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PubMed2003

Hydrophilic and hydrophobic cyclodextrins in a new sustained release oral formulation of nicardipine: in vitro evaluation and bioavailability studies in rabbits.

The feasibility of using complexes with cyclodextrins (CDs) in nicardipine (NC) controlled delivery has been examined, with a view to extending the pharmaceutical applications spectrum of these carriers. For a fast release fraction, a hydrophilic beta-cyclodextrin derivative (hydroxypropyl-beta-cyclodextrin) was employed to form a water-soluble complex. For the sustained-releasing portion, triacetyl-beta-cyclodextrin (TAbetaCD) was used to provide complexes with appropriate hydrophobicity. An optimal formulation was designed by the combination of each fraction in different mixing ratios. The release behaviour of the complexes, as well as of their mixtures, was examined in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids. The formulations released the drug rapidly at the initial stage, followed by a slow release. The drug release rate was markedly retarded in the increasing order of the amount of NC/TAbetaCD complex. When NC was administered to rabbits, its absorption was very rapid with a short elimination half-life, while a prolonged maintenance of the plasma levels was obtained for the two selected formulations. The drug bioavailability was considerably improved especially after the administration of the mixture of hydrophilic and hydrophobic complexes, when compared with the NC/TAbetaCD complex. The results suggested that the critical combination of hydrophilic and hydrophobic CDs complexes, in appropriate ratios, could be a promising drug delivery system with a prolonged therapeutic effect coupled with a more balanced bioavailability.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2002

Effect of inclusion complexation with cyclodextrins on photostability of nifedipine in solid state.

Nifedipine is a highly photosensitive drug that requires restricted protection from light during manufacturing, storage and handling of its dosage forms. Inclusion complexation of nifedipine with cyclodextrins (CDs) could be advantageous in protecting the drug against the effect of light. In this study, solid inclusion complexes of nifedipine with beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-CD) were prepared using the coprecipitation method. The obtained solid inclusion complexes have been confirmed by differential scanning calorimetry (DSC), X-ray diffraction and infrared spectroscopy (IR). The IR spectra indicated partial inclusion of nifedipine molecules into CD cavities through the dihydropyridine ring. Inclusion complexation was also associated with a dramatic enhancement of drug dissolution with magnitudes depended on the type of CD. The effect of exposure to fluorescent lamp and sunlight on the photodegradation of uncomplexed and complexed nifedipine was tested. Photodegradation of nifedipine was monitored using a high performance liquid chromatographic (HPLC) assay method. Inclusion complexation of nifedipine showed to retard drug photodegradation as indicated by degradation rate constant lowering with values depended on light source and type of complexing agent. This effect was the least with beta-CD compared with that of modified beta-CD. It was also interesting to notice that inclusion complexation of nifedipine offered much higher protection against the effect of fluorescent lamp than that of sunlight. The obtained results suggests that the design of solid dosage forms of nifedipine such as a fast dissolving nifedipine tablets is possible with the advantages of low required light protection.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2003

Preparation and in-vitro release rate of fentanyl-cyclodextrin complexes for prolonged action in epidural analgesia.

Fentanyl was complexed with cyclodextrin derivatives with the intention to obtain parenteral solutions able to provide prolonged analgesia following epidural administration. Three cylodextrins (CDs) suitable for parenteral use were used: hydroxypropyl-beta-cyclodextrin (HP-beta-CD), sulfobutylether-beta-cyclodextrin (SBE-7-beta-CD), and maltosyl-beta-cyclodextrin (malt-beta-CD). Analysis of fentanyl was done with HPLC-UV. The inclusion capacity of HP-beta-CD was determined from phase-solubility diagrams at pH 6.5, 7.2 and 8.0, and those of SBE-7-beta-CD and of malt-beta-CD at pH 8.0. Solubility of fentanyl increased linearly (i) as a function of the CD concentration, and (ii) with decreasing pH. Complexation was highest with HP-beta-CD and malt-beta-CD, much higher than with SBE-7-beta-CD, with stability constants at pH 8.0 of 801, 729 and 1309 M(-1), respectively. The CD concentration was calculated to obtain a fentanyl-CD formulation, with the desired amount free fentanyl as loading dose in solution and the rest complexed with CD, as reservoir for prolonged action. A suitable membrane and a release-rate apparatus were selected for in-vitro release-rate studies. Best results were obtained with Spectrapor membranes and a home-made release-rate apparatus. Release rate was evaluated in static and dynamic conditions. For both modes, the release rate of fentanyl decreased as a function of CD concentration, due to complex formation of fentanyl, which suggests the possibility to provide prolonged pharmacodynamic effects in vivo.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2003

