) were also explored. The spectrofluorimetric host–guest experiments included double-reciprocal Benesi-Hildebrand plots as well as the molar ratio and continuous variation plots (Job’s plots), which established a 1:1 β-CD to CENU binding stoichiometry and relatively high affinities of β-CD for CENU derivatives.

Riboflavin sensitized photodegradation of Furaneol in a β-cyclodextrin complex

A study on the photodegradation of the widely employed flavoring compound Furaneol (FUR), in the presence of vitamin B2 (Riboflavin, Rf) was carried out, in aqueous and microheterogeneous media. The system as a whole allows the evaluation of FUR stability, since the vitamin is an endogenous natural photosensitizer. In a visible-light-irradiated solution of Rf plus FUR, a complex mechanism of competitive reactions occurs. FUR quenches the singlet (2.7 × 109 M−1s−1) and triplet (6.0 × 108 M−1s−1) Rf electronically excited states and reacts with singlet molecular oxygen (O2(1Δg)) generated from the triplet excited state of the sensitizer, with a reactive rate constant of 1.97 × 107 M−1s−1. In the oxidation process, two oxygen molecules are incorporated. In the presence of β-cyclodextrin (βCD), experimental and theoretical results show the formation of an inclusion 1:1 complex of FUR with the oligosaccharide. The Rf- photosensitized oxidation rates of FUR were higher in the microheterogeneous medium, probably due to the incorporation of FUR in the non-inclusion complex between Rf and βCD which may produce O2(1Δg) near the oxidizable substrate. The overall result of this study demonstrates that visible-light exposure of formulations containing Rf and FUR may cause significant oxidation of the flavoring agent.

Supramolecular host-guest complex of methylated β-cyclodextrin with polymerized ionic liquid ([vbim]TFSI)n as highly effective and energy-efficient thermo-regenerable draw solutes in forward osmosis

Supramolecular inclusion complexes with lower critical solution temperature (LCST) properties were investigated for the first time as forward osmosis (FO) draw solutes. Randomly methylated-β-cyclodextrin (Rm-β-CD) host molecules accommodate polymerized ionic liquids (([vbim]TFSI)n PILs) through their hydrophobic TFSI− anions as guests. LCST properties were tuned by varying the chain lengths of ([vbim]TFSI)n, from which, short-chain oligo([vbim]TFSI) was found most suitable. Draw solutions (DS) of Rm-β-CD/oligo([vbim]TFSI) complex have highly tunable cloud-point temperatures (Tc), fast LCST kinetics and sufficient osmotic properties for an efficient FO. Under PRO mode, 0.5 M Rm-β-CD/0.078 M oligo([vbim]TFSI) induced competitive FO water flux (Jv ~13.73 L m−2h−1) and negligible reverse solute flux (Js ~4.41 × 10−3 mol m−2h−1) against DI water feed. It successfully processed different saline feeds (0.034 M and 0.6 M NaCl) with reasonable FO performance and superior Js/JV ~0.001 mol m−2h−1, demonstrating its competence for FO desalination. When heated slightly above its Tc = 29 °C (TTP = 30 °C), thermal precipitation (TP) is ensued with the release of TFSI− anions in oligo([vbim]TFSI) from Rm-β-CD. Due to its hydrophobicity, oligo([vbim]TFSI) precipitates while entrapping the suspended Rm-β-CDs between its chains causing flocculation and sedimentation. Thus, with only +5 °C heating above FO temperature (25 °C), 95% of draw solutes are effectively recovered from the spent DS after settling. Residual (~5%) Rm-β-CD in the DS supernatant is subsequently removed via nanofiltration at 99.33% rejection, producing non-toxic water effluent based on in vitro cytotoxicity results. Energy consumption estimates reveal the feasibility of Rm-β-CD/oligo([vbim]TFSI) as it requires minimal heat energy for recovery. This study offers new insights on the potential of host-guest complexes as a new class of energy-efficient draw solutes for FO desalination technology.

