Inclusion complexation of volatile chlorinated hydrocarbons in aqueous solutions of branched cyclodextrins

The inclusion complexation of five volatile chlorinated hydrocarbons, i.e., chloroform, carbon tetrachloride, trichloroethylene, tetrachloroethylene, and monochlorobenzene, with branched cyclodextrins (CDs) such as monoglucosyl--CD and monomaltosyl--CD in aqueous solutions was examined. Their inclusion complexes were found to be very water soluble and the solubilities of the chlorinated hydrocarbons in aqueous solutions increased almost linearly or gradually with increasing concentration of the branched CDs. The amounts of the chlorinated hydrocarbons included in the branched CDs were well related to their molecular size and shape. In addition, the viability of application to pollution prevention is discussed.     

A comparison investigation on the solubilization of betulin and betulinic acid in cyclodextrin derivatives

Betulin (BET) and betulinic acid (BA) are naturally occurring pentacyclic lupane triterpenes, exhibit great promise as bioactive agents for the treatment of many diseases. The poor solubilities of BET and BA in water have limited their applications. In the present work, BET and BA were selected as guest molecules, three hydrophilic gamma-cyclodextrin (CD) thioethers were synthesized and selected as host molecules. beta-, Hydroxypropyl-beta-CD, (HP-beta-CD), gamma-CD and HP-gamma-CD were also investigated as hosts in order to compare the solubilization abilities of these host molecules. The solubilities of BET and BA were estimated from 1H NMR measurements by comparing the relative integral areas of the proton signals between CDs and guests. gamma-CD thioethers 5-7solubilized BET and BA to much higher extends than other host molecules. The obtained maximal solubilities of BET and BA were 5.2 and 4.5 mM, respectively. The topographies of the inclusion compounds were determined by ROESY NMR spectroscopy.     

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).     

The formation of homogeneous and heterogeneous 2:1 complexes between dialkyl- and diarylammonium ions and α-cyclodextrin and cucurbit[6]uril in aqueous formic acid

Dialkyl- and diarylammonium ions are able to form complexes with α-cyclodextrin and cucurbit[6]uril. These amines are able to complex two guest molecules simultaneously resulting in the formation of homogeneous or heterogeneous 1:2 (ratio of dialkylammonium to ligand) complexes. The stability constants and reaction enthalpies for the formation of 1:1 complexes have been measured using potentiometric and calorimetric titrations. Differences between the values obtained by these methods can be attributed to solvent composition. Only for the 1:2 complex formation with cucurbit[6]uril, the ligands influenced each other. The polar carbonyl groups at each portal of the cucurbit[6]urils interacted simultaneously with the protonated amino group resulting in an electrostatic repulsion between both molecules. No further interactions between two complexed molecules of α-cyclodextrin or cucurbit[6]uril and α-cyclodextrin were observed. The absence of polar groups in the case of α-cyclodextrin led to unaffected formation of homogeneous and even heterogeneous 1:2 complexes.     

Efficient Chemical Syntheses of Branched Cyclomalto‐Oligosaccharides Using the Trichloroacetimidate Method

Glycosylation using the trichloroacetimidate method was investigated in order to synthesize branched cyclomalto‐oligosaccharides (cyclodextrins, CDs). We examined the chemical syntheses of galactosyl CDs, directly β‐linked to the CD ring, which could not be synthesized by enzyme catalyzed reactions. We prepared 6‐O‐(d‐galactosyl)‐γCD and 6‐O‐(d‐mannosyl)‐γCD as basic model compounds using a combination of protecting groups on the glycosyl donor, catalysts to synthesize imidate derivatives, and catalysts for glycosylation. The configurational isomers were determined by HPLC and NMR spectroscopy.     

