Cyclodextrins In Aqueous Solution Research Articles

Changes in the reactivity of the fluorescent reagents carbazole-9-carbonyl chloride and 9-carbazolylacetic acid in the presence of cyclodextrins

Carbazole-9-carbonyl chloride (C9CC) and 9-carbazolylacetic acid (9CAA) were selected as model fluorescent reagents. The effect of different chemically modified cyclodextrins (CDs) added to the aqueous solutions of these reagents was studied in water and in buffered aqueous solutions at pH 4.5 and 8.8. The CDs employed were 2-hydroxypropyl-β-cyclodextrin (HP-βCD), 2,3-di-O-methyl-β-cyclodextrin (DM-βCD) and 2,3,6-tri-O-methyl-β-cyclodextrin (TM-βCD). The inclusion of these reagents inside the cavities of the CDs was verified and this process can affect the derivatization reaction because CDs can modify the reactivity of the guest molecules. The basic conditions necessary for the derivatization reaction between C9CC and amines lead to the formation of carbazole anion through hydrolysis followed by decarboxylation. In the presence of CDs, the hydrolysis-decarboxylation of carbazole-9-carbonyl chloride is faster than in buffered aqueous homogeneous solutions. The behaviour observed for these reagents in aqueous solutions of CDs was compared to the one observed in basic ethanolic solutions. These changes are particularly noticeable in the case of 2,3-di-O-methyl-β-CD and 2-hydroxypropyl-β-CD. The characteristics of the fluorescent reagents are compared to carbazole and 9-methylcarbazole as model compounds.

Cyclodextrin effects on physical–chemical properties of novocaine

The UV-vis absorption and the fluorescence emission spectra of novocaine were analysed in aqueous cyclodextrin (CD) solutions. Either the absorbance read at λmax 290 nm or the fluorescence emission intensity at λems 346 nm increase in the presence of both α- and β-CD due to the formation of 1:1 inclusion complexes. The lower polarity of the CD-cavity sensed by the included drug enhances the emitted fluorescence; in fact, the same effect was observed in aqueous mixtures of acetonitrile, dioxane, or dimethylsulfoxide. The inclusion complex formation between the monocation of novocaine and CDs diminishes the electrical conductance of aqueous solutions of novocaine hydrochloride (NoHCl). Both the nitrosation reaction in aqueous acid medium and the ester hydrolysis in alkaline medium are retarded in the presence of CDs. The strongest effect was observed with β-CD as a consequence of the higher stability inclusion complex.

Interaction of Omeprazole with a Methylated Derivative of β-Cyclodextrin: Phase Solubility, NMR Spectroscopy and Molecular Simulation

Cyclodextrins are known to be good solubility enhancers for several drugs, improving bioavailability when incorporated in pharmaceutical formulations. In this work we intend to assess and characterize the formation of inclusion complexes between omeprazole (OME) and a methylated derivative of beta-cyclodextrin, methyl-beta-cyclodextrin (MbetaCD). A comparison with results obtained from the most commonly used natural cyclodextrin, beta-cyclodextrin (betaCD) is also presented in most cases. The interaction of OME with the mentioned cyclodextrins in aqueous solutions was studied by phase solubility studies, 1D (1)H and 2D rotating frame nuclear overhauser effect NMR spectroscopy (ROESY) and Molecular Dynamics. The solubility of OME was significantly increased by formation of inclusion complexes with each cyclodextrin. Phase solubility studies and continuous variation plots revealed that OME forms an inclusion complex in a stoichiometry of 1:1 with both cyclodextrins. (1)H NMR and ROESY spectra of the inclusion complexes indicated that the benzimidazole moiety is included within the cyclodextrins cavities. Molecular dynamics showed that OME is more deeply included in the MbetaCD than in betaCD cavity, in agreement with a larger apparent stability constant (K (S)) obtained for the inclusion complex with MbetaCD. MbetaCD proved to be an efficient enhancer of OME solubility, thus possessing characteristics for being an useful excipient in pharmaceutical formulations of this drug.