Stability of natamycin and its cyclodextrin inclusion complexes in aqueous solution.

Aqueous solutions of natamycin and its beta-cyclodextrin (beta-CD), hydroxypropyl beta-cyclodextrin, and gamma-cyclodextrin (gamma-CD) inclusion complexes were completely degraded after 24 h of exposure to 1000 lx fluorescent lighting at 4 degrees C. After 14 days of storage in darkness at 4 degrees C, 92.2% of natamycin remained in active form. The natamycin:beta-CD complex and natamycin:gamma-CD complex were significantly more stable (p < 0.05) than natamycin in its free state in aqueous solutions stored in darkness at 4 degrees C. Clear poly(ethylene terephthalate) packaging with a UV light absorber allowed 85.0% of natamycin to remain after 14 days of storage under 1000 lx fluorescent lighting at 4 degrees C. Natamycin:cyclodextrin complexes can be dissociated for analysis in methanol/water/acetic acid, 60:40:5, v/v/v. Natamycin and its complexes in dissociated form were quantified by reverse phase HPLC with detection by photodiode array at 304 nm.

Antifungal Agents↗
PubMed1996

Hydroxypropyl cyclodextrins: potential synergism with carcinogens.

The solubility of the lipophilic carcinogens benzo[a]pyrene and aflatoxin B1 in water increases linearly and substantially with the concentration of hydroxypropyl beta-cyclodextrin present. Results of a kinetic study of naphthalene, a model for more potent carcinogens, indicate that the increase in the dissolution rate and in the transport through the aqueous phase into a nonpolar phase is on the same order of magnitude as the increase in solubility. Consequently, hydroxypropyl beta-cyclodextrin, when used in pharmaceutical formulations, has the potential to increase the absorption of carcinogens which enter the gastrointestinal tract either as food components or from air pollution through saliva. Only the above mechanism's simple proportionality needs be considered for estimating the increases in carcinogen absorption in the upper gastrointestinal tract and in the colon. In the presence of bile, however, additional factors are involved and the proportionality does not apply. Bile micelles, which themselves are effective solubilizers of lipophilic carcinogens, were disrupted by hydroxypropyl beta-cyclodextrin because of the formation of complexes with bile salts. Thus, in the presence of bile, two systems for delivery of carcinogens may coexist: that of cotransport with lipids and that of delivery through solubilization by hydroxypropyl beta-cyclodextrin.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2003

Examination of 19F-NMR as a tool for investigation of drug-cyclodextrin complexes.

Fluorine nuclear magnetic-resonance spectroscopy (19F-NMR) was used to measure complexation of three fluorine-containing drugs--dexamthasone, fluoxetine hydrochloride, and diflunisal sodium--with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). Poor aqueous solubility inhibited investigation of dexamethasone complexes with this method. Complexation caused separation of the fluorine peaks that could be assigned to the two enantiomers of fluoxetine hydrochloride. The trifluoromethyl group of the drug was not included, or only partially included, in the cyclodextrin cavity and the shift changes resulting from complexation were small (0.04 and -0.05 ppm). The NMR method, therefore, could not be used to determine complex stoichiometry and complex stability constants, as chemical-shift changes were influenced by changes in the composition of the solvent medium. The difluorophenyl group of diflunisal sodium was fully included in the cyclodextrin cavity and the chemical-shift changes were large, 2.0 and 1.4 ppm, for C2' and C4' fluorine atoms, respectively. Using the continuous variation method, a 1:1 stoichiometry was determined for the complex. The chemical shift changes could also be used to determine the stability constant (Kc) for complex formation. The value obtained for the fluorine that enters deeper into the cavity was 2000 M(-1). The data shows that, given that the drug has sufficient solubility, one-dimensional 19F-NMR can be a fast and convenient method to investigate drug-cyclodextrin complexes. However, when the results are interpreted it must be taken into account that the solvent medium can affect the chemical shifts of the fluorine peaks.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2003