RSM-CCD optimized microwave assisted synthesis of chitosan and sodium alginate based nanocomposite containing inclusion complexes of β-cyclodextrin and amlodipine besylate for sustained drug delivery systems

The aim of present work to prepare inclusion complexes of amlodipine besylate (APB) drug and β-Cyclodextrin (β-CD) by microwave and kneading method for sustain release of drug. Microwave irradiation completes the process in very short time and is more environmentally benevolent method. The complexation of APB with β-CD was characterized by 1H NMR and XRD. A nanocomposite was synthesized by incorporating the graphene oxide (GO) in the polymer network of chitosan (CH) and sodium alginate (ALG) under microwave conditions. Poor loading of drugs in traditional drug delivery was improved by introducing inclusion complexes (ICs) directly into the nanocomposite. The operation parameters like ratio of backbones, time, amount of solvent, amount of graphene oxide and pH were optimized by response surface methodology (RSM) in order to obtain maximum percentage swelling. From normal plot and pareto chart it was found that ratio of backbones, amount of GO and solvent are the optimized variables. Furthermore, to get most optimized variables central composite design (CCD) was analyzed. The ICs were directly loaded into the nanocomposite and their release kinetics was studied by six kinetic models under different pH at 37 °C. The preparatory kinetic analysis, acknowledge that the cyclodextrin affects the relaxation rate of nanocomposite, leading to slower release of drug.

A novel quercetin/β-cyclodextrin transdermal gel, combined or not with therapeutic ultrasound, reduces oxidative stress after skeletal muscle injury.

A gel containing the inclusion complex of quercetin and β-cyclodextrin was developed in order to verify its effects, isolated or using phonophoresis, on oxidative biomarkers after skeletal muscle injury. 30 male rats were divided into one of five groups: Control (CTRL), Muscle Injury (MI), Therapeutic Pulsed Ultrasound (TPU), Therapeutic Pulsed Ultrasound plus Quercetin (TPU plus gel-QUE) or Quercetin gel (QUE). Quercetin gel was complexed with β-Cyclodextrin (β-CD) using chromatography (HPLC). TPU and quercetin application occurred with 2, 12, 24, 48, 72, 96 hours intervals after injury. Gastrocnemius muscle was injured by mechanical trauma. Lipid peroxidation, superoxide dismutase activity, and catalase activity were assessed. The inclusion complex exhibited adequate entrapment efficiency, relative density and pH. The viscosity of the complex showed a non-Newtonian pseudoplastic behavior. Quercetin/β-cyclodextrin gel reduced lipid peroxidation, superoxide dismutase activity and catalase activity compared to muscle injury group. Similarly, phonophoresis and TPU also reduced the levels of these oxidative biomarkers. In conclusion, quercetin/β-cyclodextrin transdermal gel reduces oxidative stress biomarkers after skeletal muscle injury irrespective of using phonophoresis.

Effect of inclusion of citric acid and Lutrol® F-68 on ziprasidone and β-cyclodextrin complexation: Characterization, solubility and dissolution studies

Ziprasidone (ZPR) is an antipsychotic agent having less solubility. It is used for the treatment of schizophrenia. Complexation of hydrophobic drugs with cyclodextrins leads to enhanced solubility and dissolution. In this study, inclusion complexes were prepared by different methods, using ZPR, β-cyclodextrin (β-CD), and different auxiliary agents like hydrophilic polymer and hydroxy acid (1:1:0.5) to improve the aqueous solubility. The characterization of the ternary complexes was carried out using solubility study, Differential scanning calorimetry (DSC), Powder X-ray diffraction (PXRD), Fourier transformation infrared spectroscopy (FT-IR) and in vitro dissolution studies. DSC, XRD, and FT-IR studies showed interaction in drug, cyclodextrin, and auxiliary agents which are confirmed by enhancement of solubility and dissolution. Spray-dried dispersion showed less crystallinity and higher solubility as compared to the kneading method for both citric acid and Lutrol® F-68. Thus, the investigation concludes that the presence of the auxiliary agent has a synergistic action on complexation with cyclodextrin, which helps to modify the physicochemical properties of the drug.

