Β-cyclodextrin Nanocavity Research Articles

Inclusion of a Catechol-Derived Hydrazinyl-Thiazole (CHT) in β-Cyclodextrin Nanocavity and Its Effect on Antioxidant Activity: A Calorimetric, Spectroscopic and Molecular Docking Approach.

The aim of the present research was to obtain a supramolecular complex between a strong antioxidant compound previously reported by our group, in order to extend its antioxidant activity. The formation of the inclusion complex of a catechol hydrazinyl-thiazole derivative (CHT) and β-cyclodextrin in aqueous solution has been investigated using isothermal titration calorimetry (ITC), spectroscopic and theoretical methods. The stoichiometry of this inclusion complex was established to be equimolar (1:1) and its equilibrium constant was determined. An estimation of the thermodynamic parameters of the inclusion complex showed that it is an enthalpy and entropy-driven process. Our observations also show that hydrophobic interactions are the key interactions that prevail in the complex. 1H NMR spectroscopic method was employed to study the inclusion process in an aqueous solution. Job plots derived from the 1H NMR spectral data demonstrated 1:1 stoichiometry of the inclusion complex in a liquid state. A 2D NMR spectrum suggests the orientation of the aromatic ring of CHT inside the β-CD cavity. The antiradical activity of the complex was evaluated and compared with free CHT, indicating a delayed activity compared with free CHT. To obtain additional qualitative and visual insight into the particularity of CHT and β-CD interaction, molecular docking calculations have been performed.

High barrier and durable self-healing composite coating: Boron nitride combined with cyclodextrin for enhancing the corrosion protection properties of waterborne epoxy coating

In recent years, a great deal of research has been devoted to designing smart anti-corrosion coatings with diverse self-healing capabilities, effective passive barrier properties, and long-lasting protection. Herein, the tetraethyl orthosilicate (TEOS) was used as a pH response guardian encapsulated on a BTA-loaded β-cyclodextrin (β-CD) nanocavity shells (CD(BTA)@TEOS), which would be ineffective in acidic environments, thus causing the release of BTA. Meanwhile, the polydopamine (PDA) was coated on the hexagonal boron nitride (h-BN) nanosheets (h-BN@PDA) to enhance its dispersibility and provide reactive sites. Further, the h-BN@PDA-CD(BTA)@TEOS (BPCT) hybrids were synthesized by linking CD(BTA)@TEOS nanocavity shells and h-BN@PDA nanosheets through PDA and KH560 as bridging agents. The dispersion of BPCT in waterborne epoxy coating (WEC) can effectively fill the coating defects and prolong the diffusion path of corrosive media, showing excellent barrier properties due to the excellent barrier properties of h-BN@PDA nanosheets against corrosive media. Meanwhile, the excellent self-healing properties of the composite coating under corrosive conditions were mainly derived from the released BTA and stripped PDA in response to pH variation. The corrosion resistance of the composite coating was tested by electrochemical, salt spray tests and microscopic corrosion morphology, and the self-healing properties of the coating were demonstrated by scratch electrochemistry. The expiration time of the BPCT/WEC sample was extended by 15 d, the persistence time in the salt spray test increased by 100 h, and the self-healing properties appeared after 4 h of coating rupture compared to the control WEC. The results proved that the WEC loaded with BPCT nanocontainers had a high barrier effect along with self-healing function and durable corrosion resistance.

Inclusion Complexation of Acetanilide into the β-Cyclodextrin Nanocavity: A Computational Approach

Host–guest inclusion complexation of acetanilide (AA) into the β-cyclodextrin (β-CD) nano-hydrophobic cavity has been investigated using computational technique. Two different orientation of guest (AA) into host (β-CD) are considered for the inclusion of AA in to the nanocavity through the 2o rim of β-CD. The energy differences in the inclusion process are calculated using PM3 semi-empirical method. By the investigation of stabilization energies, it is found that the “orientation 1” in which the benzene ring of AA oriented towards 2o rim of β-CD nanocavity is the stable complex. The conclusions obtained from the computational analysis are in good correlation with the docking analysis.

