Thermal analysis of cyclodextrins and their inclusion compounds

This review examines the literature concerning the thermal properties of natural and semisynthetic cyclodextrins and their inclusion compounds. Particular emphasis is given to recent results of investigations by thermal methods of the hydrated forms of cyclodextrins. The limitations and advantages of the applications of thermal analyses concerning water- and drug-cyclodextrin interactions are also discussed.     

Can cyclodextrins really improve the selectivity of extraction of BTEX compounds?

Solubility of BTEX compounds was determined in aqueous solutions of natural CDs (α-, β-, γCD) as well as of some industrial βCD derivatives (RAMEB, HPBCD, AcβCD) measured by UV photometry. From the phase solubility diagrams the complex association constants were determined. The βCD derivatives increased the solubility of individual monoaromatic compounds, depending on the structure of the guest molecule. We have found that RAMEB (randomly methylated βCD) and AcβCD (partially acetylated βCD) are the most effective solubilizers while the effect of natural CDs is not significant because the complexes precipitate from the solutions. Extraction experiments were performed to see how the complexation of components influences the extraction using a mixture modeling the composition of these pollutants in soil. We have found that although the soluble CD derivatives are not as selective as expected based on complex association constants, they increased the efficacy of extraction by 4–6 times. The reason of the low selectivity is that the concentration ratio of certain BTEX compounds in CD solutions is smaller than in water. CD derivatives seem to have an equalizing effect: the solubility of the least soluble p-xylene is improved in the highest extent, but that of benzene the least. This result, however, is an advantage in the application of these CD derivatives in soil remediation (the availability of each BTEX compounds will be enhanced).     

Stabilization of dyes against hydrolytic decomposition by the formation of inclusion compounds

The decomposition reactions of the dyes phenol blue and murexide were measured spectroscopically in acidic solution at different temperatures. From these reaction rates and their temperature dependence in the absence and presence of various hosts, the stability constants and the reaction enthalpies of the dye complexes with noncyclic dextrins, cyclodextrins and cucurbituril were calculated.-Cyclodextrin enhances the stability of phenol blue in acidic solution. This effect is even more pronounced with cucurbituril. Due to the molecular structure of murexide this dye cannot form inclusion complexes with hosts containing hydrophobic cavities.     

Supramolecular aggregations through the inclusion complexation of cyclodextrins and polymers with bulky end groups

Mono‐polyhedral oligomeric sillsesquioxane‐end capped poly(ε‐caprolactone) (mPPCL) can form inclusion complexes (ICs) with α‐ and γ‐cyclodextrins (CDs) but not with β‐CD. These CD ICs have been characterized with X‐ray diffraction, solid‐state ¹³C cross‐polarization/magic‐angle‐spinning NMR spectroscopy, ¹H NMR spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and scanning electron microscopy. The poly(ε‐caprolactone) (PCL) chain of mPPCL is included within the channel provided by the CDs to form a columnar, crystalline structure. The PCL/CD ratios determined by ¹H NMR spectroscopy for the ICs with α‐ or γ‐CDs are higher than the stoichiometries because of the steric hindrance of the bulky polyhedral oligomeric silsesquioxane chain end and result in a fraction of the ε‐caprolactone units free from complexation with the CDs. On the basis of these analyses, we propose some possible structures for these CD/mPPCL ICs. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 125–135, 2007     

Crystallization of zeolites as formation of inclusion compounds

We consider the process of crystallization of aluminosilica gels under hydrothermal conditions as formation of inclusion compounds. We show that the possibility and direction of crystallization of zeolites, like formation of other types of inclusion compounds, are determined by the principle of maximum utilization of space and the energy factor. We establish the limits on the variation in the packing density of water molecules and organic templates occluded within the zeolite cavities. Using the classical theory of crystal formation, we explain the interconnection established in this paper between the characteristics of the reaction mixture (the nature of the cations, the alkalinity, the water content) and the integral heat of hydration of the zeolite crystals formed upon hydrothermal treatment of aluminosilica gels. For the example of ZSM-5-type zeolites, we consider the combined effect of the geometric and energy factors on the process of zeolite formation.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 30, No. 3, pp. 130–142, May–June, 1994.     

