Rate Of Mutarotation Research Articles

Study on the role of alkali halides on the mutarotation and dehydration of d-xylose in aqueous solution

Although the xylose mutarotation and transformation have been investigated largely separately, their relationship has been rarely systematically elaborated. The effect of several factors such as xylose concentration, temperature, and salt concentration, affecting the mutarotation of xylose are discussed. Nine alkali halides (LiCl, NaCl, KCl, LiBr, NaBr, KBr, LiI, NaI, and KI) are used to test salt effects. The relationship between xylose rotation rate constant (kM), specific optical rotation at equilibrium ([α]eqm), α/β ratio, H chemical shift difference (ΔΔδ), Gibbs free energy difference (ΔG), hydrogen ion or hydroxide ion concentration ([H+] or [OH−]), and xylose conversion is discussed. Different salts dissolved in water result in different pH of the solutions, which affect the mutarotation of xylose, with the nature of both cation and anion. Shortly, the smaller the cation radius is and the larger the anion radius is, the greater the mutarotation rate is. In the dehydration of xylose to furfural in salty solutions, xylose conversion is positively correlated to mutarotation rate, H+ or OH− concentration, and the energy difference between α-xylopyranose and β-xylopyranose. Although the [α]eqm of xylose is positively correlated with α/β configuration ratio, there is no obvious correlation with xylose dehydration. The conversion to furfural in chlorides is superior to that in bromines and iodides, which is due to the fact that the pH of chloride salts is smaller than that of the corresponding bromide and iodized salts. Higher H+ concentration prefers to accelerate the formation of furfural. In basic salt solutions, the xylulose selectivity is higher than that of furfural at the initial stage of reaction. The furfural selectivity and carbon balance are better in acidic condition rather than in basic condition. In H2O-MTHF (2-Methyltetrahydrofuran) biphasic system, the optimal furfural selectivity of 81.0 % is achieved at 190 °C in 1 h with the assistance of LiI and a little HCl (0.2 mmol, 8 mmol/L in aqueous phase). A high mutarotation rate represents rapid xylose conversion, but a high furfural selectivity prefers in acidic solutions, which would be perfect if organic solvents were available to form biphasic systems.

Intramolecular Catalytic Hydrogen Atom Transfer (CHAT).

Intramolecular catalysis (IntraCat) is the acceleration of a process at one site of a molecule catalyzed by a functional group in the same molecule; an external agent such as a solvent typically facilitates it. Here, we report a general first-principles-based IntraCat mechanism, which strictly occurs within a single molecule with no coreagent being involved─we call it intramolecular catalytic transfer of hydrogen atoms (CHAT). A reactive part of a molecule (chat catalyst moiety or chat agent, represented by -OOH, -COOH, -SH, -CH2OH, -HPO4, or another bifunctional H-donor/acceptor group) catalyzes an interconversion process, such as keto-enol or amino-imino tautomerization, and cyclization in the same molecule, while being regenerated in the process. It can thus be regarded as an intramolecular version of the intermolecular H atom transfer processes mediated by an external molecular catalyst, e.g., dihydrogen, water, or a carboxylic acid. Earlier, we proposed a general mechanistic systematization of intermolecular processes, illustrated in the simplest case of the H2-mediated reactions classified as dihydrogen catalysis [Asatryan, R.; et al. Catal. Rev.: Sci. Eng., 2014, 56, 403-475]. Following this systematization, the CHAT catalysis belongs to the category of relay transfer of H atoms, albeit in an intramolecular manner. A broader class of intramolecular processes includes all types of H-transfer reactions stimulated by an H-migration, which we call self-catalyzed H atom transfer (SC-HAT). The CHAT mechanism comprises a subset of SC-HAT in which the catalytic moiety is regenerated (i.e., acts as a true catalyst and not a reagent). We provide several characteristic examples of CHAT mechanism based on detailed analysis of the corresponding potential energy surfaces. All such cases showed a dramatically reduced activation barrier relative to the corresponding uncatalyzed H-transfer reactions. For example, we show that CHAT can facilitate long-range H-migration in larger molecules and can occur multiple times in one molecule with multiple interconverting groups. It also facilitates amino-imino tautomerization of unsaturated GABA-analogues and peptides, as well as intramolecular cyclization processes to form heterocycles, e.g., oxygenated rings. CHAT pathways may also explain the pH-dependent increase of mutarotation rate of glucose-6-phosphate demonstrated in pioneering experiments that introduced the classical IntraCat concept. In addition, we identify a ground electronic state CHAT pathway as an alternative to the UV-promoted long-range molecular crane keto-enol conversion with a remarkably low activation energy. To initially assess the possible impact of the new keto-enol conversion pathway on combustion of n-alkanes, we present a detailed kinetic analysis of isomerization and decomposition of pentane-2,4-ketohydroperoxide (2,4-KHP). The results are compared with key alternative reactions, including direct dissociation and Korcek channels (for which a new alkyl group migration channel is also identified), revealing the competitiveness of the CHAT pathway across a range of conditions. Taken together, this work provides insight into a general class of reaction pathways that has not previously being systematically considered and that may occur in a broad range of contexts from combustion to atmospheric chemistry to biochemistry.

