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The separation of the enantiomers of phenylalanine amide and N-methyl derivatives as well as some amino alcohols was studied by CE in acidic BGEs using CDs as chiral selectors. The native CDs displayed only low chiral recognition ability at a concentration of 15 mg/mL in 20 mM sodium phosphate buffer, pH 2.5. In contrast, the analyte enantiomers were separated in the presence of randomly sulfated CDs under reversed polarity of the applied voltage. Sulfated β-CD proved to be the most universal selector resulting in the enantioseparation of all analytes. Opposite enantiomer migration order depending on the size of the CD cavity was observed for phenylalanine amide and 2-amino-2-phenylethanol. The R-enantiomers migrated first in the presence of sulfated α-CD and γ-CD while the S-enantiomers were detected first in the presence of sulfated β-CD. The enantioseparations could be rationalized based on analyte complexation by the respective CDs except for 2-amino-2-phenylethanol and sulfated β-CD where essentially equal complexation constants were derived for the enantiomers. In this case, the migration behavior could be attributed to the mobilities of the enantiomer-CD complexes adding another example to the CE-specific phenomenon of enantioseparations based primarily on complex mobilities., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Despite the fact that extensive research in the field of separations by capillary electrophoresis (CE) has been carried out and many reviews have been published in the last years, a specific review on the use and future potential of cyclodextrins (CDs) in CE is not available. This review focuses the attention in the CD-CE topic over the January 2013-February 2014 period (not covered by previous more general CE-reviews). Recent contributions (reviews and research articles) including practical uses (e.g. solute-CD binding constant estimation and further potentials; 19% of publications), developments and applications (mainly chiral and achiral analysis; 38 and 24% of publications, respectively) are summarized in nine comprehensive tables and are commented. Statistics and predictions related to the CD-CE publications are highlighted in order to infer the current and expected research interests. Finally, trends and initiatives on CD-CE attending to real needs or practical criteria are outlined., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Host-guest complexes of alpha-, beta-, and gamma-cyclodextrins (α-CD, β-CD, and γ-CD, respectively) with amantadine (1-aminoadamantane, AMA; an antiviral agent) were characterized in aqueous solutions using proton nuclear magnetic resonance (NMR) spectroscopy. Host-guest molecular interactions were manifested by changes in the chemical shifts of AMA protons. NMR Job's plots showed that the stoichiometry of all the studied complexes was 1:1. Two-dimensional T-ROESY experiments demonstrated that the complexes were formed by different degrees of incorporation of the adamantyl group of AMA into the CD cavity. The mode of AMA binding was proposed. The AMA molecule came into the α-CD cavity (the smallest size) or β-CD cavity (the intermediate size) through its wide entrance to become shallowly or deeply accommodated, respectively. In the complex of AMA with γ-CD (the largest cavity size), the adamantyl group was also quite deeply inserted into the CD cavity, but it arrived there through the narrow cavity entrance. It was found that the adamantyl group of AMA was best accommodated by the β-CD cavity. The binding constants Kaa of the studied complexes (in M(-1) ), determined from DOSY NMR, were fairly high; their values in an ascending order were: α-CD (183) < γ-CD (306) ≪ β-CD (5150)., (© 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.)

The interaction between (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and water-soluble betulin derivatives, betulin 3,28-disulfate (DSB) and betulin 3-acetate-28-sulfate (ASB), belonging to the class of pentacyclic lupane triterpenoids, was studied using affinity capillary electrophoresis. It was found that 1:1 and 1:2 complexes were formed. The stability constants of the complexes in the temperature range of 293.15–318.15 K were determined. The values obtained are sufficiently large; log K (1:1) and log K (1:2) are 4.25–5.02 and 6.08–7.59, respectively. This phenomenon can be explained by the presence of broad hydrophobic regions in the molecules of the compound studied. The stability constants decrease with increasing temperature. The stability constants for ASB complexes are slightly higher as compared to the constants for DSB complexes. The thermodynamic parameters for the complexation were calculated from the van't Hoff plots. The complexation was found to be controlled by the enthalpy change. The obtained values of stability constants at 298 K were compared with values for the β-CD complexes of the compounds under study and for the HP-β-CD and β-CD complexes of water-insoluble betulin derivatives. It was found that water-soluble betulin derivatives form more stable complexes with CDs as compared to water-insoluble derivatives (betulonic and betulinic acids), and the HP-β-CD complexes are more stable than the β-CD complexes. • Betulin 3,28-disulfate and betulin 3-acetate-28-sulfate form 1:1 and 1:2 complexes with (2-hydroxypropyl)-β-cyclodextrin • Logarithms of stability constants are >4 • The complexation is controlled by the enthalpy change • Water-soluble betulin derivatives form more stable complexes with CDs as compared to water-insoluble derivatives • The HP-β-CD complexes are more stable than the β-CD complexes [ABSTRACT FROM AUTHOR]

