Stability cyclodextrin effect

Scalia S, Mohnari A, Casolari A, Maldotti A. 2004. Complexation of the sunscreen agent, phenyl-benzimidazole sulphonic acid with cyclodextrins Effect on stability and photo-induced free radical formation. European Journal of Pharmaceutical Sciences 22(4) 241-249. 

Excipients such as cyclodextrins, which form inclusion complexes with drug substances, can have a significant effect on drug stability. These effects will be described in... 

Cevallos, R A. R, Buera, M. R, and Elizalde, B. E. (2010). Encapsulation of cinnamon and thyme essential oils componenk (cinnamaldehyde and thymol) in P-cyclodextrin Effect of interactions with water on complex stability. Journal of Food Engineering, 99, 70-75. 

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... 

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... 

The present review deals with a particular aspect of the chemistry of cyclodextrins the effects that they can have on organic reactions by virtue of their abilities to bind to many organic and inorganic species (Bender and Komiyama, 1978 Saenger, 1980 Szejtli, 1982). It is a considerable expansion of an earlier work (Tee, 1989) which first showed how the Kurz approach to transition state stabilization can be employed profitably in discussing reactions mediated by cyclodextrins. Most of the large amount of data that are analysed is collected in tables in the Appendix so as to avoid breaking up the discussion in the main text too frequently. 

By virtue of their complexing ability, CDs may influence the course of chemical reactions in respect of rates and/or product selectivity. In consequence, there is a large body of data in the literature on the effect of CDs on many types of reactions (Fendler and Fendler, 1975 Bender and Komiyama, 1978 Szejtli, 1982 Tabushi, 1982 Sirlin, 1984 Ramamurthy, 1986 Ramamurthy and Eaton, 1988). The present review concentrates on reactions for which sufficient kinetic data are available to allow quantification of the effects of CDs on transition state stability, in an attempt to understand how cyclodextrins influence reactivity in either a positive or negative sense. 

The object of this review was to show how Kurz s approach to quantifying transition state stabilization is useful in the discussion of the kinetic effects of cyclodextrins on organic reactions, while at the same time pointing out its comparable utility for various other types of catalyst. It is hoped that the approach gains wider acceptance and employment since it provides a framework for the discussion of factors affecting transition state stability in both catalysed and retarded reactions. 

Some modifications to the cyclodextrin structure have also been found to improve their complexing ability. Casu and coworkers prepared 2,3,6-tri-O-methyl and 2,6-di-O-methyl derivatives of alpha and beta cyclodextrin. They observed that tri-O-methyl-alpha cyclodextrin shows an almost ten-fold increased stability of the complex with the guest, Methyl Orange, compared with the unmodified alpha cyclodextrin. A possible reason for this increase in stability is that the methyl groups are responsible for an extension of the hydrophobic cavity of the cyclodextrin. Other workers,however, observed a much smaller enhancement of stability of complexes on methylation of the cyclodextrin, and a decrease in stability has even been reportedfor the one host-two guests complex of tropaeolin with beta cyclodextrin. Thus, the effect of methylation on the stability of a complex varies with the guest species involved, and cannot be readily predicted. 

Hydrogenation of unsaturated carboxylic acids, such as acrylic, methacryUc, maleic, fumaric, cinnamic etc. acids was studied in aqueous solutions with a RhCU/TPPTS catalyst in the presence of p-CD and permethylated P-cyclodextrin [7]. In general, cyclodextrins caused an acceleration of these reactions. It is hard to make firm conclusions with regard the nature of this effect, since the catalyst itself is rather undefined (probably a phosphine-stabilized colloidal rhodium suspension, see 3.1.2) moreover the interaction of the substrates with the cyclodextrins was not studied separately. 

Decene was hydrocarboxylated with a [PdClaj/TPPTS catalyst in acidic aqueous solutions (pH adjusted to 1.8) in the presence of various chemically modified cyclodextrins (Scheme 10.11) [18]. As in most cases, the best results were obtained with DiOMe-P-CD. In an interesting series of reactions 1-decene was hydrocarboxylated in 50 50 mixtures with other compounds. Although all additives decreased somewhat the rate of 1-decene hydroformylation, the order of this inhibitory effect was 1,3,5-trimethylbenzene < cumene < undecanoic acid, which corresponds to the order of the increasing stability of the inclusion complexes of additives with p-CD, at least for 1,3,5-trimethylbenzene (60 M ) and cumene (1200 M ). These results clearly show the possible effect of competition of the various components in the reaction mixture for the cyclodextrin. 

Let us compare the methods applied by Pedersen for establishing the complex formation with a modern approach. Today tedious solubility studies are carried out almost exclusively with practical applications in mind, but they are not performed to prove the complex formation. For instance, one ofthe main reasons for the use of cyclodextrin complexes in the pharmaceutical industry is their solubilizing effect on drugs [8]. There, and almost only there, solubility studies are a must. As concerns spectroscopic methods, at present the NMR technique is one ofthe main tools enabling one to prove the formation of inclusion complex, carry out structural studies (for instance, making use of the NOE effect [9a]), determine the complex stability [9b, c] and mobility of its constituent parts [9d]. However, at the time when Pedersen performed his work, the NMR method was in the early stage of development, and thus inaccurate, and its results proved inconclusive. UV spectra retained their significance in supramolecular chemistry, whilst at present the IR method is used to prove the complex formation only in very special cases. 

The present paper is intended to provide a survey on the stabilizing effects of cyclodextrin complexation. Beyond this,other practical consequences of the molecular entrapment of flavors will also be mentioned. 

Table VII (51). The relevant free dimensions are often similar for zeolite and nonzeolite. Urea (free diameter 5.2 A) is like Sieve A (free diameter of windows 4.3 A) in accommodating n- but not isoparaffins. Thiourea (6.1 A) and offretite (6.3 A) have channels with similar free diameters as do 0-cyclodextrin (7-8 A) and zeolite L (7.1 X 7.8 A). In thiourea the loose fit of n-paraffins in the tunnel appears to destabilize the adducts (85, 36). The same is true of disc-shaped molecules comprising only benzenoid rings. However, if suitably bulky saturated side chains are attached (cyclohexyl-benzene or fertf-butylbenzene), then adduction readily occurs. Heterocy-clics, like unsubstituted aromatics, do not readily form adducts. Thus flat molecules also exert a destabilizing effect upon the tunnels of a circular cross section. Such stability problems do not arise with the robust, permanent zeolite structures, and this constitutes an interesting distinction. Offretite, for example, readily sorbs benzene or heterocyclics with or without alkyl side chains, provided only that they are not too large to permeate the structure.

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