Preparation and characterization of the inclusion complex of furosemide with hydroxypropyl-beta-cyclodextrin.

A highly hydrophobic drug, furosemide, was treated with 2-Hydroxypropyl-beta-Cyclodextrin in an attempt to produce modified compounds with increased water solubility. Following a freeze-drying process, the interactions of furosemide and cyclodextrin led to the formation of an inclusion complex, whose dissolution rate in water was studied by the solubility method. Furthermore, mechanical mixtures of furosemide and cyclodextrin were also prepared and tested for their solubility. The reaction products were characterized in the solid state by differential scanning calorimetry (DSC), which provided some evidence about complexation. Additional evidence was obtained by recording the 1H NMR spectra of aqueous solutions of these same products. The study of phase solubility was based on the Higuchi & Connors method and showed an impressive enhancement of the miscibility of furosemide with water. In fact, a 11 fold increase of the drug solubility was recorded for the inclusion complex, in the first stages of dissolution. The experimental results of this work show that 2-Hydroxypropyl-beta-Cyclodextrin is an efficient complexation agent for furosemide. Combination of those two substances can be carried out by simple techniques, providing easy control and the obtained inclusion complex is characterized by acceptable water solubility and increased dissolution rate.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2001

Synthesis and molecular recognition of novel oligo(ethylenediamino) bridged bis(beta-cyclodextrin)s and their copper(II) complexes: enhanced molecular binding ability and selectivity by multiple recognition.

Four bridged bis(beta-cyclodextrin)s tethered by different lengths of oligo(ethylenediamine)s have been synthesized and their inclusion complexation behavior with selected substrates elucidated by circular dichroism spectroscopy and fluorescence decay. In order to study their binding ability quantitatively, inclusion complexation stability constants with four dye guests, that is, brilliant green (BG), methyl orange (MO), ammonium 8-anilino-1-naphthalenesulfonic acid (ANS), and sodium 6-(p-toluidino)-2-naphthalenesulfonate (TNS), have been determined in aqueous solution at 25 degrees C with spectrophotometric, spectropolarimetric, or spectrofluorometric titrations. The results obtained indicate that the two tethered cyclodextrin units might cooperatively bind to a guest, and the molecular binding ability toward model substrates, especially linear guests such as TNS and MO, could be extended. The tether length plays a crucial role in the molecular recognition, the binding constants for ANS and TNS decrease linearly with an increase in the tether length of dimeric cyclodextrin. The Gibbs free energy changes (-deltaGo) for the unit increment per ethylene are 0.99 kJ mol(-1) for ANS and 0.44 kJmol(-1) for TNS, respectively. On the other hand, the presence of a copper(II) ion in metallobis(beta-cyclodextrin)s oligo(ethylenediamino) tethers enhances not only the original binding ability, but also the molecular selectivity through triple or multiple recognition, as compared with the parent bis(beta-cyclodextrin)s.

Journal Article↗
PubMed2001

Cooperative multipoint recognition of organic dyes by bis(beta-cyclodextrin)s with 2,2'-bipyridine-4,4'-dicarboxy tethers.