Preparation and characterization of novel branched beta-cyclodextrins having beta-D-galactose residues on the non-reducing terminal of the side chains and their specific interactions with peanut (Arachis hypogaea) agglutinin

Six novel branched beta-cyclodextrins (betaCDs) having beta-D-galactose residues on the non-reducing terminal of the sugar side chains, namely 6(1),6(4)-di-O-(beta-D-galactosyl)-betaCD (10), 6-O-(beta-D-galactosyl)-betaCD (11), 6(1),6(4)-di-O-(beta-lactosyl)-betaCD (14), 6-O-(beta-lactosyl)-betaCD (15), 6(1),6(4)-di-O-(4'-O-beta-D-galactosyl-beta-lactosyl)-betaCD (18), and 6-O-(4'-O-beta-D-galactosyl-beta-lactosyl)-betaCD (19), were chemically synthesized using the trichloroacetimidate method. The reaction products were separated by HPLC on an amino column into dibranched and monobranched betaCDs. Their structures were confirmed by mass spectrometry (MS) and two-dimensional (2D) NMR spectroscopic analysis. To study the length of the sugar side chains attached to the CD ring, which leads to differences in the functions of the branched CDs, interactions of these compounds with peanut (Arachis hypogaea) agglutinin (PNA) were investigated using an optical biosensor and an inhibition assay based on hemagglutination. The results showed that all branched betaCDs interacted with PNA, and the binding affinity was 18>14>10 and 19>15>11 when the derivatives were compared on the basis of side chain length.     

Control of photoluminescence quantum yield and long-lived triplet emission lifetime in organic alloys

Two-component crystalline organic alloys with a wide range of compositional ratios (from 30% to 90% of one component) are employed to tune excited-state lifetimes and photoluminescence quantum yields (PLQYs). Alloy crystals exhibit homogeneous distribution of parent compounds by X-ray crystallography and differential scanning calorimetry. The alloys display a 1.5- to 5-fold enhancement in thermally activated delayed fluorescence (TADF) lifetime, compared to the parent compounds. PLQYs can also be tuned by changing alloy composition. The reverse intersystem crossing and long-lived lifetime of the parent compounds give rise to long-lived TADF in the alloys. Organic alloys enable tunability of both lifetime and efficiency, providing a new perspective on the development of organic long-lived emissive materials beyond the rules established for host–guest doped systems.

Two structurally similar organic triplet emitters crystallize together to form organic alloys in varying ratios, exhibiting tunable photoluminescence quantum yields and long-lived TADF.     

Review: fluorescent cyclodextrins for molecule sensing

Cyclodextrins (CDs), which are spectroscopically inert, were converted into fluorescent CDs by modification with one or two fluorophores. Many fluorescent CDs changed the fluorescent intensities upon addition of guest compounds, causing the locational change of the fluorophore mostly from inside to outside of the CD cavities. On this basis, the fluorescent CDs were used as fluorescent chemosensors for molecule recognition. Modified CDs bearing two naphthalene or pyrene moieties exhibit intramolecular excimer emission and their guest-responsive excimer intensity variations were used for molecule sensing. Fluorescent CDs bearing a dansyl moiety decreased the fluorescence intensity upon guest addition, reflecting the environmental change around the fluorophore from the hydrophobic interior of the CD cavities to bulk water solution. Modified CDs bearing a p-N,N-dimethylaminobenzoyl (DMAB) moiety exhibit dual emissions from nonpolar planar (NP) and twisted intramolecular charge transfer (TICT) excited states, and the TICT emission intensity was useful for sensing molecules. A biotin-bound DMAB system was also constructed, and the presence of the protein (avidin) was found to enhance the NP fluorescence. This avidin-bound DMAB system showed higher sensitivities and stronger binding ability for guest species than the system without avidin.     

