Hydrolysis base catalysis

Edsall, J. T. George Scatchard, John G. Kirkwood, and the electrical interactions of amino acids and proteins. Trends Biochem. Sci. 7 (1982) 414-416. Eigen, M. Proton transfer, acid-base catalysis, and enzymatic hydrolysis. Angew. Chem. Int. Ed. Engl. 3 (1964) 1-19. 

En me Mechanism. Staphylococcal nuclease (SNase) accelerates the hydrolysis of phosphodiester bonds in nucleic acids (qv) some 10 -fold over the uncatalyzed rate (r93 and references therein). Mutagenesis studies in which Glu43 has been replaced by Asp or Gin have shown Glu to be important for high catalytic activity. The enzyme mechanism is thought to involve base catalysis in which Glu43 acts as a general base and activates a water molecule that attacks the phosphodiester backbone of DNA. To study this mechanistic possibiUty further, Glu was replaced by two unnatural amino acids. 

Either acid or base catalysis may be employed. Alkaline catalysts such as caustic soda or sodium methoxide give more rapid alcoholysis. With alkaline catalysts, increasing catalyst concentration, usually less than 1% in the case of sodium methoxide, will result in decreasing residual acetate content and this phenomenon is used as a method of controlling the degree of alcoholysis. Variations in reaction time provide only a secondary means of controlling the reaction. At 60°C the reaction may takes less than an hour but at 20°C complete hydrolysis may take up to 8 hours. 

Hydrolysis of aspirin in H2 0 leads to no incorporation of into the product salicylic acid, ruling out the anhydride as an intermediate and thereby excluding mechanism 1. The general acid catalysis of mechanism III can be ruled out on the basis of failure of other nucleophiles to show evidence for general acid catalysis by the neighboring carboxylic acid group. Because there is no reason to believe hydroxide should be special in this way, mechanism III is eliminated. Thus, mechanism II, general base catalysis of hydroxide-ion attack, is believed to be the correct description of the hydrolysis of aspirin. 

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 16.12 Catalysis of nitrophenylacetate hydrolysis by imidazole—an example of general base catalysis. Proton transfer to imidazole in the transition state facilitates hydroxyl attack on the substrate carbonyl carbon. 

Eigen, M., 1964. Proton transfer, acid-base catalysis, and enzymatic hydrolysis. Angewandte Chemie, Int. Ed. 3 1—72. 

The metabolic breakdown of triacylglycerols begins with their hydrolysis to yield glycerol plus fatty acids. The reaction is catalyzed by a lipase, whose mechanism of action is shown in Figure 29.2. The active site of the enzyme contains a catalytic triad of aspartic acid, histidine, and serine residues, which act cooperatively to provide the necessary acid and base catalysis for the individual steps. Hydrolysis is accomplished by two sequential nucleophilic acyl substitution reactions, one that covalently binds an acyl group to the side chain -OH of a serine residue on the enzyme and a second that frees the fatty acid from the enzyme. 

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 pH profile for the hydrolysis of methyl aspirin, which shows specific acid-base catalysis. The solid line shows the fit according to Eq. (10-21), and the dashed one where ko = 0. Data are from Ref. 16. 

The effects of a series of added tertiary amines on the rate of chedn scission of other polyesters, including poly( e-caprolactone-co-lactic acid), has been studied and found to be equally great (65). The mechanism with tertiary amines can only be general base catalysis for the effectiveness of the amines was not related to their pK values or lipophilicities. The acceleration of the hydrolysis of the polyesters was used as a strategy for controlling the drug release rate. 

When the drug is nonionizable in water, three hydrolytic pathways are available [Eq. (33)] it can degrade by specific acid catalysis represented by the first kinetic term in Eq. (33), water hydrolysis (second term), and specific base catalysis (third term) ... 

General acid/base catalysis is less significant in natural fresh waters, although probably of some importance in special situations. This phenomenon can be described fairly well via the Bronsted law (relating rate constants to pKa and/or pKb of general acids and bases). Maximum rates of general acid/base catalysis can be deduced from a compound s specific acid/base hydrolysis behavior, and actual rates can be determined from relatively simple laboratory experiments (34). 

A bottle labelled as 12% acid in aqueous methanol, and probably two years forgotten, exploded in storage, breaking adjacent bottles[l]. Trichloracetic acid is known to be more unstable, with respect to carbon dioxide and chloroform, in aqueous solution than pure. The reaction usually requires either heat or base catalysis [2], Storage of trichloroacetic acid at less than 30% concentration is not advised [3], Hydrolysis of the trichlorogroup is also conceivable, which would yield intermediate oxalyl monochloride, which habitually breaks down to give carbon monoxide, dioxide and hydrogen chloride. 

Base catalysis, general, of ester hydrolysis and related reactions, 5, 237 Basicity of unsaturated compounds, 4, 195... 

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. 

Earlier pioneering work by Eigen (56) showed that the exchange process of a proton in aqueous acidic/basic medium between species MOH and MO - can in general be represented by Scheme 4 (which can also be adapted to include the proton transfer between a [MOH2] and a [MOH] species). This mechanism, involving protolysis and hydrolysis (acid and base catalysis) and direct proton transfer, can be... 

Proton transfer reactions on the aqua oxo complex are described by Eq. (8) (acid catalysis or protolysis), Eq. (9) (base catalysis or hydrolysis), and Eq. (10) (direct proton exchange). 

E. l Intramolecular general base catalysis of ester hydrolysis 259, E.2 Intramolecular... 

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