Effects of Modified β-Cyclodextrins on the Hydrolysis Reaction of p-Nitrophenyl α-Methoxyphenylacetate

Effects of -cyclodextrin (-CD) 1and its derivatives 2–7 on the deacylationreaction of p-nitrophenyl (R or S)--methoxyphenylacetatewere studied. The-CD derivatives used were6--D-glucosyl--CD 2, sulfated-CD (7–11 sulfate groups/CD ring) 3,dimethylated -CD 4, carboxymethylated-CD (3.5 carboxymethyl groups/CD ring) 5,2-tri(2-hydroxypropyl)--CD 6, and-CD appended on poly(allylamine) 7. Therate constant (k ^CD) of thesubstrate/-CD complexes and the formationconstants (K) of the complexes were determinedfrom the dependence of the pseudo-first order rateconstants of the deacylation reaction on theconcentration of -CDs. The order ofk ^CD for the R-enantiomer at pH8.0 is 45H₂O3 6 1 2 7, whilethat for the S-enantiomer is 4 5 6H₂O 1 2 3 7: H₂O denotes the rate in theabsence of -CDs. The order of K values is3 7 6 2 1 4 5. This work indicates that, though thesecondary hydroxyl groups of -CD play criticalroles in the deacylation reactions of the esterscomplexed with -CDs, the reactivity of theester/-CD complexes depends highly on thenature of the substituents at the secondary face of-CD. It also suggests that the substratesinserted from the secondary side as well as theprimary side of -CD of poly(allylamine)-bound-CD undergo the reaction by attack of aminogroups on the polymer chain.     

Changes in the Solubility of β-Cyclodextrin on Complex Formation: Guest Enforced Solubility of β-Cyclodextrin Inclusion Complexes

The most common native host molecule, -cyclodextrin (cycloheptaamylose) is able toform inclusion complexes with a large variety of guestmolecules (or ions) of different size and shape. Theproperties of the included guest molecule are highlyinfluenced by the host-guest interaction, and thepractical usefulness of -cyclodextrin isdependent on these effects. These changes are mainlyinvestigated from the point of view of the guest andto a lesser extent from that of the host. In spite ofthis, the kind of guests and that of the host-guestinteractions during the formation of the inclusioncomplex seem to influence the properties of thehydrophilic domain of -cyclodextrin (i.e. thatof the supramolecule itself), too, and this effect canbe well demonstrated by the change of solubility ofdifferent -cyclodextrin inclusion complexes.This change can be best correlated with the solubilityof the guest as if the guest enforced its solubilityon the supramolecule.     

Thermoanalytical Studies on Complexes of Furosemide with β-Cyclodextrin Derivatives

Solid formulas obtained between furosemide and two β-cyclodextrin derivatives (HP-β-CD and RAMEB) were prepared by different methods and in various ratios (1:1 and 1:2). The inclusion complex formation between the drug and the β-CDs of 1:1 ratio was evaluated by mean of thermal analysis (DSC, TG and EGD). Supplementary techniques, such as X-ray diffraction, were also applied to interpret the results of the thermal study of physically mixed and kneaded products. Both studies demonstrated the formation of inclusion complexes in all samples except the physical mix samples; formation of true inclusion complexes was then possible only when the components were in melted form. The complexation increased the solubility and the rate of dissolution of the drug. RAMEB was found to be a better complexing agent than HP-β-CD; in both ratios it can be selected as a vehicle in furosemide tablet preparations. This revised version was published online in August 2006 with corrections to the Cover Date.     

Influence of protein hydrolysis on the growth kinetics of β-lg fibrils

Recently it was found that protein hydrolysis is an important step in the formation of β-lactoglobulin fibrils at pH 2 and elevated temperatures. The objective of the present study was to further investigate the influence of hydrolysis on the kinetics of fibril formation. Both the hydrolysis of β-lactoglobulin and the growth of the fibrils were followed as a function of time and temperature, using SDS polyacrylamide gel electrophoresis and a Thioflavin T fluorescence assay. As an essential extension to existing models, the quantification of the effect of the hydrolysis on the fibrillar growth was established by a simple polymerization model including a hydrolysis step.     