Semi-convertible Hydrogel Enabled Photoresponsive Lubrication

Summary A semi-convertible hydrogel with reversible photoresponsive supramolecular lubricating ability is demonstrated by integrating a responsive supramolecular system of α-cyclodextrins/polyethylene glycol (α-CD/PEG) and competitive guest 1-[p-(phenylazo)benzyl]pyridinium bromide (AzoPB) within a poly(vinyl alcohol) (PVA) and polyacrylamide (PAAm) framework. The competitive host-guest interaction between α-CD/PEG supramolecular network and AzoPB after UV and visible-light irradiation enables the appearance and disappearance of the sol-state layer on the hydrogel surface while the PVA and PAAm consistently keeps the framework. This semi-convertible process realizes the reversible photoresponsive lubricating ability and variable toughness. We envision that this finding will offer a possible way for fabricating novel smart devices far beyond lubrication, leading to an emerging branch of interdisciplinary materials science that integrates supramolecular chemistry, hydrogel, and surface science.

Inclusion complexation of chloroquine with α and β-cyclodextrin: Theoretical insights from the new B97-3c composite method

Inclusion complexes of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) with chloroquine drug (CQ) have been explored using the recently developed B97-3c composite method. Calculated complexation energies were negatively higher for both CQ@α-CD and CQ@β-CD complexes indicating a thermodynamically favorable process. The inclusion mode involves the partial encapsulation of the fused aromatic ring of chloroquine in α- and β-CD cavities from the wider side, in agreement with proton NMR data. NCI-RDG, IGM and NBO analysis showed that weak Van der Waals intermolecular interactions and in particular strong intermolecular hydrogen bonding stabilize the inclusion of chloroquine that forms complex with β-CD more favorably than with α-CD.

A robust composite hydrogel consisting of polypyrrole and β-cyclodextrin-based supramolecular complex for the label-free amperometric immunodetection of motilin with well-defined dual signal response and high sensitivity

The label-free amperometric immunosensor is a simple, convenient and reliable method for the detection of diseases markers. Its performance heavily relies on the properties of the sensing substrate. In this paper, we proposed a robust composite hydrogel that consists of polypyrrole and vinyl ferrocene/mono-aldehyde β-cyclodextrin (β-CD) complex as a sensing and immobilizing substrate. Surprisingly, it was observed that the microstructure of the hybrid hydrogel could be well regulated by the feed ratio of vinylferrocene and so are the electrochemical properties. Depending on the dual electrochemical active compositions, a large loading capacity of antibodies and meanwhile the excellent conductivity, the square wave voltammetry results of the optimized immunosensor for the detection of motilin exhibited a well-defined dual signal response, with a wide linear range both from 10 pg mL−1 to 100 ng mL−1 for motilin, and an ultralow limit of detection of 6.29 pg mL−1 and 2.73 pg mL−1. More importantly, the immunosensor exhibited an especially sensitive response with the slope value as high as 31.342 and 25.751 respectively, which makes great sense in the practical diagnosis.

Corona Charged Aerosol Detector in studying retention and β-cyclodextrin complex stability using RP-HPLC