Spectral, thermal, and molecular modeling studies on the encapsulation of selected sulfonamide drugs in β-cyclodextrin nano-cavity

In the present work the inclusion complexation of three sulfonamide (SA) drugs, namely sulfisoxazole (SSX), sulfamethizole (SMZ), and Sulfamethazine (STM) with β-cyclodextrin (β-CD) has been investigated using UV–Vis spectroscopy, DSC, 1H NMR spectroscopy, and molecular modeling methods. The binding constant (Kb) of SA:β-CD inclusion complexation was determined via applying the modified form of Benesi–Hildebrand equation employing the changes in absorbance at λmax. Obtained results revealed that SA drugs form 1:1 inclusion complex with β-CD with Kb of 650, 1532, 714M−1 at 25°C for SSX, SMZ, and STM, respectively. The UV–Vis absorption spectra displayed solvatochromic behavior of bathochromic shift with decreasing solvent polarity that in turn is good agreement with their behavior in the presence of β-CD in terms of environment polarity dependency. The inclusion complex formation between β-CD and tested SA drugs in liquid and solid states was confirmed by 1H NMR and DSC, respectively. Using semi-empirical quantum chemistry methods at PM3 theoretical level, inclusion complexes’ structures as well as energetic and thermodynamic parameters of encapsulation were elucidated. Obtained results revealed that the encapsulation is favorably energetic and enthalpic in nature with the inclusion of the aniline moiety through the wide rim side of β-CD nano-cavity. Further, molecular modeling revealed that β-CD encapsulation of SA drugs reduced their (EHOMO−ELUMO) gap.

Spectroscopic study on encapsulation of two structurally similar donor–acceptor dyes in model cyclodextrin nanocavity

Encapsulation of two structurally similar donor–acceptor dyes in β-cyclodextrin (β-CD) nanocavity has been studied by steady state and time resolved fluorescence spectroscopic procedures. In the dye, (E)-2-((E)-3-(methyl(phenyl)amino)allylidene)-2,3-dihydro-1H-inden-1-one, the rotation about C–N bond is possible, while such a rotation is strategically restricted in the dye (E)-2-((1-methyl-3a,7a-dihydro-1H-indol-3-yl)methylene)-2,3-dihydro-1H-inden-1-one. Results indicate that both the dyes form complexes with β-CD but the stoichiometry and the nature of encapsulation are different. The dye in which the C–N bond rotation is permissible forms a 1:1 complex, with the acceptor centre (carbonyl group), rather than the donor centre (N atom) being encapsulated. The dye where the above mentioned rotation is restricted forms a 1:1 complex at a lower concentration of β-CD, encapsulating the donor centre (indole N). However, at a higher concentration of β-CD, 1:2 complex is formed involving both the acceptor and donor centres. Semi-empirical calculations at the PM3 level provide support to experimental findings. It is evidenced that the molecular structure of the guest is extremely important for encapsulation.

A novel water soluble solvatochromic probe as a micropolarity reporter for homogeneous and microheterogeneous media

A new water soluble donor–acceptor dye, sodium 4-(methyl((1E,3E)-3-(1-oxo-1H-inden-2(3H)-ylidene)prop-1-enyl)amino)benzoate (DN3) has been synthesized. Optical response of the solvatochromic dye (DN3) has been studied in various homogeneous (neat and mixed binary solvents) and heterogeneous (SDS and CTAB homomicelle and β-cyclodextrin nanocavity) media. To get information regarding the change in the solvation interaction of the dye with the alteration in its microenvironment in different media, the photophysical properties of the dye have been monitored in various media using steady state and time resolved spectral analysis. Results obtained for mixed binary solvents containing water indicate that the solute is preferentially solvated by one of the component solvents and solvent–solvent interactions are also important in determining the preference. Effect of variation of pH in aqueous medium on the spectroscopic parameters of the dye has been studied and its pKa has been estimated. Studies in homomicelles (SDS and CTAB) reveal that the dye distributes itself between the aqueous and the micellar phase and the values of distribution coefficient have been estimated from the fluorescence parameters. The dye is encapsulated in β-cyclodextrin nanocavity and a 1:2 dye-β-cyclodextrin host–guest interaction is indicated. Semi-empirical quantum chemical calculations have been carried out to support the experimental results.

Dynamics under confinement: torsional dynamics of Auramine O in a nanocavity

Confinement inside the novel anionic sulphobutylether β-cyclodextrin nanocavity significantly slows down the torsional relaxation in Auramine O as compared to native β-CD.