Encapsulation of 6-Hydroxyquinoline in Heptakis(2,6-di-O-methyl)-β-cyclodextrin

Cyclodextrins have attracted long-standing interests in the field of artificial catalysts. Their cone-shaped cages consist of α,D-glucose subunits and possess nonpolar cavities with polar rims containing primary hydroxyl and secondary methoxy groups. Cyclodextrins are soluble in water and their hydrophobic interiors are capable of sequestering a variety of polar and nonpolar compounds, controlling the chemistry of reactive molecules. Three different types of water are generally assumed to exist in aqueous cyclodextrin solutions: water inside the cavity, water near the rim, and bulk water. A number of studies have reported the effects of micelles and cyclodextrins on proton transfer to shed light on the influence of lipophilic environment. Proton transfers of hydroxyquinolines having two prototropic groups of enol and imine in a molecule have been extensively explored. The excited-state proton transfer of 7-hydroxyquinoline (7HQ) in the molecular cage of βcyclodextrin or heptakis(2,6-di-O-methyl)-β-cyclodextrin (CD) has also been studied. The anionic intermediate during the excited-state proton transfer of 7HQ forms slower but decays faster in β-cyclodextrin cages than in water. However, the fluorescence spectral overlaps of normal molecule, enol-deprotonated anion, and imine-protonated and enol-deprotonated tautomer at S1, as well as the low solubility in water and the low association constant of βcyclodextrin with 7HQ, make the excited-state proton transfer kinetics of 7HQ very complex to require a sophisticated analysis. This has led us to investigate the encapsulation of 6-hydroxyquinoline (6HQ) in the molecular cage of CD in this work. CD is a derivative of β-cyclodextrin with a greatly improved solubility in water, encapsulating a predominant fraction of 6HQ to form host-guest complexes. The observed H chemical shifts of CD in water decrease

Study on the aggregation and electrochemical properties of Rose Bengal in aqueous solution of cyclodextrins

The interactions of Rose Bengal (RB) with α-cyclodextrin (α-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxypropyl-γ-cyclodextrin (HP-γ-CD), heptakis(2,3,6-tri- O-methyll)-β-cyclodextrin (TM-β-CD) were studied in aqueous solutions of 0.1 M KClO 4 and 0.1 M LiClO 4 by vis absorption, fluorescence spectroscopy as well as electrochemical measurements at 298 K. The spectrophometric results indicate that RB is included in all β- and γ-CDs forming complexes with a stoichiometry 1:1 whose stability is slightly higher in KClO 4 than in LiClO 4 solutions. The complex stability constants determined for salt-containing CD solutions are lower than those for water solutions. The complexation of RB with β- and γ-CD and the differences between the complexes obtained in the presence of the two salts were confirmed by an electrochemical study.

Extraction of toluene, o-xylene from heptane and benzyl alcohol from toluene with aqueous cyclodextrins

The separation of aromatic compounds (toluene and o-xylene) from heptane and of benzyl alcohol from toluene with aqueous solutions of cyclodextrins has been experimentally investigated, because cyclodextrins and its derivatives can selectively incorporate several organic compounds, whereas the separation of the aqueous solution of complexed cyclodextrins from the organic feed is simple. Cyclodextrins are not soluble in organic liquids, but cyclodextrin derivatives are highly soluble in water. Hydroxypropyl-β-cyclodextrins with different degrees of substitution and methylated β-cyclodextrin were selected for the extraction of toluene and o-xylene from heptane. Hydroxypropyl-β-cyclodextrin (two different substitution degrees) and hydroxypropyl-α-cyclodextrin were selected for the extraction of benzyl alcohol from toluene. The liquid–liquid distribution experiments were carried out at room temperature. Toluene and o-xylene form 1:1 complexes with different cyclodextrins and heptane can form 1:1 to 1:3 complexes. Benzyl alcohol forms 1:3 complexes with hydroxypropylated cyclodextrins. The models developed describe the experimental data reasonably well, considering the large deviations in the analyses. Aqueous cyclodextrin solutions are not feasible for the separation of aromatic components from aliphatic hydrocarbons, due to low distribution ratios of toluene (0.05) and o-xylene (0.023) between the aqueous and organic phase. With high distribution ratios of benzyl alcohol, between 0.3 and 2.2 depending on the CD concentration (at a solvent-to-feed ratio of 1) and a benzyl alcohol/toluene selectivity of at least 100, aqueous hydroxypropylated cyclodextrin solutions have sufficient potential for extracting benzyl alcohol from toluene.

