Stabilizers cyclodextrins

The applications of quantitative structure-reactivity analysis to cyclodextrin com-plexation and cyclodextrin catalysis, mostly from our laboratories, as well as the experimental and theoretical backgrounds of these approaches, are reviewed. These approaches enable us to separate several intermolecular interactions, acting simultaneously, from one another in terms of physicochemical parameters, to evaluate the extent to which each interaction contributes, and to predict thermodynamic stabilities and/or kinetic rate constants experimentally undetermined. Conclusions obtained are mostly consistent with those deduced from experimental measurements. 

Water plays a crucial role in the inclusion process. Although cyclodextrin does form inclusion complexes in such nonaqueous solvents as dimethyl sulfoxide, the binding is very weak compared with that in water 13 Recently, it has been shown that the thermodynamic stabilities of some inclusion complexes in aqueous solutions decrease markedly with the addition of dimethyl sulfoxide to the solutions 14,15>. Kinetic parameters determined for inclusion reactions also revealed that the rate-determining step of the reactions is the breakdown of the water structure around a substrate molecule and/or within the cyclodextrin cavity 16,17). 

Matsui and Mochida24) have determined the thermodynamic stabilities (log 1 /Kd) for a- and P-cyclodextrin complexes with a variety of alcohols (Table 2) and analyzed the results in connection with the physicochemical properties of the guest molecules by the multivariate technique. The log 1/Kd values were plotted against log Pe, where Pe is the partition coefficient of alcohol in a diethyl ether-water system. The plots for the a- and P-cyclodextrin complexes with eight 1-alkanols gave approximately straight lines with slopes of around one. 

In these equations, MR3 4, MR, and MR4 are the molar refractivities of 3- and 4-substituents, of R-, and of 4-substituents, respectively. All the equations exhibited positive coefficients of the MR terms. This suggests that the dispersion forces of substituents are actually responsible for the binding of ligands to cyclodextrin. Eq. 14 shows that the stability of a-cyclodextrin-RCOO complexes increases linearly up to MR = 4.0 and then falls off linearly. 

Upon formulating these relationships, phenols with branched alkyl substituents were not included in the data of a-cyclodextrin systems, though they were included in (3-cyclodextrin systems. In all the above equations, the n term was statistically significant at the 99.5 % level of confidence, indicating that the hydrophobic interaction plays a decisive role in the complexation of cyclodextrin with phenols. The Ibrnch term was statistically significant at the 99.5% level of confidence for (3-cyclo-dextrin complexes with m- and p-substituted phenols. The stability of the complexes increases with an increasing number of branches in substituents. This was ascribed to the attractive van der Waals interaction due to the close fitness of the branched substituents to the (3-cyclodextrin cavity. The steric effect of substituents was also observed for a-cyclodextrin complexes with p-substituted phenols (Eq. 22). In this case, the B parameter was used in place of Ibmch, since no phenol with a branched... 

The results were simple and clear-cut Only the two terms ofa° and Emin were involved for the a-cyclodextrin systems, and the two terms of k and Emin, for (S-cyclodextrin systems. This means that the stabilities of the inclusion complexes are mainly governed by the electronic and steric interactions in a-cyclodextrin systems and by the hydro-phobic and steric interactions in (i-cyclodextrin systems, regardless of the position of the substituents in the phenols. These observations agree well with those by Harata23), who showed that there is no appreciable difference in thermodynamic parameters between cyclodextrin complexes of m- and p-di substituted benzenes and that the contribution of the enthalpy term to the complexation is more significant in a-cyclodextrin systems than in P-cyclodextrin systems, where the inhibitory effect... 

The longest lifetime, highest incorporation yield (74%), and stabilization were observed for a fraction of bound bixin in 95% Arabic gum plus 5% sucrose as the matrix. The minor fraction of bixin, non-encapsulated, showed a short lifetime. When encapsulated in Arabic gum or in p-cyclodextrin compared with DE-20 and... 

Szente, L. et al.. Stabilization and solubilization of lipophilic natural colorants with cyclodextrins, J. Inclusion Phen. Mol. Recognition Chem., 32, 91, 1998. 

Tpnnesen, H.H, Masson, M., and Loftsson, T., Studies on curcumin and curcuminoids. XXVII. Cyclodextrin complexation solubility, chemical an photochemical stability, Int. J. Pharm., 244, 127, 2002. 

A good deal of attention recently has been directed towards the use of derivatives of cyclodextrin for the solubilization and stabilization of pharmaceuticals [124 126]. One cautionary note—complexation may adversely affect the dissolution an/or permeability characteristics of the drug, thereby possibly decreasing drug bioavailability. 