A series of novel 6,6'-bis(beta-cyclodextrin)s linked by 2,2'-bipyridine-4,4'-dicarboxy tethers; that is, 2,2'-bipyridine-4,4'-dicarboxy-bridged bis(6-O-beta-cyclodextrin) (2) and N,N'-bis(2-aminoethyl )-2,2'-bipyridine-4,4'-dicarboxamide-bridged (3), N,N'-bis(5-amino-3-azapentyl)-2,2'-bipyridine-4,4'-dicarboxamide-bridged (4) and N,N'-bis(8-amino-3,6-diazaoctyl)-2,2'-bipyridine-4,4'-dicarboxamide-bridged bis(6-amino-6-deoxy-beta-cyclodextrin) (5), has been synthesized as cooperative multipoint-recognition receptor models. The inclusion complexation behavior of 2-5 with organic dyes; that is, ammonium 8-anilino-1-naphthalenesulfonate, Brilliant Green, Methyl Orange, Acridine Red, and Rhodamine B, has been investigated in aqueous phosphate buffer solutions (pH 7.20) at 25 degrees C by means of ultraviolet, fluorescence, and circular dichroism spectrometry as well as by fluorescence lifetime measurements. The spectral titrations gave the complex stability constants (Ks) and Gibbs' free energy changes (deltaG degrees) for the inclusion complexation of 2-5 with the organic dyes and other thermodynamic parameters (deltaH degrees and deltaS degrees) for the inclusion complexation of 2-4 with the fluorescent dyes Acridine Red and Rhodamine B. Bis(beta-cyclodextrin)s 2-5 displayed higher binding abilities toward most of the examined dye molecules than native beta-cyclodextrin 1; this is discussed from the viewpoints of the size/shape-fit concept, the induced-fit interaction, and cooperative, multipoint recognition by the bridging chain and the dual hydrophobic cavities. Thermodynamically, the inclusion complexation of 2-4 with Acridine Red is totally enthalpy driven with a negative or minor positive entropic contribution, but the inclusion complexation with Rhodamine B is mainly entropy-driven with a mostly positive, but occasionally negative, enthalpic contribution; in some cases this determines the complex stability.

Journal Article↗
PubMed2002

Photoinduced electron transfer between metal-coordinated cyclodextrin assemblies and viologens.

Two novel tris(bipyridine)ruthenium(II) complexes bearing two and six beta-cyclodextrin binding sites on their ligands have been synthesised and characterised. Complex 1, bearing two cyclodextrins, adopts a conformation in aqueous solution where parts of the aromatic ligands are self-included into the cyclodextrin moieties. This results in a loss of symmetry of the complex and gives rise to a much more complicated 1H NMR spectrum than expected. Photophysical studies indicate that the appended cyclodextrins protect the luminescent ruthenium core from quenching by oxygen, which results in longer excited state lifetimes and higher emission quantum yields compared with the reference compound, the unsubstituted ruthenium tris(bipyridine). Inclusion of suitable guests such as dialkyl-viologens leads to a quenching of the luminescence of the central unit. In these supramolecular donor-acceptor dyads an efficient photoinduced electron transfer from the excited ruthenium moiety (the donor) to the viologen unit (the acceptor) is observed. The alkyl chain length of the acceptor plays an important role on the binding properties; when it exceeds a certain limit the binding becomes strong enough for electron transfer to occur. Interestingly, a viologen with only one long alkyl tail instead of two shows no efficient quenching; this indicates that cooperative interactions between two cyclodextrins binding one viologen are essential to raise the binding constant of the supramolecular dyad.

Journal Article↗
PubMed1978

Phase solubility analysis and PMR study of complexing behavior of dinoprostone with beta-cyclodextrin in water.

