Cyclodextrin catalysis

All the reactions catalyzed by CyDs (and by their derivatives) proceed via their complexes with substrates, in which the chemical transformation takes place. This reaction scheme is exactly parallel to that employed by naturally occurring enzymes, and both high specificity and large reaction rates are primarily associated with this reaction scheme. Catalyses by CyDs are divided into three categories (1) covalent catalysis in which a covalent intermediate is first formed from CyD and substrate and this intermediate is converted to the final products in the following step, (2) general acid-base catalysis by OH groups, and (3) non-covalent catalysis in which CyDs participate in the reactions only in a noncovalent fashion without even proton-transfer processes. The number of papers on catalysis by CyDs has 

Cyclodextrins and Their Complexes. Edited by Helena Dodziuk Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31280-3 

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Quantitative Structure-Reactivity Analysis of Cyclodextrin Catalysis.82... 

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. 

The present review is concerned with the applications of the quantitative structure-reactivity analysis to cyclodextrin complexation and cyclodextrin catalysis, mostly from our laboratories, as well as the experimental and theoretical backgrounds of these approaches. 

The importance of the proximity effect in cyclodextrin catalysis has been discussed on the basis of the structural data. Harata et al. 31,35> have determined the crystal structures of a-cyclodextrin complexes with m- and p-nitrophenols by the X-ray method. Upon the assumption that m- and p-nitrophenyl acetates form inclusion complexes in the same manner as the corresponding nitrophenols, they estimated the distances between the carbonyl carbon atoms of the acetates and the adjacent second-... 

In these equations, Dmax is the larger of the summed values of STERIMOL parameters, Bj, for the opposite pair 68). It expresses the maximum total width of substituents. The coefficients of the ct° terms in Eqs. 37 to 39 were virtually equal to that in Eq. 40. This means that the a° terms essentially represent the hydrolytic reactivity of an ester itself and are virtually independent of cyclodextrin catalysis. The catalytic effect of cyclodextrin is only involved in the Dmax term. Interestingly, the coefficient of Draax was negative in Eq. 37 and positive in Eq. 38. This fact indicates that bulky substituents at the meta position are favorable, while those at the para position unfavorable, for the rate acceleration in the (S-cyclodextrin catalysis. Similar results have been obtained for a-cyclodextrin catalysis, but not for (S-cyclodextrin catalysis, by Silipo and Hansch described above. Equation 39 suggests the existence of an optimum diameter for the proper fit of m-substituents in the cavity of a-cyclodextrin. The optimum Dmax value was estimated from Eq. 39 as 4.4 A, which is approximately equivalent to the diameter of the a-cyclodextrin cavity. The situation is shown in Fig. 8. A similar parabolic relationship would be obtained for (5-cyclodextrin catalysis, too, if the correlation analysis involved phenyl acetates with such bulky substituents that they cannot be included within the (5-cyclodextrin cavity. 

A few examples have been reported in which no steric parameter is involved in the correlation analysis of cyclodextrin catalysis. Straub and Bender 108) showed that the maximal catalytic rate constant, k2, for the (5-cyclodextrin-catalyzed decarboxylation of substituted phenylcyanoacetic acid anions (J) is correlated simply by the Hammett a parameter. 

As shown above, quantitative structure-reactivity analysis is very useful in elucidating the mechanisms of cyclodextrin complexation and cyclodextrin catalysis. This method enables us to separate several intermolecular interactions, acting simultaneously,... 

Figure 5.5. The cyclodextrin catalysis of phenylester hydrolysis (Saenger, 1980).

Ihbushi I (1982) Cyclodextrin catalysis as a model for enzyme action. Acc Chem Res 15 66-72... 

Since the effective catalysis by g-cyclodextrin is evident from these observations, the observed rates were analyzed by the Linewe-aver-Burk treatment to give satisfactory straight line from which and K2 were estimated, where kQ g is the observed pseudo first order rate constant and each k is the rate constant of the cyclodextrin catalysis. The rate constants thus obtained are listed in Table III. 

Therefore, a conclusion can be drawn that a base partecipating in the E2 mechanism is the monoanion of 3-cyclodextrin. Careful examination of the recovered cyclodextrin did not show the formation of any naphthylethyl derivative of cyclodextrin, suggesting that the reaction of the cyclodextrin monoanion does not contribute appreciably. The present reaction may be conveniently depicted in the Scheme 3. The fact that the E2 reaction is specifically accelerated in the cyclodextrin catalysis is in accord with the observation that the solvolysis of the present substrate in 50% EtOH was considerable decelerated, even though the predominant elimination reaction took place. 

Sangwan and Schneider have studied the effect of cyclodextrins on a number of aqueous Diels-Alder reactions between acrylate, fumarate and maleate derivatives of varying hydrophobicities and (mainly) cyclopenta-diene [26]. No simple correlation between substrate hydrophobicity and cyclodextrin-catalyzed rate enhancement was found. However, those systems that did respond to p-cyclodextrin catalysis exhibited enzyme-like saturation kinetics. This led these workers to conclude that the hydrophobic effect can, in fact, be counterproductive to the Diels-Alder reaction if it leads to unproductive orientation of the reactants. The same can be said about the effect of amphiphiles (detergents capable of micellization) on aqueous Diels-Alder reactions since sodium dodecylsulfate (SDS) decelerated the reaction between cyclopentadiene and methyl acrylate. Those cases in the literature claiming micellar catalysis of the aqueous Diels-Alder reaction may simply be benefiting from the solubilizing effect of the amphiphilic additives rather than any bona fide preorganization of the reactants within a micelle [27,28]. 

Stembach, D.D. Rossana, D.M., Cyclodextrin catalysis in the intramolecular Diels-Alder reaction with the furan diene, J. Am. Chem. Soc., 1982,104,5853-4. 

Inokuma, S., Kimura, K., and Nishimura, J., Synthesis and complexation of azacrownophanes the cyclodextrin catalysis of the photochemical cyclization reaction, /. Inclusion Phenomena, 39, 35, 2001. 

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