BETA W7 MCT — new ways in surface modification

BETA W7 MCT is the first reactive cyclodextrin derivative manufactured on an industrial scale. It has a monochlorotriazinyl group as a reactive anchor well known from many reactive dyes. This derivative is able to form stable covalent bonds with nucleophilic groups and can be easily prepared in water in an effective one pot synthesis from cyanuric chloride and -cyclodextrin in a yield of approx. 90% based on the triazinyl group. The optimised degree of substitution of DS = 0.4 per anhydroglucose ensures a good complexation capacity even when this derivative is fixed to surfaces like textiles. This cyclodextrin derivative containing 2–3 reactive groups in the ring can be used as building block for new CD derivatives, as a crosslinking agent or as an excellent material for surface modification.     

A facile synthesis of novel types of cyclodextrin derivatives by insertion of an aromatic dicarbonyl spacer into a permethylated alpha-cyclodextrin skeleton

Novel types of cyclodextrin derivatives are easily synthesized by the insertion of an aromatic dicarbonyl spacer into the skeleton of permethylated alpha-cyclodextrin, and the isophthaloyl-inserted one shows almost the same complexing ability toward p-nitrophenol as permethylated beta-cyclodextrin.     

The influence of chitosan on cyclodextrin complexing and solubilizing abilities towards drugs

The present work was performed to investigate the effect of chitosan, a well known hydrophilic polymer with both enhancer and solubilizing properties, on the solubilizing and complexing abilities of cyclodextrins towards drugs. With this aim, phase-solubility studies were carried out with a series of model drugs, both of acid and basic nature and with different water-solubility and lipophilicity values, in the presence of chitosan and cyclodextrin (ß- or hydroxypropyl-ß-cyclodextrin), both separately (binary systems) and in combination (ternary systems). Unexpectedly, differently from the favorable effect reported in literature for various hydrophilic polymers, the addition of chitosan to the cyclodextrin complexation medium caused a decrease in the cyclodextrin complexing power towards all the examined drugs, independent from their very different physicochemical properties. On the contrary, the influence of the polymer on the cyclodextrin solubilizing efficiency was found to be dependent on the type of drug and both positive, or negative or non-significant effects were observed. The overall results are explained in terms of a common basic mechanism due to the presence of chitosan–cyclodextrin interactions, which hindered the drug–cyclodextrin complex formation, thus causing the binding constant reduction; the simultaneous presence of drug–chitosan and/or chitosan–(drug–cyclodextrin complex) interactions, different from drug to drug, were considered responsible for the distinct (and sometimes opposite) effects observed in the drug solubilizing efficiency of ternary systems.     

Cyclodextrin knowledgebase a web-based service managing CD-ligand complexation data

Cyclodextrins are cyclic oligosaccharides that are able to form water-soluble inclusion complexes with small molecules. Because of their complexing ability, they are widely applied in food, pharmaceutical and chemical industries. In this paper we describe the development of a free web-service, Cyclodextrin KnowledgeBase: (http://www.cyclodextrin.net). The database contains four modules: the Publication, Interaction, Chirality and Analysis Modules. In the Publication Module, almost 50,000 publication details are collected that can be retrieved by text search. In the Interaction and Chirality Modules relevant literature data on cyclodextrin complexation and chiral recognition are collected that can be retrieved by both text and structural searches. Moreover, in the Analysis Module, the geometries of small molecule-cyclodextrin complexes can be predicted using molecular docking tools in order to explore the structures and interaction energies of the inclusion complexes. Complex geometry prediction is made possible by the built-in database of 95 cyclodextrin derivatives, where the 3D structures as well as the partial charges are calculated and stored for further utilization. The use of the database is demonstrated by several examples.     

Differentiation of enantiomers using matrix-assisted laser desorption/ionization mass spectrometry

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has successfully been used to differentiate pseudo-enantiomeric (isotopically labelled) amino acids by using cyclodextrin as complexing host. By using different pseudo-enantiomeric mixtures (i.e. R(Dn) + S; and R + S(Dn)), it has been demonstrated that the preference of cyclodextrin for S-enantiomers is not due to the size differences caused by the hydrogen/deuterium substitution. It is postulated that this method can be extended to differentiate enantiomers (and determine enantiomeric excess) by using a pair of enantiomeric hosts, as demonstrated previously using other ionization techniques, but with much higher sensitivity.     

