Mutarotation activation energies

In the absence of steric effects the activation energy of the form I — form II transition should approximate the energy barrier to rotation about the peptide linkage (21 kcal/mole) provided that mutarotation involves the proposed cis — froas-isomerization. Downie and Randall (1959) measured the rates of forward mutarotation of poly-L-proline I in acetic acid at various temperatures and obtained an activation energy, AE = 23 kcal/mole. The rate of the reaction was independent of concentration over a sevenfold dilution of the polymer. That is, at any stage of mutarotation (as measured by [ ][,) the velocity constant, fc, was found to be independent of concentration. On the other hand k decreased from 15 X 10 sec to 2.5 X 10 sec during the course of mutarotation. 

Downie and Randall (1961) have recently measured the mutarotation of poly-O-acetyl-L-hydroxyproline in formic acid and the reverse mutarotation in Ar,iV -dimethylformamide at various temperatures and polymer concentrations. The activation energy of forward mutarotation was 22.4 kcal/mole and of reverse mutarotation, 23.8 kcal/mole, consistent with a tram- m-isomerization mechanism involving rotation about the peptide bonds. 

The concept of bifunctional catalysis was first introduced to account for the unusually large catalytic efficiency of 2-hydroxypyridine in the mutarotation of tetramethylglucose (42). In this reaction, phenol acts as an acid catalyst and pyridine as a basic catalyst and it was, therefore, concluded that a compound with the phenolic hydroxyl and the basic nitrogen at the proper spacing should be able to produce a concerted attack on the sensitive bond of the reactive molecule, with a corresponding reduction of the required activation energy. A similar effect was invoked to explain the unusual pH dependence of the hydrolysis of p-nitrophenyl acetate in the presence of poly-4(5)-vinylimidazole (PVI) (43). 

Aldose-1-epimerase), quite widespread in animal tissue and bacteria, which catalyses mutarotation. The Escherichia coli enzyme has a maximum activity close to neutral pH. The activation energy 4G =11.9 kcal mol" is greatly lowered, as usual with respect to that of the non-enzymically catalysed reaction, close to 17 kcal mol". o-Glucose, D-galactose, and D-fucose are substrates but not D-mannose (Hucho and Wallenfels 1971). 

This formula has been checked in a good number of cases (Isbell and Pigman 1968). The rate is multiplied by a factor of about 2.5 for a temperature of 10°C which corresponds to an activation energy close to 17 kcal mol . Sometimes, as in the case of D-galactose, we can observe an appreciable discrepancy and even, with D-ribose, a variation which is not at all linear. These abnormalities can be easily explained by the presence of more than two tautomers interconverting in solution. Mutarotation is catalysed by acids and bases and is slowest between pH... 

Ea was called the apparent activation energy, and the true activation energy ( ) was calculated from the relationship EA = E +JT. For the mutarotations of D-xylose, D-mannose, D-glucose, and lactose, values of EA were found to be 16,245, 16,375, 16,945, and 17,225 cal. mol-1, respectively. Later, Dyas and Hill, and coworkers289,290 pointed out that Ea is the same as AGf. They calculated AGt and ASf from the reaction constant (k) by die Eyring equation ... 

Activation energies reported229,291,292 for mutarotations of D-glucose catalyzed by the water molecule, the hydrogen ion, the hydroxyl ion, and the D-glucosate anion show no consistent differences in the values corresponding to mutarotations accelerated by these catalysts. 

Smith and Smith230 compared the activation energies for catalysis of the mutarotations by the water molecule, and by each of three acids and four bases, by use of the equation k = PZe EIHT. The values of E found for the various catalysts differed only slightly, and the observed... 

At mutarotational equilibrium in water, D-fructose (51) exists preponderantly as the j8-D-pyranose anomer in the 1C(d) conformation. A 1,2-alkylidene acetal (52) is formed in the same way as for L-sorbose, but this monoacetal has cts-disposed hydroxyl groups at C-4 and C-5 that react readily, forming a l,2 4,5-di-0-alkylidene-)8-D-fructopyranose (53). No evidence is available to indicate that the 1,2-alkylidene acetal might rearrange to a 1,3-alkylidene acetal, and it is to be expected that the activation energy for this isomerization would exceed that for formation of an acetal at 0-4 and 0-5. 

The mutarotations of the sugars listed in Table III and those for many other sugars follow the first-order equation. The activation energy averages about 17,000 cal./mole this value corresponds to an increase in rate of 2.5 times for a 10° rise in temperature. The conformity of the mutarotation data to the first-order equation makes it probable that the main constituents of the equilibrium solution are the a- and jS-pyranose modifications. The actual composition may be calculated from the optical rotations of the equilibrium solution when the rotations of the pure a- and /3-isomers are known. Data of this type are included in Table III. Independent confirmation of the composition of the equilibrium solutions is provided by studies of the rates of bromine oxidation of the sugars, the results of which are also found in Table III. 

Mutarotation Coefficients and Activation Energies for Some Sugars... 

The mutarotation reactions which follow equation (6) may be considered to consist of two simultaneous or consecutive reactions, one of which is slow and the other of which is rapid. The values of mi (which represents the reaction constant for the slowest reaction) are about the same as those for ki + 2 for glucose, and the activation energies also have almost the same value as for glucose (49). It is probable then that the slower reactions... 

A DFT Study of the acid catalysis of the mutarotation of erythrose and threose has looked at reaction in the gas phase, and in a continuum water model.Sodium cation can act as an inhibitor, whereas borane acts as a Lewis acid catalyst. Brpnsted acids H+ and HjO" " are particularly effective, with the activation energy being further lowered using H30" with one bridging H2O. 

We can influence markedly the activation energy for the rotation of the amide bond in polyprolines by appropriate substitution on the pyrrolidine ring. 3y introducing a methyl substituent in the 2-position of proline, we can prepare a polymer which does not mutarotate under ordinary conditions. We expect to continue research in this area. 

The curves for this mutarotation in water [2] are shown in Figure 3. The change is strictly first order, with a half-hfe of 62.1, 29.4 and 15.3 minutes at 15.0, 20.05 and 25.2 °C respectively, corresponding to an activation energy of 98 kJ mof and frequency factor 1.3X10 s . The final specific rotation is [a] = +107°, and there is a positive Cotton... 

Free Energies, Heats, and Entropies of Activation for the Mutarotation of D-GIucose in Water and Aqueous Methanol 0... 

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