[Display omitted] • QSPR models are developed for binding constants of cyclodextrin complexes. • Molecular size and shape parameters are considered specifically for modeling. • Experiments and predictions of binding constants for ionic liquids are performed. A generic method for predicting the complexation performance of cyclodextrins complexes is desirable. Two quantitative structure–property relationship models are established for the complexation performance of α- and β-cyclodextrins. The datasets consist of 229 α-cyclodextrin and 330 β-cyclodextrin complexes, including conventional organic molecules, ionic organic compounds, and drugs. Internal validation, indicated by the squared correlation coefficient (Q 2) of 0.8949 and 0.8954 for α- and β-cyclodextrin models, demonstrates the stability and robustness of these models. For external validation, the squared correlation coefficients of test sets (R 2 test) are 0.9315 (α-cyclodextrin model) and 0.9171 (β-cyclodextrin model), confirming the predictive ability of both models. Furthermore, the complexation performances of two ionic liquids are measured using UV spectrometric titration for our models' external prediction. The mean absolute error between measured and calculated values for β-cyclodextrin complexes is 0.20 M−1, indicating the satisfactory transferability of the model. For the α-cyclodextrin model, the mean absolute error of 1.25 M−1 is deemed acceptable. Both the model validations and experimental results underscore the robustness and predictive performance of these models. In conclusion, these developed models could effectively predict binding constants of several types of molecules with cyclodextrins, which can become valuable tools for cyclodextrin design. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Association constants of 5-fluorouracil, thymine, and uracil with 2-hydroxypropyl-beta-cyclodextrin have been measured. • Host:guest (1:1) complex formation constants were determined in the ground state from absorption spectra. • Host:guest (2:1) complex formation constants were determined in the excited state from emission spectra. • The polarity of the guest molecule has an effect on the strength of the host:guest binding energy. Abstract Host:guest interactions of 2-hydroxypropyl-beta-cyclodextrin:nucleobases derivatives have been studied via absorption and fluorescence spectroscopy in aqueous medium. The effect of the polarity of guests (pyrimidine nucleobases such as uracil, thymine and 5-fluorouracil) on the binding constant of the cyclodextrin-nucleobases complexes has been investigated. Benesi-Hildebrand method and nonlinear regression analysis were applied to determine the association constants of the formed complexes at room temperature. The formation constants derived from absorption titration experiments suggest that 1:1 host:guest complexes are formed and the least polar molecules in the ground state, 5-fluourouracil and thymine, are more strongly bound to the hydrophobic nonpolar cavity of the cyclodextrin compared to uracil. Similarly, excited state association constants derived from fluorescence titration experiments suggest that 2:1 host:guest complexes are formed and the least polar molecule in the excited state, uracil, is more strongly bound to the cyclodextrin. In addition, the emission spectra of bound pyrimidine nucleobases are blue shifted relative to the spectra of their counterpart, unbound pyrimidine nucleobases. The latter indicates a change in the environment of the guest molecule as it is displaced from the polar environment, water, into the nonpolar environment, cavity of the 2-hydroxypropyl-beta-cyclodextrin. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • mTHPC easily forms 1:2 inclusion complexes with β-CDs following 2 step mechanism. • Methylation of β-CD's core enhances the affinity to mTHPC. • mTHPC aggregation reduce the binding constant of the first β-CD molecule. • Corrected binding constant values are several times higher than previously reported. • High binding constants allow the use the β-CDs for mTHPC delivery in PDT. Abstract The interaction between the potent photosensitizer meta -tetrakis(3-hydroxyphenyl)chlorin (temoporfin, mTHPC) and a series of β-cyclodextrins (β-CDs) was investigated using spectroscopic analysis and molecular dynamics simulations. The possibility of improving its poor aqueous solubility with β-CDs was estimated by measuring both equilibrium solubility and association constants. Parameters of binding isotherms revealed that mTHPC strongly interacts with β-CD derivatives, forming 1:2 inclusion complexes in aqueous solution. We demonstrated that apparent binding constants strongly depend on mTHPC concentration due to the porphyrin self-aggregation. The estimated "correct" binding constants demonstrated that completely methylated β-CD exhibits the highest affinity (K = 1.1 × 107 M−1) as compared to randomly methylated β-CD (K = 7.1 × 105 M−1) and 2-hydroxypropyl substituted β-CD (K = 1.7 × 105 M−1). In fine , our results indicate that TM-β-CD should be considered as a potent vector for mTHPC targeted delivery. [ABSTRACT FROM AUTHOR]

