Ester hydrolysis rates

In ester hydrolysis, rate-limiting formation of the tetrahedral intermediate usually apphes (Sec. 6.3.1) since the alkoxide group is easily expelled. In contrast, amide hydrolysis at neutral pH involves rate-limiting breakdown of the tetrtihedral intermediate, because RNH is a poor leaving group. The catalytic effect of metal ions on amide hydrolysis has been ascribed to accelerated breakdown of the tetrahedral intermediate. 

L.A. (2005) Estimation of phosphate ester hydrolysis rate constants. I. Alkaline hydrolysis. QSAR Comb. Sci., 25 (2), 123-133. 

Collette, T.W. (1990) Ester hydrolysis rate constant prediction from infrared interferograms. Environ. Sci. Technol. 24, 1671-1676. 

Esterase Activity. Esterase activity was determined as described previously (7). The standard for calculating activity was the ester hydrolysis rate constant for the native protein at the same concentration in the dilution buffer (50 mM Tris sulfate, 5 mM EDTA, pH 7.5). 

A modified y-CD bearing an 0-2-naphthylacetyl substituent prodnced larger overall ester hydrolysis rates in water (pH 8.7) than native y-CD. A 12-fold increase was observed for p-nitrophenyl acetate, arising from both an inaeased rate of intracomplex hydrolysis... 

Complexatlon with Ni to form 17 gives a 56x increase in the ester-hydrolysis rate, while ionization of the sallcyl carboxyl produces a further 1.7x increase, leading to the postulate of biTfunctlonal (carboxylate-metal Ion) catalysis. The carboxylate effect is in the wrong direction for... 

Base hydrolysis of the methyl 6-aminohexanoate ester complex cis-[Co(en)2 NH2(CH2)5COaMe Cl] + takes place in two stages. In the first step chloride ion is displaced, with a second-order rate constant of 13 1 moI s at 25 C. The second step is base hydrolysis of the co-ordinated ester, for which the second-order rate constant is 0.221 mol s at 25 °C. This ester hydrolysis rate is only slightly larger than that for the free ester, which is 0.148 1 mol s. This small difference between rates of hydrolysis of free and complexed ester is the result of the large distance between the cobalt(in) cation and the actual reaction site in the molecule. ... 

Figure 5.37 Effect of ortho and para substitution on ester hydrolysis rate.

The first was proposed by Iraoto and Otsuji (511) and Otsuji et al (512) and concerned the pK of substituted 2-, 4-, and 5-carboxylic acids and the alkaline hydrolysis rate k of their respective ethyl esters (259, 260, and 261, where Y = Et). When Hammett cr , values were used for... 

CycHc esters show accelerated hydrolysis rates. Ethylene sulfate compared to dimethyl sulfate is twice as fast ia weak acid (first order) and 20 times as fast ia weak alkaH (second order) (50). Catechol sulfate [4074-55-9] is 2 x 10 times faster than diphenyl sulfate ia alkaline solution (52). Alcoholysis rates of several dialkyl sulfates at 35—85°C are also known (53). 

The acetylation reaction is stopped by the addition of water to destroy the excess anhydride, causing rapid hydrolysis of the combined sulfate acid ester (Eig. 7). This is followed by a much slower rate of hydrolysis of the acetyl ester groups. The rate of hydrolysis is controlled by temperature, catalyst concentration, and, to a lesser extent, by the amount of water. Higher temperatures and catalyst concentrations increase the rate of hydrolysis. Higher water content slightly iacreases the hydrolysis rate and helps minimize degradation (85). The amount of water also influences the ratio of primary to secondary... 

Hydrolysis of esters and amides by enzymes that form acyl enzyme intermediates is similar in mechanism but different in rate-limiting steps. Whereas formation of the acyl enzyme intermediate is a rate-limiting step for amide hydrolysis, it is the deacylation step that determines the rate of ester hydrolysis. This difference allows elimination of the undesirable amidase activity that is responsible for secondary hydrolysis without affecting the rate of synthesis. Addition of an appropriate cosolvent such as acetonitrile, DMF, or dioxane can selectively eliminate undesirable amidase activity (128). 

This variation from the ester hydrolysis mechanism also reflects the poorer leaving ability of amide ions as compared to alkoxide ions. The evidence for the involvement of the dianion comes from kinetic studies and from solvent isotope effects, which suggest that a rate-limiting proton transfer is involved. The reaction is also higher than first-order in hydroxide ion under these circumstances, which is consistent with the dianion mechanism. 

Apply the steady-state approximation to Scheme XXII for ester hydrolysis to find how the experimental second-order rate constant qh is related to the elementary rate constants. 

A catalyst is a substance that increases the rate of a reaction, other than by a medium effect, regardless of the ultimate fate of this substance. For example, in hydroxide-catalyzed ester hydrolysis the catalyst OH is consumed by reaction with the product acid some writers, therefore, call this a hydroxide-promoted reaction, because the catalyst is not regenerated, although the essential chemical event is a catalysis. 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

In the acidic and alkaline hydrolysis rates of the same ester, the steric and resonance effects. re the same. 

Table 7-17. Relative Rates of Intramolecular Catalysis of Ester Hydrolysis by Carboxylate Groups...

The cyclic phosphonate ester analog of the cyclic transition state. Antibodies raised against this phosphonate ester act as enzymes they are catalysts that markedly accelerate the rate of ester hydrolysis. 

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. 

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