General acid catalysis, definition

The polarographic measurements permit deduction of rate coefficients for hydrolysis of the intermediate. This reaction is also subject to general acid catalysis. Table 3 lists values which have been obtained for the acids HsO , HCOJ and NH4 at three temperatures, together with the energies of activation derived from them. Russian polarographic work gave the first definite indication of the presence of an intermediate in BH4 hydrolysis. Surprisingly, Russian workers... 

General acid catalysis occurs when the rate law includes a concentration term due to added acid (rate = AhaIHA]). Specific acid catalysis involves a rate law with only the oxonium ion (rate = itHlHjOq). Similar definitions apply to general base and specific base catalysis involving base and hydroxide ion respectively. 

Figure 10.15 A shows the steps and relative rates involved in the addition with the strongly basic amines. The addition step has three possible pathways (step 1) direct addition, general-acid catalyzed addition, or specific-acid catalyzed addition. Because the amines are good nucleophiles, they add directly at all pHs, but below pHs around 4 this direct addition becomes rate-determining. This is because there is a low concentration of unproton-ated amine present at low pHs. In some circumstances, enforced general-acid catalysis of the first step is found (see Section 9.3.6 for the definition of enforced catalysis). At the high pHs...

Although the concepts of specific acid and specific base catalysis were useful in the analysis of some early kinetic data, it soon became apparent that any species that could effect a proton transfer with the substrate could exert a catalytic influence on the reaction rate. Consequently, it became desirable to employ the more general Br0nsted-Lowry definition of acids and bases and to write the reaction rate constant as... 

The proposal of the general-acid catalysed expulsion of the leaving group (28) raises the question of possible catalysis by other electrophilic species. No definitive case of catalysis by metal ions has been reported (Lam and Miller, 1966 Giles and Parker, 1970), which may be a consequence of competition from the uncatalysed step which is believed to occur via the entropically favoured transition states [13] or [14] (Kirby andjencks, 1965 Bemasconi, 1973). 

Cage, solvent, 134 Cancellation assumption. 447 Catalysis, 263 acid, 453 buffer, 269 definitions of, 263 electrophilic, 265 general acid, 265, 268 general base, 265, 268, 271 intermolecular, 266 intramolecular, 266 nucleophilic, 266, 268, 271... 

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... 

Many chemical reactions involve a catalyst. A very general definition of a catalyst is a substance that makes a reaction path available with a lower energy of activation. Strictly speaking, a catalyst is not consumed by the reaction, but organic chemists frequently speak of acid-catalyzed or base-catalyzed mechanisms that do lead to overall consumption of the acid or base. Better phrases under these circumstances would be acid promoted or base promoted. Catalysts can also be described as electrophilic or nucleophilic, depending on the catalyst s electronic nature. Catalysis by Lewis acids and Lewis bases can be classified as electrophilic and nucleophilic, respectively. In free-radical reactions, the initiator often plays a key role. An initiator is a substance that can easily generate radical intermediates. Radical reactions often occur by chain mechanisms, and the role of the initiator is to provide the free radicals that start the chain reaction. In this section we discuss some fundamental examples of catalysis with emphasis on proton transfer (Brpnsted acid/base) and Lewis acid catalysis. 

To discuss acid-base catalysis, it is helpful to recall the definitions of acids and bases. In the Brpnsted-Lowry definition, an acid is a proton donor and a base is a proton acceptor. The concept of general acid-base catalysis depends on donation and acceptance of protons by groups such as the imidazole, hydroxyl, carboxyl, sulfhydryl, amino, and phenolic side chains of amino acids all these functional groups can act as acids or bases. The donation and acceptance of protons gives rise to the bond breaking and re-formation that constitute the enzymatic reaction. 

For the definition of general and specific acid catalysis see H. MaskUl, The physical basis of organic chemistry, Oxford University Press, New York, 1993. 

The first indication of the importance of proton-transfer reactions in enzyme catalysis come from the observation that the rate of most enzyme-catalysed reactions displays a relatively simply, sigmoidal or bell-shaped pH dependence. Thus enzymatic reactions require a small number of acids in a definite state of ionization. Later mechanistic studies indeed confirmed that in many cases these acids and bases - usually identifiable from the pK values of the pH-rate profile -act as proton donors and proton acceptors in the rate-limiting step of the catalytic process. Since in biological systems enzymatic reactions occur almost invariably near neutrality, where oxonium and hydroxide ion concentrations are at a minimum, it is not surprizing to find that enzymes make extensive use of general acid and general base catalysis. 

Proton, by definition, is called specific acid, and if the overall energy barrier (activation energy) of a reaction is reduced in the presence of proton as a catalyst, then the reaction is said to involve specific acid catalysis. Generally, catalyst proton reacts with reactant (substrate) in a so-caUed acid-base reaction process, which, in turn, activates the reaction system (by either the preferential destabilization of reactant state or stabilization of transition state in the rate-determining step) for the product formation. The products do not contain any molecular site, which has enough basicity to trap the proton catalyst irreversibly or even reversibly. Thus, for a detectable S A catalysis, the basicity (measured by the magnitude of basicity constant, KJ of the basic site of electrophilic reactant, products, and solvent should vary in the order K, (for electrophilic reactant) > (for solvent) > Kb (for products). 

The catalytic center is formed by residues from both lobes. Sequence comparisons, mutation experiments and biochemical studies indicate an essential fimction in catalysis of phosphate transfer for the conserved amino acids Lys72, Aspl66 and Aspl84 (numbering of PKA). However, the catalytic mechanism of phosphate transfer is not definitely established. It is generally assumed that Aspl66, which is invariant in all protein kinases, serves as a catalytic base for activation of the Ser/Thr hydroxyl and that the reaction takes place by an in-line attack of the Ser-OH at the y-phosphate. 

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