Evaluation of cyclodextrin solubilization of drugs

The most common stoichiometry of drug/cyclodextrin complexes is 1:1, i.e. one drug molecule forms a complex with one cyclodextrin molecule, and the most common method for stoichiometric determination during formulation studies is the phase-solubility method. However, in recent years it has becoming increasingly clear that solubilizing effects of cyclodextrins are frequently due to the formation of multiple inclusion and non-inclusion complexes. The aqueous solubility of 38 different drugs was determined in pure aqueous solution, aqueous buffer solutions and aqueous cyclodextrin solutions, and the apparent stability constant ( K 1:1) of the 1:1 drug/cyclodextrin complexes calculated by the phase-solubility method. For poorly soluble drugs (aqueous solubility <0.1 mM) the intrinsic solubility ( S 0) is in general much larger than the intercept of the phase-solubility diagram ( S int) resulting in non-linearity of otherwise linear ( A L-type) phase-solubility diagram. This can lead to erroneous K 1:1-values. A more accurate method for determination of the solubilizing efficiency of cyclodextrins is to determine their complexation efficiency (CE), i.e. the concentration ratio between cyclodextrin in a complex and free cyclodextrin. CE is calculated from the slope of the phase-solubility diagrams, it is independent of both S 0 and S int, and more reliable when the influences of different pharmaceutical excipients on the solubilization are being investigated.

Cyclodextrins in Nitrosation Chemistry: New Insights of the NO-Transfer Processes

The chemistry of nitroso compounds has received considerable attention from several directions in recent years. This review will focus on describing the practical aspects, and current and potential applications of cyclodextrins in mechanistic studies of NO-transfer processes. The first section describes some physicochemical aspects of aqueous cyclodextrin solutions that are of crucial importance in relation to mechanistic studies. The next section analyses all types of information that can be obtained from different nitrosation reaction patterns either in acid or basic media, by paying special attention to the nitrosatable substrates and nitrosating agents. Relevant aspects concerning the biological activity of nitroso compounds is also included. The last section covers a detailed analysis of the effects of cyclodextrins on reactions undergone by nitroso compounds, such as hydrolysis or NO-transfer, as well as on reactions that produce nitroso compounds.

Inclusion complexes of spin-labeled indoles with cyclodextrins in aqueous solutions

Guest-host complexes of β- and γ-cyclodextrins (CDs) with two spin-labeled indole derivatives having the same molecular weights but different structures were studied by EPR spectroscopy in aqueous solutions and semiempirical quantum-chemical calculations of these systems were carried out. In the presence of CD the polarity of the NO group environment decreases and the rotational correlation time (τ) of guest molecules increases. Both indole derivatives form 1 : 1 complexes with γ-CD, the binding constants of the complexes being different more than twice. Simulation of EPR spectra made it possible to determine the indole ring orientation relative to the plane of the host molecule (at angles in the range 30–60°) and the rotational diffusion coefficients of the complexes, which corresponded to the hydrodynamic volume of one γ-CD molecule. In contrast to the complexes with γ-CD the rotational correlation times, τ, of the complexes with β-CD correspond to a hydrodynamic volume which much exceeds the volume of a single β-CD molecule. The complexes with β-CD are also characterized by more hydrophobic environment for guest molecules and absence of spin exchange with Ni2+ ions in the aqueous solution. There results are consistent with a dimeric structure of β-CD in the complex and with the orientation of the long axis of the guest molecule along the dimer axis. The energies and geometric parameters were calculated for all complexes by the PM3 method with a conventional set of parameters. The optimized energetically stable structures of the 1 : 1 complexes with γ-CD and of the 1 : 2 complexes with β-CD are consistent with experimental data.