In this work, a glassy carbon electrode modified with β–cyclodextrins and multi–walled carbon nanotubes (β–CDs/MWCNTs/GCE) was constructed and applied for the square-wave adsorptive stripping voltammetric (SWAdSV) determination of the pesticide dichlorophen ( Dcp ). For the first time, this compound was electrochemically investigated. The voltammetric measurements were conducted in phosphate buffer (PBS) at pH 6.5 as a supporting electrolyte, and SWAdSV technique parameters were optimized. A linear calibration curve in the wide concentration range from 5.0 × 10 −8 mol L −1 to 2.9 × 10 −6 mol L −1 was obtained. Excellent analytical performance in terms of limit of detection (LOD) of 1.4 × 10 −8 mol L −1 was achieved. The utility of the proposed method was verified by the quantitative analysis of Dcp in Pilica River water samples with satisfactory results. The characterization of modified electrodes was conducted by means of atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). Moreover, in this work, the dissociation constants (pK a ) of Dcp using potentiometric pH titration were estimated. The stoichiometry of the Dcp –β–CDs inclusion complex formed in solution was determined by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy, and a binding constant ( β 2 ) was estimated from NMR titration studies. [ABSTRACT FROM AUTHOR]

The host-guest interaction of tolmetin (TOL) with β-cyclodextrin (β-CD) and the influence of human serum albumin (HSA) on the formation of the inclusion complex were studied by 1D and 2D NMR spectroscopy. The TOL/β-CD inclusion complex formed at a molar ratio of 1:1 with a binding constant value of 2164.5 L·mol. Data analysis showed that the addition of 10 μmol·L of HSA weakened the strength of TOL binding to β-CD ( K = 1493 L·mol). The interaction of TOL with HSA in the absence and presence of β-CD was studied by analyzing the fluorescence quenching data. The Stern-Volmer quenching constants and the binding constants are found to be smaller in the presence of β-CD, suggesting that β-CD hinders the strong interaction of TOL with HSA by complex formation. Additionally, the presence of β-CD does not induce conformational and microenvironmental changes on HSA. [ABSTRACT FROM AUTHOR]

The state of the art of inclusion complex formation between cyclodextrins and ionic liquids is reported. Mechanisms, stoichiometries, and binding constants are summarized and classified by anion. We investigated the supramolecular interactions between the β-cyclodextrin cavity and six ionic liquids based on 1-dodecyl-3-methylimidazolium by affinity capillary electrophoresis and compared the results with those obtained by isothermal titration calorimetry. We show that the presence of basic or acidic buffers leads to a metathesis reaction, underlining the limitation of the affinity capillary electrophoresis technique. [ABSTRACT FROM AUTHOR]

The separation and migration behavior of six isomeric dichlorophenols (DCPs) in cyclodextrin-modified capillary zone electrophoresis (CD-CZE) using a phosphate-borate buffer at alkaline pH with β-CD and hydroxypropyl-β-CD (HP-β-CD) as electrolyte modifiers were investigated. The influence of buffer pH and the concentration of β-cyclodextrins were examined. The results indicate that baseline separation of six isomeric DCPs can be achieved with addition of β-CD concentration in the range of 2.0-10 mM or HP-β-CD concentration in the range of 4.0-10 mM at pH 10.0. Binding constants of DCPs to β-CDs were evaluated for a better understanding of the interaction of DCPs with β-CDs. [ABSTRACT FROM AUTHOR]