Binding between cyclodextrin (CD) cavity and guest molecule in Reversed Phase High-Performance Liquid Chromatography (RP-HPLC) is dynamic process. In general, increasing CD concentration is inducing inclusion complex formation, leading to reduction of analyte’s retention time. Consequently, the shortness in retention time is a measure of complex stability in HPLC. However, under certain experimental conditions, the retention of some analytes could be prolonged even when concentration of CD in the mobile phase is increased. In order to reveal the cause of this unexpected retention behavior, the present study was carried on. The model mixture consisted of risperidone, olanzapine and their related impurities, while β-CD was selected among CDs, as in the previous study. In order to achieve fast equilibrium between free analyte and β-CD-analyte complex, β-CD was not added to the mobile phase, but only to the sample. Detection was performed with Corona Charged Aerosol Detector (CAD), suitable for non-chromophoric β-CD. When analyzing olanzapine impurity B-β-CD sample, three peaks were detected, namely free β-CD, β-CD-analyte complex and free analyte. The complex stability constant was calculated employing a modification of the Benesi-Hildebrandt equation and CAD has proven to be useful in complex stability constants assessment if retention of free analyte and β-CD-analyte complex is distinguished. For all other analytes only two peaks could be detected, because free analyte and formed complex are eluting at the same retention time. Under such circumstances, the authors proposed the methodology for calculating stability constants and confirmed its applicability to studied model mixture.

IMPROVEMENT OF WATER SOLUBILITY AND IN VITRO DISSOLUTION RATE OF DEFLAZACORT BY COMPLEXATION WITH Β-CYCLODEXTRIN THROUGH FREEZE DRYING PROCESS

Deflazacort is a poorly water-soluble drug and is practically insoluble in water. The objective of this study was to improve the solubility of deflazacort by using as solubility enhancer β-cyclodextrin and also to study the effect of the water-soluble polymer PEG 4000 on solubility of the deflazacort:β-cyclodextrin binary system. The inclusion complexes of deflazacort with β-cyclodextrin in 1:1 w/w, 1:2 w/w and 1:3 w/w proportions were prepared by kneading, microwave irradiation and freeze-drying techniques. The in vitro dissolution study showed improved dissolution rate for deflazacort for freeze-dried binary deflazacort: β-cyclodextrin 1:2 w/w complex, as compared to ternary deflazacort:β-cyclodextrin: PEG 6000 1:2 w/w complexes, plain deflazacort, physical mixtures and complexes prepared by kneading and microwave technique. This was confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction study, scanning electron microscopy and 1 H nuclear magnetic resonance spectroscopy study. Thus, deflazacort:β-cyclodextrin complex with improved solubility was successfully developed using freeze drying technique.

Dexamethasone-loaded β-cyclodextrin for osteogenic induction of mesenchymal stem/progenitor cells and bone regeneration.

Dexamethasone (DEX) is a glucocorticoid commonly used as an in vitro osteogenic inducer of mesenchymal stem/progenitor cells (abbreviated MSCs). However, several studies investigating the effects of glucocorticoids on bone regeneration through systemic injections have demonstrated negative impacts of the drugs at high concentration on the healing of hard tissues. These contrasting evidences suggest that application of glucocorticoids should be limited to low dosages but at the same time a long enough treatment period is preferred, which prompted us to evaluate the effects of different local release systems of DEX on MSC differentiation and bone repair. Two types of DEX-loaded β-cyclodextrin (CD) complexes, including CD/DEX and CD/AD-DEX, were fabricated via host-guest interactions and characterized by FTIR, 1H-NMR, MS-ESI, and UV-vis. The results demonstrated that these CD-based assemblies released DEX in differentiated profiles, with CD/DEX releasing significantly faster than CD/AD-DEX. Although CD/DEX were slightly more powerful than CD/AD-DEX in inducing rat bone marrow MSCs (rBMSCs) into osteogenic lineage in vitro, CD/AD-DEX was advantageous over CD/DEX in accelerating bone regeneration over a time period of 4 weeks in a rat tibia defect model. The results suggest that DEX-loaded assemblies via host-guest interactions are flexible in modulating DEX release patterns and have great potential in bone tissue engineering.

Supramolecular Complexes of β-Cyclodextrin with Clomipramine and Doxepin: Effect of the Ring Substituent and Component of Drugs on Their Inclusion Topologies and Structural Flexibilities.

