Hydroxide ion catalysis

Finally, in the pH range of 9—10, the slope of the pH profile was unit positive, indicating specific hydroxide ion catalysis. It is thus apparent that the unprotonated N-terminal group imparts more reactively to the... 

Hubbard and Kirsch (1972) have recently proposed that histidine may act as a nucleophile in a-chymotrypsin acylation reactions of esters having a good leaving group (jO-nitrophenol). This suggestion was based on a similarity in p-value for acylation by p-substituted nitrophenyl and dinitrophenyl benzoates and nucleophilic attack on these compounds by imidazole, in contrast with less positive p-values for hydroxide ion catalysis. Hammett p-values for hydrolysis of substituted phenyl esters are given in Table 6 and show little apparent trend. The values for hydroxide ion and alcoholate ions are... 

The Ni - and Zn " " -complexes of phenyl and salicyl esters of pyridine-2,6-dicarboxylic acid [50a and b] hydrolyse much faster than the uncomplexed esters (Breslow and McAllister, 1971) the rate of hydroxide ion catalysis of the Ni " -complexes increases 9300... 

The third test of the conjugate base mechanism that we put forward was based on the idea that the first step should be written as an equilibrium, and the reaction rate should show specific hydroxide ion catalysis. If this is indeed in equilibrium, and deuterium exchange studies say that it must be, then the rate of the reaction must depend on the hydroxide ion concentration, and on nothing else. 

Comparison of the entropies of activation of the forward reactions, AS, with AaS ° indicates that the activated complex is solvated more than the neutral reactants but less than the product ions (Pearson, 1948). The similarity of ASt and A S ° for hydroxide-ion catalysis suggests that here the transition state closely resembles the products. 

Calculated Values of knlkh for Hydroxide Ion Catalysis by Different Mechanisms and kBjka = b5 and 1-0 (OL = 0-47)... 

In the first studies of isotope exchange of the haloforms, general base catalysis could not be clearly observed [164]. In more recent studies of the detritiation of chloroform in aqueous morpholine and piperidine buffers, general base catalysis could not be detected and the reaction was dominated by hydroxide ion catalysis [114]. In this latter study it was assumed that the mechanism of isotope exchange consisted of a slow triton transfer to base (99), viz. 

A reaction with mechanism (99) should show general base catalysis but under some conditions this catalysis is difficult to detect and the rate may be dominated by hydroxide ion catalysis. However, recent work has now been carried out on the detritiation of chloroform in which general base catalysis by amines was observed [171(a)]. In the work with chloroform in which general base catalysis was not detected [114], since it was not possible to obtain a Bronsted exponent by measuring catalytic coefficients for a series of bases, an alternative procedure first suggested by Bell and Cox [172] was used. The rate of detritiation of chloroform was measured in a mixed solvent of water with varying amounts of dimethylsulphoxide and a constant concentration of hydroxide ion. As discussed briefly in Sect. 4.4 an acidity function (H ) has been determined for these solvent... 

Shilov et al studied the rate of oxidation of formate ions in phosphate and carbonate buffers, and showed that the reaction with molecular chlorine is negligible in solutions of pH > 6. At 20 °C the rate of reaction with hypochlorous acid is constant in the range pH 5.5-7, then it decreases with increase of pH, and becomes negligible at pH 13. The kinetics are second-order with respect to hypochlorous acid, and first with respect to formate ions. In alkaline solution hydroxide ion catalysis is apparent viz. 

The pH-rate profiles for the hydrolysis of diltiazem,358 fenprostalene,359 and E09 (a derivative of aziridinylquinone)360 are all V-shaped (Fig. 54), indicating only apparent hydronium ion and hydroxide ion catalysis. The dehydration reaction of streptovitacin A shown in Scheme 32 also exhibits a V-type pH-rate profile.147... 

As can be seen from this equation, kobs should be independent of pH. Thus, when this term is numerically dominant, a pH-independent region is often seen as part of the pH-rateprofile (see profile 4, Fig. 50). That is, U-shaped pH-rateprofiles occur when water catalysis can compete with hydronium ion and hydroxide ion catalysis. The hydrolyses of cephalothin, cephaloridine, and cefotaxime70-73-75 (Fig. 55) are three examples. Although these drug substances have an ionizable carboxylic group at the 4-position, apparent pH-rateprofiles are U-shaped because there is no difference in degradation rate between the ionized and un-ionized forms of these substances. A U-shaped pH-rateprofile has also been reported for hydrolysis of 4 -azidothymidine.133... 

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