Broadband Mueller ellipsometer as an all-in-one tool for spectral and temporal analysis of mutarotation kinetics.

Spectroscopic Mueller matrix ellipsometry is becoming increasingly routine across physical branches of science, even outside optics. The highly sensitive tracking of the polarization-related physical properties offers a reliable and non-destructive analysis of virtually any sample at hand. If coupled with a physical model, it is impeccable in performance and irreplaceable in versatility. Nonetheless, this method is rarely adopted interdisciplinarily, and when it is, it often plays a supporting role, which does not take benefit of its full potential. To bridge this gap, we present Mueller matrix ellipsometry in the context of chiroptical spectroscopy. In this work, we utilize a commercial broadband Mueller ellipsometer to analyze the optical activity of a saccharides solution. We verify the correctness of the method in the first place by studying the well-known rotatory power of glucose, fructose, and sucrose. By employing a physically meaningful dispersion model, we obtain 2π-unwrapped absolute specific rotations. Besides that, we demonstrate the capability of tracing the glucose mutarotation kinetics from just one set of measurements. Coupling the Mueller matrix ellipsometry with the proposed dispersion model ultimately leads to the precisely determined mutarotation rate constants and spectrally and temporally resolved gyration tensor of individual glucose anomers. In this view, Mueller matrix ellipsometry may stand as an offbeat yet equal technique to those considered classical chiroptical spectroscopy techniques, which may help open new opportunities for broader polarimetric applications in biomedicine and chemistry.

Ultrafast CEST line scanning as a method to quantify mutarotation kinetics

The process of mutarotation of sugars caused by a balanced reaction between their corresponding α and β isomers, has been known for almost 200 years. Still, it remains essential in modern biochemical research, as enzymatic reactions catalyzed by mutarotases are crucial for various pathways in the energy metabolism.In our study a fast magnetic resonance technique based on chemical exchange saturation transfer (CEST) line scanning (LS) was implemented as a method to measure mutarotation kinetics on a 9.4 T small animal MRI scanner. As proof of concept, the isomeric conversion of two hexoses (glucose and galactose) and pentoses (xylose and arabinose) was investigated in an aqueous solution over time. The technique allowed for ultrafast data acquisition without the implementation of complicated encoding schemes and acceleration procedures. Thus, CEST LS provided complete CEST spectra with a frequency step size of 19.6 Hz in less than one minute.For the mutarotation analysis, CEST spectra were acquired over a time duration of four hours and analyzed with four established CEST quantification approaches - based on either asymmetry of CEST spectra or a multi-pool Lorentzian fit. The isomer ratios of the different sugars at equilibrium were determined with an overall accuracy of 94 %, using an adapted 2-side chemical exchange (CE) model. The estimated mutarotation rate constants at 22 °C were in good agreement with conventionally measured reference values, derived from optical and spectroscopic techniques.