Effects of water and alcohol on the formation of inclusion complexes of d-limonene and cyclodextrins

Abstract

Systematic studies have been carried out on the role of water and alcohol in the formation of inclusion complexes between d-limonene and α-, β- and γ-cyclodextrin (CD) by a micro-aqueous method. The inclusion complex was barely formed at zero water content for all CDs. Above the specific water content for each CD, formation of the inclusion complex correlated well with an equation which was derived on the autocatalytic assumption for the inclusion phenomenon. The inclusion complex correlated well with an equation which was derived on the autocatalytic assumption for the inclusion phrnomenon. The minimum water content, which was defined as 1% of the maximum concentration of the inclusion complex formed, coincided with the number of water molecules inside the cavity of the CD. In the presence of ethanol, a significant amount of the inclusion complex was formed for β- and γ-CD/limonene systems, particularly at lower moisture content. However, for α-CD the inclusion fraction decreased significantly in the presence of ethanol. This means that ethanol inhibits the formation of the inclusion complex between x-CD and d-limonene. For other linear alcohols, the formation of the inclusion complex between d-limonene and β-CD increased with decreasing alkyl chain length. This suggests that the more hydrophilic and the smaller (in molecular size) the alcohol is, the more enhanced is the inclusion of d-limonene to β-CD.     

Universality behaviour for polarity formation in channel-type inclusion compounds

A statistical investigation based on a Markov chain theory of polarity formation applied to channel-type inclusion compounds loaded with both dipolar A–π–D and non-polar N–π–N (N: A or D) guests is presented. The key parameters effecting polarity formation are identified and their effects are explored. A number of paradoxes are set out and an attempt to explain the mechanisms behind them is made: dependence of macroscopic polarity on orientational selectivity induced by intermolecular interactions, tuning of polarity through (i) the concentration of non-polar guest and (ii) growth temperature. An erratum to this article can be found at     

Modification of spin crossover behavior through solvent assisted formation and solvent inclusion in a triply interpenetrating three-dimensional network

The 3D coordination polymer [Fe(4ditz)3](PF6)2.solv consists of three interpenetrating infinite networks. There are cavities between iron atoms of different networks, which are partly filled with solvent molecules. With a change of the solvent used during synthesis from methanol to ethanol, the magnetic behavior of the materials changes. Both show an abrupt two-step spin crossover from low spin (S = 0) to high spin (S = 2) with the methanolate curve lying 7 K higher and showing a small hysteresis. Single crystal and powder diffraction studies show that they both have the same structure, but in powder form, the methanolate slowly loses methanol to finally leave about 0.075 MeOH/Fe. In comparison, the bigger ethanol remains at 0.25 EtOH/Fe. These results, in conjunction with thermodynamic data, strongly suggest that the differences in magnetic behavior are largely entropic in nature. Possible reasons for this are discussed.     

Solvent‐dependent formation of inclusion complexes between methylated cyclodextrins and biodegradable polymers

The inclusion complexes (ICs) of unmodified natural and methylated α‐cyclodextrins (CDs) with biodegradable polymers, polyethylene glycol and poly(ε‐caprolactone), were prepared by two methods, that is, the one using water and the other using chloroform as the solvent for the respective CDs. The ICs obtained were characterized by IR, WAXD, DSC, and ¹³C CP/MAS NMR. It was found that the possibility and the phenomena of IC formation could be varied with the degree of methyl substitution of CD as well as the type of solvents used. Methylated α‐CDs showed the prominent characteristics of IC formation with polymers in the case where chloroform was used than in the case where water was used as the solvent for CDs, while vice versa in the case of native α‐CD. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 879–891, 2008     

Scrutinizing ITC-study on the formation of inclusion complexes of nonionic surfactant Triton X-100 and cyclodextrins