The mechanism of inclusion compound formation by dinoprostone (prostaglandin E2) with beta-cyclodextrin was studied by phase solubility analysis and PMR spectroscopy. As indicated by the linear increase of aqueous solubility of dinoprostone with beta-cyclodextrin concentration, some types of molecular interactions definitely exist between dinoprostone and the complexing ligands. The temperature dependence of a 1:1 complex formation constant yielded the following thermodynamic data at 20 degrees : deltaG degrees = -4.11 kcal/mole, deltaH degrees = 7.20 kcal/mole, and deltaS degrees = 10.5 e.u. Since water was the solvent system, these parameters appear to be largely determined by solvent reorganization through hydrogen bonding rather than solely by the binding of desolvated free dinoprostone and beta-cyclodextrin entities. PMR data indicate that dinoprostone is included within the cavity and also interacts with protons on the exterior of the beta-cyclodextrin molecule. A model consisting of a 1:1 complex, in which a dinoprostone molecule is partially included within the cavity and the remainder of the molecule extends around the edge of the opening of the cavity to the exterior of the beta-cyclodextrin molecule, is proposed as the most probable structure of this inclusion compound.

Chemical Phenomena↗
PubMed1983

Cyclodextrin glycosyltransferases from Klebsiella pneumoniae M 5 al and Bacillus macerans: quantitative analysis by high-performance liquid chromatography of the (1 leads to 4)-alpha-D-glucopyranosyl transfer-products from some linear and cyclic substrates.

The analysis of the (1 leads to 4)-alpha-D-glucopyranosyl transfer-products from some linear and cyclic substrates by quantitative h.p.l.c. illuminated the mode of action of the cyclodextrin glycosyltransferases [1 leads to 4)-alpha-D-glucan:[(1 leads to 4)-alpha-D-glucopyranosyl]transferase (cyclising), EC 2.4.1.19) from Klebsiella pneumoniae M 5 al and Bacillus macerans. D-Glucopyranosyl transfer, obligatory for maltose (poor substrate), was preferred for maltotriose (good substrate). The lengths of linear disproportionation-products increased with the lengths of the linear substrates. Cyclodextrins were produced from maltotriose and maltopentaose, but not from maltose. The cyclodextrins were substrates in the absence of acceptors. The cyclodextrin transformation started without the formation of detectable amounts of linear transfer-products. The cyclodextrin composition of long-term digests was nearly the same with all the cyclic substrates, cycloheptaamylose being the main cyclic compound. The linear carbohydrate was uniformly distributed from maltose up to at least maltononaose. The enzyme from Bacillus macerans was the least active, but long-term digests yielded results comparable to those obtained with the enzyme from Klebsiella pneumoniae M 5 al.

Bacillus↗
PubMed1999

Cyclodextrins in nasal drug delivery.

Nasal drug delivery is an attractive approach for the systemic delivery of high potency drugs with a low oral bioavailability due to extensive gastrointestinal breakdown and high hepatic first-pass effect. For lipophilic drugs nasal delivery is possible if they can be dissolved in the dosage form. Peptide and protein drugs often have a low nasal bioavailability because of their large size and hydrophilicity, resulting in poor transport properties across the nasal mucosa. Cyclodextrins are used to improve the nasal absorption of these drugs by increasing their aqueous solubility and/or by enhancing their nasal absorption. With several cyclodextrins very efficient nasal drug absorption has been reported, but also large interspecies differences have been found. Studies concerning the safety of cyclodextrins in nasal drug formulations demonstrate the non-toxicity of the cyclodextrins and also clinical data show no adverse effects. Therefore, some cyclodextrins can be expected to become effective and safe excipients in nasal drug delivery.

Journal Article↗
PubMed1999

Cyclodextrins in ophthalmic drug delivery.

Most ocular diseases are treated by topical drug application in the form of aqueous eye drop solutions. Recent studies have shown that cyclodextrins are useful additives in ophthalmic formulations for increasing the aqueous solubility, aqueous stability and bioavailability of ophthalmic drugs, and to decrease drug irritation. However, these studies have also shown that there are some basic differences between ophthalmic administration of cyclodextrins and administration of cyclodextrins via other routes. These differences have induced some limitations in the ophthalmic application of these most recently developed pharmaceutical excipients. The objective of this review is to summarize recent findings and applications of various cyclodextrins in ophthalmic drug delivery. Their mechanism of action in aqueous eye drop formulations is also discussed. Finally, the formulation of a couple of cyclodextrin containing eye drop solutions is described.