Phosphate buffer-catalyzed kinetics of mutarotation of glucosamine investigated by NMR spectroscopy

Glucosamine (2-amino-2-deoxy-d-glucose, GlcN) is a naturally occurring amino monosaccharide that is essential for a variety of biological functions, it is mainly involved in the formation of polysaccharide structures. It was recently reported to enable the imaging of cancerous tumors as an exogenous contrast agent using the MRI technique of chemical exchange saturation transfer (CEST). In preparation for the clinical use of GlcN, its anomeric equilibrium and mutarotation rate constants were directly investigated in this study utilizing high resolution 1H and 13C NMR spectroscopy. The effects of GlcN concentration, temperature, pH and buffer on the mutarotation rate constant and mutarotation equilibrium were measured. The mutarotation rate constant increased markedly with increasing GlcN concentrations. The rate constant of mutarotation of GlcN at room temperature was 2.2 × 10−4 - 5.0 × 10−4 s−1 at concentrations of 0.02–0.5 M, corresponding to a time of 3.8–1.7 h to reach 95% equilibrium. The anomeric ratio was strongly pH-dependent. The influence of phosphate buffer on the apparent rate constant of GlcN mutarotation was investigated. For phosphate buffer saline values between 0 and 50 mM, there was a six-fold increase in rate at pH 7.0. The mutarotation rate constant rose rapidly with pH at a phosphate concentration of 50 mM: from 0.4 × 10−3 s−1 at pH 5.0 to 7.8 × 10−3 s−1 at pH 9.4, suggesting that the catalysis is due to the HPO42− and PO43− ions. These findings might help researchers design the experimental setting for employing GlcN for cancer detection using GlcN-CEST MRI.

Glucose Binding Drives Reconfiguration of a Dynamic Library of Urea-Containing Metal-Organic Assemblies.

A bis-urea-functionalized ditopic subcomponent assembled with 2-formylpyridine and FeII , resulting in a dynamic library of metal-organic assemblies: an irregular FeII4 L6 structure and three FeII2 L3 stereoisomers: left- and right-handed helicates and a meso-structure. This library reconfigured in response to the addition of monosaccharide derivatives, which served as guests for specific library members, and the rate of saccharide mutarotation was also enhanced by the library. The (P) enantiomer of the FeII2 L3 helical structure bound β-D-glucose selectively over α-D-glucose. As a consequence, the library collapsed into the (P)-FeII2 L3 helicate following glucose addition. The α-D-glucose was likewise transformed into the β-D-anomer during equilibration and binding. Thus, β-D-glucose and (P)-3 amplified each other in the product mixture, as metal-organic and saccharide libraries geared together into a single equilibrating system.

Glucose Binding Drives Reconfiguration of a Dynamic Library of Urea‐Containing Metal–Organic Assemblies

AbstractA bis‐urea‐functionalized ditopic subcomponent assembled with 2‐formylpyridine and FeII, resulting in a dynamic library of metal–organic assemblies: an irregular FeII4L6 structure and three FeII2L3 stereoisomers: left‐ and right‐handed helicates and a meso‐structure. This library reconfigured in response to the addition of monosaccharide derivatives, which served as guests for specific library members, and the rate of saccharide mutarotation was also enhanced by the library. The (P) enantiomer of the FeII2L3 helical structure bound β‐D‐glucose selectively over α‐D‐glucose. As a consequence, the library collapsed into the (P)‐FeII2L3 helicate following glucose addition. The α‐D‐glucose was likewise transformed into the β‐D‐anomer during equilibration and binding. Thus, β‐D‐glucose and (P)‐3 amplified each other in the product mixture, as metal–organic and saccharide libraries geared together into a single equilibrating system.

EFFECT OF HIGH-FREQUENCY ELECTROMAGNETIC FIELD ON THE MUTAROTATION OF AQUEOUS SOLU-TIONS OF GLUCOSE AND FRUCTOSE

The indirect influence of the high-frequency electromagnetic field of the 30–200 MHz low power range on the reaction rate of the mutation of D-glucose solutions and on the equilibrium in D-fructose and D-glucose solutions was studied. Solutions were prepared using both deionized water and water exposed to a high-frequency electromagnetic field. Control of the process of mutarotation was carried out polarimetrically. To assess the effectiveness of field exposure, the effective constants of the reaction rate of mutarotation were calculated. It has been established that the rate of mutarotation of D-glucose solutions non-linearly decreases with increasing frequency of the electromagnetic field. The effect of pretreatment of the solvent by an electromagnetic field on the equilibrium in solutions of fructose and glucose, which have been subjected to field exposure, has been studied. The observation was carried out for 30 days. It was found that the equilibrium specific rotation in the fructose solution as a result of the influence of the electromagnetic field shifts towards negative values, and in the case of glucose solution it does not change. An explanation of the results obtained is proposed, which is based on the assumption of a change in the structural organization of the solvent - water as a result of the high-frequency electromagnetic field, which can significantly change the hydration interactions of the reaction participants: carbohydrates and hydrogen ions.

