Interaction Of Β-cyclodextrin Research Articles

DFT computational and mass spectrometry studies of intermolecular interaction of β-cyclodextrin with nifedipine

A systematic investigation of intermolecular interactions of β- cyclodextrin(β-CD)and Nifedipine(Nif)in gas phase and in water were done by the mass spectrometry and DFT calculation method. The results obtained clearly indicated that the aromatic ring containing the nitro moiety of Nifedipine inverted into the wider rim of β cyclodextrin, the high collision induced dissociation (CID) energy in mass spectrometry experiments demonstrated the stability of the 1:1 Nif-β-CD complexes. Compared to the native β-CD, HP- β-CD and DM- β-CD are more easily to form complexes with Nif due to their approximately double lower binding energy, the thermodynamic parameters, HOMO, LUMO, the global reactivity descriptors of these complexes were calculated and interpreted. Furthermore, the study of natural bonding orbitals (NBO) and quantum theory of protons in molecules (QTAIM) supports the existence of various hydrogen bonds and van der Waals interactions in three complex structures, as predicted by chemical bonding principles. IGMH analysis give the visualized origin of weak attractive interactions between the CDs and the Nifedipine.

β-cyclodextrin and calix[4]arene-functionalized thieno[3,2-b]thiophene based polymers as fluorescent ion sensors

Design, synthesis, and applications of four novel thienothiophene-based polymers as sensing probes (G1-CD, G2-CD, G1-Cal, and G2-Cal), incorporating π-bridges of thiophene (T) and biphenyl (BP) benefiting from the unique cone-shaped structure and intramolecular interactions of β-cyclodextrin and calix[4]arene, are reported. They exhibited remarkable fluorescent alterations in response to Hg2+, Fe3+, Ni2+, and Cu2+. Their syntheses involved Suzuki coupling, and a comprehensive analysis of the optical and electronic properties of the resulting polymers was conducted using UV–Vis spectroscopy, fluorescence spectroscopy, and cyclic voltammetry. Photophysical characterizations of these novel polymers showed a remarkable mega Stokes shift, reaching up to 162 nm and optic/electronic band gaps between 1.95 and 2.92 eV. Notably, G2-CD, functionalized with β-cyclodextrin, stands out as the most promising sensor, demonstrating superior sensitivity and selectivity in detecting Hg2+ ions with a remarkable turn-off fluorescence response down to concentrations as low as 1 ppm. This research contributes to advancing the development of electronically and optically responsive materials, with potential applications in the sensitive detection of biologically and toxicologically significant ions.

Unravelling Competitive Interactions between Polymer Side Chains and End Groups with β-Cyclodextrin.

This study investigates unexpected competitive host-guest interactions of β-cyclodextrin (β-CD), which can occur with polymers in aqueous solution, using the examples of the two polymers poly(oligo(ethylene glycol) methyl ether methacrylate) and poly(glycerol mono methacrylate). Systematic structural modifications of the polymer provide insight into the host-guest interaction with β-CD and the competition between side chains and end groups such as hydrophobic end groups remaining from reversible addition fragmentation chain transfer polymerization or intentionally implemented molecular recognition units such as arylazopyrazole photoswitches.

Synthesis, optical properties, DNA, β-cyclodextrin interaction, hydrogen isotope sensor and computational study of new enantiopure isoxazolidine derivative (ISoXD)

