Mutarotation catalysis

In equation 8.2-6a, the slope of -1 with respect to pH refers to specific hydrogen-ion catalysis (type B, below) and the slope of + 1 refers to specific hydroxyl-ion catalysis (Q if k0 predominates, the slope is 0 (A). Various possible cases are represented schematically in Figure 8.5 (after Wilkinson, 1980, p. 151). In case (a), all three types are evident B at low pH, A at intermediate pH, and C at high pH an example is the mutarotation of glucose. Cases (b), (c), and (d) have corresponding interpretations involving two types in each case examples are, respectively, the hydrolysis of ethyl orthoacetate, of P -lactones, and of y-lactones. Cases (e) and (f) involve only one type each examples are, respectively, the depolymerization of diacetone alcohol, and the inversion of various sugars. 

Various possibilities that may arise in the reactions have been classified by Skrabal who plotted log k against the pH of the solution as shown in Fig. 6.5. Curve (a) represents a most general type of behavior for catalysis by H+ and OH ions. The velocity in the intermediate region is equal to H2o [S] so that h2o can also be determined directly from the rate in this region. A curve of the type a is given by the mutarotation of glucose, if k 2o is sufficiently... 

Another fundamental idea that has been invoked to explain enzymatic catalysis is that such reactions utilize bifunctional or multifunctional catalysis that is, several functional groups in the active site are properly aligned with the substrate so that concerted catalysis may occur. Mutarotation of tetramethyl glucose is frequently cited as an example of bifunctional catalysis. Lowry and... 

Zeffren and Hall (1973) have commented that, since reactions with polar transition states in nonpolar solvents can be accelerated by several orders of magnitude by the presence of low concentrations of salts (Winstein et al., 1959), the rate enhancement of tetramethylglucose mutarotation provided by the presence of acid-base pairs such as phenol and pyridine may be due to formation of ion pairs in benzene solution. Salts which do not act as acids and bases catalyse mutarotation of tetramethylglucose in aprotic solvents (Eastham et al., 1955 Blackall and Eastham, 1955 Pocker, 1960). The efficiency of enzymatic catalysis could arise largely from electrostatic catalysis... 

Br0nsted plot for base catalysis of the mutarotation of glucose. 

The idea that simultaneous (i.e., concerted) acid and base catalysis could strongly accelerate reactions was probably introduced by T. M. Lowry in his considerations of general acid-general base catalysis of the mutarotation of glucose (Lowry and Faulkner, 1925). The concept was provided with strong experimental support by C. G. Swain and J. F. Brown (1952a,b), who used... 

Effects of Metal Ions on Imidazole Catalysis of the Mutarotation of Glucose... 

A scheme for the imidazole catalysis of the mutarotation of glucose, similar to the concerted mechanism proposed by Swain and Brown (13), is shown below, in which a proton is transferred from the D-glucose to imidazole or benzimidazole and from the H20 (represented as an acid) to the D-glucose in the rate-determining step. 

Table III. Effect of Ni(ll) on Benzimidazole Catalysis of Mutarotation of Glucose at 25°...

The catalysis of mutarotation of glucosamine hydrochloride involves an intramolecular mechanism, and so the catalytic coefficient of glucosamine. fcc,iNH2> must have the dimension, min.-1, instead of liters/mole min. The total rate is then... 

General base and general acid catalysis. Base-catalyzed mutarotation might be formulated as follows A hydroxyl ion or some other base attacks the proton on the anomeric -OH group of the sugar, removing it to form an anion and the conjugate acid BH+ (Eq. 9-87,... 

Catalysis of mutarotation by acids occurs if an acid donates a proton to the oxygen in the sugar ring as... 

A third possible type of catalysis requires that a base and an acid act synchronously to effect the breaking and formation of bonds in a single step. Thus, tetramethyl-glucose mutarotates very slowly in benzene containing either pyridine (a base) or phenol (an acid). However, when both pyridine and phenol are present, mutarota-tion is rapid. This suggested to Swain and Brown132 a concerted mechanism (Eq. 9-92) in which both an acid and a base participate. 

The original experimental evidence for concerted acid-base catalysis of the mutarotation in benzene is now considered unsound133 134 and concerted acid-base catalysis has been difficult to prove for nonenzy-matic reactions in aqueous solution. However, measurements of kinetic isotope effects seem to support Swain and Brown s interpretation.135 Concerted acid-base catalysis by acetic acid and acetate ions may have been observed for the enolization of acetone136 and it may be employed by enzymes.1363... 

Gibbs energy of dissociation, table 293 pKa values of, table 293 strengths of 95-96 Acid -base catalysis 469,486 - 491 concerted 490 of mutarotation 487 Acid - base chemistry... 

Mutarotation of 0.3% solutions of the freshly dissolved sugars in 12 ml of 5 mM EDTA, pH 7.4 was followed. Significant differences in mutarotation rates (AK) in the presence and absence of 100 units of bovine kidney enzyme were expressed as the ratio AK/Ksp. Differences of less than 5% in these rate constants were not considered significant. Of the 18 sugars listed, nine have been tested previously as substrates for other mammalian mutarotases with essentially the same pattern as described here. The pattern of specificity indicates that a 3-point attachment of enzyme and substrate is necessary for catalysis of mutarotation. b Data from 72). 

The rapid spontaneous mutarotation of glucose-6-phosphate has been shown to result from an intramolecular catalysis of the reaction by the phosphate group at carbon 6 (81). The cleavage of glucose into three carbon fragments, which is essentially a reversal of the aldol condensation reaction, requires the ketohexose as substrate. The necessary isomerization reaction to form the ketohexose then uses the open-chain form intermediate of the mutarotation reaction. Salas et al. (80) have speculated that the enhanced mutarotation of glucose-6-phosphate may thus have been the key requirement which led to the evolution of the phosphorolytic pathway for glucose metabolism. 

A number of other reactions in this general area such as the mutarotation of D-(+)-glucose431,432 and aldose-ketose isomerizations433 are also subject to catalysis by metal ions. 

A possibility that was proposed quite early for the glucose mutarotation, and that could conceivably be of importance for other reactions, is simultaneous catalysis by an acid and a base. It will be recalled from Section 8.1 that hydration requires addition of a proton at one site and removal of a proton from another. If both these processes were to occur in one step, either by means of separate acid and base molecules acting together or by action of a single molecule containing both an acidic and a basic center, we would designate the process as a concerted acid and base catalysis (Equation 8.39).60 Swain found that the rate of... 

Polarimetry is extremely useful for monitoring reactions of optically active natural products such as carbohydrates which do not have a useful UV chromophore, and samples for study do not need to be enantiomerically pure. Nevertheless, compared with spectrophotometry, the technique has been applied to relatively few reactions. It was, however, the first technique used for monitoring a chemical reaction by measuring a physical property when Wilhemy investigated the mutarotation of sucrose in acidic solution and established the proportionality between the rate of reaction and the amount of remaining reactant [50]. The study of a similar process, the mutarotation of glucose, served to establish the well-known Bronsted relationship, a fundamental catalysis law in mechanistic organic chemistry. 

It was generally believed that the characteristic non-linear dependence of the rate constant on n was associated with the existence of the preequilibrium (Bell, 1941). For the mutarotation of glucose a linear variation of rate constant with n had been reported (Hamill and La Mer, 1936c) and cited as an example of a mechanism of acid catalysis without pre-equilibrium. 

A reaction exhibiting general acid catalysis, the ester hydrolysis (XXXVIII), has been discussed in Sect. 2.3. The present section deals with a classic reaction which is subject to both general acid and base catalysis in homogeneous media, the mutarotation of D-glucose. 

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