3-O-Methyl-D-glucose mutarotation and proton exchange rates assessed by 13C, 1H NMR and by chemical exchange saturation transfer and spin lock measurements.

3-O-Methyl-D-glucose (3OMG) was recently suggested as an agent to image tumors using chemical exchange saturation transfer (CEST) MRI. To characterize the properties of 3OMG in solution, the anomeric equilibrium and the mutarotation rates of 3OMG were studied by 1H and 13C NMR. This information is essential in designing the in vivo CEST experiments. At room temperature, the ratio of α and β 3OMG anomers at equilibrium was 1:1.4, and the time to reach 95% equilibrium was 6h. The chemical exchange rates between the hydroxyl protons of 3OMG and water, measured by CEST and spin lock at pH 6.14 and a temperature of 4°C, were in the range of 360-670s-1.

D/H control of chemical kinetics in water solutions under low deuterium concentrations

Variations in the isotopic composition drastically changes properties of molecules. This also applies to H2O, one of the most indispensable substances on Earth. Here we investigated physical, chemical and biological characteristics of deuterium depleted water (0.5 mM HDO) compared to water with natural deuterium content (16 mM HDO) and heavy water D2O. Reaction systems of different organization levels were probed: molecular (galactose mutarotation), supramolecular (destabilase-lysozyme activity), two-phase heterogenic (suspension of slightly water-soluble active pharmaceutical ingredients), and living cells (unicellular biosensor S. ambigua lifespan). We have shown that the mutarotation rate constant for the l-galactose was 2-fold less than that for the D-isomer over the whole temperature range without dependence on HDO concentration in low values, whereas the first-order mutarotation kinetics was not observed for l-galactose in heavy water. Interestingly, the initial rate of lysozyme activity of destabilase-lysozyme increased two-fold in deuterium-depleted water whereas there was no activity change in heavy water. In suspension system, the dissolution kinetics of active pharmaceutical ingredients conformed with the normal kinetic isotope effect when kH/kD > 1. This confirms the important role of variations in the solvent (water) isotopic composition in the dissolution process acceleration. However, the most important isotope effect was observed in the living cells, where the rate constant for the processes of irreversible S. ambigua cell transition (from an active state to an immobilized state) increased up to 800 times under deuterium depletion.

Isomeric distribution of monosaccharides in deep eutectic solvents: NMR study

As counter parts of ILs, DESs have received general interest because of their comparable physicochemical properties to ILs and facile preparation from readily available chemicals. In this work, the isomeric distributions of fructose, glucose, xylose and GlcNAc in CCU, CCG and CCO, i.e. basic, neutral and acidic DES, have been determined by 13C NMR. Higher furanose fraction of fructose was observed in CCO compared to CCG and CCU. The glucose was chosen as model compound to reveal the effect of DES on the mutarotation behavior with DMSO‑d6 as co-solvents. The experimental results showed that a high ratio of CCU to glucose speed up the mutarotation rate of glucose in DMSO‑d6, but have little influence on the anomeric distribution. Furthermore, the mutarotation of glucose in DESs is mainly driven by the HBD, whereas HBA provides little influence. However, HBD and HBA display a synergistic effect on the glucose mutarotation process. Hydrogen bonding between hydrogen of amino in urea and oxygen of hydroxyl in glucose is the driving force for the interconversion of anomers.

A study on the progress of mutarotation above and below the Tg and the relationship between constant rates and structural relaxation times.

Comprehensive FTIR studies on the progress of mutarotation in d-fructose mixed with maltitol have been carried out over a wide range of temperatures, both above and below the glass transition temperature Tg. In addition to the analysis of single bands, we have developed a completely new approach considering the full spectral range to follow the overall progress of the reaction. We have found that at the calorimetric Tg, there is a clear change in the temperature dependence of constant rates. The activation barrier for mutarotation changes from around 59 kJ mol-1 (the supercooled state) to around 249 kJ mol-1 (the glassy state). This dramatic variation in the activation barrier is consistent with the change in the mechanism of this specific chemical conversion, as theoretically considered by Wlodarczyk et al. [Phys. Chem. Chem. Phys., 2014, 16, 4694-4698]. Alternatively, it can also be connected to the change in the viscosity of the sample. Additionally, we investigated the relationship between constant rates (k) of mutarotation, structural relaxation times (τα), and dc conductivity (σdc) above and below the glass transition temperature. It was found that there was a linear correlation between all these quantities; they scale with various exponents changing at Tg. Our results also indicate that a single activation barrier might not be sufficient to describe the mutarotation process.