Cyclomaltooligosaccharide (cyclodextrin)-assisted enantiomeric recognition of benzo[ lmn][3,8]phenanthroline-derived amino acids

Formation of self-assembly molecular aggregates and cyclomaltooligosaccharide (cyclodextrin) molecular aggregates with benzo[ lmn][3,8]phenanthroline-derived amino acids is presented. The nature of the molecular aggregates was studied by negative-ion electrospray-ionization mass spectrometry (ESIMS). The enantiomeric recognition was demonstrated by NMR enantiomeric discrimination of the amino acid derivatives in aqueous solutions of cyclodextrins.

Interaction of naproxen with ionic cyclodextrins in aqueous solution and in the solid state

The possible role of the cyclodextrin charge in the interaction with an acidic drug such as naproxen (p K a 4.8) has been evaluated. Sulfobutylether-ß-cyclodextrin (SBE-ßCyd) and trimethylammonium-ß-cyclodextrin (TMA-ßCyd) were selected as, respectively, anionically and cationically charged carriers and their performance was compared with that of the parent ß-cyclodextrin (ßCyd) and of its methyl-derivative (MeßCyd) previously found as the best partner for the drug. Interactions in solution were investigated by phase-solubility, fluorescence and circular dichroism analyses. Equimolar drug–carrier products prepared by different techniques (blending, cogrinding, sealed-heating, colyophilization) were characterized by differential scanning calorimetry and X-ray powder diffractometry and tested for drug dissolution properties. Anionic charges of SBE-ßCyd did not negatively influence interactions in unbuffered aqueous solutions (pH ≈5) with the acidic drug. In fact, it was a very effective carrier, exhibiting solubilizing and complexing properties considerably better than the parent ßCyd and comparable to those of MeßCyd. On the contrary, the positive charges of TMA-ßCyd did not favour interactions with the counter-ionic drug (despite the presence of about 60% ionised drug) and it was less efficacious also than native ßCyd. Therefore, the role of the Cyd charge on the complexing and solubilizing properties towards naproxen was not important whereas other factors, such as steric hindrance effects and favourable hydrophobic interactions were significant in determining the drug affinity for the Cyd inclusion. Solid state studies evidenced similar amorphizing properties of both charged Cyds towards naproxen. On the other hand, dissolution tests, in agreement with solution studies, showed that all products with SBE-ßCyd exhibited significantly better dissolution properties than the corresponding ones with TMA-ßCyd. A clear influence of the preparation method of drug–Cyd solid systems on the performance of the end product was also observed. Colyophilization was the most effective technique, followed by the cogrinding one. Colyophilized product with SBE-ßCyd allowed a 10-times increase in drug dissolution efficiency (D.E.) (with respect to the five-times increase obtained with the corresponding coground product) and a reduction of t 50% from about 60 min (for the coground product) to less than 2 min.

Spectroscopic and electrochemical study of Rose Bengal in aqueous solutions of cyclodextrins

The interaction of Rose Bengal (RB) in aqueous solution of LiClO4 0.1 M with α-cyclodextrin (α-CD), hydroxypropyl-β-cyclodextrins (HP-β-CD) and hydroxypropyl-γ-cyclodextrins (HP-γ-CD) were studied by spectrophotometric measurements. The presence of Induced Circular Signals and the results of the analysis of the modifications in the absorbance spectra of RB produced by the presence of CDs in solution indicate that RB forms inclusion complexes only with HP-β-CD and with HP-γ-CD.

Formation of poly(ethylene glycol) inclusion complexes in aqueous solutions of mixed cyclodextrins

AbstractEven though the addition of modified cyclodextrins (modified CDs) accelerates the precipitation in aqueous solutions of poly(ethylene glycol) (PEG) and α‐cyclodextrin (α‐CD) the final amount of formed solid complex remains unchanged, with no significant presence of modified CDs detected by MALDI‐TOF mass spectrometry. Thus unsuitability of kinetic turbidity measurements for determination of binding parameters was confirmed. On the other hand, theoretical calculations based on a model of a chain of freely accessible binding sites demonstrated that the results do not necessarily contradict the finding that individual modified CD molecules can thread onto PEG chains with the efficiency comparable to that of natural (unmodified) α‐CD.