The formation of host–guest-complexes of Triton X-100 (1), a nonionic surfactant comprising of an oligo ethylene glycol chain and a bulky hydrophobic tail, with alpha-, beta- and gamma-Cyclodextrin (α-, β- and γCD) has been investigated by isothermal titration calorimetry (ITC). Especially, the interaction of βCD with Triton X-100 has been subject-matter of a series of analytical studies though the results are contradictorily. Equilibrium constants diversify in the range of 200–200000?M^?1. Among these, even an isothermal titration calorimetric study is reported, indicating an association constant of 9100?M^?1. In contrast, the findings we report in the present paper approve an exceptionally high association constant reported just recently. Moreover, the stoichiometry of the formed complexes and the binding sites were investigated. βCD and γCD interact with the octylphenyl residue of 1. In contrast, αCD forms pseudorotaxanes by threading onto the oligo ethylene glycol-part of the surfactant molecule.     

Aggregation in aqueous media of tri-block copolymers tuned by the molecular selectivity of cyclodextrins

The water + cyclodextrin + poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) mixtures have been investigated to explore the temperature effect on the aggregation of the copolymer in the presence of cyclodextrins (CDs). The CDs with different cavity sizes were chosen because they may include either the hydrophilic poly(ethylene oxides) block or both kinds of blocks. The differential scanning calorimetry and viscosity experiments straightforwardly evidenced that the critical micellar temperature is shifted to larger values by adding a CD which is able to include the middle poly(propylene oxide) block while it is not influenced by the presence of CD which is selective to the poly(ethylene oxide) block. The enthalpy of aggregation decreases upon the CD addition for all the investigated systems.     

Reorganization of the structures,morphologies, and conformations of polymers by coalescence from their crystalline inclusion compounds formed with cyclodextrins

We and several other research groups have recently reported the ability of cyclodextrins (CDs) to act as hosts in the formation of inclusion compounds (ICs) with guest polymers. Polymer-CD-ICs are crystalline materials formed by the close packing of host CD stacks, which results in a continuous channel of ∼5-10Å in diameter running down the interior of the CD stacks. The guest polymers are confined to the narrow, continuous CD channels, and so are necessarily highly extended and segregated from neighboring polymer chains by the walls of the CD stacks. We have shown that coalescence of guest polymers from their CD-IC crystals can result in a significant reorganization of the structures, morphologies, and even conformations that are normally observed in their bulk samples. For example, when poly(ethylene terephthalate) (PET) is coalesced from its γ-CD-IC, we find that in the non-crystalline regions of the sample the PET chains are adopting highly extended kink conformations, which result in their facile recrystallization from the melt and prevent quenching of the coalesced PET to achieve an amorphous sample during rapid cooling from above T_m. We have also created well-mixed blends of normally incompatible polymers by coalescing them from CD-ICs containing both polymers, where they are necessarily spatially proximal. Finally we have found the unique morphologies created by the coalescence of homopolymers, block copolymers, and homopolymer pairs from their CD-ICs are generally stable to heat treatment for substantial periods above their T_m's and/or T_g's, and so may be thermoplastically processed without loss of the unique morphologies achieved through coalescence from their CD-IC crystals.     

The formation of inclusion compounds of alginic acid in aqueous solution

From the microscopic visualization of metal alginates, the alginate fine structure was found to be a regularly arranged network having many host spaces in its fiber net. Under acid solution such a fiber net took the rounded, buckled and twisted form as much as possible and finally changed to a porous cluster form. Then the binding properties of sodium alginate, calcium or cadmium alginate and granular alginic acid obtained from the treatment with hydrochloric acid to iodine, cholesterol and dyes were investigated. Sodium alginate and calcium or cadmium alginate formed adducts with iodine, cholesterol and dyes; accordingly the amount of these materials in solution was reduced by the addition of alginates. The high uptake of alginates by these materials were cleary observed under acid solution giving inclusion compounds. Granular alginic acid also showed high uptake of iodine and dyes, but not of cholesterol. The blue stained alginate-iodine compound formed at pH about 1 having maximum absorption at 587nm was found to be an inclusion compound judging from the distance of 3.13 Å for included iodine I-I and the number of uronic residues bound to the iodine molecule in the granular alginic acid-iodine compound. The binding mechanism for the high uptake behavior of alginic acid was clarified with the observation of inclusion compounds by scanning electron microscopy (SEM) and transmission electron microscopy (TEM).     