Synthesis of Rigid Cyclodextrin-Containing Polymeric Resins for Adsorption

Cyclodextrins (CDs) are a family of cyclic-oligosaccharides with usually 6–8 glucopyranose units. Because of their unique donut-shaped steric structure they are able to form inclusion complexes selectively with some guest molecules. CDs are in starch-like powder form and are soluble in water to certain extents. It is desirable to produce insoluble CD-containing particles for adsorption, liquid chromatography and other applications. This work presents a novel method of synthesizing CD-containing resins. Resins synthesized with this method possess high contents of CDs and some favorable physical properties. Adsorption isotherms for three small aromatic compounds, namely phenylalanine, tryptophan and aspartame, were obtained experimentally.     

Solubilization of Polycyclic Aromatics in Water by γ‐Cyclodextrin Derivatives

A series of hydrophilic per‐6‐thio‐6‐deoxy‐γ‐cyclodextrins (CDs) were synthesized from per‐6‐iodo‐6‐deoxy‐γ‐CD. These new hosts are able to solubilize polycyclic aromatic guests in aqueous solution to much higher extents than native CDs. Phase‐solubility diagrams were mostly linear in accordance with both 1:1 and 1:2 CD–guest complexes in aqueous solution. The stoichiometry of the inclusion complexes was further investigated by fluorescence spectroscopy, which revealed very pronounced Stokes shifts typical for 1:2 complexes. This finding was further consolidated by quantum mechanical calculations of dimer formation of the guests and space‐filling considerations by using the cross‐sectional areas of the CDs and guests. The calculated dimerization energies correlated well with the binding free energies measured for the 1:2 complexes, and provided the main contribution to the driving force of complexation in the γ‐CD cavity.     

Metallodendrimers: homo- and heterogeneous tier construction by bis(2,2′:6′,2″-terpyridinyl)Ru(II) complex connectivity

A convenient combinatorial-style route for the incorporation of multiple, differing functional groups, in a controllable ratio, onto a dendritic poly(propylene imine) scaffolding is described. Attachment of the functionality is accomplished by the connective formation of bis(2,2′:6′,2-terpyridine)Ru(II) complexes via reaction of a terpyridine-modified dendritic surface with 1→3 branched monomers each possessing a focal terpyridine moiety. This synthetic approach produces a heterogeneous surface coating that is compared and contrasted to that of analogous homogeneous surfaced constructs. UV-vis absorption and TGA data for the metallodendrimers are also reported.     

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. This paper was presented at XIIIth International Cyclodextrin Symposium. Torino, Italy, May 14–17, 2006.     

1H NMR study of the inclusion of Costa-type organocobalt(III) complexes in cyclodextrins

The inclusion behavior between Costa-type complexes and cyclodextrins (CDs) was studied by 1H NMR in aqueous solution. The results indicated that 1:1 inclusion complex was formed, in which the alkyl group of the guest was included in the cavity of CDs. The stability constants of the inclusion complexes were determined by the quantitative 1H NMR method. The effects on stability constants were discussed when various host and guest compounds were used.     

Structure of the Molecular Complexes of 18-Crown-6 with 1,2,5-Oxadiazole Derivatives

This paper reports on an X-ray diffraction analysis of host–guest type molecular complexes of 18-crown-6 with 1,2,5-oxadiazole derivatives: ethyl 4-amino-1,2,5-oxadiazole-3-carboxylic ether (1:1) (complex I), 4-(2-chloroethylamino)-1,2,5-oxadiazole-3-carboxylic acid hydrazide (1:2) (complex II), and 4-amino-1,2,5-oxadiazole-3-carboxylic acid amide monohydrate (1:1:1) (complex III). Crystals I are monoclinic with cell parameters a = 8.960(2), b = 18.118(4), c = 14.405(3) , = 106.9(3)°, space group P2₁/n, R = 0.054 for 4082 reflections. The 18-crown-6 and guest molecules are linked by hydrogen bonds of NHO(crown) and CHO(crown) types based on the head-to-tail principle, alternating in infinite chains along the y axis in the crystal. Crystals II are triclinic with cell parameters a = 8.615(2), b = 9.249(2), c = 10.987(2) , = 106.86(3), = 95.25(3), = 97.74(3)°, space group P1, R = 0.046 for 3006 reflections. The guest molecules are united into dimers by N–HO=C hydrogen bonds. The 18-crown-6 molecules and the dimer associates of the guest form chains along [110] in the crystal. Crystals III are monoclinic with cell dimensions a = 13.238(3), b = 19.004(4), c = 8.485(2) , = 100.75(3)°, space group Cc, R = 0.051 for 2032 reflections. The crown ether molecule is disordered over two positions. The NHO=C and NHN type hydrogen bonds link the guest molecules into chains. The water molecules serve to bridge the chains with crown ether molecules, forming ribbons whose axis lies along the z direction in the crystal.     