Enhancing Excited State Intramolecular Proton Transfer in 2-(2′-Hydroxyphenyl)benzimidazole and Its Nitrogen-Substituted Analogues by β-Cyclodextrin: The Effect of Nitrogen Substitution

Excited state intramolecular proton transfer (ESIPT) in nitrogen-substituted analogues of 2-(2'-hydroxyphenyl)benzimidazole (HPBI), 2-(2'-hydroxyphenyl)-3H-imidazo[4,5-b]pyridine (HPIP-b), and 2-(2'-hydroxyphenyl)-3H-imidazo[4,5-c]pyridine (HPIP-c) have been investigated in a β-cyclodextrin (β-CD) nanocavity and compared with that of HPBI. The stoichiometry and the binding constants of the complexes were determined by tautomer emissions. Both pKa and NMR experiments were employed to determine the orientation of the molecules inside of the β-CD cavity. Huge enhancement in the tautomer emission of HPIP-b and HPIP-c compared to that of HPBI in β-CD suggests that not only is the ESIPT favored inside of the cavity, but also, the environment reduces the nonradiative decay through the formation of an intramolecular charge-transfer (ICT) state. Unlike HPBI, the tautomer emission to normal emission ratio of HPIP-b increases from 0.9 to 2.6, and that of HPIP-c increases from 4.9 to 7.4 in 15 mM β-CD. The effect of dimethylsulfoxide (DMSO) on complexation was also investigated for all three guest molecules. In DMSO, HPBI is present in neutral form, but the nitrogen-substituted analogues are present in both neutral and monoanionic forms. However, in DMSO upon encapsulation by β-CD, all three molecules are present in both neutral and monoanionic forms in the nanocavity. The monoanion is stabilized more inside of the β-CD cavity. The studies revealed that the ESIPT of nitrogen-substituted analogues is more susceptible to the environment than HPBI, and therefore, they are more promising probes.

Spectral Narrowing of UV-Visible Absorption and Emission Spectra of Anthracene-Derivatives in β-Cyclodextrin Nanocavity: Effects of Host/Guest Stoichiometry

Cyclodextrins (CD) are cyclic oligosaccharides consisting of six or more D-glucopyranose units, the interior of which forms a hydrophobic cavity. In the present study, we employed the CD confinement effects as a tool to suppress an electronic decoherence of guest wavefunction by reducing intermolecular interactions between a guest molecule and the surrounding environment. Effects of host/guest stoichiometry on the decoherence suppresion were investigated by comparing native β-CD with trimethyl-β-CD that should form only a 1:1 complex. Both fluorecence and fluorecence-excitation spectra of inclusion complexes exhibited spectral narrowings only for the β-CD host, suggesting that the formation of barrel-type β-CD dimer plays a key role for the pronounced spectral narrowings.

Explicit Spectral Response of the Geometrical Isomers of a Bio-Active Pyrazoline Derivative Encapsulated in β-Cyclodextrin Nanocavity: A Photophysical and Quantum Chemical Analysis

The existence of two geometrical isomers (cis- and trans-) of a biologically significant pyrazoline derivative [5-(-1'-(4-bromo-phenyl)-3a',7a'-hexahydro-1'H-indazol-3'-yl)-3-methyl-1-phenyl-1H-pyrazole-4-carbonitrile] (PZ) has been established using a combined theoretical and experimental investigation. Solvatochromic analysis of PZ revealed the existence of said cis- and trans- isomers. The unique solvatochromic response of the PZ isomers and their preferential encapsulation within β-cyclodextrin (β-CD) nanocavity clearly shows the difference in the behavioral nature of the isomers of PZ in homogeneous and heterogeneous medium. Solvent polarity, time-resolved study, and anisotropy results also reinforce in favor of the existence of the isomers. To evaluate the actual orientation of cis and trans-PZ, the ground and excited state geometry of these isomers were optimized by the DFT/LanL2DZ and CIS/LanL2DZ methods, respectively. The experimentally observed results and the theoretically calculated results are found to be in close agreement.