Emulsion polymerization of hydrophobia monomers

Emulsion polymerization is the most important industrial polymerization process for manufacturing water based polymers. The heterogeneous nature of the process requires the diffusion of monomers from the emulsified droplets, through the aqueous medium, into the polymer particles where the polymerization takes place. Adequate solubility of the monomer is necessary for the diffusion process to occur effectively. Consequently, very hydrophobic monomers cannot be readily incorporated by emulsion polymerization. The use of a catalytic level of cyclodextrin allows the use of very hydrophobic monomers in emulsion polymerization.^[1] The mechanism of the process is believed to involve a catalytic cycle in which cyclodextrin acts as a “Phase Transport Catalyst”, continuously complexing and solubilizing the hydrophobic monomers and releasing them to the polymer particles. The kinetics and thermodynamics are favorable for the reaction to proceed.     

Macrocycle-based oligo- and polylactides: synthesis and prospects of application

The review considers methods for modifying oligo- and polymers of lactic acid by macrocyclic moieties (cyclodextrin, tetrapyrrole, and calixarene) and the effect of modifiers on the complexing, thermal, and aggregation properties. Analytical characteristics of oligolactide-based sensors and biosensors are discussed, with particular emphasis on the mechanism of signal generation and the contribution of modified materials to the selectivity and sensitivity of analysis.

     

Metal ion complexes with native cyclodextrins. An overview

The review presents a survey of the metal complexing properties of native cyclodextrins (including deprotonation in alkaline medium) and a report on some recent results on composition and stability of metal–cyclodextrin complexes.     

Pressure-controlled high-performance liquid chromatographic study on the influence of rim chemistry on partial molar volume differences between free and complexed cyclodextrins

Pragmatic comparison of pressure dependent retention for differing cyclodextrin rim chemistries is assessed using controlled-pressure HPLC. For pressure differences of <300 bar, systematic shifts in solute capacity factor are observed for both native and methylated beta-cyclodextrin stationary phases. In addition to the importance of this observation for the practice of liquid chromatography, this technique can also be implemented in the fundamental determination of the influence of rim chemistry on the cyclodextrin partial molar volume both with and without solute inclusion. That is, pressure-controlled measurements provide a direct comparison between the partial molar volumes for native cyclodextrin (CD) and methylated cyclodextrin (MCD) in the presence and absence of the complexing solute (comp). Surprisingly, direct comparison of the measured partial molar volumes for the two rim chemistries indicates that the presence of neutral solutes does not contribute significantly to the volumetric component of complexation, V(comp,CD) - V(comp,MCD) approximately V(CD) - V(MCD). In contrast, their ionized counterparts are shown to exhibit marked rim chemistry differences in the partial molar volume of cyclodextrins with and without anion inclusion, V(comp(-),CD) - V(comp(-),MCD) < V(CD) - V(MCD). Not previously demonstrated by direct chromatographic measurement, these results have interesting implications for advancing the fundamental understanding of host-guest solvation properties.     

New Textile Applications of Cyclodextrins

New areas of applications of cyclodextrins with textiles are possible. The abilityof cyclodextrins to form inclusion complexes can be used, e.g., to remove malodorfrom textile materials. The permanent fixation of cyclodextrins offers new textileswith interesting properties. Thus the formation of body odor is reduced by thecomplexation of the organic compounds of sweat. The release of perfumes fromcyclodextrins is possible by the use of textiles with fixed cyclodextrins. Pharmaceutical compounds are also set free in contact with the skin. Last but not least the analysis of the different compounds of the human sweat complexed by the cyclodextrins offers new possibilities in medical diagnostics.     

A comparison of analytical methods for the quantification of a reactive β-cyclodextrin fixed onto cotton yarns

Cotton yarns bobbins were treated in a water bath with different concentrations of a reactive β-cyclodextrin derivative. To quantify the amount of cyclodextrin fixed on the fiber different analytical methods were tested but none of them was reliable enough in the concentration range under investigation. Therefore, a new analytical method, fast and effective, was developed. From the measurement of cyclodextrin bath exhaustion, the amount of cyclodextrin chemically fixed and that physically adsorbed on the textile substrate was estimated. Two washing cycles were carried out to investigate the cyclodextrin washing fastness.     

