Cyclodextrins, imidazole-functionalized

Classically, the bell-shaped dependence of rate of the enzymic reaction on pH has been attributed to general acid and base catalysis by the two histidine residues in the active site, His-12 and His-119 (66). Support for this explanation based on the kinetic properties of a model system was first provided by an observation by Breslow and co-workers that 8-cyclodextrin functionalized with two imidazole groups will catalyze the 1,2-cyclic phosphate of 4-rert-butylcatechol (67). The dependence of hydrolysis rate on pH mimics that of RNase A, and this behavior demonstrates that the presence of two imidazole functional groups on a nonionizable framework is the simplest kinetic mimic of the enzyme. 

Breslow s P-cyclodextrine ribonuclease model system represents one of the best examples concerning the construction of small enzyme-like molecules [33]. Breslow functionalized the P-cyclodextrine with two imidazole moieties (Figure 10.1). Selectively, catechol cyclic phosphate carrying a 4-tert-butyl group (Figure 10.1a) binds into the cavity of the catalyst (Figure 10. lb) in water solution, and is then hydrolyzed by the... 

We created a mimic of the cleavage of the cyclic phosphate by this enzyme by attaching two imidazole groups to a cyclodextrin molecule in well-defined positions (18). In water, the cyclodextrin bound a cyclic phosphate substrate—not, however, one derived from RNA—and performed the cleavage of the cyclic phosphate by using the two imidazoles as the enzyme does. That is, one functioned as a base, which delivered water... 

We had invoked a simultaneous two proton transfer mechanism rather than a sequential mechanism - in which one catalytic group followed the other in the overall process - and were able to test this with a technique called proton inventory." We examined the original cyclodextrin fcfv-imidazole in mixtures of water and D2O and saw that the rate constant as a function of deuterium concentration followed a curved line, indicating that the isotope effect involved two different protons rather than a single one. To validate this, we also examined the same kind of plot with the cyclodextrin mono-imidazole, in which only one proton would be expected to be moving in the transition state, and this indeed followed a linear plot supporting a single proton motion in the isotope effect. 

Over the last two decades, a thousand structural and functional models for carbonic anhydrase were reported to address the features of the active site and the mechanism of the catalytic reaction. One of the earliest functional models is the supramolecular composite of the Z /5(histamino)cyclodextrin-Zn-imidazole complex 3 that accelerates CO2 hydration at pH 7.0. although the catalytic activity is not good compared with the native... 

The primary hydroxyls are better nucleophiles than the secondary ones so they can be selectively modified using a weak base. Using tert-butyldimethylsilyl chloride (TBSCl) in dimethylformamide (DMF) with imidazole as a base, or in pyridine, gives access to cyclodextrins 5a-c persilylated on their primary rim (Scheme 9.2) [13]. Once these positions are protected, the position 2 can be efficiently functionalized... 

Supramolecular catalysts using synthetic host molecules have been well researched. Early studies realized a hydrolysis reaction for ester derivatives using modified cyclodextrins (CDs). CDs are suitable for the study of two-substrate supramolecular catalysis and for the synthesis of artificial enzymes. 2-Benzyimidazoleacetic acid-modified a-cyclodextrin hydrolyzes m-tert-butylphenyl acetate at an accelerated rate. The imidazole has a benzoate group in a position that imitates the function of the aspartate ion with the catalytic triad characteristics of serine proteases such as chymotrypsin (Figure 12.1). ... 

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