Noncovalent complexes between cyclodextrins and small molecules have been extensively studied recently because of their widespread application in the pharmaceutical industry for chiral and molecular recognition. To date, gas phase noncovalent binding affinities between α-cyclodextrin and amino acids have not been widely investigated. In this study, gas-phase binding of noncovalent complexes between α-CD and amino acids was investigated by electrospray ionization mass spectrometry (ESI-MS), demonstrating the formation of 1:1 stoichiometric noncovalent complexes. The binding of the complexes were further confirmed by collision-induced dissociation by tandem mass spectrometry. Mass spectrometric titrations between α-cyclodextrin and phenylalanine, glutamic acid, and arginine were performed to provide binding constants (lgKa) as references for competitive ESI-MS. Calibration curves for the complexes of α-cyclodextrin with phenylalanine, glutamic acid, and arginine were plotted. Through competitive ESI-MS, the lgKafor the complexes of α-CD with aspartic acid, lysine, proline, glycine, alanine, asparagine, cystine, glutamine, histidine, leucine, isoleucine, methionine, serine, threonine, and valine were measured directly. By comparison, it is seen that the measured binding constants for the complexes of α-cyclodextrin with basic amino acids such as arginine and lysine are lower than those for most complexes of neutral amino acids. The chiral selectivity of α-cyclodextrin for L- and D-isomers of methionine, threonine, asparagine, and phenylalanine determined by ESI-MS revealed its application as a chiral selector. [ABSTRACT FROM AUTHOR]

Highlights: [•] Diacerhein (DARh) is a prodrug of the IL-1 converting enzyme inhibitor Rhein (Rh). [•] The interaction of DARh with HPβCD has been studied by molecular spectroscopy. [•] Both the free and the complexed DARh can undergo hydrolysis to generate Rh. [•] DARh and Rh have some coincident spectroscopic parameters. [•] Accurate experimental and spectroscopic settings are essential parameters. [ABSTRACT FROM AUTHOR]

One of the relatively recent and most widely used approaches to reduce side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the complexation of NSAIDs with Cyclodextrins (CyD). So far, CyD interaction with drugs is not well understood. There have been many reports along these lines; however, rarely do these studies exploit the full potential of optical techniques. The purpose of this work is to produce a versatile, compact, low-volume, routine apparatus for the simultaneous measurements of absorbance and circular dichroism (CD) which allows for the concurrent use of three different pathlengths for binding studies of NSAIDs/CyD as a function of pH. A new rotating multi-cell holder which holds four cells was designed and manufactured. The work was achieved using an effective novel method for binding titration employing four separate flow cells connected in series in a flow system involving a titration flask and a pump. The p K, binding constants, stoichiometry and structural co-conformations of NSAIDs/β-CyD complexes were elucidated and determined with accuracy. The system proved to be efficient and the analysis time was reduced to less than or equal to one fourth of total analysis time used in one-cell systems, with possible automation for high-throughput analysis. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Two novel methods for determination of binding constants in the systems with borate and cyclodextrin complexation were developed. The methods enable to determine all binding parameters in these systems and even the binding constants of interaction of a neutral analyte with a neutral cyclodextrin. The first method is based on nonlinear fitting of experimental data and further evaluation of fitting parameters. The second method requires a multiple regression. The methods provide identical results with low experimental error. Only one set of measurements is required for both methods. Thus the binding parameters can be mutually compared. The binding parameters for neutral analytes ((R,R)-(+)-hydrobenzoin and (S,S)-(−)-hydrobenzoin) and neutral cyclodextrin (heptakis(2,6-di-O-methyl)-β-cyclodextrin) were evaluated and the effect of individual types of interaction was revealed. The interaction of the analytes with cyclodextrin governs the chiral recognition, while the complexation of analyte with borate is responsible for electromigration. Very low values of the binding constants of mixed analyte–cyclodextrin–borate complexes indicate that this type of complexation has negligible effect on enantioseparation. [Copyright &y& Elsevier]

The interaction between 6-aminobenzothiazole (6ABT) and β-cyclodextrin (β-CDx) has been investigated in solution and solid state. The stoichiometry and binding constants of the complex between 6ABT and β-CDx in solution have been determined by steady state and time-resolved fluorescence spectroscopy. Fluorescence intensity of neutral form decreases during complexation which is contrary to the usual observation. This is explained by hydrogen bonding interaction between lone pair of nitrogen with OH groups of β-CDx. The FT-IR spectral study and SEM images of solid complex confirmed the formation of inclusion complex. Excited state acidity constants for 6ABT have been determined in aqueous and β-CDx medium and discussed. [ABSTRACT FROM AUTHOR]

