General acid-base catalysis, determination

FIGURE 16.11 Specific and general acid-base catalysis of simple reactions in solution may be distinguished by determining the dependence of observed reaction rate constants (/sobs) pH and buffer concentration, (a) In specific acid-base catalysis, or OH concentration affects the reaction rate, is pH-dependent, but buffers (which accept or donate H /OH ) have no effect, (b) In general acid-base catalysis, in which an ionizable buffer may donate or accept a proton in the transition state, is dependent on buffer concentration. 

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). 

It appears that all these possibilities can be excluded. If reactions (a) or (gf) were rate-limiting the reaction velocity would be independent of the concentration of the substrate, while reaction (e) (identical with (Z)) would predict no catalysis by acids or bases. If reactions (b), (d) or (h) determined the rate the reaction would show specific catalysis by hydrogen or hydroxide ions, in place of the general acid-base catalysis actually observed. Reactions (c), (f) and (m) are unacceptable as rate-limiting processes, since they involve simple proton transfers to and from oxygen. Reactions (j) and (k) might well be slow, but their rates would depend upon the nucleophilic reactivity of the catalyst towards carbon rather than on its basic strength towards a proton as shown in Section IV,D it is the latter quantity which correlates closely with the observed rates. 

The hydrolysis rate of dmgs in liquid dosage forms is strongly influenced by the pH of the solution and can be catalysed not only by H+ and OH ions (specific acid-base catalysis) but also by the components of the buffer used (general acid-base catalysis). We have looked at the ways in which the effect of the buffer components can be removed so that the pH of maximum stability of the solution can be determined from the pH-rate profile and the rate constants for specific acid-base catalysis can be calculated. 

PT step, AGpj. This quantity is determined by the difference between the pKa s of the donor and acceptor (ApKJ. The value of this ApKa in water is the "chemical part" of the general acid-base catalysis and is independent of the specific enzyme active site. In fact, this effect can be simply considered as the result of using different reaction mechanisms with different reactants rather than an actual catalytic effect. The change of the given ApKa from its value in water to the corresponding value in the enzyme active site is a true catalytic effect. This change reflects the electrostatic effect of the enzyme active site which is the subject of the next section. 

An exactly similar treatment can be applied to basic catalysis. The important general result of these considerations is that if general acid-base catalysis is observed in a reaction involving only one proton transfer, then this proton transfer is rate determining. However, it is not safe to assume that the converse is true, i.e., that the substrate and catalyst are effectively in equilibrium in reactions found experimentally to be specifically catalyzed by hydrogen or hydroxyl ions. This is because (as shown in Sec. II.4) catalysis by species other than H+ or OH- may frequently escape observation, giving a false impression of specific catalysis. 

We have indicated how to determine the various kinetic constants appearing in the expression for specific acid and base catalysis. Let us now consider how to evaluate the various contributions to the rate constant in the case of general acid-base catalysis. For reactions of this type in a solution of a weak acid or base and its corresponding salt, the possible catalysts indicated by equation (7.3.3) are the hydro-nium ion, the hydroxide ion, the undissociated weak acid (or base), and the conjugate base (or acid), In the case of acetic acid the general acid would be the neutral CHjCOOH species and the conjugate base would be the acetate ion (CH3COO"). In this case the apparent rate constant can be written as... 

In this section we would like to approach what it concerns the general acid-base catalysis and its associated proton transfer. For example, what determines whether a reaction proceeds by stepwise acid-base catalyzed or concerted reaction mechanisms , or does catalysis take place in such a way as to avoid the most unstable intermediate , etc. Answers to these queries may be found in a rule which states that "Concerted general acid-base... 

Polarographic data yield ki2 = 1.3 X lO W" sec, which agrees well with specific rates of similar reactions shown in Table II. The specific rate kn of the much slower dehydration reaction has been determined by both the temperature and pressure jump methods to be about 0.5 sec at pH 3 and 25 °C with some general acid-base catalysis. While the hydration-dehydration equilibrium itself involves no conductivity change, it is coupled to a protolytic reaction that does, and a pressure jump determination of 32 is therefore possible. In this particular case the measured relaxation time is about 1 sec. The pressure jump technique permits the measurement of chemical relaxation times in the range 50 sec to 50 tisec, and thus complements the temperature jump method on the long end of the relaxation time scale. 

Khan, M.N. Intramolecular general acid-base catalysis and the rate-determining step in the nucleophilic cleavage of maleimide with primary amines. J. Chem. Soc. Perkin Trans. 2. 1985, 1977-1984. 

Much of the study of kinetics constitutes a study of catalysis. The first goal is the determination of the rate equation, and examples have been given in Chapters 2 and 3, particularly Section 3.3, Model Building. The subsection following this one describes the dependence of rates on pH, and most of this dependence can be ascribed to acid—base catalysis. Here we treat a very simple but widely applicable method for the detection and measurement of general acid-base or nucleophilic catalysis. We consider aqueous solutions where the pH and p/f concepts are well understood, but similar methods can be applied in nonaqueous media. 

The systematic variation of cH+, cOH-, etc. allows the experimental determination of each rate constant. If the terms in the first summation on the right of equation 8.2-9 predominate, we have general acid catalysis if those in the second summation do so, we have general base catalysis otherwise, the terminology for specific acid-base catalysis applies, as in the previous section. 

Fig. 11.2 (A) Manifestation of acid, base and acid-base catalysis at constant pH (B) determination of general acid and general base catalysis parameters (FB = [base]/([acid] + [base]). ...

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. 

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