Journal Article↗
PubMed1995

Site-directed mutations in tyrosine 195 of cyclodextrin glycosyltransferase from Bacillus circulans strain 251 affect activity and product specificity.

Tyrosine 195 is located in the center of the active site cleft of cyclodextrin glycosyltransferase (EC 2.4.1.19) from Bacillus circulans strain 251. Alignment of amino acid sequences of CGTases and alpha-amylases, and the analysis of the binding mode of the substrate analogue acarbose in the active site cleft [Strokopytov, B., et al. (1995) Biochemistry 34, (in press)], suggested that Tyr195 plays an important role in cyclization of oligosaccharides. Tyr195 therefore was replaced with Phe (Y195F), Trp (Y195W), Leu (Y195L), and Gly (Y195G). Mutant proteins were purified and crystallized, and their X-ray structures were determined at 2.5-2.6 angstrum resolution, allowing a detailed comparison of their biochemical properties and three-dimensional structures with those of the wild-type CGTase protein. The mutant proteins possessed significantly reduced cyclodextrin forming and coupling activities but were not negatively affected in the disproportionation and saccharifying reactions. Also under production process conditions, after a 45 h incubation with a 10% starch solution, the Y195W, Y195L, and Y195G mutants showed a lower overall conversion of starch into cyclodextrins. These mutants produced a considerable amount of linear maltooligosaccharides. The presence of aromatic amino acids (Tyr or Phe) at the Tyr195 position thus appears to be of crucial importance for an efficient cyclization reaction, virtually preventing the formation of linear products. Mass spectrometry of the Y195L reaction mixture, but not that of the other mutants and the wild type, revealed a shift toward the synthesis (in low yields) of larger products, especially of beta- and gamma- (but no alpha-) cyclodextrins and minor amounts of delta-, epsilon-, zeta- and eta-cyclodextrins.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Three histidine residues in the active center of cyclodextrin glucanotransferase from alkalophilic Bacillus sp. 1011: effects of the replacement on pH dependence and transition-state stabilization.

Cyclodextrin glucanotransferase (CGTase) catalyzes the formation of cyclodextrins from amylose through an intramolecular transglycosylation reaction. On the basis of the three-dimensional structures of CGTases three histidine residues, which are conserved between CGTases and alpha-amylases, are located at the active center and are proposed to constitute the substrate binding sites. The three histidine residues (His-140, His-233, and His-327) of CGTase from alkalophilic Bacillus sp. 1011 were individually replaced by site-directed mutagenesis to probe their roles in catalysis. Asparagine-replaced CGTases (H140N-, H233N-, and H327N-CGTase) retained cyclization activity but had altered production ratios of alpha-, beta-, and gamma-cyclodextrin. Replacement of histidine by asparagine residues strongly affected the kcat for beta-cyclodextrin-forming, coupling, and hydrolyzing activities, whereas it barely affected the Km values. The activation energies for alpha-cyclodextrin hydrolysis were increased more than 12 kJ/mol by the replacement. Furthermore, the Ki values of acarbose, which is thought to be a transition-state analog of glycosidase catalysis, were 2-3 orders of magnitude larger in asparagine-replaced CGTases than that in wild-type CGTase. Therefore, the three histidine residues participate in the stabilization of the transition state, whereas they participate little in ground-state substrate binding. H327N-CGTase had decreased activity over an alkaline pH range, indicating that His-327 is important for catalysis over an alkaline pH range.

Acarbose↗
PubMed2006

Entropy-controlled supramolecular photochirogenesis: enantiodifferentiating Z-E photoisomerization of cyclooctene included and sensitized by permethylated 6-O-modified beta-cyclodextrins.