Abstract: NMR spectroscopy has been used to study and characterize the interactions in solution between β-CD and alkyl-α,ω-bis(dodecyldimethyl ammonium bromide) gemini surfactants with the following head-group spacer lengths: 2, 4, 6, 8, and 10. The application of the method of continuous variation gives as a result that 1:1 and 2:1 (β-cyclodextrin-gemini) complexes are formed; the association stoichiometry is dependent on the spacer chain length, varying from 1.5 (for s =2) to 1.8 (for s =10). Assuming a two-step mechanism, the binding constants have been computed. In general, the overall binding constant slightly increases with an increase of the number of methylene groups in the spacer. The 1H NMR spectra of the N-(CH3)2 groups in β-cyclodextrin/gemini mixed solutions are split into two peaks for 12-10-12, suggesting that the gemini spacer can thread the β-cyclodextrin so that the latter is positioned between the gemini head-groups. Inspection of the ROESY spectra allowed the establishment of several spatial proximities between the protons from the β-CD and the gemini and for a spacer length of 10, the data indeed indicate that complexes are formed with the CD molecule positioned between the two charged head groups with the spacer passing through the CD molecule. [ABSTRACT FROM AUTHOR]

Abstract: The binding constants of 14 different flavors (Maltol, Furaneol, Vanillin, Methyl Cinnamate, Cineole, Citral, Menthol, Geraniol, Camphor, Nootkatone, Eugenol, p-vinil Guayacol and Limonene) to cyclodextrins (α-cyclodextrin and β-cyclodextrin) have been determined by an UV–Vis spectrophotometric technique. In all cases the binding constant of flavors to β-cyclodextrin are bigger than the corresponding one to α-cyclodextrin. This fact is due to the different size of cyclodextrin cavity. As well as, a relationship between log P of each flavor and the binding constants was found, proving that the driving force for host–guest complex formation is hydrophobic/hydrophilic interactions. [Copyright &y& Elsevier]

The aim of this work was to study the complexation capability of new sulfobutyl ether-alkyl ether (SBE-AE-CD) mixed β- and γ-cyclodextrin derivatives with a series of structurally related steroids (6α-methylprednisolone, prednisolone, triamcinolone, D(-) norgestrel and hydrocortisone) and a number of dihydropyridine calcium channel blockers (nimodipine, nitrendipine, nifedipine) that traditionally interact poorly with other cyclodextrins (CDs). The effect of the total degree of substitution (TDS) and of the length of the alkyl side chain on binding capacity of these new modified CDs was evaluated as was their ability to induce red blood cell hemolysis. An attempt was made to correlate hemolysis to surface activity. Binding constants between the SBE-AE-CDs and selected molecules were determined by spectroscopic studies, and only in few cases by solubility studies. Hemolysis percentage was determined using citrated rabbit blood and citrated human blood with UV analysis. The surface activity was measured with a tensiometer. A significant improvement in the binding capacity between various substrates and the new SBE-AE-CDs was observed when compared to the SBE-CDs. The length of the alkyl chain and total degree of alkylation affected the binding with the relationship being complex. For most compounds, an intermediate degree of substitution appeared to be advantageous. The hemolysis studies showed that some of the derivatives may induce hemolysis and this correlated with higher surface activity for some but not all of the derivatives. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4769–4780, 2009 [ABSTRACT FROM AUTHOR]

Abstract: The complexation of native β-cyclodextrin (CD) and seven aromatic compounds, namely, phenetole, toluene, m-xylene, naphthalene, biphenyl, fluorene and phenanthrene, has been studied for first time utilizing a solid-phase microextraction (SPME)–high-performance liquid chromatography (HPLC) method. The stoichiometries of the analyte:β-CD complexes were found to be either 1:1 or 1:2. The formation of 1:2 complexes was confirmed for naphthalene, biphenyl, fluorene, and phenanthrene only when utilizing relatively high concentrations of β-CD (up to 6.6mM). The 1:2 stoichiometries were confirmed using the classical modified Benesi–Hildebrand (BH) method. The calculated binding constants for 1:1 stoichiometries (K 1) using the SPME method varied from 115.3M−1 for toluene to 3510M−1 for phenanthrene, whereas the corresponding values to the 1:2 stoichiometries (K 3) varied from 7.30×105 M−2 for biphenyl to 9.03×106 M−2 for naphthalene. [Copyright &y& Elsevier]