Compressed-tube pressure cell for optical studies at ocean pressures: Application to glucose mutarotation kinetics.

A self-contained compressed-tube pressure cell is tested to 25 MPa. The cell is very simple to construct and offers stable pressure control with optical access to fluid samples. The physical path length of light through the cell is large enough to measure optical activity. The entire system is relatively small and portable, and it is vibration-free, since a compressor is not used. Operation of the cell is demonstrated by measuring the mutarotation rate of aqueous glucose solutions at 25 °C. A logarithmic plot of the rate constant vs. pressure yields an activation volume for mutarotation of -22 cm3/mol, approximately twice the value measured previously at higher pressures.

Mathematical modelling and analysis of an industrial scale evaporative crystallizer producing lactose monohydrate

Lactose is industrially produced by a series of concentration steps to supersaturate the solution allowing crystallization to take place. This papers deals with the operation and analysis of a forced circulation evaporative crystallizer producing pharmaceutical lactose. A mathematical model of the operation of the crystallizer was developed. The model comprises of the mass balance, population balance, nucleation kinetics, growth kinetics and lactose solubility and mutarotation rate expressions. The steady state operation of the crystallizer was analysed from the classical mixed suspension mixed product removal (MSMPR) model perspective. It was found that the crystallizer behaviour deviated from ideal MSMPR behaviour with a steep upward curvature in the population density curve for crystal sizes below 40μm. A size dependent growth (SDG) rate model was used to model the deviation from ideal behaviour. The parameters of the SDG model were estimated by fitting it to the measured population density curve from the crystallizer. The crystallization kinetic parameters like growth and nucleation rate constants were then estimated by fitting the simulated trends to the measured date. The model showed that the average crystal size follows a transient decaying dynamics before settling down to a constant value. This was reflected in the actual data collected from the crystallizer. The transient dynamics disappeared from the model results when a simple size independent growth model was used.

Mechanism of mutarotation in supercooled liquid phase: Studies on L-sorbose

We have studied mutarotation in anhydrous supercooled L-sorbose by means of dielectric spectroscopy. The phenomenon observed in L-sorbose is much faster than in the structurally similar D-fructose. The kinetics of this process has been determined by applying 1st order kinetics model. Activation energy equal to 68 kJ/mol was obtained from temperature dependence of rate constants. To understand differences in mutarotation rate between D-fructose and L-sorbose, quantum mechanical calculations were performed to study mechanism of this phenomenon. The possible impact of water absorbed from air on the mutarotation in supercooled liquid state has been checked. It turned out that the process is probably intermolecular and the water molecules or other carbohydrate molecules assist in the proton transfer process. Finally we have shown that the rate constant can be alternatively determined from frequency of the maximum of peak, obtained by performing Fourier transform of kinetic curve.

Kinetics of Glucose Mutarotation Assessed by an Equal-Amplitude Paired Polarized Heterodyne Polarimeter

A dual-frequency equal-amplitude paired polarization heterodyne polarimeter (DEPHP) was set up in order to precisely measure the mutarotation rate constants of D-glucose in tridistilled water. The DEPHP is based on a balanced detector detection scheme for measurement of the optical rotation angle of D-glucose/water solution during the conversion process between alpha-D-glucose and beta-D-glucose while in a nonequilibrium state. The DEPHP can perform shot-noise-limited detection, so that the total optical rotation angle together with the mutarotation rate constants of alpha-D-glucose and beta-D-glucose conversion can be measured with high sensitivity. In this experiment, the sensitivity of the optical rotation angle measurement was 8.3 x 10(-5) deg/cm, while the total (k), forward (k(1)) and reverse (k(2)) mutarotation rate constants of D-glucose were found to be k = 7.67 x 10(-5) s(-1), k(1) = 2.76 x 10(-5) s(-1), and k(2) = 4.91 x 10(-5) s(-1), respectively, in tridistilled water. Moreover, using the DEPHP, we can measure the specific rotation angles of alpha-D-glucose and beta-D-glucose in water at 632.8 nm. They were 105 degrees and 12 degrees, respectively. Finally, the detection sensitivity of the DEPHP system is also discussed.