A novel isoxazolidine derivative (ISoXD) dye was successfully synthesized and comprehensively characterized. In this study, we conducted a thorough examination of its various properties, including optical characteristics, interactions with DNA and β-cyclodextrin (β-CD), molecular docking, molecular dynamic simulation, and density functional theory (DFT) calculations. Our investigation encompassed a systematic analysis of the absorption and emission spectra of ISoXD in diverse solvents. The observed variations in the spectroscopic data were attributed to the specific solvent's capacity to engage in hydrogen bonding interactions. Remarkably, the most pronounced intensities were observed in glycol, which can establish many hydrogen bonds with ISoXD.Furthermore, our study revealed a significant distinction in the fluorescence behavior of ISoXD when subjected to different solvents, particularly between CHCl3 and CDCl3. Moreover, we explored the fluorescence intensity of the ISoXD complex in the presence of various metals, both in ethanol and water. The ISoXD complex exhibited a substantial increase of fluorescence upon interaction with different metal ions. The utilization of DFT calculations allowed us to propose an intramolecular charge transfer (ICT) mechanism as a plausible explanation for this quenching phenomenon. The interaction of ISoXD with DNA and β-CD was studied using absorption spectra. The binding constant (K) and the standard Gibbs free energy change (ΔGo) for the interaction between DNA and β-CD with ISoXD were determined. In docking study, ISoXD exhibited significant docking scores (−6.511) and MM-GBSA binding free energies (−66.27 kcal/mol) within the PARP-1 binding cavity. Its binding pattern closely resembles to the co-crystal ligand veliparib, and during a 100ns MD simulation, ISoXD displayed strong stability and formed robust hydrogen bonds with key amino acids. These findings suggest ISoXD's potential as a PARP-1 inhibitor for further investigation in therapeutic development.

β-Cyclodextrin-crosslinked synthetic neuropeptide Y-based nanosponges in epilepsy by contributing GABAergic signal

Neuropeptide Y (NPY) is a polypeptide sequence useful in regulating physiological functions like homeostasis, feeding, etc., but its usage is restricted due to its short half-life. β-cyclodextrin-crosslinked nanosponges improve the drug release and stability due to its wide cavity, which is helpful to deliver therapeutics. The present work aimed to formulate synthetic NPY-based nanocarriers as sponges by polymer condensation mechanism using design experiment to improve the peptide release and stability. The validated nanosponges exhibited a particle size of 423.42 ± 5.32 nm, 75.82 ± 7.43 % entrapment efficiency and 83.50 ± 6.54 % NPY release for 24 h. The NPY and β-cyclodextrin interaction was confirmed by X-ray diffraction, Fourier transform infrared and nuclear magnetic resonance spectroscopy. The NPY-loaded nanosponges were found stable for 6 months at two conditions (5 ± 2 °C and 25 ± 2 °C). The cross-linked nanocarriers of synthetic peptide-based nanosponges powder at different doses were administered intranasally using a metered-dose inhaler in the animal model to check its antiepileptic activity. The synthetic NPY-loaded nanosponges at higher doses showed significant antiepileptic effects equivalent to the standard drug (administered orally) in maximal electroshock and chemically-induced seizures with an increase of NPY in the brain directly proportional to GABAergic signalling by increase in GABA levels resulting in convulsions attenuation.

Novel aspartic chiral optical sensor based on β-cyclodextrin-functionalized CdTe nanoparticles

Based on the quenching effect of fluorescence intensity of CdTe nanoparticles coated β-cyclodextrin, a novel aspartic chiral assay is suggested. The CdTe nanoparticles were synthesized by co-precipitate and then modified with β-cyclodextrin through a sonication technique to get CdTe@βCD nanoparticles. To characterize CdTe@βCD, FT-IR spectra, fluorescence spectroscopy, and transmission electron microscope were applied. The coupling of host–guest interaction of β-cyclodextrin and aspartic and the fluorescence quenching effect resulted in high selectivity on aspartic of CdTe@βCD sensor. The quenching process was described by the Stern–Volmer equation. The available mechanism of the assay is proposed. Under optimal conditions, the limit of detection of the assay for D-aspartic form was calculated to be 19 ng/mL. The proposed aspartic chiral assay exhibited as a simple and rapid sensing method.

Multifunctional Self-Healing Dual Network Hydrogels Constructed via Host-Guest Interaction and Dynamic Covalent Bond as Wearable Strain Sensors for Monitoring Human and Organ Motions.