Spectrophotometric thermodynamic study of orientational isomers formed by inclusion of methyl orange into β-cyclodextrin nanocavity

Spectrophotometry has been used to investigate the interaction of methyl orange (MO), an azo dye as a guest, with β-cyclodextrin (CD) as the host. Inclusion of methyl orange into β-cyclodextrin nanocavity leads to two orientational isomers, so-called inclumers, because of the asymmetric structure of methyl orange. This study was performed in basic and acidic media to yield the microconstants and thermodynamic parameters for inclusion complex formation equilibria in each media.The recorded data set at a constant temperature is rank deficient, because there is a linear dependency between concentration profiles of inclumers. This problem is overcome through the augmentation of multiwavelength data recorded at different temperatures. Titration of methyl orange solution with β-cyclodextrin solution was performed in five different temperatures, in order to calculate the formation microconstants for inclumers, pure spectra for absorbing components in each media and thermodynamic parameters such as change in enthalpy, entropy and Gibbs free energy for inclusion equilibria. Then globalization was performed to analyze the augmented data sets. The titration of acidic methyl orange with sodium hydroxide was also performed, to calculate the microconstants and thermodynamic parameters related to ionization.The interaction of the basic form of methyl orange with β-cyclodextrin in basic medium led to two orientational isomers. In acidic medium methyl orange has two tautomeric forms, called ammonium and azonium. The inclusion of azonium in β-cyclodextrin has been neglected in the considered model for simplicity and the inclusion of ammonium is modeled, because it forms more stable complexes with β-cyclodextrin nanocavity.Newton–Raphson algorithm was used to produce concentration profiles and Newton–Gauss–Levenberg/Marquardt algorithm was used to optimize the parameters of interest.

Confined ultrafast torsional dynamics of Thioflavin-T in a nanocavity

The influence of confinement in the supramolecular β-cyclodextrin nanocavity on the excited state torsional dynamics of the amyloid fibril sensor, Thioflavin-T, is explored using subpicosecond fluorescence up-conversion spectroscopy. In the presence of β-cyclodextrin, the emission intensity and the fluorescence lifetime of Thioflavin-T significantly increases, indicating the confinement effect of the nanocage on the photophysical behaviour of the dye. Detailed time-resolved fluorescence studies show an appreciable dynamic Stokes' shift for the dye in the β-cyclodextrin nanocavity. Analysis of the time-resolved area normalized emission spectra (TRANES) indicates the formation of an emissive TICT state. The rate of formation of the TICT state, as calculated from the time dependent changes in the peak frequency and the width of the emission spectra, is found to be substantially slower in the β-cyclodextrin nanocavity compared to that in bulk water. Present results indicate that ultrafast torsional motion in Thioflavin-T is significantly retarded due to confinement by the β-cyclodextrin nanocavity.

Constrained photophysics of an ESIPT probe within β-cyclodextrin nanocavity and chaotrope-induced perturbation of the binding phenomenon: Implication towards hydrophobic interaction mechanism between urea and the molecular probe

The present work demonstrates the effect of β-cyclodextrin (β-CD) nanocaging on the photophysical properties of Excited-State Intramolecular Proton Transfer (ESIPT) probe 3,5,6-trichlorosalicylic acid (TCSA) through steady-state absorption, emission and time-resolved emission spectroscopy. The remarkable enhancement of tautomer (proton transferred form) emission of TCSA as a result of inclusion complex formation with β-CD has been argued to be principally due to retardation of radiationless decay channels within the encapsulated state. A quantitative assessment of the emission intensity data on Benesi-Hildebrand equation reveals a 1:1 stoichiometry for TCSA:β-CD complex. The steady-state anisotropy, REES, and time-resolved fluorescence decay measurements are consistent with other experimental findings. Additionally, chaotrope (urea)-induced perturbation of the phenomenon of host-guest inclusion complex formation has been elucidated for a series of urea concentration. The present findings have been interpreted on the basis of the hydrophobic interaction mechanism of urea, rather than water 3-D structure rupture. The data unravel that the perturbation of solvation of the β-CD receptor is not important in the presence of urea, while the hydrophobic interaction with free probe molecules could be instrumental behind the observed lowering of TCSA:β-CD binding strength in the presence of urea.