Molecular mixing of incompatible polymers through formation of and coalescence from their common crystalline cyclodextrin inclusion compounds

We describe the successful mixing of polymer pairs and triplets that are normally incompatible to form blends that possess molecular‐level homogeneity. This is achieved by the simultaneous formation of crystalline inclusion compounds (ICs) between host cyclodextrins (CDs) and two or more guest polymers, followed by coalescing the included guest polymers from their common CD–ICs to form blends. Several such CD–IC fabricated blends, including both polymer1/polymer2 binary and polymer1/ polymer2/polymer3 ternary blends, are described and examined by means of X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and solid‐state NMR to probe their levels of mixing. It is generally observed that homogeneous blends with a molecular‐level mixing of blend components is achieved, even when the blend components are normally immiscible by the usual solution and melt blending techniques. In addition, when block copolymers composed of inherently immiscible blocks are coalesced from their CD–ICs, significant suppression of their normal phase‐segregated morphologies generally occurs. Preliminary observations of the thermal and temporal stabilities of the CD–IC coalesced blends and block copolymers are reported, and CD–IC fabrication of polymer blends and reorganization of block copolymers are suggested as a potentially novel means to achieve a significant expansion of the range of useful polymer materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4207–4224, 2004     

Study of inclusion complex formation between a cationic surfactant, two cyclodextrins and a drug

In this study inclusion of hexadecyltrimethylammonium bromide (HTAB) with α-, and β-cyclodextrin (CD) in the presence and the absence of bromhexine (BH) was investigated using ion-selective electrode method. The association constants of HTAB with CDs were determined by potentiometry and were close to literature values. The obtained results indicated that α-CD formed 1:1 and 1:2 inclusion complexes, but β-CD formed only a 1:1 inclusion complex. In the presence of drug, the interaction between CDs and HTAB decreased, because both drug and HTAB could interact with CDs. The results showed that the interaction between drug and CDs are greater than HTAB and CDs. The stoichiometry of the inclusion complexes, the critical aggregation concentration (CAC), the monomer surfactant concentration of HTAB, [HTAB]_f, and also the effect of the inclusion complex on the micellization process of the HTAB were determined by conductivity measurements.     

Enhancement of selectivity and resolution in the enantioseparation of uncharged compounds using mixtures of oppositely charged cyclodextrins in capillary electrophoresis

The enantiomeric separation of some nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated in capillary electrophoresis (CE) using dual systems with mixtures of charged cyclodextrin (CD) derivatives. A significant enhancement of selectivity and resolution could be achieved in the enantioseparation of these analytes in their uncharged form by the simultaneous addition of two oppositely charged CD derivatives to the background electrolyte. The combination of the single-isomer cationic CD, permethyl-6-monoamino-6-monodeoxy-beta-CD (PMMAbetaCD) and the single-isomer polyanionic CD, heptakis-6-sulfato-beta-cyclodextrin (HSbetaCD) in a pH 2.5 phosphoric acid-triethanolamine buffer, was designed and employed for the enantioseparation of profens. The improvement in selectivity and resolution can be attributed to the fact that the two CDs, which lead to independent and enantioselective complexation with the analyte enantiomers, have not only opposite effects on the electrophoretic mobility of these compounds but also opposite affinity patterns towards the enantiomers of these compounds. Binding constants for these enantiomers with each CD were determined using linear regression approach, in order to be able to predict the effect of the concentrations of the two CDs on enantiomeric selectivity and resolution in such dual systems.