Kinetics of acetal and orthobenzoate hydrolysis as probes of cyclodextrin-guest binding (original) (raw)
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Modelling enzyme-substrate binding with functionalized cyclodextrins
1995
In serine protease enzymes, the interaction between the imidazole and carboxylate fbnctional groups is believed to play an important catalytic role in the mechanism of these enzymes. Recently, this interaction has been classified as a Low Bamer Hydrogen Bond (LBHB) which can contribute around 6 kcaVmol of energy to the lowering of the transition state for the hydrolysis in the enzymatic system. Thus, an understanding of such an interaction is crucial in the design of potential catalytic systems that control the selectivity and efficiency of enzymes.
The Journal of Organic Chemistry, 2003
The rate of hydrolysis of esters CF 3 (CF 2 ) n COOPh (1 (n ) 1), 2 (n ) 2), and 3 (n ) 6)) was measured at pH 6.00 and at pH higher than 9.00 in the presence of -cyclodextrin ( -CD). For compounds 1 and 2 the reaction rate decreases as the -CD concentration increases, and they show saturation effects at all pH. It is suggested that the substrate forms an inclusion complex with cyclodextrin. Analysis of the rate data allows calculation of the association equilibrium constant, K CD , the rate constant for the reaction of the included compound, k c , and K TS which is the hypothetical association equilibrium constant for the transition state of the cyclodextrin-mediated reaction. The dependence of log K CD and log K TS with the number of atoms in the chain is different. We suggest that the reactions of 1 and 2 take place with the perfluorinated alkyl chain included in the cavity, whereas the transition state for the reaction of phenyl trifluoroacetate involves a complex with the aryl ring inside the cavity. At low pH the inhibition comes from the protection of the carbonyl group toward nucleophilic attack by water. In basic pH the reaction of HOas an external nucleophile is also inhibited. The cyclodextrin-mediated reaction involves the ionized OH group at the rim of the cyclodextrin cavity with poor efficiency due to an unfavorable orientation of the substrate in the complex. On the other hand, the reaction of compound 3 is strongly accelerated by cyclodextrin because the association of the substrate with cyclodextrin competes with the monomer-aggregate equilibrium and at high enough cyclodextrin concentration the main species present in solution is the complex between 3 and cyclodextrin.
Peculiarities of β-cyclodextrin acid hydrolysis
2008
Acidic hydrolysis of β-cyclodextrin in acetic acid solutions was investigated. It was found from kinetic observations and reverse kinetic isotope effect that the reaction proceeded according to the mechanism of specific acid catalysis. Investigation of cyclodextrin hydrolysis in the presence of some aromatic and aliphatic compounds was carried out. The rate of the reaction was found to decrease with an increase in the concentration of a guest.
The Journal of Organic Chemistry, 1994
The effects of DMSO on the kinetics of cleavage of m-and p-nitrophenyl alkanoates (mNPAlk and pNPAlk) by aand P-cyclodextrin (a-CD and P-CD) in basic aqueous solution have been studied. For the two acetates addition of up to 60% (v/v) of DMSO increases rates but overall it has little effect on substrate binding, transition state binding, or the acceleration due to complexation. By contrast, in 50% (v/v) aqueous DMF these characteristics are greatly affected such that the normal difference in reactivity of the isomers is almost removed. The cleavage of mNPAlk and pNPAlk (C2 to C10) by the CDs in 60% (v/v) aqueous DMSO have very different chain length dependences for substrate binding and transition state binding, and there are significant changes from their behavior in water. Even though hydrophobic effects seem to be largely removed in 60% aqueous DMSO, and the difference between the reactivities of the isomers is reduced, reaction of mNPAlk proceeds through aryl group inclusion and that of pNPAlk through acyl group inclusion, as in water. The cleavage of m-tert-butylphenyl acetate is accelerated more in 60% (v/v) aqueous DMSO than in water because the solvent change weakens substrate binding more than transition state binding.
Binding of substituted acetic acids to?-cyclodextrin in aqueous solution
Journal of Pharmaceutical Sciences, 1997
0 Complex binding constants of 23 aliphatic acids with R-cyclodextrin in aqueous solution were measured by potentiometry, solubility, or competitive spectrophotometry at 25°C. All systems formed 1:1 acid:cyclodextrin complexes, and some of them also formed 1:2 complexes. The conjugate acids formed stronger complexes than did the conjugate bases (except for glycine). Empirical correlations of complex stabilities are shown with partition coefficients, surface areas, molar refraction, and other descriptors. Complex stability appears to result from the hydrophobic effect, the dispersion interaction, and interaction of the carboxylic acid group with the cyclodextrin.
Binding and Catalytic Properties of 2-O- and 3-O-Permethylated Cyclodextrins
Bulletin of the Chemical Society of Japan, 2009
Hexakis(3-O-methyl)-¡-cyclodextrin (3¡) bound to m-and p-nitrophenolate ions more strongly, whereas hexakis(2-O-methyl)-¡-cyclodextrin (2¡) bound less strongly than native ¡-cyclodextrin. ROESY spectra showed that the 3-Omethyl groups of 3¡ interact with the guest protons, whereas 2-O-methyl groups of 2¡ do not. 3¡ accelerated and 2¡ decelerated the cleavage of m-nitrophenyl acetate in an alkaline solution, suggesting that the C(2)ÍOH of ¡-cyclodextrin is more catalytic than the C(3)ÍOH. However, the catalytic effect of 3¡ was much smaller than that of native ¡cyclodextrin. Loss of hydrogen bonding between the C(3)ÍOH and C(2)ÍOH by 3-O-permethylation is responsible for the small catalytic effects of 3¡. Similar results were obtained for ¢-cyclodextrin analogs.
Reaction Kinetics and Catalysis Letters, 2000
The acid catalyzed hydrolysis of two N−substituted hydroxamic acids (C 6 H 5 CON(OH)R', R' = C 6 H 5 (PBHA), R' = C 6 H 5 CH 2 (BBHA)) in mixed systems containing β−cyclodextrin (β−CD) and a surfactant (sodium dodecyl sulfate, SDS) has been studied. The reactions are inhibited by β−CD. The inhibition is attributed to the formation of inclusion complex and competition between the micellization and complexation processes.