Acid-base catalysis, versus

General acid-base catalysis is often the controlling factor in many mechanisms and acts via highly efficient and sometimes intricate proton transfers. Whereas log K versus pH profiles for conventional acid-base catalyzed chemical processes pass through a minimum around pH 7.0, this pH value for enzyme reactions is often the maximum. In enzymes, the transition metal ion Zn2+ usually displays the classic role of a Lewis acid, however, metal-free examples such as lysozyme are known too. Good examples of acid-base catalysis are the mechanisms of carbonic anhydrase II and both heme- and vanadium-containing haloperoxidase. 

The non-linear plot in Fig. 11.2A indicates acid-base catalysis (i.e. when both acid and base are involved in the same catalytic mechanism with rate = 1cha.b[HA] [B] [HS]), and the Icha.b parameter can be determined from the slope of a plot of k0bs/(l - FB)( [acid] + [base])2 versus FB (not shown). 

There are several types of pH-dependent kinetic behavior that can be interpreted in terms of one or more of the various forms of the specific acid-base catalysis relation [equation (7.3.2)]. Skrabal (33) classified the various possibilities that may arise in reactions of this type, and Figure 7.3 is based on this classification. The various forms of the plots of log k versus pH reflect the relative importance of each of the various terms in equation (73.2) as the pH shifts. Curve a represents the most general type of behavior. This curve consists of a region where add catalysis is superimposed on the noncatalytic reaction, a region where neither acid nor base catalysis is significant. 

A reaction catalyzed by undissociated acid will have the dependence of log k on pH shown in Figure 3g. Specific acid and specific base catalysis are presumed to be absent. If specific and general acid and base catalysis are both operative, one is able to obtain a variety of interesting log k versus pH curves, depending on the relative contributions of the different terms in various pH ranges. Curves i and j of Figure 7.3 are simple examples of these types. 

Hydrolysis of sucrose (acid versus base catalysis)... 

General Acid Catalysis Versus Specific Acid-General Base Catalysis ... 

A variety of kinetic experiments is used to deduce this information. The algebraic form of the rate equation as a function of substrate concentrations limits the kinetic mechanism, wh inhibition patterns for products or dead-end inhibitors versus the various substrates pin it down, and often help to determine the rate-limiting step. Isotope exchange and partitioning studies complete the analysis of kinetic mechanism. The chemical mechanism is deduced by studying the pH variation of the kinetic parameters, which identifies the acid-base catalysts, and necessary protonation states of the substrate for binding and catalysis, and by certain kinetic isotope effect studies. 

The log (V7A versus pH profile for a nonsticky substrate shows the correct pKj, values of groups necessary for binding and catalysis. Those p Ta values not present in profiles are groups that act as acid-base catalysts during... 

The following is a hypothetical exampleof a logjfc,, ) versus pH profile for the hydrolysis of an ester with an added acid such as acetic acid. Examine this curve and state which form of acid or base catalysis is occurring at the various pH regions. Write a rate law that would describe this curve. 

The second and third terms in rate expression Eq. 11.1 ( rLHsO" ] and Aoh[OH"], respectively) clearly indicate that the hydrolysis of styrene oxides is subject to both and OH" catalysis. Acid-base catalyzed reactions have characteristic profiles when plotting log Aobs versus pH (a typical profile is represented in Fig. 11.1). The plots would reflect the contribution of the acid catalysis (a), the spontaneous (uncatalyzed) mode (b) and the basic catalyzed reaction (c). ... 

Researchers fundamentally interested in C-C bond-forming methods for polyketide synthesis have at times viewed allylation methods as alternatives, and maybe even competitors, to aldol addition reactions. Both areas have dealt with similar stereochemical problems simple versus absolute stereocontrol, matched versus mismatched reactants. There are mechanistic similarities between both reaction classes open and closed transition states, and Lewis acid and base catalysis. Moreover, there is considerable overlap in the prominent players in each area boron, titanium, tin, silicon, to name but a few, and the evolution of advances in both areas have paralleled each other closely. However, this holds for an analysis that views the allylation products (C=C) merely as surrogates of or synthetic equivalents to aldol products (C=0). The recent advances in alkene chemistry, such as olefin metathesis and metal-catalyzed coupling reactions, underscore the synthetic utility and versatility of alkenes in their own right. In reality, allylation and aldol methods are complementary The examples included throughout the chapter highlight the versatility and rich opportunities that allylation chemistry has to offer in synthetic design. 

Intramolecular general acid catalysis is normally detected in the first instance by a horizontal portion on the plot of logiokobs versus pH, governed by the add dissociation constant of the substrate. Thus, the hydrolyses of various salicyl acetals (including the P-D-glucopyranoside below pH 10, " where a base-catalysed process occurs) obey the rate law of eqn (3.7), where ko is the first-order rate constant for hydrolysis of the neutral molecule and ka is the second-order rate constant for the acid-catalysed hydrolysis of the neutral molecule ... 

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