Preparation of inclusion complex between polyaniline and β‐cyclodextrin in aqueous solution

AbstractTwo routes have been developed inorder to prepare an inclusion complex of polyaniline (PANI) and β‐cyclodextrin (βCyD). The first route was to in situ polymerize N‐phenyl‐1,4‐phenylenediamine (PPD) which was encapsulated in βCyD in advance. The formation of an inclusion complex was confirmed by UV‐vis, circular dichroism (CD), and NMR spectra. It was found that the synthesized complex was readily dissolved in a range of solvents due to the solubility of βCyD. In these solvents, PANI was well encapsulated by βCyD with some conformation change in the chain of PANI, which was proved by the CD spectra of PANI. The second route involved preparing the inclusion complex by post‐encapsulation of PANI emeraldine base (EB) into βCyD in aqueous solution at room temperature. The encapsulation of EB into βCyD was confirmed by FT‐IR and UV‐vis spectra. The band shift in UV‐vis spectra indicated that the inclusion complexation was a gradual process, and the change in the chain conformation of PANI was also observed after it was encapsulated into βCyD. Copyright © 2003 John Wiley &amp; Sons, Ltd.

Fabrication and Characterization of Gold Nanoparticles by Femtosecond Laser Ablation in an Aqueous Solution of Cyclodextrins

Gold nanoparticles were produced by femtosecond laser ablation of a gold metal plate in an aqueous solution of α-cyclodextrin (CD), β-CD, or γ-CD. The gold nanoparticles exhibited the UV−vis absorption spectrum with a maximum absorption band at 520 nm, similar to that of gold nanoparticles chemically prepared in a solution. The size distribution of the nanoparticles measured by transmission electron microscopy (TEM) shifted to a drastically smaller size of ∼2−2.4 nm and narrower size distribution of less than 1−1.5 nm fwhm with an increase in the concentration of cyclodextrins. Both the particle size and size distribution were also dependent on the type of cyclodextrins used in aqueous solution. In particular, the gold colloids resulting from ablation in 10 mM β-CD were conspicuously stable under aerobic conditions without any protective agent present. CDs formed an inclusion complex with ablated atoms to reduce the total concentration of embryonic nanoparticles formed in the plume CDs, as evident by Raman spectroscopy. The consecutive particle growth due to the mutual coalescence between nanoclusters and their neighboring free gold atoms was severely limited in the presence of CDs.

The Curious World of Polypseudorotaxanes: Cyclodextrins As Probes of Water Structure

Polymeric chains and cyclodextrins in water produce supramolecular host−guest assemblies called polypseudorotaxanes (PPR). The guest polymers thread the host cyclodextrin molecules such as beads on a string. Once formed, these molecular necklaces aggregate into larger assemblies that reveal themselves in a significant increase of turbidity. This astonishing phenomenon is enthalpically driven and its kinetics depends strongly on choice of reactants, concentration, solvent nature, addition of cosolutes, and temperature. We have studied the effects on PPR assembly induced by temperature, surface nature, and solute. These studies provide some insights into the cooperative mechanisms behind the formation of these organized structures. Hydrophilic surfaces (e.g., glass), low temperatures, and high concentrations of host molecules all favor the threading process. The addition of sugars to the solution promotes the assembly process in a way that provides strong hints on the nature of aqueous solution structure. The highly specific effects induced by sugars and electrolytes mimic precisely those seen in bubble−bubble coalescence phenomena. They reflect the capacity of solutes to modify bulk solvent and solution structure. In agreement with previous observations, the experimental results can be explained by invoking the formation of pre-assembled, wormlike aggregates of cyclodextrins in aqueous solutions. Once formed, these worms instantly swallow the polymer chain.

Aggregation processes and photophysical properties of chlorophyll a in aqueous solutions modulated by the presence of cyclodextrins

In the present paper we report the preliminary results on the behaviour of chlorophyll a (Chl a), the main photosynthetic amphiphilic pigment of green plants, in water and aqueous solutions of cyclodextrins (α-cyclodextrin, hydroxypropyl-β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin). In particular our study was aimed to understand the influence of CDs on solubility and aggregation of Chl a in water and to get information on the interactions between different cyclodextrins and the pigment. The role played by different CDs in affecting the photoactivity of the chlorophyll, with particular attention to the quantum yield of the singlet oxygen production, has been also discussed. The study was carried out by using different spectroscopic (UV–Vis, fluorescence, circular dichroism, time resolved absorption and luminescence) and calorimetric (ITC) techniques.