The Influence of β-Ammonium Substitution on the Reaction Kinetics of Aminooxy Condensations with Aldehydes and Ketones

The click-chemistry capture of volatile aldehydes and ketones by ammonium aminooxy compounds has proven to be an efficient means of analyzing the carbonyl subset in complex mixtures, such as exhaled breath or environmental air. In this work, we examine the carbonyl condensation reaction kinetics of three aminooxy compounds with varying β-ammonium ion substitution using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). We determined the activation energies for the reactions of the aminooxy compounds ATM, ADMH and AMAH with a panel of ketones and aldehydes that included acrolein and crotonaldehyde. The measurements indicate that the activation energies for the oximation reactions are quite low, less than 75 kJ mol⁻¹. ADMH is observed to react the fastest with the carbonyls studied. We postulate this result may be attributed to the ADMH ammonium proton effecting a Brønsted-Lowry acid-catalyzed elimination of water during the rate-determining step of oxime ether formation. A theoretical study of oxime ether formation is presented to explain the enhanced reactivity of ADMH relative to the tetraalkylammonium analog ATM.     

Selective Modification of β-Cyclodextrin on the Secondary Side 4:Preparation of Arylated β-Cyclodextrins with a Flexible Chain

Cyclodextrins(CDs,includinga-,o-,a-CD,etc.)havegainedprominenceinrecentyearsbecauseoftheirtorus-shapedcavity,whichishydrophilicoutsideandhydrophobicinside,caPableofprovidingidealprototypestoconstructefficientartificialenzymes,molecuIarrecognitionsensorsandotherfunctionalmodels.l-3Forbuildingmoreefficientartificialenzymesandmolecularrecognitionsensors,wehavepreparedaseriesof6-CDderivativesbearingchromophores'-'andfoundthat3"-'anarylmoietycouldactasaspectrometryprobeaswellasafunctionalgroup.F…     

The Influence of β-Diketones on the Hydrolysis and Growth of Particles from Zirconium(IV) n-Propoxide

The influence of low ligand/Zr mole ratios ( = 0–0.1) on the hydrolysis and growth of oligomers from Zr(O ⁿ Pr)₄ modified with a series of -diketones (trifluoroacetylacetone, hexafluoroacetylacetone, benzoylacetone, dibenzoylmethane and dipivaloylmethane), and their subsequent aggregation to form uniform, dense spheres, has been investigated by light scattering and turbidometry. The addition of -diketones results in a large increase in the induction time, t _i (reduction in hydrolysis/condensation rates). A remarkable feature of the data is the dramatic reductions in rate observed even when a maximum of one in forty Zr–OR bonds have been replaced by the -diketone and are no longer available for hydrolysis or further condensation. The largest effect is observed with dibenzoylmethane, which increases t _i by a factor of 26 relative to acetylacetone.A mechanism rationalising the origin of the effect is discussed, which involves segregation of the -diketone ligands on the surface of the growing particle, with subsequent particle growth restricted to those sites not occupied by the chelating ligands.     

Influence of β-cyclodextrin on the protolytic and complexing ability of p-aminobenzoic acid

UV spectroscopy was used to study the protolytic properties and determine the ionization constants of p-aminobenzoic acid in the presence of β-cyclodextrin. Formation of supramolecular structures of 1: 1 composition was established. Stability constants of the β-cyclodextrin-p-aminobenzoic acid inclusion complex were calculated, as were the thermodynamic parameters (ΔG°, ΔH°, and ΔS°) of its formation. The complexing process between β-cyclodextrin and p-aminobenzoic acid was found to occur spontaneously in the temperature range under investigation while being accompanied by energy liberation and leading to a reduction in the system’s entropy.     

Guest-Binding and Catalytic Properties of Immobilized β-Cyclodextrins

Abstract

Cyclodextrins¹(CyDs), cyclic oligomers of 6–8 glucose units, form inclusion complexes with guest compounds and have been used as catalyst for the selective syntheses.² Previously, immobilization of CyD with epichlorohydrin as crosslinking agent have been described.^3-4 Here, we report the first successful immobilization of β-CyD using various crosslinking agents. The guest binding abilities and the catalytic abilities of these immobilized β-CyDs are shown.     

