Mutarotation proton

Lowry is best known to chemistry students through the tradition of eponymony, since the proton theory of acidity is known as the "Bronsted/Lowry theory" of proton donors. His most important experimental investigation likely was a long series of studies on optical rotatory dispersion.49 For our purposes, there is special interest in his discovery of mutarotation in camphor derivatives and his theory of dynamic tautomerism, which led him to an ionic theory of organic reaction mechanisms. 

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. 

It is easy to see from Equation 8 why —NH3+ ion does not catalyze the mutarotation The positively charged ion cannot extract the proton from the hydroxyl group on carbon 1. When no NaOH is added, in the presence of 0.0114M Cd(N03)2, the rate constant of mutarotation is 0.0122, practically the same as in the absence of the metal. This is as expected, since no glucosamine complex is present. 

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... 

Fig. 2.16. Phase corrected 22.63 MHz PFT 1 C NMR spectrum of mutarotated D-galactose 100 mg/mL deuterium oxide 30 C proton decoupled 512 accumulated pulse interferograms ...

Fig. 2.54 presents a two-dimensional carbon-proton shift correlation of D-lactose after mutarotational equilibration (40% a-, 60% / -D-lactose in deuterium oxide), demonstrating the good resolution of overlapping proton resonances between 3.6 and 4 ppm by means of the larger frequency dispersion of carbon-13 shifts in the second dimension. The assignment known for one nucleus - carbon-13 in this case - can be used to analyze the crowded resonances of the other nucleus. This is the significance of the two-dimensional CH shift correlation, in addition to the identification of CH bonds. For practical evaluation, the contour plot shown in Fig. 2.54(b) proves to be more useful than the stacked representation (Fig. 2.54(a)). In the case of D-lactose, selective proton decoupling between 3.6 and 4 ppm would not afford results of similiar quality. 

Fig. 2.54. Two-dimensional carbon-proton shift correlation of mutarotated D-lactose (1 mol/L in deuterium oxide , 3C 100.6 MHz H 400.1 MHz measuring time 90min transform lime 2.5 min) (a) stacked plot [64] (b) contour plot. 

Wallenfels (64) has proposed that proton abstraction and addition by the concerted action of a histidine imidazole nitrogen and the SH group could form the basis for the enzyme-catalyzed mutarotation. Amino acid analysis indicates the presence of ten histidine residues per molecule of enzyme (88). 

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... 

Carbodiimide Polymers An optically active carbodiimide, (/ )-152 ([a]365 +7.6°), gives a polymer by polymerization using a titanium (IV) isopropoxide catalyst (Scheme 11.9) [203], The polymer showed optical activity essentially identical to the monomer however, on heating, the polymer indicated mutarotation and specific rotation reached a plateau value of [a]363 -157.5°, which is considered to be based on excess helical sense of the main chain. The mutarotation has been ascribed to a conformational transition from a kinetically controlled one to a thermodynamically controlled one. Excess single-handed helical conformation can be induced for polyfdi-/ -hexyl carbodiimide) by protonating the polymer with chiral camphorsul-fonic acid. 

The mutarotation when an amino-acid component is changed from alanine to proline is illustrated in Figure 13. In the case of amino pyrrolidine, mutarotation occurs, whereas with N-isopropylpropylene diamine, no mutarotation is observed. The deuterium-incorporation velocity of the methine proton in heavy methanol (CH3OD) parallels the mutarotation velocity. 

Carbohydrates in nature are optically active and polarimetry is widely used in establishing their structure. Measurement of the specific rotation gives information about the linkage type (a or (3 form) and is also used to follow mutarotation. Nuclear magnetic resonance spectroscopy (NMR) can be used to differentiate between the anomeric protons in the a- or /3-pyranose and furanose anomers and their proportions can be measured from the respective peak areas. 

Mutarotation at coordinated sulfenate S is slow, which is analogous to the situation with organic thiols. Introduction of the S=0 group imparts a high resistance to inversion. Racemization in p-(S )-[Co(cystO)(tren)]2+ occurs at the rate 9.92 x 10 5s l (30 °C pH independent) and the t-(S) isomer is some 80 times slower.1045 Other diastereoisomeric sulfenate systems have also been shown to be optically very stable. Protonation to form Co—S(OH)R (pATa 0) does not alter this, but addition of alkali does with mutarotation of A(S)-[Co (J )cysO (en)2]+ being rapid at both S and Co in 0.1 moldm 3OH (but not at C). This may occur via a labile Co11—SO(R) intermediate.1036... 

This, in fact, is the interpretation found compatible with the data. In acid-catalyzed reactions, the sequence of reactions usually starts with the transfer of a proton from the acid HA to the substrate molecule M (or its hydrate). In the mutarotation of glucose it is presumed to be ... 

At pH 4.4, 5-thio-D-xylopyranose (215) shows a slow mutarotation, namely, [a]p +202 - +178° (half-time, 10 hours). At pH 6.6, however, the half-time is only about 10 minutes. The direction of the rotation shows that 215 crystallizes in the a-D form. The nuclear magnetic resonance spectrum of 215 in deuterium oxide shows the presence of the H-1 proton of both anomers. The diaxial coupling of 8.2 Hz for the H-1 proton at the higher field (t 5.25) corresponds to the )8-D anomer in the CJ(d) conformation of the molecule having a sulfur-containing ring. 

This possible mechanism is applicable only to compounds having a hydrogen atom attached to the nitrogen atom, yet Kuhn and Birkofer found that mutarotation occurs in pyridine solutions of derivatives of secondary amines, namely, n-glucosylpiperidine and iVjiV -dibenzyl-D-glucosylamine, where no such hydrogen atom is available. To explain mutarotation in such cases they postulated the formation of an acyclic imonium ion by expulsion of a proton from a substituted ammonium ion. 

The work of Brpnsted and Pedersen (23) on the catalytic decomposition of nitramide and the kinetic studies of Lowry and Faulkner (24) on the mutarotation of tetramethylglucose led to the formulation of a more general viewpoint on acids and bases which logically showed that the hydrogen ion and hydroxyl ion were not the unique carriers of acid and basic properties. An acid was defined as any substance capable of donating a proton, and a base any substance capable of accepting a proton. In accordance with this definition (Lowry, 25 Brpnsted, 26), the following substances are typical acids and bases ... 

A part of the evidence for the mechanisms given in equations (40) and (42) is provided by the work of Lowry and co-workers (Lowry and Richards, 113 Lowry and Faulkner, 24) on the mutarotation of tetra methylglucose. In water the reaction proceeds at a measurable rate, and it is clearly catalyzed by both acids and bases. In aqueous solution pyridine is a powerful catalyst but in pure dry pyridine no reaction occurs, and likewise in pure dry re-cresol there is no reaction. Upon investigating the reaction in a mixture of pyridine and n-cresol, Lowry and Faulkner (24) found it to take place very rapidly. From these experiments Lowry drew the important conclusion that a proton cannot by itself wander from one part of the molecule to another. The transformation can occur only if the medium in which the molecule is placed has both acidic and basic properties, so that a proton can be removed from the molecule at one place and a proton added to the molecule at another place. Now these experiments furnish strong support to the mechanism of reactions (40) and (42) whereby both members of the conjugate acid-base pair play a part in the reaction. Instead of representing this mutual dependence by means of consecutive bimolecular reactions, Lowry chose to represent it by means of one trimolecular reaction... 

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