Acid-base catalysis reaction rate

The variation with pH of the rate of an enzyme-catalyzed reaction. Contrast this behavior with that found for acid-base catalysis, where rates may pass through a minimum (see Figure 9.19, p. 419). 

A catalyst is defined as a substance that influences the rate or the direction of a chemical reaction without being consumed. Homogeneous catalytic processes are where the catalyst is dissolved in a liquid reaction medium. The varieties of chemical species that may act as homogeneous catalysts include anions, cations, neutral species, enzymes, and association complexes. In acid-base catalysis, one step in the reaction mechanism consists of a proton transfer between the catalyst and the substrate. The protonated reactant species or intermediate further reacts with either another species in the solution or by a decomposition process. Table 1-1 shows typical reactions of an acid-base catalysis. An example of an acid-base catalysis in solution is hydrolysis of esters by acids. 

FIGURE 16.11 Specific and general acid-base catalysis of simple reactions in solution may be distinguished by determining the dependence of observed reaction rate constants (/sobs) pH and buffer concentration, (a) In specific acid-base catalysis, or OH concentration affects the reaction rate, is pH-dependent, but buffers (which accept or donate H /OH ) have no effect, (b) In general acid-base catalysis, in which an ionizable buffer may donate or accept a proton in the transition state, is dependent on buffer concentration. 

A reaction with a rate constant that conforms to Eq. (10-21)—particularly to the feature that the catalysts are H+ and OH-, and not weak acids and bases—is said to show specific acid-base catalysis. This phenomenon is illustrated by the kinetic data for the hydrolysis of methyl o-carboxyphenyl acetate16 (the methyl ester of aspirin— compare with Section 6.6) ... 

The rate of a reaction that shows specific acid (or base, or acid-base) catalysis does not depend on the buffer chosen to adjust the pH. Of course, an inert salt must be used to maintain constant ionic strength so that kinetic salt effects do not distort the pH profile. 

The ionizable functional groups of aminoacyl side chains and (where present) of prosthetic groups contribute to catalysis by acting as acids or bases. Acid-base catalysis can be eithet specific ot general. By specific we mean only protons (HjO ) or OH ions. In specific acid or specific base catalysis, the rate of reaction is sensitive to changes in the concenttation of protons but... 

Rates of addition to carbonyls (or expulsion to regenerate a carbonyl) can be estimated by appropriate forms of Marcus Theory. " These reactions are often subject to general acid/base catalysis, so that it is commonly necessary to use Multidimensional Marcus Theory (MMT) - to allow for the variable importance of different proton transfer modes. This approach treats a concerted reaction as the result of several orthogonal processes, each of which has its own reaction coordinate and its own intrinsic barrier independent of the other coordinates. If an intrinsic barrier for the simple addition process is available then this is a satisfactory procedure. Intrinsic barriers are generally insensitive to the reactivity of the species, although for very reactive carbonyl compounds one finds that the intrinsic barrier becomes variable. ... 

In aqueous solution, the rates of many reactions depend on the hydrogen-ion (H+ or h3o+) concentration and/or on the hydroxyl-ion (OH-) concentration. Such reactions are examples of acid-base catalysis. An important example of this type of reaction is esterification and its reverse, the hydrolysis of an ester. 

It appears that all these possibilities can be excluded. If reactions (a) or (gf) were rate-limiting the reaction velocity would be independent of the concentration of the substrate, while reaction (e) (identical with (Z)) would predict no catalysis by acids or bases. If reactions (b), (d) or (h) determined the rate the reaction would show specific catalysis by hydrogen or hydroxide ions, in place of the general acid-base catalysis actually observed. Reactions (c), (f) and (m) are unacceptable as rate-limiting processes, since they involve simple proton transfers to and from oxygen. Reactions (j) and (k) might well be slow, but their rates would depend upon the nucleophilic reactivity of the catalyst towards carbon rather than on its basic strength towards a proton as shown in Section IV,D it is the latter quantity which correlates closely with the observed rates. 

It has been shown by H naff (1963) that the rate of reaction of several carbonyl reagents (bisulphite, hydrazine, phenylhydrazine, semi-carbazide and hydroxylamine) with aqueous formaldehyde solutions is independent of the nature and concentration of the reagent, and is therefore determined by the rate of dehydration of methylene glycol. He obtained catalytic constants for hydrogen and hydroxide ions, and a detailed study of acid-base catalysis has been made by the same method by Bell and Evans (1966). 

Such behavior is more common than the full rate/pH profile of (1.207). Equation (1.208) is observed in acid catalysisand (1.209) in base catalysis. The rate constant for the reaction of only one of the two forms can be obtained directly, that is, in (1.208) and in (1.209). Ancillary information on is required to assess the rate constant of the acid-base partner. The absence of reliable data on A jj can pose a problem in assessing the missing rate constant. 

Acid-base catalysis appears to be an important factor in virtually all enzymatic reactions. The rates of proton transfer reactions have been well studied in model systems,30 but not during the course of enzyme catalysis. The protonation and deprotonation of acids and bases can be represented as... 

Most enzymes employ a combination of several catalytic strategies to bring about a rate enhancement. A good example of the use of both covalent catalysis and general acid-base catalysis is the reaction catalyzed by chymotrypsin. The first step is cleavage of a peptide bond, which is accompanied by formation of a covalent linkage between a Ser residue on the enzyme and part... 

Fumarase. See Fumarate hydratase Fumarase-aspartase family 685 Fumarate 481s, 516s, 683s Fumarate hydratase (fumarase) 526, 683,688 acid-base catalysis 471 concerted reaction 685 Fumarase A 688 Fumarase B 688 Fumarase C 683 mechanism 683 - 685 pH dependence 684 rates of substrate exchange 684 turnover number of 683 Fumarate reductase 785 Fumarylpyruvate 690s Function of state R 476 Fungal infections 20 Fungi 20... 

The intermolecular general-base catalysis of the hydrolysis may also be measured. Comparing the rate constants for this with those of the intramolecular reaction shows that a 13-M solution of an external base is required to give the same first-order rate as the intramolecular reaction has.12 The effective concentration of the carboxylate ion in aspirin is therefore 13 M. This is a typical value for intramolecular general-acid-base catalysis. 

Acid-base catalysis is seen to be an effective way of catalyzing reactions. We should now like to know the contribution of this to enzyme catalysis, but there is a fundamental problem in directly applying the results of the last section to an enzyme. The crux of the matter is that the rate constants for the solution catalysis are second-order, the rate increasing with increasing concentration of... 

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