A Convenient Procedure for the Synthesis of 6-O-Mono-Phosphate β-Cyclodextrins

Abstract

The synthesis of β-cyclodextrin derivatives bearing one phosphate group on the primary rim is reported. These compounds were prepared in good to excellent yields, by reacting β-cyclodextrin with dialkyl chlorophosphates in the presence of 4-dimethyl amino pyridine (DMAP) catalyst and dimethylformamide (DMF) as solvent. The methodology described is highly selective and the purification of the title compounds is simple, because difficulties due to phosphate regioisomers mixture are avoided.     

Complexation of Monosulfonated Triphenylphosphine with Chemically Modified β-Cyclodextrins: Effect of Substituents on the Stability of Inclusion Complexes

Interactions between the meta-substituted monosulfonated triphenylphosphine and chemically modified β-cyclodextrins were investigated in aqueous solution by NMR and UV–vis spectroscopy. Titration and continuous variation plots obtained from ³¹P NMR data indicate that the monosulfonated triphenylphosphine forms 1:1 inclusion complexes with the 2-hydroxypropylated β-cyclodextrin, the methylated β-cyclodextrin and the (2-hydroxy-3-trimethylammoniopropyl)-β-cyclodextrin chloride. These inclusion complexes are more stable that those formed with native β-cyclodextrin, confirming that poisoning of the chemically modified β-cyclodextrins by the hydrosoluble phosphine occurs when modified cyclodextrins are used as mass transfer promoters in aqueous-phase organometallic catalysis.This revised version was published online in July 2005 with a corrected issue number.     

Freeze-Dried Complexes of Furosemide with β-Cyclodextrin Derivatives

A freeze-drying method was used to prepare complexes of furosemide (guest) with three derivatives of -cyclodextrin (hosts) in different molecular ratios in order to increase the aqueous solubility and rate of dissolution of the drug, and also to study the influence of this method on different parameters of the guest and the host, such as the diffusion rate constant and the partition coefficient, and additionally the surface tension activity of the host (if any). The hosts were found to have significant, increasing effects on the solubility and the rate of dissolution of furosemide. X-ray diffraction confirmed the host–guest interaction, in support of the earlier results. The freeze-drying method increased the diffusion rate of the drug in complex form, while the partition coefficient varied with the type of -cyclodextrin in the product. It is well known that CD derivatives are highly surface active which gives rise to their hemolytic action. Our observations showed that their presence with furosemide in complex form might decrease (if not diminish) the hemolytic action.     

H-Nuclear Magnetic Resonance and Phase Solubility Studies of the Stoichiometries in 2,4-D: α- and β-Cyclodextrins Inclusion Complexes

The interaction in solution between2,4-dichlorophenoxyacetic acid with - and-cyclodextrins was evaluated by phasesolubility studies. Association constants werecalculated by this technique. The stoichiometries were1 : 2 and 1 : 1 for the - and -cyclodextrincomplexes, respectively. In order to corroborate thecomplexation and the knowledge of structural aspectsof the host : guest interaction, proton nuclearmagnetic resonance (¹H-NMR) spectroscopy wasemployed. The application of the continuous variationtechnique corroborated the calculated complexstoichiometries by solubility assays. ComplementaryNOE studies were applied in order to corroborate theproposed complex structures.     

Influence of degree and patterns of substitution on the inclusion properties of ethylated β-cyclodextrins

Different batches of ethylated derivatives of -cyclodextrins (Et-CD) obtained by various synthetic routes were used as host molecules to prepare inclusion compounds of salbutamol. Previous results showed that these complexes were suitable to achieve variable sustained-release behaviour of salbutamol. The mechanism of sustained-release was related to the inclusion capacity and physicochemical properties of Et-CD. Among the various analytical techniques carried out to characterize them, high resolution NMR afforded relevant information in terms of degree and patterns of subtitution, which could explain the differences observed between CD derivatives.     