Chiral separation of the four stereoisomers of a novel antianginal agent using a dual cyclodextrin system in capillary electrophoresis

Reported here is an analytical method enabling the stereochemical resolution of a new antianginal compound possessing two stereogenic centers, leading to four stereoisomers. Only one of these isomers is currently under development as a novel antianginal agent and consequently, the other three isomers are considered as unwanted chiral impurities. Therefore, an enantioselective method is required in order to check its enantiomeric purity. This paper presents a method exploiting the high efficiency of capillary electrophoresis and the complexing properties of cyclodextrins to achieve the separation of the four stereoisomers of this weakly basic compound (pKa = 7.4). For this purpose, the combination of a neutral cyclodextrin, hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), and an anionic cyclodextrin, carboxymethyl-beta-cyclodextrin (CM-beta-CD), was added to the separation buffer running in an uncoated silica capillary. After selection of the suitable cyclodextrin system, satisfactorily separation conditions were as follows: 30 mM phosphate buffer (pH 6.4) containing 10 mM of HP-gamma-CD and 10 mM of CM-beta-CD, running voltage +30 kV. The resulting run time and resolutions were respectively about 17 min and between 1.95 and 2.84. Linearity curves (0.993 < r2 < 0.998) are also shown.     

Oxidation stability of eicosapentaenoic and docosahexaenoic acid included in cyclodextrins

We have proposed a novel method for complexing of the -3 polyunsaturated fatty acids (PUFA), such as eicosapentaenoic and docosahexaenoic acids, with cyclodextrin as dry powders by a twin-screw kneader. The effect of various oxidation conditions on powdery PUFA were investigated. Further, the powdery PUFA developed was employed in the preparation of fish meal as a functional sea food paste.     

Improvement of cytotoxic activity of local anesthetics against human breast cancer cell line through the cyclodextrin complexes

Among the potent anticancer agents, Local Anesthetics (LA) have been found to be efficient against many different types of cancer cells. However, the major disadvantage associated with the use of LA its low systemic bioavailability when administered due to its poor aqueous solubility. Our present work concentrates on improving the bio-availability by complexing with cyclodextrin. We synthesized the inclusion complexion by co-precipitation method which is an efficient method among other and characterized the formulation of complex by UV and fluorescence studies. The in-vitro study of cytotoxicity against breast cancer cell line is performed. Our study shows the formation of the complex with 1:1 ratio and the result show both Benzocaine and Tetracaine inclusion complex has higher potential towards breast cancer cell than the free drug.     

Effect of β-cyclodextrins based nanosponges on the solubility of lipophilic pharmacological active substances (repaglinide)

Cyclodextrin based nanosponges (CD-NS) are nanostructured cross-linked polymers, usually obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole, organic carbonates or (±) epichlorohydrin. They have been used to increase the solubility and stability of poorly soluble pharmacological active substances, as they combine the complex forming properties of CDs and properties of polymers (such as the high molecular weight). The affinity of CDs for certain lipophilic molecules is characteristic to the polymeric nano-structured system and allows the development of specific drug delivery systems. Knowing that cyclodextrin capacity to form inclusion complexes is maintained and enhanced when the CD molecules form aggregates, cross-link together or copolymerize with other compounds, we have synthesized cyclodextrin based nanosponges (from β-cyclodextrin and sulfobutylether-β-cyclodextrin). The complexing properties of the polymers were investigated against repaglinide (a hypoglycemic agent, practically insoluble in water). Solubility studies were performed according to the method reported by Higuchi and Connors and the phase solubility diagrams were plotted. The repaglinide-nanosponges complexes were prepared, lyophilized and the resulted inclusion complexes were characterized by FT-IR and NMR. The solubility profile and the loading capacity of the cyclodextrin based polymers were also determined.     

A novel in situ strategy for the preparation of a β‐cyclodextrin/polydopamine‐coated capillary column for capillary electrochromatography enantioseparations

Inspired by the chiral recognition ability of β‐cyclodextrin and the natural adhesive properties of polydopamine under alkaline conditions, in this study, a rapid and in situ modification strategy was developed to fabricate β‐cyclodextrin/polydopamine composite material coated‐capillary columns for open tubular capillary electrochromatography. The results of scanning electron microscopy, FTIR spectroscopy, streaming potential, and electro‐osmotic flow studies indicated that β‐cyclodextrin/polydopamine was successfully fixed on the inner wall of the capillary column. This coating can be achieved within 1 h affording a greatly reduced capillary preparation time. The performance of the β‐cyclodextrin/polydopamine‐coated capillary was validated by the analysis of seven pairs of chiral analytes, namely epinephrine, norepinephrine, isoprenaline, terbutaline, verapamil, tryptophane, carvedilol. Good enantioseparation efficiencies were achieved for all. For three consecutive runs, the relative standard deviations for the migration times of the analytes for intraday, interday, and column‐to‐column repeatability were in the range of 0.41–1.74, 1.03–4.18, and 1.66–8.24%, respectively. Moreover, the separation efficiency of the β‐cyclodextrin/polydopamine‐coated capillary column did not decrease obviously over 90 runs. The strategy should also be feasible to introduce and immobilize other chiral selectors on the inner walls surface of capillary columns.     

