General Acid-Base Catalysis in Model Systems

General Acid-Base Catalysis in Model Systems 

Proton transfer is the most common reaction in living systems, in which reactions have to be strictly controlled, and most are catalyzed by enzymes. The great majority of enzyme catalyzed reactions are ionic, involving heterolytic bond making and breaking, and thus the creation or neutralization of charge. Under conditions of constant pH this requires the transfer of protons (Eq. (2.1)). 

General acid and general base catalysis are terms commonly used to describe two different characteristics of reactions, the (observable) form of the rate law or a (hypothetical) reaction mechanism proposed to account for it. It is important to be aware of (and for authors to make clear) which is meant in a particular case. 

General acid-base catalysis provides mechanisms for bringing about the necessary proton transfers without involving hydrogen or hydroxide ions, which are present in water at concentrations of only about 10 M under physiological conditions. At pHs near neutrality relatively weak acids and bases can compete with lyo-nium or lyate species because they can be present in much higher concentrations. 

The basics of general acid and general base catalysis are described clearly and in detail in Chapter 8 of Maskill [1]. Acid-base catalysis is termed specific if the rate of the reaction concerned depends only on the acidity (pH, etc.) of the medium. This is the case if the reaction involves the conjugate acid or base of the reactant preformed in a rapid equilibrium process - normal behavior if the reactant is weakly basic or acidic. The conjugate acid or base is then, by definition, a strong 

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I 2 General Acid-Base Catalysis in Model Systems... 

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. 

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