Influence of inclusion complexation with β-cyclodextrin on the photostability of selected imidazoline-derived drugs

In this paper, the influence of inclusion complexation with β-cyclodextrin (β-CD) on the photostability of antazoline, xylometazoline, and naphazoline in aqueous media was investigated. The photodegradation reaction of these drugs molecules was explored using UV–vis spectrophotometery-based kinetic analysis and high performance liquid chromatography (HPLC). Quantitative evaluation of the influence of β-CD was judged based on the observed rate constant (k _obs), half-life time (t _0.5) and t _0.1 of the photodegradation reaction and the peak area of the corresponding analyte after photodegradation using HPLC separation. It has been demonstrated that the photostability of these selected imidazoline-based drugs has been enhanced upon forming inclusion complexes with β-CD in aqueous media. Moreover, high consistency regarding the photostability enhancement was obtained using both techniques. Hypothetical structure for 1:1 inclusion complexes was proposed based on molecular mechanics calculations, which in turn provide an insight for the energetically preferential structure of the inclusion complexes. The results obtained demonstrate that β-CD can be utilized as photostabilizer additive for enhancing the photostability of imidazoline-derived drugs molecules.     

Affinity Capillary Electrophoresis Studies on the Influence of Alcohols on the Interaction of β-Cyclodextrin with Non-Steroidal Anti-Inflammatory Drugs

Summary The influences of methanol, ethanol, 1-propanol and 1-butanol on the binding constants of -cyclodextrin (-CD) with non-steroidal anti-inflammatory drugs such as acemetacin, indometacin, cinmetacin, sulindac and diclofenac sodium and the separation of these drugs were studied by affinity capillary electrophoresis. No obvious effect was observable upon addition of methanol up to 6% (v/v) in the running buffer, while the addition of other alcohols at the concentration of 2% resulted in obvious decrease in the binding constants of -CD with acemetacin, indometacin, cinmetacin and sulindac. With an increasing chain length of added alcohols, all of these changes increased. Upon additions of different alcohols in the running buffer the change of the binding constant of -CD with diclofenac sodium was inconspicuous. Based on these results, the separation conditions for these drugs were optimized. The presence of 6% methanol in the running buffer containing 3 mM -CD was helpful to the baseline separation of these drugs. The electrophorograms of these drugs in the presence of ethanol, 1-propanol and 1-butanol showed a worse separation due to the decrease in the binding constants. The methods for the separation of these drugs and the study on the binding constants possess the advantages of easy performance, high speed and low sample consumption. AcknowledgementThe authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (No.20275017), the Science Foundation of Jiangsu (No.BS2001063) and the Key Project of Cancer Institute of Jiangsu Province.     

The effect of β-cyclodextrin on the properties of cetyltrimethylammonium bromide micelles

The effect of ß-cyclodextrin (ß-CD) on cetyltrimethylammonium bromide (CTAB) micellar properties was studied by the determination of the diffusion coefficient, D. When the CTAB micelles have a spherical structure, D firstly increased and then remained unchanged, while the micellar aggregation number, N, decreased with the addition of ß-CD. When the CTAB concentration was less than the first critical micellar concentration, CTAB molecules could be included into ß-CD cavities with the molar ratio of CTAB to ß-CD being about 1:1. However, when the CTAB concentration was higher than the first critical micellar concentration, mixed spherical micelles were formed with the molar ratio of CTAB to ß-CD being 9:1.     

Influence of the surface structure of β-cyclodexrin-containing silica on the adsorption of mercury nitrate from dilute solutions

The construction of adsorption sites for mercury(II) by chemical immobilization of β-cyclodextrin and its functional derivatives on a surface of macroporous amorphous silica is proposed. It is shown that the adsorption of mercury(II) is adequately described by the Langmuir isotherm equation for monolayer adsorption on localized sites of energetically homogeneous surfaces. It is established that the considerably increased sorption of mercury nitrate on silica modified by different β-cyclodextrins is due to the formation of 1: 1 β-cyclodextrin-nitrate ion inclusion complexes on the surface and the participation of side functional groups of the upper edge of immobilized β-cyclodextrin molecules in the formation of mixed-ligand mercury(II) complexes.     

Emulsifying Ability of β-Cyclodextrins for Common Oils

Emulsification of various common oils was investigated using natural β-cyclodextrin (β-CD) and its derivatives as emulsifiers. An oil/water (O/W) emulsion was formed using β-CD, whereas a water/oil (W/O) emulsion was formed using tripropanoyl-β-CD and tributanoyl-β-CD derivatives. Triacetyl-β-CD gave rise to both O/W and W/O emulsions. The type of emulsion was governed by the contact angle (θ_ow), which the precipitate of CD origin make with the oil-water interface.