A Spectroscopic and Molecular Modelling Study of the Nature of the Association Complexes of Nile Red with Cyclodextrins

The polarity-sensitive fluorescent dye Nile Red forms association complexes with various cyclodextrins in aqueous solution. The formation of such association complexes has a significant effect on the Nile Red fluorescence, with the largest effect being observed in γ-cyclodextrin solution. When γ-cyclodextrin is used to increase the Nile Red concentration in solution, the absorption spectrum shows a large blue shift indicating the formation of an inclusion complex, but surprisingly the Nile Red fluorescence is strongly suppressed. A proposed explanation for this observation involves the formation of 1:2 host:guest complexes, in which the Nile Red guests are included as relatively non-fluorescent dimers. When the solutions were prepared by adding γ-cyclodextrinto a near-saturated aqueous solution of Nile Red (so that 1:1 or 2:1 complexation shouldbe favoured), significant fluorescence enhancement was observed. Analysis of thefluorescence enhancement as a function of host concentration indicated the formationof 2:1 host:guest complexes in these solutions. However, electrospray mass spectroscopic studies show no evidence for the formation of any such inclusion complexes. Furthermore, molecular modelling shows that the formation of a complex involving full insertion of Nile Red in the γ-cyclodextrin cavity is not stable, and will quickly eject the Nile Red guest molecule. These modelling results suggest that an association complex involving capping (via the association of Nile Red parallel to the cavity opening, or by partial insertion into the cavity) of the γ-cyclodextrin cavity by one or two Nile Red molecules is much more likely.

Interactions of cholesterol with cyclodextrins in aqueous solution.

The interaction of cholesterol with several cyclodextrins (CDs) was investigated in water using solubility method. It was found that heptakis (2,6-di-O-methyl)-beta-CD (DOM-beta-CD) forms two types of soluble complex, with molar ratios of 1 : 1 and 1 : 2 (cholesterol : DOM-beta-CD), and neither a soluble nor insoluble complex is formed between cholesterol and alpha-CD, beta-CD, and gamma-CD, although a minor soluble complex formation was observed between cholesterol and 2-hydroxylpropyl-beta-CD. The thermodynamic parameters for 1 : 1 and 1 : 2 complex formation of cholesterol with DOM-beta-CD obtained from the changes in K with temperature are as follows: DeltaG degrees (1 : 1)=-11.6 kJ/mol at 25 degrees C (K(1 : 1)=1.09x10(2) M(-1)); DeltaH degrees (1 : 1)=-3.38 kJ/mol; TDeltaS degrees (1 : 1)=8.25 kJ/mol; DeltaG degrees (1 : 2)=-27.1 kJ/mol at 25 degrees C (K(1 : 2)=5.68x10(4) M(-1)); DeltaH degrees (1 : 2)=-3.96 kJ/mol; and TDeltaS degrees (1 : 2)=23.2 kJ/mol. The formation of the 1 : 2 complex occurred much more easily than that of the 1 : 1 complex. The driving force for 1 : 1 and 1 : 2 complex formation was considered to be mainly hydrophobic interaction. Also, based on the measurements of proton nuclear magnetic resonance spectra and studies with Corey-Pauling-Koltun atomic models, the probable structutures of the 1 : 2 complex were estimated.

New 1:1:1 complex with N-phenyl pyrrole and nano-cavities

Interesting patterns of complexation of N-phenyl pyrrole (PPR) with α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) separately and also in binary mixture of both types of cyclodextrins in aqueous solution are reported. PPR forms only one type of 1:1 complex with α-CD with pyrrole group inside the cavity. In β-CD two types of 1:1 complexes with opposite orientations were found to occur and estimation of such complexes has been made by simple new method. A new 1:1:1 complex (α-CD · PPR · β-CD) was observed for the first time. Bigger cavity seems to play a role in binary and ternary complexation.