Hydrogel-based flexible strain sensors have shown great potential in body movement tracking, early disease diagnosis, noninvasive treatment, electronic skins, and soft robotics. The good self-healing, biocompatible, sensitive and stretchable properties are the focus of hydrogel-based flexible strain sensors. Dual network (DN) hydrogels are hopeful to fabricate self-healing hydrogels with the above properties. Here, multifunctional DN hydrogels are prepared via a combination of host-guest interaction of β-cyclodextrin and ferrocene with dynamic borate ester bonds of poly(vinyl alcohol) and borax. Carbon nanotubes are used to endow the DN hydrogels with good conductivity. The obtained DN composite hydrogels possess good biocompatibility, stretchability (436%), fracture strength (41.0 KPa), self-healing property (healing efficiency of 95%), and high tensile strain sensitivity (gauge factor of 5.9). The DN composite hydrogels are used as flexible strain sensors to detect different human motions. After cutting, the healed hydrogels also can monitor human motions and have good stability. In addition, the hydrogel sensors may track the respiratory movement of a pig lung in vitro. This work exhibits new ideas and approaches to develop multifunctional self-healing hydrogels for constructing flexible strain sensors.

Cyclodextrin-mediated gold nanoparticles as multisensing probe for the selective detection of hydroxychloroquine drug.

β-Cyclodextrin (β-CD) modified gold nanoparticles (AuNP) were rapidly synthesized using microwave assisted procedure. Parameters, such as time, pH and concentrations of β-CD and gold, were optimized for the synthesis of β-CD-AuNP. The addition of enantiomers and racemic mixture of hydroxychloroquine (R-HCQ, S-HCQ and RS-HCQ) drugs and their interaction with β-CD led to a red shift in the surface plasmon resonance of β-CD-AuNP. The changes associated with the introduction of HCQ in β-CD-AuNP were studied using various characterization techniques such as UV-vis, FT-IR, XRD, dynamic light scattering, zeta potential, transmission electron microscopy, fluorescence spectroscopy and electrochemical techniques. The host-guest interaction of β-cyclodextrin with S-HCQ, R-HCQ and RS-HCQ resulted in the aggregation of gold nanoparticles. The surface plasmon resonance at 521 nm for β-CD-AuNP was shifted to 600, 620 and 670 nm on the addition of S-HCQ, R-HCQ and RS-HCQ, respectively, with a color change from pink to blue. The selectivity and sensitivity of the developed system for RS-HCQ were investigated and the limit of detection (LOD=3 s/m) was found to be 2.61, 0.15, and 0.85 nM for optical, fluorescence and electrochemical methods, respectively. The successful monitoring of RS-HCQ drug in pharmaceutical samples is possible with these techniques.Electronic Supplementary MaterialSupplementary material is available for this article at 10.1007/s11814-020-0719-7 and is accessible for authorized users.

Self-Assembled Supramolecular Hybrid Hydrogels Based on Host-Guest Interaction: Formation and Application in 3D Cell Culture.

In recent decades, in vitro three-dimensional (3D) cell culture has been rapidly developed and widely used in many biomedical fields. Based on this background, a kind of self-assembled supramolecular hybrid hydrogel materials based on host-guest interaction of β-cyclodextrin (βCD) and adamantane (Ad) is designed for 3D cell culture. First, βCD is grafted to poly(methyl vinyl ether-alt-maleic acid) (PMM) to obtain the host polymers of βCD-grafted-PMM (PMM-βCD). Second, the guest polymers of poly(acrylamide-co-N-adamantyl acrylamide) (PAAm-Ad) are synthesized through free-radical copolymerization of acrylamide and N-adamantyl acrylamide. Finally, the self-assembled supramolecular hybrid hydrogels of PMM-βCD/PAAm-Ad are formed by simply mixing the aqueous solution of host and guest polymers with a total concentration of 3.3% (w/v) and a βCD/Ad molar ratio of 1:1. The main cross-linking interactions come from the host-guest interaction of βCD/Ad as well as hydrogen-bonding interaction of carboxyl/amide groups. The prepared hydrogels with good cytocompatibility have been successfully used as 3D cell culture scaffold for SKOV3, HUVEC, and L929 cells culture. Thus, this work provides a way and biomaterial for the preparation of a functionalized 3D cell culture scaffold, which lays an experimental and theoretical basis for cell follow-up research.

