Hydrolysis of carboxylates

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Transesterification and Hydrolysis of Carboxylic Acid Derivatives, Alcohols, and Epoxides... 

Taft, following Ingold," assumed that for the hydrolysis of carboxylic esters, steric, and resonance effects will be the same whether the hydrolysis is catalyzed by acid or base (see the discussion of ester-hydrolysis mechanisms. Reaction 10-10). Rate differences would therefore be caused only by the field effects of R and R in RCOOR. This is presumably a good system to use for this purpose because the transition state for acid-catalyzed hydrolysis (7) has a greater positive charge (and is hence destabilized by —I and stabilized by +1 substituents) than the starting ester. 

Of fhe eight mechanisms, seven have actually been observed in hydrolysis of carboxylic esters. The one that has not been observed is the BacI mechanism. 

Buchwald P. Structure-metabolism relationships steric effects and the enzymatic hydrolysis of carboxylic esters. Mini Rev Med Chem 2001 1 101-11. 

Cycloamylose-induced rate accelerations are by no means limited only to the hydrolysis of carboxylic acid derivatives. Indeed, one of the first ob-... 

Just as intramolecular catalysis has been observed in the hydrolysis of carboxylate esters, a variety of neighbouring groups can participate in the hydrolysis of phosphates. The alkaline hydrolysis of dimethyl phosphoacetoin [47] has found to be ca. 2 x 106 times faster in water at 25°C than that of... 

Heymann, E. (1982) Hydrolysis of carboxylic esters and amides. In W.B. Jakoby, J.R. Bend and J. Caldwell (Eds.), Metabolic Basis Detoxification, Academic Press, New York, pp. 229-245. 

Results have generally been disappointing. It can be difficult to remove the TSA from the polymer, but a more fundamental problem concerns the efficiency of the catalysis observed. The most efficient systems catalyze the hydrolysis of carboxylate and reactive phosphate esters with Michaelis-Menten kinetics and accelerations (koAJKM)/kunoJ approaching 103,1661 but the prospects for useful catalysis of more complex reactions look unpromising. Apart from the usual difficulties the active sites produced are relatively inflexible, and the balance between substrate binding and product inhibition is particularly acute. 

The Mechanism of, and Constitutional Factors Controlling, the Hydrolysis of Carboxylic Esters. Pt. I. The Constitutional Significance of Hydrolytic Stability Maxima," JCS (1930) 10321057, on 1037. 

Before discussmg the mechanism of cleavage of carboxylic acid esters and amides by hydrolases, some chemical principles are worth recalling. The chemical hydrolysis of carboxylic acid derivatives can be catalyzed by acid or base, and, in both cases, the mechanisms involve addition-elimination via a tetrahedral intermediate. A general scheme of ester and amide hydrolysis is presented in Fig. 3. / the chemical mechanisms of ester hydrolysis will be... 

Fig. 3.1. General scheme for chemical hydrolysis of carboxylic acid esters and amides. Pathway a Proton (general acid) catalyzed hydrolysis. Pathway b HO (general base) catalyzed...

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