Spin trapping methods were also used to show that when carotenoid-P-cyclodextrin 1 1 inclusion complex is formed (Polyakov et al. 2004), cyclodextrin does not prevent the reaction of carotenoids with Fe3+ ions but does reduce their scavenging rate toward OOH radicals. This implies that different sites of the carotenoid interact with free radicals and the Fe3+ ions. Presumably, the OOH radical attacks only the cyclohexene ring of the carotenoid. This indicates that the torus-shaped cyclodextrins, Scheme 9.6, protects the incorporated carotenoids from reactive oxygen species. Since cyclodextrins are widely used as carriers and stabilizers of dietary carotenoids, this demonstrates a mechanism for their safe delivery to the cell membrane before reaction with oxygen species occurs. 

Direct insertion probe pyrolysis mass spectrometry (DPMS) utilises a device for introducing a single sample of a solid or liquid, usually contained in a quartz or other non-reactive sample holder, into a mass spectrometer ion source. A direct insertion probe consists of a shaft having a sample holder at one end [70] the probe is inserted through a vacuum lock to place the sample holder near to the ion source of the mass spectrometer. The sample is vaporized by heat from the ion source or by heat from a separate heater that surrounds the sample holder. Sample molecules are evaporated into the ion source where they are then ionized as gas-phase molecules. In a recent study, Uyar et al. [74] used such a device for studying the thermal stability of coalesced polymers of polycarbonate, PMMA and polylvinyl acetate) (PVAc) [75] and their binary and ternary blends [74] obtained from their preparation as inclusion compounds in cyclodextrins. 

Recently, we have also prepared nanosized polymersomes through self-assembly of star-shaped PEG-b-PLLA block copolymers (eight-arm PEG-b-PLLA) using a film hydration technique [233]. The polymersomes can encapsulate FITC-labeled Dex, as model of a water-soluble macromolecular (bug, into the hydrophilic interior space. The eight-arm PEG-b-PLLA polymersomes showed relatively high stability compared to that of polymersomes of linear PEG-b-PLLA copolymers with the equal volume fraction. Furthermore, we have developed a novel type of polymersome of amphiphilic polyrotaxane (PRX) composed of PLLA-b-PEG-b-PLLA triblock copolymer and a-cyclodextrin (a-CD) [234]. These polymersomes possess unique structures the surface is covered by PRX structures with multiple a-CDs threaded onto the PEG chain. Since the a-CDs are not covalently bound to the PEG chain, they can slide and rotate along the PEG chain, which forms the outer shell of the polymersomes [235,236]. Thus, the polymersomes could be a novel functional biomedical nanomaterial having a dynamic surface. 

It has been demonstrated that the presence of CNTs greatly increases the oxidation peak current of 6-benzylaminopurine. The CNT-modified electrode is suitable for the determination of trace amounts of benzylaminopurine and has the advantages of high sensitivity, quick response, and good stability [86], Wang et al. have studied the electro-catalytic oxidation of thymine at a a-cyclodextrin incorporated CNT coated electrode in an alkaline media. A sensitive detection scheme for thymine has been further developed by using differential pulse voltammetry [87], The electrochemical determination... 

Cross-interaction constants and transition-state structure in solution, 27, 57 Crown-ether complexes, stability and reactivity of, 17,279 Crystallographic approaches to transition state structures, 29,87 Cyclodextrins and other catalysts, the stabilization of transition states by, 29,1... 

Tetrahedral intermediates, derived from carboxylic acids, spectroscopic detection and the investigation of their properties, 21, 37 Topochemical phenomena in solid-state chemistry, 15, 63 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and, 27, 1 Transition state structure, secondary deuterium isotope effects and, 31, 143 Transition states, structure in solution, cross-interaction constants and, 27, 57 Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1 Transition states, theory revisited, 28, 139... 

Transition stale structure, secondary deuterium isotope effects and, 31, 143 Transition states, structure in solution, cross-interaction constants and, 27, 57 Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1 Transition states, theory revisited, 28, 139... 

Hora et al. [3.19] described the complexity of protein stabilization by the example of recombinant, human Interleukin-2 (rhIL-2). Formulations with amino acids and mannitol/ sucrose are sensitive to mechanical stress e. g. by pumping. Hydroxypropyl-beta-cyclodextrin (HPcD) provides stability, but increases the sensitivity to oxygen. Polysor-bate 80 forms a mechanically stable product, but results in oxidation. In both cases contamination in the HPcD or traces of H202 in the Polysorbate may have been the starter for the oxidation. Brewster [3.20] reports, that HPcD stabilizes interleukin without forming aggregations and this results in 100 % biopotency. 

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