Inclusion of chrysin in β-cyclodextrin nanocavity and its effect on antioxidant potential of chrysin: A spectroscopic and molecular modeling approach

Chrysin is a naturally occurring flavone that possesses a wide range of important biological activities. β-Cyclodextrin (β-CD) on the other hand due to its property of encapsulating molecules that are hydrophobic in nature is widely applied as drug delivery vehicle. Here, we have investigated the inclusion of chrysin within β-CD in aqueous solution using spectroscopic and theoretical methods. The stoichiometry of this inclusion complex was established to be equimolar (1:1) and its equilibrium constant was determined. Estimation of the thermodynamic parameters of the inclusion complex showed that it is an enthalpy driven process. Our observations also inferred that van der Waal’s interaction and hydrogen bonding are the key interactions that prevail in the complex. The process of inclusion not only increased the solubility of chrysin but also its antioxidant potential, as inferred from ABTS radical scavenging assay. Theoretical calculations show that destabilization of HOMO energies account for the higher antioxidant potential of chrysin upon inclusion. Molecular docking of chrysin with β-CD followed by molecular modeling of the obtained complexes yielded results consistent with our experimental observation. Combining our studies on solvatochromicity with cluster and interaction analyses, we suggest the preferred mode of inclusion to be through the A-ring of chrysin.

Inclusion complex of charge transfer probe 4-amino-3-methyl benzoic acid methyl ester (AMBME) with β-CD in aqueous and non-aqueous medium: medium dependent stoichiometry of the complex and orientation of probe molecule inside β-CD nanocavity

The absorption and emission characteristics of donor−acceptor charge transfer system 4-amino-3-methyl benzoic acid methyl ester (AMBME), capable of dual emission, i.e., local emission (LE) and charge transfer (CT) emission, have been investigated inside the β-cyclodextrin (β-CD) nanocavity in the aqueous and non-aqueous dimethylsulphoxide (DMSO) medium. Large enhancement of both LE and CT band in aqueous β-CD medium is due to decrease in non-radiative processes in less polar and restricted environment. Whereas in non-aqueous DMSO medium the CT process is hindered as a result CT intensity decreases with enhancement of LE band. These spectral differences indicate that in aqueous medium the donor –NH2 group sticking in the hydrophilic region of β-CD cavity whereas in non-aqueous DMSO medium it exists in the hydrophobic part of the cavity. Spectral characteristics indicate that different stoichiometry of host–guest inclusion complexes are formed in aqueous and non-aqueous β-CD medium.

Effect of β-cyclodextrin nanocavity confinement on the photophysics of robinetin

We have studied the confinement of robinetin, a therapeutically active plant flavonol, in cyclodextrin (CDx) nanocavities, using steady state and time resolved fluorescence spectroscopy. Enhanced tautomer emission (arising from excited state intramolecular proton transfer (ESIPT)) as well as dramatically blue shifted (∼10 nm in β-CDx and ∼33 nm in SHP β-CDx) normal fluorescence observed upon addition of the β-CDxs indicate that robinetin readily enters the doughnut-shaped hydrophobic cavity of β-CDx where the chromone moiety is well shielded from external hydrogen bonding perturbations. Detailed analyses of the fluorescence data (emission profile, anisotropy, decay times) indicate that robinetin forms 1:1 inclusion complexes with both natural and chemically modified β-cyclodextrins (β-CDx and SHP β-CDx) with affinity constant values K = 195 ± 17 M −1 and 1055 ± 48 M −1 respectively, indicating the prospective utility of SHP β-CDx in particular as an effective drug carrier. Unlike β-CDxs, α-CDxs do not form inclusion complexes with robinetin. To further characterize the robinetin/β-CDxs complexes, circular dichroism (CD) spectroscopic studies have been performed, which reveal that incorporation of robinetin molecules in the chiral environment of the β-CDxs strongly affects the electronic transitions of robinetin leading to the occurrence of positive induced circular dichroism (ICD) bands in the near ultra-violet (UV) region. Molecular mechanics calculations show that the inclusion complex with the chromone ring inserted into the β-CDx cavity is most favorable, in agreement with our spectroscopic data.

Fencing of Photoinduced Electron Transfer in Nonconjugated Bichromophoric System by β-cyclodextrin Nanocavity

Fencing of photoinduced electron transfer (PET) between the donor and acceptor in nonconjugated bichromophoric system by inclusion of donor group in the hydrophobic β-cyclodextrin nanocavity has been observed using steady state and time resolved fluorescence technique. The molecular modelling calculations further confirm the inclusion of donor group in the β-cyclodextrin nanocavity.