СИНТЕЗ МОНО[6А-О-(4-ТОЛИЛСУЛЬФОНИЛ)]-β-ЦИКЛОДЕКСТРИНА

As a result of improvement of the preparation procedure of tosyl-β-cyclodextrin in
 aqueous alkaline medium by the interaction of β-cyclodextrin with tosyl chloride (TosCl) at low
 temperatures, the yield of the target product was increased from 38% to 58%.

Oxidation-Responsive Nanoassemblies for Light-Enhanced Gene Therapy.

Microenvironment-responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation-responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host-guest interaction of β-cyclodextrin based polycations and a ferrocene-functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H2 O2 concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (1 O2 ), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation-responsive nanoassemblies with light-enhanced gene transfection performance.

Supramolecular Polymeric Hydrogels for Ultrasound-Guided Protein Release.

An ultrasound-responsive carrier for protein drugs is promising for site-specific release of proteins at disease sites in a designated time course because ultrasound readily penetrates deep into the interior of the body in a non-invasive way. However, the guideline for designing ultrasound-responsive carriers that are applicable to any protein remains to be established. Here, the aim is to develop an ultrasound-responsive material for the controlled release of a variety of proteins regardless of their charge and structure. The supramolecular polymeric hydrogel crosslinked with a host-guest interaction of β-cyclodextrin and adamantane can enclose two kinds of model proteins and site-specifically and stepwisely release them in an ultrasound-guided manner without losing their activities. Furthermore, ultrasound-guided protein delivery to living cells is achieved on model tissue consisting of cells and extracellular matrix. The results of this study provide the proof of principle that the supramolecular polymeric hydrogel is applicable as the core carrier material in an ultrasound-guided protein delivery system.

Theoretical Study on the Inclusion Interaction of β-Cyclodextrin with Gabapentin and Its Stability

In this paper, dispersion corrected density functional theory (DFT-D3) with the B3LYP method and the 6–31G(d) basis set is used to study the inclusion processes of gabapentin with β-cyclodextrin and the effect of inclusion on the dehydration condensation reaction of gabapentin. The calculation results show that β-cyclodextrin and gabapentin can form stable inclusion complexes in both vacuum and water. B-β-CDs is the most stable one of four inclusion complexes. After inclusion, the dehydration condensation potential barrier of gabapentin in the β-cyclodextrin cavity is significantly increased. Notably, the reaction barrier of gabapentin in the B-β-CDs complex (a protonated active group of gabapentin with a small mouth of β-cyclodextrin and its hexatomic ring in the cavity of cyclodextrin) even reaches 331.353 kJ/mol in vacuum and 283.538 kJ/mol in water, respectively. There are two obvious increases of 223.574 kJ/mol in vacuum and 193.932 kJ/mol in water after inclusion. Thus, the inclusion complex of β-cyclodextrin with gabapentin, especially B-β-CDs, inhibits the dehydration condensation side-reaction of gabapentin most effectively.