Permethylated 6-O-modified beta-cyclodextrins 2a-2d were synthesized as novel photosensitizing hosts with a flexible skeleton. Circular dichroism (CD) and 2D NMR spectral examinations of benzoate 2a revealed that the benzoate moiety is deeply included into its own cavity in aqueous solution. Upon addition of (Z)-cyclooctene (1Z) to a 50% aqueous methanol solution of 2a at 25 degrees C, the benzoate moiety of 2a was gradually excluded from the cavity as indicated by the CD spectral changes; the Job's plot revealed the formation of a 1:1 complex of 2a with 1Z. The binding constants for the complexation of 1Z by 2a were determined by CD spectral titration in 50% aqueous methanol at various temperatures. The van't Hoff analysis of the obtained data afforded the thermodynamic parameters (DeltaH degrees = -3.1 kJ mol(-1), DeltaS degrees = 48.5 J mol(-1) K(-1)), demonstrating the entropy-driven complexation by the permethylated cyclodextrin. This is in sharp contrast to the complexation of 1Z by nonmethylated beta-cyclodextrin benzoate that is driven by enthalpy (DeltaH degrees = -31.8 kJ mol(-1) and DeltaS degrees = -51.1 J mol(-1) K(-1)). Upon supramolecular photosensitization with 2a-2d, 1Z isomerized to the (E)-isomer (1E) in moderate enantiomeric excesses (ee's), which however displayed significant temperature dependence with accompanying switching of the product's chirality in an extreme case. Such dynamic behavior of ee is very different from that reported for the photosensitization with nonmethylated cyclodextrin benzoate, where the product's ee is controlled by host occupancy. Eyring treatment of the ee obtained at various temperatures (<0 degrees C) gave the differential activation parameters for the enantiodifferentiation process occurring in the supramolecular exciplex, revealing the crucial role of entropy, as indicated by the DeltaDeltaS(++) value changing dynamically from +4 to -24 J K(-1) mol(-1). The origin of the contrasting behavior of permethylated versus nonmethylated cyclodextrin hosts is inferred to be the conformational flexibility of the former host, which enables the entropy-driven guest complexation in the ground state and the entropy-controlled enantiodifferentiation in the excited state.

Journal Article↗
PubMed1999

Molecular Recognition Studies on Supramolecular Systems. 22. Size, Shape, and Chiral Recognition of Aliphatic Alcohols by Organoselenium-Modified Cyclodextrins.

A novel cyclodextrin derivative, mono[6-(p-methoxyphenylseleno)-6-deoxy]-beta-cyclodextrin (2), has been synthesized and characterized by elemental analysis and mass, FT-IR, and (1)H NMR spectroscopy. The stability constants (K(S)) of the inclusion complexation of 2 and mono[6-(p-tolylseleno)-6-deoxy]-beta-cyclodextrin (3) with a series acyclic and cyclic alcohols have been determined in phosphate buffer solution (pH 7.20) at 25 degrees C by using the circular dichroism spectral titration method. Although the stability constants obtained for the inclusion complexation of 2 and 3 with aliphatic alcohols are generally smaller than those for native beta-cyclodextrin, the modified cyclodextrins can recognize both the size and chirality of the guest molecules. Interestingly, the complex stability constants (log K(S)), or the Gibbs free energy change (-DeltaG degrees ), increase linearly with increasing number of carbon atoms in the guest molecule (N(C)), irrespective of the topological differences of acyclic, cyclic, and bicyclic guests. The unit increment of complex stability per methylene (-dDeltaG degrees /dN(C)) is not appreciably affected by the difference of the host's substituent but is a critical function of the guest topology, affording distinctly different -dDeltaG degrees /dN(C) values of 2.4 and 2.9 kJ mol(-)(1) for alkanols and cycloalkanols, respectively. In the complexation of chiral guests with 2 and 3, the observed enantioselectivities, as measured by the stability difference (DeltaDeltaG degrees ), are mostly in the range of 1-2 kJ mol(-)(1).

Journal Article↗