Abstract: The interactions of gemfibrozil with γ- and HP-γ-cyclodextrin (CD) have been studied in aqueous solution by fluorescence and NMR spectroscopy and by solubility measurements and in the solid state by X-ray diffraction, thermal analysis and FTIR spectroscopy. The influence of the technique employed in the analysis of complexation is discussed. The fluorescence of gemfibrozil increased in the presence of γ- and hydroxypropyl-γ-cyclodextrin (HP-γ-CD), especially with the later, because the inclusion of the aromatic ring in the cavity, evidenced by 1H NMR, has a protective effect on the excited state of the drug. The fluorescence enhancement allowed the determination of the binding constants at pH 2.8. Complexation was a both entropy and enthalpy driven process. The solubility diagrams obtained with γ-CD and HP-γ-CD were Bs and AL type, respectively. The apparent stability constants calculated from the solubility data at 25°C were compared with those obtained from the fluorescence assays. It was found that drug solubilization with γ-CD involves other contributions together with the inclusion phenomena. Solid complexes of gemfibrozil with γ-CD (and not with HP-γ-CD) have been obtained by kneading, coevaporation and coprecipitation methods. The solid complexes crystallised in the channel structure, in a process involving the carboxyl and aryl-ether groups. [Copyright &y& Elsevier]

The influence of β-CD concentration on the acid hydrolysis of N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) has been studied in the presence and absence of different alcohol concentrations. The rate of the denitrosation reaction in bulk water decrease as the β-CD concentration increases due to MNTS complexation in the CD cavity and the reaction taking place exclusively outside the cyclodextrin. Changes in this inhibition due to the presence of β-CD allow us to obtain the binding constants of different alcohols to the cyclodextrin. These binding constants are in very good agreement with those determined in the bibliography by other methods. [ABSTRACT FROM AUTHOR]

The objective of this study is to see if random alkyl ethers of various sulfoalkyl ether cyclodextrins can be synthesized and characterized. The purpose of the alkylation was to test the hypothesis that an increase in the “height” of a cyclodextrins cavity would help in the binding/complexation of larger more structurally complex molecules. The synthesis of new cyclodextrin derivatives comprising a mixture of sulfoalkyl ether and alkyl ether substituents on the same cyclodextrin ring was performed in aqueous alkaline solutions using various sultones and alkylsulfates. The method presented provided an easy and efficient way to modify cyclodextrins avoiding the use of organic solvents and high quantities of alkylating agents and could be carried out in either a two step or “one pot” single step process. Purification was by neutralization followed by ultrafiltration. The derivatives were characterized by 1D, (1H and 13C), and a 2D NMR technique (HMQC, Heteronuclear Multiple Quantum Coherence). The combination of these techniques allowed an analysis of the degree of substitution and the site of substitution on the cyclodextrin (CD) nucleus. For both β- and γ-CD, sulfoakylation was preferred on the 2 > 3 > 6 hydroxyls while alkylation was preferred 6 > 2 > 3. Due to the simultaneous presence of short alkyl ether chains and negatively charged sulfoalkyl ether chains, these mixed water-soluble cyclodextrin derivatives, especially those of γ-cyclodextrin, should be able to bind more complex drugs. The improved binding capacity of these new modified CDs with the model drug 6α-methylprednisolone is reported. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2380-2392, 2005 [ABSTRACT FROM AUTHOR]

Abstract: The absorption and fluorescence spectral features of a dioxin-like compound, 2-dibenzofuranol (DBFOH), have been studied in aqueous and non-aqueous media and in the presence of cyclodextrins (CDs). The fluorescence of DBFOH is structured in cyclohexane and shifts towards red when the polarity of the solvent is increased. The pKs in the ground and first electronic excited states are pK =9.95 and pK * =1.5, as calculated by the Förster cycle from the absorptometric and fluorimetric data. DBFOH forms inclusion complexes with β and γ-CDs but not with α-CD, the spectral behavior being dependent on the type of macrocycle. β-CD enhances the emission of DBFOH by forming a 1:1 complex, whereas the γ-CD forms 1:1 and 2:1 stoichiometries, (DBFOH)2:γ-CD, as deduced from absorption, fluorescence, and 1H NMR experiments. No excimer emission is perceived, unlike the case of dibenzofuran (DBF) and 2-dibenzofurancarboxylic acid with γ-CD. The complexation does not modify the excited-state reactivity of DBFOH, in contrast to other condensed aromatic alcohols. The binding constants have been obtained from the emission spectra by multivariable non-linear regression analysis at several wavelengths and, from the dependence on the temperature, the thermodynamic parameters of the binding, enthalpy and entropy, have been deduced. The effect of the hydroxyl group on the stability and on the proton transfer in the excited state of DBFOH is compared to the non-substituted DBF and the corresponding carboxylate derivative (DBFC). The similarities between the enthalpies indicate that the complex formation is governed by the inclusion of the aromatic part in the cavity, the functional group having a negligible effect on the binding. [Copyright &y& Elsevier]