Formation of a rotaxane from the end-capping process of a pseudorotaxane. Effects of the solvent

The effects that the solvent exerts on the end-capping process of a pseudorotaxane formed by the [Ru(NH 3) 5(4,4'-bpy)]2+ complex and beta-cyclodextrin were studied. In this process the 4,4'-bpy ligand acts as rigid axle and the cyclodextrin as ring or macrocycle. The stopper used was the [Fe(CN) 5 H2O]3(-) complex. The solvents used were mixtures of ethyleneglycol-water and tert-butyl alcohol-water. Results showed similar, although strange, behavior in both media studied. Thus, a decrease of the observed rate constant was obtained when the concentration of cyclodextrin increases for all the media studied. However, at fixed cyclodextrin concentrations, an increase of k obs was obtained when small quantities of the cosolvent were added to the medium and, further, a decrease of k obs for the higher quantities of the organic solvents. This strange behavior could be explained by taking into account electrostatic and specific solvent (solvent-solvent and solvent-solute) effects.     

Physicochemical Investigation of Engineered Nanosuspensions Containing Model Drug,Lansoprazole

Lansoprazole is a proton-pump inhibitor used in treatment of gastric ulcers, gastroesophageal reflux disease (GERD), and Zollinger–Ellison syndrome. The objective of the study was physicochemical investigation and comparative characterization of nanosuspensions of lansoprazole by complexing with β-cyclodextrin and β-cyclodextrin-based nanosponges to enhance its solubility and stability. Inclusion complexes of lansoprazole with β-cyclodextrin and nanosponges were prepared by physical method and polymer condensation method, respectively. Particle size, zeta potential, encapsulation efficiency, in vitro release, FTIR, and Differential Scanning Calorimeter (DSC) studies were used as characterization parameters. The average particle size of lansoprazole nanoparticles was found to be in the range of 178.7 ± 6.39 nm to 204.9 ± 2.91 nm. The high zeta potential values were attained to ensure a high-energy barrier and favor a good stability of nanosuspensions. In vitro release study showed the controlled release of lansoprazole, which was more satisfactory than individual drug. FTIR spectroscopy showed that there was interaction of cyclodextrin and its nanosponges with drug. DSC study revealed that drug was involved in complexion with cyclodextrin and nanosponges. Solubility and stability of lansoprazole were remarkably improved by inclusion complexation. Based on these findings, it can be concluded that engineered nanosuspension of lansoprazole is a promising carrier for nanoparticulate drug delivery in gastric ulcer.     

Use of Quantum Chemical Methods to Study Cyclodextrin Chemistry

Studies of cyclodextrin chemistry by quantum chemical methods are briefly surveyed. Emphases are put on what types of quantum chemical methods can be used for cyclodextrin chemistry, how to use quantum chemical methods to find the global minimum, to study the structures, binding energies, driving forces for cyclodextrin complexes, as well as chemical reactions occurring inside cyclodextrin cavities. Problems associated with the application of quantum chemical methods in cyclodextrin chemistry are also discussed.     

A novel approach for fixation of β-cyclodextrin on cotton fabrics

Cyclodextrins are cyclic oligosaccharides, which form complexes with different organic substances such as drugs, odors, and etc. Due to the complexing abilities of cyclodextrins (CDs), they may also be used in textile industry as an auxiliary in washing, dyeing, and wastewater treatment. Fixation of CDs on textiles is possible using reactive derivatives of cyclodextrins or crosslinking agents. In this study we have investigated the use of polyaminocarboxylic acids (PACAs) as novel crosslinking agents for the fixation of β-CD on cotton fabrics. Fixation of β-CD on cotton fabric has been quantified by measuring the weight increase of the treated samples. The influence of the concentration of the catalyst (sodium hypophosphite) was studied, too. The presence of β-CD on the cotton has been investigated by the phenolphthalein test and host–guest complexation with organic volatile molecules: cyclohexene, chlorobenzene, cyclohexene-1-one and toluene.