Constrained polymer chain behavior observed in their non-stoichiometric cyclodextrin inclusion complexes

Much has been learned from inclusion compounds (IC’s) formed between guest polymers and host cyclodextrins (CDs) [polymer-CD-ICs] by examining the properties of the fully covered guest polymers, as well as those coalesced neat bulk samples of guest polymers obtained upon removal of the host CDs. However, what can be gained from studying the properties of the restrained unthreaded portions of polymer chains that “dangle” from non-stoichiometric (n-s)-polymer-CD-IC’s? We attempt to assist in answering this question by observing (n-s)-polymer-CD-IC’s formed between amorphous atactic-poly(methyl methacrylate) (PMMA) and γ-CD, as well as the IC formed between a synthesized poly(ε-caprolactone)-poly(propylene glycol)-poly(ε-caprolactone) (PCL-PPG-PCL) triblock copolymer and β-CD, which was presumed to have threaded and unthreaded PPG and PCL blocks. Though our (n-s)-PMMA-γ-CD-IC samples were found to exhibit extremely heterogeneous behaviors, glass transition temperature increases of up to 27?°C above that of neat PMMA were observed. X-ray diffraction data indicates modest γ-CD crystallinity at partial coverages of PMMA, with a crystal structure similar to that of the IC with full coverage. On the other hand, XRD, DSC and FTIR data revealed an almost total disruption of PCL block crystallinity upon complexation of PCL-PPG-PCL with β-CD, suggesting either partial threading and coverage of the PCL blocks by β-CD or their partial mixing with the PPG blocks covered with β-CD.     

Development of a Total Organic Carbon method for the quantitative determination of solubility enhancement by cyclodextrins: Application to essential oils

Formation of inclusion complexes with cyclodextrins (CDs) is known to enhance guest solubility in aqueous medium. Different techniques allow determining the evolution in solubility of individual guest compounds. However, examination of mixtures solubility encapsulated in CDs is still a challenge. This is mainly related to the difference in the response of mixture components to the applied technique or to the fact that most of the conventional methods examine the signal of an individual constituent of the mixture. Thus, applying current techniques may not reflect the behavior of the whole mixture. Here, we used for the first time Total Organic Carbon (TOC) analysis to explore and assess the efficiency of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance the solubility of natural complex mixtures such as essential oils (EOs). Phase solubility studies were performed for eleven EOs with HP-β-CD. The TOC method has provided good validation parameters for linearity, precision and accuracy. For further validation of the method, phase solubility studies were performed with HP-β-CD for eugenol, as a model EO component. The eugenol solubility was determined by UV–Visible and TOC analyses in order to compare the results. Data obtained from both methods were similar (p < 0.05), thereby proving the effectiveness of the developed TOC method. Finally, the phase solubility diagrams of EOs showed that the solubilizing potential of CD increased proportionally with the decrease in EO intrinsic solubility. Results proved that TOC could be successfully applied to investigate CD/guest inclusion complexes and is expected to have a broad range of applications in the field of mixtures encapsulation.     

