Cyclodextrins kinetics

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). 

Nishioka and Fujita78) have also determined the Kd values fora- and (S-cyclodextrin complexes with p- and/or m-substituted phenyl acetates through kinetic investigations on the alkaline hydrolysis of the complexes. The Kd values obtained were analyzed in the same manner as those for cyclodextrin-phenol complexes to give the Kd(X) values (Table 5). The quantitative structure-activity relationships were formulated as Eqs. 30 to 32 ... 

Only the hydrophobic and steric terms were involved in these equations. There are a few differences between these equations and the corresponding equations for cyclo-dextrin-substituted phenol systems. However, it is not necessarily required that the mechanism for complexation between cyclodextrin and phenyl acetates be the same as that for cyclodextrin-phenol systems. The kinetically determined Kj values are concerned only with productive forms of inclusion complexes. The productive forms may be similar in structure to the tetrahedral intermediates of the reactions. To attain such geometry, the penetration of substituents of phenyl acetates into the cyclodextrin cavity must be shallow, compared with the cases of the corresponding phenol systems, so that the hydrogen bonding between the substituents of phenyl acetates and the C-6 hydroxyl groups of cyclodextrin may be impossible. 

The kinetic effects of water and of cyclodextrins on Diels-Alder reactions. Host-guest chemistry, part 18 [65c]... 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

Cyclodextrins as catalysts and enzyme models It has long been known that cyclodextrins may act as elementary models for the catalytic behaviour of enzymes (Breslow, 1971). These hosts, with the assistance of their hydroxyl functions, may exhibit guest specificity, competitive inhibition, and Michaelis-Menten-type kinetics. All these are characteristics of enzyme-catalyzed reactions. 

Lopez-Nicolas JM, Perez-Lopez AJ, Carbonell-Barrachina A and Garcia-Carmona F. 2007. Kinetic study of the activation of banana juice enzymatic browning by the addition of maltosyl-beta-cyclodextrin. J Agric Food Chem 55(23) 9655-9662. 

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. 

Tetrahedral intermediates, derived from carboxylic acids, spectroscopic detection and the investigation of their properties, 21, 37 Thermodynamic stabilities of carbocations, 37, 57 Topochemical phenomena in solid-state chemistry, 15, 63 Transition state analysis using multiple kinetic isotope effects, 37, 239 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... 

Czamieki and Breslow (22) have studied the rate of acyl transfer from a substrate that is bound by the acyl part rather than by the leaving group. Having shown that ferrocene binds strongly to -cyclodextrin, Czamiecki and Breslow employed the p-nitrophenyl ester of ferrocinnamic acid in kinetic studies using DMSO-buffer mixtures. A rate acceleration of 51,000 times background was observed for acylation of /i-cyclodextrin. 

In order to determine the mechanism of complex-formation, however, kinetic methods must be used. Consider one host-two guests complex-ation. The two possible mechanisms are dimerization of the guest outside the cyclodextrin cavity followed by inclusion, and dimerization within the cyclodextrin cavity. Equilibrium measurements alone cannot distinguish between these two possibilities. The same is the case for 2 2 complex-formation, where a larger number of possible mechanisms exist. 

Until 1984, all of the stopped-flow and temperature-jump kinetic studies of alpha cyclodextrin inclusion-complex formation were explainable in terms of a single-step, binding mechanism. According to this mechanism, the observed rate constant, kobs, (for stopped-flow) and the reciprocal relaxation time, 1/t, (for temperature-jump) should show a linear dependence on the edpha cyclodextrin concentration. Sano and coworkers, however, in the case of the iodide-alpha cyclodextrin interaction, and Hersey and Robinson,in the case of various azo dye-alpha cyclodextrin interactions (see Fig. 7), found that certain guest species exhibit a limiting value of kobs and 1/t at high concentrations of alpha cyclodextrin. This behavior can most simply be explained in terms of a mechanism of the type,... 

Hersey and Robinson also foundthat many guest species that show kinetic behavior apparently explicable in terms of a single-step binding, give a discrepancy between the values of the equilibrium constant determined kinetically and those determined from equilibrium studies. It was found that the equilibrium constant, deterrmned spectrophotometrically, was usually greater than the ratio of the forward and backward rate-constants, determined kinetically. They therefore suggested that this discrepancy could be adequately explained if the two-step mechanism just described was used to interpret the results. A similar proposal has also been made by Hall and coworkers, who observed a large discrepancy between AV° values for the inclusion of 1-butanol and 1-pentanol by alpha cyclodextrin, calculated from equilibrium-density measurements and kinetic, ultrasonic-absorption data. 

A study similar to that of Hersey and Robinson has been reported by Seiyama and coworkers.From a stopped-flow, kinetic study of the interaction of various azo dyes and some azo dye-metal complexes with alpha cyclodextrin, they observed two kinetic processes. The dependence of the observed rate-constants for these two processes on the alpha cyclodextrin concentration was found to be explainable in terms of a mechanism identical to that proposed earlier by Hersey and Robinson. In the case of the guests used by Seiyama and coworkers, however, values for the rate constants of the binding step could be determined from the concentration dependence of kobs for the faster process thus,... 

Up to now, evidence for the presence of a conformational change during the inclusion process has been presented only for alpha cyclodextrin, and then only in the case of certain guest molecules. Whether the two-step mechanism is generally applicable is not known, because, owing to the nature of kinetic studies, the results are frequently open to more than one interpretation. Nevertheless, sufficient support for the two-step mechanism has appeared to necessitate its consideration in any future kinetic studies. 

Pyronine Y (PY) with beta cyclodextrin by using the temperature-jump technique. It was found that the kinetic data could be adequately explained by a mechanism involving the stepwise association of two beta cyclodextrin molecules (C) to the dye. Thus,... 

The same mechanism was also proposed by Herkstroeter and coworkers,who carried out absorption and fluorescence measurements on the interaction of 4-pyrenyl butanoate with gamma cyclodextrin. No kinetic studies, however, have yet been performed on these systems in order to verify the proposed mechanism. 

Reddy L. R. Bhanumathi, N. Rao, K. R. (2000) Dynamis kinetic asymmetric synthesis of y -aminoalcohols from racemic epoxides in cyclodextrin complexes under solid state conditions., Chem. Commun. 2321-2322. 

Prbpy, 5-(2-MePr)bpy and 5-(2,2-Mc2Pr)bpy have been prepared and characterized. The mer-and /uc-isomers of each complex have been isolated by use of cation-exchange column chromatography as the steric requirements of the R group increase, the percentage of the /uc-isomer decreases. Enantiomers of [Ru(5-Prbpy)3] + were separated on SP Sephadex C-25. Electro-kinetic chromatography has been used to separate the enantiomers of [Ru(104)3] " anionic carboxymethyl-/ -cyclodextrin was employed as the chiral mobile phase additive. ... 

Preparation and catalysis of disubstituted cyclodextrin as an excellent enzyme model is demonstrated by the RNAase model reported by Breslow et al. (68, 83). The enzyme models 10 and II, derived from 1, show a bellshaped pH versus rate profile for the hydrolysis of the cyclic phosphate of 4-terf-butylcatechol, indicating the cooperative catalysis by two imidazole groups (Fig. 21). The reactions catalyzed by 10 and II give exclusively 12 and 13, respectively. This interesting specificity indicates that the geometry of the P—O bond cleavage is quite different from each other. Another interesting enzyme-like kinetic behavior that these hosts exhibited is successful demonstration of the so-called bell-shaped pH profile. 

---