Abstract: The binding capacity of β-cyclodextrin polymers (β-CDP), cross-linked with epichlorohydrin, has been compared with that of unimeric β-cyclodextrin for the inclusion of dibenzofuran (DBF) and two of its derivatives: 2-hydroxydibenzofuran (DBFOH) and dibenzofuran 2-carboxylate (DBFC). Gel permeation chromatography, 1H and 13C NMR, and dynamic light scattering, together with membrane ultrafiltration, were used to characterize and fractionate the polymeric samples. Their interactions with the dibenzofuran derivatives have been analyzed by absorption and fluorescence spectroscopies. Fluorescence anisotropy titrations were used to obtain the apparent binding constants. The affinity of the neutral dibenzofurans for the polymers is significantly higher than those of the unimeric β-CD, irrespective of the molecular weight or the microstructure of the polymer, whereas the charge in the anionic dibenzofuran derivative hinders the formation of the complex. The most hydrophobic DBF shows a higher affinity for the polymer with a higher content in β-CD, whereas the opposite behavior is displayed for DBFOH. The results are explained in terms of the synergic effect produced by the glyceryl cross-linking bridges, the relative hydrophobicity of the guest–host system and the density of the polymer network. [Copyright &y& Elsevier]

The formation of inclusion complexes between methoxypoly(ethylene glycol)s (MPEG)s bearing one hydrophobic group (phenyladamantyl) per chain and β-cyclodextrin (β-CD) was studied by capillary electrophoresis (CE). The effect of highly sulphated β-CD (HS-β-CD) on the migration behaviour of the phenyladamantyl-modified MPEG (MPEG-PhAd) analyte was investigated. It was established that the interaction between the modified PEG and β-CD involved a 1:1 stoichiometry. Non-linear regression and three usual linearization methods (y-reciprocal, x-reciprocal and double reciprocal) were employed to estimate the binding constants. It was demonstrated that the binding constants were similar (around 400 M−1) for two MPEG-PhAd having different chain lengths (2000 and 5000 g/mol). [Copyright &y& Elsevier]

Naphthalene excited dimer (excimer) fluorescence is observed in the presence of β- and γ-cyclodextrin (CD) at elevated naphthalene (NAP) concentrations (100 μM) but not at low NAP concentrations (5 μM). This is attributed to formation of 2:2 CD:NAP complexes in the former situation. Complexes of NAP with hydroxypropyl β-CD are exclusively 1:1 and no excimer emission is observed. Complexes of NAP with α-CD do not show excimer emission either but the complex stoichiometry is 2:1 CD:NAP in this case. The formation constants for both the 1:1 and 2:2 β-CD:NAP complexes have been determined and they have been found to depend on the ionic strength of the salting out agent NaCl. K1:1 = 377 ± 35 M-1 in the absence of salt and 657 ± 60 M-1 at 1 M NaCl. The corresponding values for K2:2 are (1.0 ± 0.2) × 104 and (4.0 ± 0.5) × 104 M-1, respectively. Stern-Volmer fluorescence quenching studies of the 1:1 and 2:2 species by water-based quenchers (NaI and CsBr) show that both types of complexes protect the fluorophore from the quencher. However, the more completely encapsulated NAP in the 2:2 complex is protected to a greater extent. This is also the case for the 2:2 γ-CD:NAP complex. This protective effect is reflected in the observed rate constants for NAP quenching. For example, kQ = 7.1 × 109 M-1 s-1 for NaI in the absence of CD. This is reduced to 2.1 × 109 M-1 s-1 for the 1:1 complex and 1.2 × 109 M-1 s-1 for the 2:2 complex when 10 mM β-CD is present. A similar pattern is observed for CsBr as quencher. The 2:2 complexes are disrupted in the presence of additives such as linear alcohols and surfactants. The implications of these results for application of CDs for drug stabilization are discussed. [ABSTRACT FROM AUTHOR]

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