Isothermal batch crystallization of alpha-lactose: A kinetic model combining mutarotation, nucleation and growth steps

A kinetic model combining first-order differential equations of the three consecutive steps of lactose crystallization, i.e., mutarotation, nucleation and crystal growth rate, was developed. Numerical solutions successfully fitted the variations of crystal mass growth rate as a function of lactose concentration during unseeded isothermal batch crystallization, at different initial lactose concentrations and temperatures. The model allowed the induction phase and the influence of seeding to be simulated by taking into account the dependency of crystal growth rate on total crystal surface area and, consequently, on nucleation rate. The proposed model highlights the large influence of the mutarotation step, even in unseeded crystallization kinetics. The effects of high lactose supersaturations that prevail at industrial scale during whey powder manufacturing and the effects of alkaline pH (9.5) on lactose crystallization kinetic were successfully predicted.

Simultaneous Determination of Hydrolysis and Mutarotation Rates during the Enzymatic Hydrolysis of Lactose

An experiment is described in which a custom-made glucose electrode is used to directly monitor the enzymatic hydrolysis of lactose to glucose. The transient profile of beta- d-glucose can be used to simultaneously determine the rate constants for mutarotation and for enzymatic hydrolysis by applying a dynamic nonlinear regression routine. Due to differences in the mutarotation rate constants between lactose and glucose, the beta- d-glucose concentration "overshoots" equilibrium under certain conditions, which can be modeled mathematically. This overshoot can be observed reliably and used to quantify the differences in mutarotational equilibria between glucose and lactose. These observations may be important for the analysis of dairy products and commercial lactase preparations and illustrate an unusual kinetic phenomenon caused by intramolecular forces. This approach may also be important for the accurate determination of a variety of oligosaccharides such as glycogen, which tend to be composed primarily of one stereoisomer.

Kinetic modeling of glucose and fructose dissolution in 2-methyl 2-butanol

With the objective of developing simulation models for sugar bioconversion processes in non-aqueous media, the present study investigated the dissolution kinetics of glucose and fructose in 2-methyl 2-butanol at temperatures between 20 °C and 80 °C. For both sugars a two-phase dissolution process was observed, characterized by an initially fast dissolution lasting a few minutes, followed by a much slower dissolution phase extending up to 24 h. The experimental results are described by a combined sugar dissolution and mutarotation kinetic model that considers the dissolution of the sugar anomeric form present in the solid particles, namely α- d-glucopyranose and ß- d-fructopyranose, and its subsequent mutarotation in solution. The initial dissolution step is assumed limited by the solute transport from the surface to the bulk solution, and the corresponding sugar transport coefficient evaluated from established mass transport correlations. The second slower dissolution phase is solely controlled by the sugar mutarotation rate, and modeled as a first-order reversible reaction. The determined values of the mutarotation rate and equilibrium constants can be related to the solution temperature by an Arrhenius and Van’t Hoff relationship, respectively.

Tin(iv) catalyzed d-galacturonic acid anomerization

A comparative kinetic study of anomerization between the four main forms (alpha/beta-pyranosides and alpha/beta-furanosides) of D-galacturonic acid (GalAH(2), 1) and tin(IV) complexed D-galacturonate ([Sn(CH(3))(2)(GalA)(H(2)O)(2)], 2) in D(2)O, is reported. Important differences are shown by pD vs. mutarotation rate profiles of 1 and 2. Coordination, in fact, causes: i) a spectacular increase of the rate due to kinetic template assistance of the carboxylic tail holding the metal in close proximity to the reactive centre and ii) a change in the dependence of the rate on the pD. Entropic and enthalpic factors contribute to the huge activation energy decrease in 2. Anomerization rates of the complexed ligand are determined by 2D-EXSY cross-peak integration. Analysis of up to twelve direct and reverse rate constants in the pD range 7.0-2.5 evidences ring size memory, and at least one reaction path which bypasses the aldehydo open chain intermediate. Solvent oxygen atom incorporation into the ligand is, at pH 4.5, about ten fold faster when catalyzed by the metal, and proves that the metal-assisted nucleophilic attack of water on the anomeric carbon atom cannot significantly contribute to mutarotation rates that are thousands of times faster.