Modeling and conformation analysis of β-cyclodextrin complexes

Summary A series of -cyclodextrin complexes containing various guest molecules was studied using computer-aided molecular modeling and conformation analysis techniques. The geometry of each complex was studied using crystallographic data. The positions of the glycosidic O4 atoms indicate that the -cyclodextrin molecules are elliptically distorted. This distortion can be related to the van der Waals volume of the guest molecules. This correlation is different for aromatic and non-aromatic guest compounds. Rigid body docking experiments demonstrated that in crystal structures the guest molecule occupies a position in the cavity of nearly minimum interaction energy when there are no other molecules having interactions with the guest molecule. From the crystallographic data several rules could be deduced which seem to determine the conformation of -cyclodextrin molecules in complexes. A procedure was developed to construct -cyclodextrin molecules that are able to encompass guest molecules having a given van der Waals volume.     

Interactions of cyclodextrins with aromatic compounds studied by vibrational circular dichroism spectroscopy

The host/guest complexation between cyclodextrins (CDs) and aromatic compounds was studied by vibrational circular dichroism (VCD) spectroscopy in mid-IR region. Benzoic acid, 4-aminobenzoic acid, and 2,6-naphthalene-dicarboxylic acid acting as the guests with aromatic skeleton, cause the significant changes in VCD patterns of CD, which indicate that the secondary hydroxyl groups of the CDs are involved in the host/guest complexation. In addition, the intensities and dissymmetry factors (deltaA/A) of the VCD bands, which belong to skeletal CD vibrations, depend on the sizes of the guest molecules. Our results indicate that the formation of the CD inclusion complexes can be followed by VCD spectroscopy.     

Review of the quantitative structure–activity relationship modelling methods on estimation of formation constants of macrocyclic compounds with different guest molecules

There is an increasing interest in the use of quantitative structure–activity relationship (QSAR) approaches as a progressive tool in modelling and prediction of many physicochemical properties in host–guest interactions of macrocyclic complexes. A review is presented on the QSAR modelling of macrocyclic compounds formation constants, which focus on two most interesting macrocycles, e.g. crown ethers and cyclodextrins (CDs), with different guest molecules. The review starts with a short overview on experimental methods of stability constant measurement, followed by a short explanation of the QSAR methodologies. In the next section, we focus on and discuss QSAR techniques that used to predict the stability (binding) constants or free energy complexation of some most interesting macrocyclic compounds, e.g. CDs and crown ethers, with different guest molecules including anionic, cationic and neutral molecules.     

The phase diagrams of the systems MgCl2 + MgB6O10 + H2O and MgSO4 + MgB6O10 + H2O at 323.15 K and Pitzer model

The solubilities and the relevant physicochemical properties of the systems MgCl₂ + MgB₆O₁₀ + H₂O and MgSO₄ + MgB₆O₁₀ + H₂O at 323.15 K were determined by the method of isothermal dissolution, and the phase diagrams and the diagrams of physicochemical properties versus composition were plotted. Both of the systems belong to a simple eutectic type, and neither double salts nor solid solution were found. Based on the extended Harvie-Weare (HW) model and its temperature-dependent equations, the value of the singlesalt Pitzer parameters ??⁽⁰⁾, ??⁽¹⁾, ??⁽²⁾, and C ^? for MgCl₂, MgSO₄, and Mg(B₆O₇)(OH)₆, the mixed ion-interaction parameters $\theta _{Cl, B_6 O_{10} }$ , $\theta _{SO_4 , B_6 O_{10} }$ , $\Psi _{Mg, Cl, B_6 O_{10} }$ , $\Psi _{Mg, SO_4 , B_6 O_{10} }$ , the average equilibrium constants (lnK _aver) of solids in the systems and the Debye-Hückel parameter A ^? were fitted. Using the Pitzer parameters and the average equilibrium constants of solids at equilibrium, the solubilities of the two systems at 323.15 K have been calculated. Comparisons between the calculated and experimental results show that the predicted solubilities agree well with experimental data.