Esters specific acid/base catalysis

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) ... 

A classical example of specific acid-base catalysis is the hydrolysis of esters. The hydrolysis is catalyzed by H30" and OH" but not by other acids or bases. The rate of hydrolysis in the absence of acid or base is extremely slow. 

The reaction of ester hydrolysis and backward reaction of esterification of carboxylic acids are studied in detail. Ester hydrolysis is catalyzed by both hydrogen ions and hydroxyl ions, that is, is an example of specific acid-base catalysis. Two different methods for the cleavage of ester bonds are possible and observed experimentally acyl-oxygen and alkyl-oxygen... 

The other kind of acid/base catalysis is called general rather than specific and abbreviated GAC or GBC. As the name implies this kind of catalysis depends not only on pH but also on the concentration of undissociated acids and bases other than hydroxide ion. It is a milder kind of catalysis and is used in living things. The proton transfer is not complete before the rate-determining step but occurs during it. A simple example is the catalysis by acetate ion of the formation of esters from alcohols and acetic anhydride. 

The reactivity, fate, and distribution of bound solutes are certainly changed by association with stream humic substances. The rate of photolysis of certain organic compounds (Zepp et al., 1981a,b), the rate of volatilization of polychlorinated biphenyls (Griffin and Chian, 1980), the bioaccumulation of polynuclear aromatic hydrocarbons in fish (Leversee, 1981), the rate of humic acid induced acid-base catalysis (Perdue, 1983), and the rate of microbiological decomposition are some specific examples. The octyl ester of 2,4-D (2,4 DOE) was predicted by theoretical and mathematical models and found by experimentation to be resistant to base hydrolysis when bound to humic substances (Perdue, 1983). The same model predicted the humic acid catalyzed hydrolysis of atrazine as demonstrated by Li and Felbeck 11972). 

RNase Tl cleaves P-05 ester bonds in ssRNA, specifically at the 3 -P of the guanylic acid residues. As in RNase A (see Fig. 3.3), the catalysis occurs by a two-step mechanism, i.e., the formation of a terminal guanosine 2, 3 -cyclic phosphate intermediate (transesterification step) and the hydrolysis of the cyclic ester to guanosine 3 -monophosphate (hydrolysis step). The transesterification step involves a general acid—base catalysis. 

Poly(L-malate) decomposes spontaneously to L-ma-late by ester hydrolysis [2,4,5]. Hydrolytic degradation of the polymer sodium salt at pH 7.0 and 37°C results in a random cleavage of the polymer, the molecular mass decreasing by 50% after a period of 10 h [2]. The rate of hydrolysis is accelerated in acidic and alkaline solutions. This was first noted by changes in the activity of the polymer to inhibit DNA polymerase a of P. polycephalum [4]. The explanation of this phenomenon was that the degradation was slowest between pH 5-9 (Fig. 2) as would be expected if it were acid/base-catalyzed. In choosing a buffer, one should be aware of specific buffer catalysis. We found that the polymer was more stable in phosphate buffer than in Tris/HCl-buffer. 

Acids and bases provide the best known ways of speeding up reactions. If you want to make an ester—add some acid. If you want to hydrolyse an ester—add some base. It may all seem rather simple. However, there are actually two kinds of acid catalysis and two kinds of base catalysis and this section is intended to explain the difference in concept and how to discover which operates. When we talk about acid catalysis we normally mean specific acid catalysis. This is the kind we have just seen—epoxides don t react with methanol but, if we protonate the epoxide first, then it reacts. Specific acid catalysis protonates electrophiles and makes them more electrophilic. 

The data above indicate that more is involved in the reaction than just the amino acid ester serving as a nucleophile in competition with water. A specificity of the enzyme toward the amino acid ester also exists. Perhaps a better understanding of the reaction can be obtained by considering some of the properties of papain. Considerable data are available on the structure of papain, in particular its active site. His-159 is thought to be involved in catalysis as a general acid-base in which Cys-25 becomes acylated in an intermediate step (64). Schechter and Berger (27, 28) postulated from data of studies on the specificity of... 

As you have seen throughout this book, acids and bases provide the most widely used ways of speeding up reactions. If you want to make an ester—add some acid. If you want to hydrolyse an ester—add some base. We explained in Chapter 12 the ways in which acid and base catalysts help reactions along, and we introduced you to the terms specific acid and specific base, general acid and general base. We will now look in a little more detail at these types of catalysis and give some pointers as to how to establish which of them, if any, is operative in any given reaction. 

It is quite common for specific acid and specific base catalysis to operate on the same reaction, depending on the pH at which the reaction is carried out. In fact, you have already seen this for ester hydrolysis in Chapter 12. The pH-rate profile (Chapter 12) for the hydrolysis of a simple ester such as ethyl acetate shows just two straight lines meeting each other (and zero rate) at about neutrality. Ethyl acetate hydrolysis occurs by SAC or SBC only. 

Some evidence appears to support intramolecular general acid-specific base catalysis through electrostatic bonding as in 15139.141-143 recent worki , especially that on the relative order of hydrolysis, selenoester > thiolester > ester, suggests intramolecular nucleophilic catalysis through anchimeric assistance of the dimethylamino group as in 16 . 

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