Interaction of β-cyclodextrin with tosyl chloride in an aqueous alkaline medium

The regioselective functionalisation of the cyclodextrin matrix provides the possibility of purposefully altering the ability of cyclodextrins to form inclusion compounds, as well as to ensure their solubility, thus expanding the scope of their practical application [1, 2]. The most significant and promising trend in the selective modification of β-cyclodextrins consists in the preparation of tosyl derivatives, given that the substitution of such nucleophilic reagents as iodide, azide, thioacetate, hydroxylamine, alkylamide or polyalkylamide for the tosyl group results in the corresponding monosubstituted derivatives. In this study, we impl emented a method for the synthesis of mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin, which was improved by β-cyclodextrin reacting with tosyl chloride in an aqueous medium in the presence of a base. The reaction of β-cyclodextrin with tosyl chloride in an aqueous alkaline medium produced a 58% yield of mono -6- O-(p-toluenesulphonyl)-β-cyclodextrin not requiring additional purification. The optimal concentrations of β-cyclodextrin and tosyl chloride were found to be 0.0032 mol/l and 0.0015 mol/l, respectively. It was shown that a decrease in the rate of filtering the unreacted tosyl chloride out of the reaction mixture is acc ompanied by an increase in the proportion of ditosyl derivatives and mono(3,6-anhydro)-β-cyclodextrin resulting from the intramolecular cyclisation of mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin at room temperature under alkaline conditions. The structure of the obtained mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin was confirmed using Proton NMR Spectroscopy. The proton NMR spectrum of the product resulting from the reaction of β-cyclodextrin with tosyl chloride contains signals corresponding to a tosyl radical: a singlet (2.42 ppm) and two doublets (7.41–7.43 ppm) produced by hydrogens of the benzene ring having radicals in the para position. Monosubstitution was confirmed by comparing the integrated intensities of signals produced by the protons of the cyclodextrin skeleton and the protons from the aromatic part of the reaction product. Their ratio indicated that only one of the seven primary hydroxyl groups of β-cyclodextrin was substituted.

Theoretical study on the inclusion interaction of β-cyclodextrin with gabapentin and its stability

In this paper, dispersion corrected density functional theory (DFT-D3) with the B3LYP method and the 6-31G(d) basis set is used to study the inclusion processes of gabapentin with β-cyclodextrin and the effect of inclusion on the dehydration condensation reaction of gaba­pentin. The calculation results show that β-cyclodextrin and gabapentin can form stable inclusion complexes in both vacuum and water. B-β-CDs is the most stable one of four inclusion complexes. After inclusion, the dehydration condensation potential barrier of gabapentin in the β-cyclodextrin cavity is significantly increased. Notably, the reaction barrier of gabapentin in the B-β-CDs complex (a protonated active group of gabapentin with a small mouth of β-cyclo­dextrin and its hexatomic ring in the cavity of cyclodextrin) even reaches 331.353 kJ/mol in vacuum and 283.538 kJ/mol in water, respectively. There are two obvious increases of 223.574 kJ/mol in vacuum and 193.932 kJ/mol in water after inclusion. Thus, the inclusion complex of β-cyclodextrin with gabapentin, especially B-β-CDs, inhibits the dehydration condensation side-reaction of gabapentin most effectively.

Separation of terbutaline enantiomers in capillary electrophoresis with cyclodextrin-type chiral selectors and investigation of structure of selector-selectand complexes

The affinity pattern of terbutaline enantiomers towards various cyclodextrins was studied using capillary electrophoresis. The affinity pattern of terbutaline enantiomers was the same towards all studied cyclodextrins except heptakis(2-O-methyl-3,6-di-O-sulfo)-β-CD. Nuclear magnetic resonance spectroscopy was used for understanding of fine structural mechanisms of interactions of β-cyclodextrin and its two sulfated derivatives with the enantiomers of terbutaline. The structure of terbutaline complexes with all 3 cyclodextrins studied was different from each other. In confirmation with our earlier studies it was shown again that capillary electrophoresis represents very sensitive technique for studies of affinity patterns in cyclodextrin complexes with chiral guests. Other instrumental (e.g. NMR spectroscopy and X-ray diffraction analysis) and theoretical techniques, although very useful for obtaining the information regarding the stoichiometry, binding constants and structure of intermolecular complexes, as well as about the forces involved in selector-selectand binding and chiral recognition, may sometimes fail to properly sense those fine differences in the affinity patterns. Therefore, it is recommended to use capillary electrophoresis in order to examine correctness of affinity pattern determined for intermolecular complexes of cyclodextrins with guest molecules by other instrumental or computation techniques.