Depression is a global threat. Tricyclic antidepressants (TCAs) are still efficacious in treating depression, albeit with more side effects. Cyclodextrins (CDs) with a suitable nanocavity are potential drug carriers and can enhance the drug bioavailability. Aiming for an atomistic understanding of the CD encapsulation facilitating the improvement of drug stability and the reduction of side effects, a comprehensive study series of the β-CD–TCA inclusion complexes through single crystal X-ray diffraction and density functional theory (DFT) calculation was undertaken. This work reports the supramolecular complexes of β-CD with two pivotal TCAs, clomipramine (CPM; 1) and doxepin (DXP; 2). The different inclusion topologies of the β-CD–TCA complexes were notable. X-ray analysis revealed that, in 1, the CPM B-ring (without chloro group) was entrapped in the β-CD cavity, whereas, in 2, the E-DXP A-ring and the Z-DXP B-ring were disordered in the cavity, yielding energetically favorable complexes primarily maintained by intermolecular C–H⋯π interactions, as indicated by DFT calculation. Because both wings of TCAs were similar, an alternative inclusion scenario of the A-ring was evidenced crystallographically in four other TCA complexes. The enhanced TCA thermodynamic stabilities via CD inclusion complexation helped to reduce the side effects and to increase the bioavailability. Moreover, the scrutinization of six TCAs in different lattice circumstances revealed the greater TCA structural flexibilities for their optimum pharmacological activity while binding with proteins.

Preparation and Characterization of Inclusion Complexes of β-Cyclodextrin and Phenolics from Wheat Bran by Combination of Experimental and Computational Techniques.

Bitterness often associated with whole wheat products may be related to phenolics in the bran. Cyclodextrins (CDs) are known to form inclusion complexes. The objective was to form inclusion complexes between β-CD and wheat phenolics. Pure phenolic acids (trans-ferulic acid (FA), caffeic acid (CA), and p-coumaric acid (CO)) and phenolic acids from wheat bran were used to investigate complex formation potential. Complexes were characterized by spectroscopy techniques, and a computational and molecular modeling study was carried out. The relative amount of complex formation between β-CD and wheat bran extract was CA > CO > FA. The phenolic compounds formed inclusion complexes with β-CDs by non-covalent bonds. The quantum-mechanical calculations supported the experimental results. The most stable complex was CO/β-CD complex. The ΔH value for CO/β-CD complex was −11.72 kcal/mol and was about 3 kcal/mol more stable than the other complexes. The QSPR model showed good correlation between binding energy and 1H NMR shift for the H5 signal. This research shows that phenolics and β-CD inclusion complexes could be utilized to improve the perception of whole meal food products since inclusion complexes have the potential to mask the bitter flavor and enhance the stability of the phenolics in wheat bran.

Certain carboxylic acid buffers can destabilize β-cyclodextrin complexes by competitive interaction.

Thirteen buffers were investigated for their effect on the binding of adamantanol to β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Stability constants for the β-cyclodextrin complex ranged from 14,800 to 46,000M-1, and the binding enthalpies were between -23.2 and -10.4kJ/mole. Compared to water, the stability constant in seven carboxylic acid buffers (citric acid, maleic acid, fumaric acid, succinic acid, malonic acid, malic acid and tartaric acid) was reduced. All seven buffers exhibited a competitive mechanism. Binding constants for the interaction between β-cyclodextrin and buffers ranged from 4 to 44M-1, and binding enthalpies were in the range -19 to -11kJ/mole. There was a relation between the chemical structures of the buffers and their ability to bind to cyclodextrin. All seven buffers had a carbon chain consisting of more than three carbons in the backbone. Hydroxyl groups on the carbon chain decreased the binding affinity. 1H and ROESY NMR spectroscopy supported inclusion of the citric acid into the cyclodextrin cavity, although the results for succinic and maleic acids were ambiguous. The results demonstrated that some buffers can interact with cyclodextrin complexes, and careful considerations are necessary when choosing a buffer for cyclodextrin research.