Enzyme-free homogeneous electrochemical biosensor for DNA assay using toehold-triggered strand displacement reaction coupled with host-guest recognition of Fe3O4@SiO2@β-CD nanocomposites

Taking advantages of the toehold-triggered strand displacement reaction (TSDR) and host-guest interaction of β-cyclodextrin (β-CD), a facile enzyme-free and homogeneous electrochemical sensing strategy was designed for the sensitive assay of target DNA using Fe3O4@SiO2@β-CD nanocomposites and ferrocene-labeled hairpin DNA (H-1) as the capture and electrochemical probes, respectively. Upon addition of target molecule, the initiated TSDR process induced the conformational change of H-1, and subsequently stimulated the dynamic assembly of assist probes (A-1 and A-2) to generate H-1:A-1:A-2 duplex along with the release of target sequence. The released target could drive the next TSDR recycling and finally result in the formation of numerous DNA duplex. After the molecular recognition of Fe3O4@SiO2@β-CD nanocomposites, a large number of duplex were easily separated from the supernatant solution under an external magnetic field, which led to a decreased H-1 concentration in residual solution, concomitant with a remarkable reduction of peak current. Under the optimized conditions, wide linear range (1–5000 pM), low detection limit (0.3 pM), desirable reproducibility, good selectivity, and satisfactory practical analysis were obtained by the combination of the superior recognition capability of β-CD, TSDR-induced signal amplification, and homogeneous electroanalytical method. The proposed detection strategy could offer a universal approach for the monitoring of various biological analytes via the rational design of probe sequences.

Study of the interaction of β-cyclodextrin with albendazole in aqueous solutions

We performed calorimetric titration (ITC) measurements of aqueous albendazole solutions with aqueous β-cyclodextrin solutions. The obtained results were used to determine the enthalpy and entropy of the drug–β-cyclodextrin interaction, the stoichiometry of the resulting inclusion complex and its formation constant. Using the UV spectrophotometer, we determined the solubility of albendazole in water, as well as the increase of the drug solubility driven by the increase of β-cyclodextrin concentration. Biological studies carried out on mouse cultures confirmed an increase of the albendazole–β-cyclodextrin complex bioavailability, as compared to the uncomplexed drug.

Photoresponsive smart hydrogel microsphere via host-guest interaction for 3D cell culture

In this study, we designed a kind of photoresponsive hydrogel microsphere for three-dimensional (3D) cell culture, which is based on the host-guest interaction of β-cyclodextrin (β-CD) and Azobenzene. The hydrogel microsphere consists of polyethylene glycol (PEG) and β-CD modified poly(methyl vinyl ether-alt-maleic acid) (PMVE-alt-MA) which was allowed to assemble with azobenzene-arginine-glycine-aspartate (Azo-RGD) via host-guest interaction for controlling cell adhesion and detachment. UV irradiation led to the detachment of Azo-RGD from hydrogel microsphere, and the number of cells cultured on the hydrogel microsphere surface was reduced subsequently. This photo-switchable surface can achieve the controllability of cells adhesion and detachment.

Host-guest interaction of β-cyclodextrin with isomeric ursolic acid and oleanolic acid: physicochemical characterization and molecular modeling study.

Ursolic acid (UA) and oleanolic acid (OA) are insoluble drugs. The objective of this study was to encapsulate them into β-cyclodextrin (β-CD) and compare the solubility and intermolecular force of β-CD with the two isomeric triterpenic acids. The host-guest interaction was explored in liquid and solid state by ultraviolet-visible absorption,1 H NMR, phase solubility analysis, and differential scanning calorimetry, X-ray powder diffractometry, and molecular modeling studies. Both experimental and theoretical studies revealed that β-CD formed 1: 1 water soluble inclusion complexes and the complexation process was naturally favorable. In addition, the overall results suggested that ring E with a carboxyl group of the drug was encapsulated into the hydrophobic CD nanocavity. Therefore, a clear different inclusion behavior was observed, and UA exhibited better affinity to β-CD compared with OA in various media due to little steric interference, which was beneficial to form stable inclusion complex with β-CD and increase its water solubility effectively.