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The concerted mechanism of mutarotation of D D-glucose, obtained from Models 1 and 2, and their labels, used in the text. The reported structures are those obtained from Model 1.
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In this work the mechanism of glucose mutarotation is investigated in aqueous solution considering the most likely pathways proposed from experimental work. Two mechanisms are studied. The first involves an intramolecular proton transfer as proposed by textbooks of organic chemistry, and the second uses one solvent water molecule to assist proton t...
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Context 1
... the mechanism of glucose mutarotation that is not assisted by a water molecule is the same as that in the gas phase and in the continuum, the results of Models 1 and 2 will be discussed in parallel. The six corresponding stationary points located on the potential energy surface of the system obtained from both models are reported in Figure 3. The structures reported were obtained from Model 1. ...
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Citations
... Therefore, glucose is converted to GA by selective C-C bond cleavage, followed by further hydrogenation to form EG. Due to the rapid hydrogenation of GA observed in experiments [18,28,29,39], the selective C-C bond cleavage step becomes the ratedetermining step. In aqueous solution with a Lewis acid catalyst, the straight-chain configuration of glucose with an aldehyde termination group is favorable for the subsequent reaction [48][49][50]. Considering the above-mentioned facts, this study focuses on how straight-chain glucose selectively breaks into GA with three different catalytic models. The fast hydrogenation of GA by Ru/AC [29,31] is beyond the concern of this work. ...
... Hence, glucose would undergo protonation when it coordinates with tungsten oxide-based catalysts. This aldehyde protonation is common during the mutarotation between pyranoses and the aldehyde form of glucose [50]. ...
... The stereoisomers, α and β, vary in their chemical structure relative to the orientation of the C-1 chiral carbon. The conversion between the two isomers is initiated by the breaking of bond C 1 -O (figure 1) as a consequence of the protonation of the oxygen atom (Silva et al., 2006) and followed by rotation of bond C1 -C2 bond. Finally, the C 1 -O bond reforms (Jawad et al., 2012), all of which is described as the epimerisation of lactose. ...
Lactose is present as an excipient in nearly half of all solid medicines. Despite the assumption of chemical stability, in aqueous solution the chiral composition of lactose is prone to change. It is not known whether such epimerisation could also occur as solid crystalline α-lactose undergoes thermal desorption of its hydrated water. Thus, the aim of this study was to investigate the anomeric composition of lactose powders after heating in a differential scanning calorimeter. During thermal analysis, the heating cycles were interrupted to allow anomer-composition analysis by NMR. The onset for monohydrate desorption occurred at 143.8±0.3 °C. Post water-loss, at 160°C for example, α-lactose suffered partial conversion (11.6±0.9%) to the β-anomer. When held at 160°C for 60 min this increased to 29.7±0.8% β-anomer (p<0.05). This process of epimerisation was found to be close to zero-order with a rate constant of 0.28% per min⁻¹. Optical microscopy indicated that the solid-state was maintained throughout thermal desorption and up to the onset of melting at 214.2±0.9°C. Only epimerisation was observed, with no additional chemical degradation detected by NMR. Similar results were observed when heating α-lactose to 190°C, which resulted in a conversion of 29.1±0.7% to β-lactose. Thus, the exothermic peak observed after monohydrate loss, which has often been attributed to re-crystallisation, comprises a contribution from epimerisation. No epimerisation or hydrate loss was observed for β-lactose powders when heated. In summary, it has been shown unequivocally for the first time that hydrate desorption (dehydration) leads to solid-state epimerisation in α-lactose powders.
... This is due to the α/β inter-conversion of the glucose in the punicalagin molecule (Kraszni, Marosi, & Larive, 2013). This mutarotation reaction is possible when glucose is linearized prior to a new hemiacetalisation which closes the sugar in one anomeric form or the other (Silva, da Silva, & da Silva, 2006). In our separation Table 3 Minimal inhibitory concentrations of punicalagin (α and β anomers) against various strains of yeast, Gram-positive bacteria and Gram-negative bacteria. ...
Extracts from ‘Zhéri’ and ‘Hicaznar’ varieties of pomegranate, Punica granatum L., were obtained by subjecting powdered peels to extraction using water, water/ethanol (1:1; v/v), ethanol, acetone and heptane. Using the agar diffusion assay, extracts with water and/or ethanol were shown to display significant antimicrobial activity with diameters of inhibition zones up to 20 mm. Ethanolic extracts, which were the most active, were fractionated using SPE, HPLC and UHPLC, and the active compounds they contain were identified by mass spectrometry. Punicalagin, under its α and β anomeric forms, was identified as the antibacterial compound in pomegranate peel extracts. Both forms were active with MIC values between 0.3 and 1.2 µg.ml⁻¹, and they easily converted from one to the other with an α/β equilibrium ratio of 3/7. Their spectrum of activity targeted 10 out of 13 Gram positive and two out of three Gram negative bacteria as well as a yeast strain.
... [117,124,125] Various hypotheses exist on how water assists mutarotation, including the mechanism proposed by Silva et al. with one water molecule acting in a concerted reaction ( Figure 5). [126] Without added catalyst, an increasing concentration of nonaqueous cosolvent reduces the mutarotation rate, as demonstrated by experimental data. [124,125] The general effect of acid-base catalysis on the mutarotation has been extensively studied, with early contributions by Lowry [21] and Brønsted. ...
... The concerted mechanism of glucose mutarotation assisted by one water molecule in the transition state (TS). [126] Reproduced with permission, Copyright Elsevier Ltd (2006). a catalyst other than water on mutarotation [129] should be systematically investigated. ...
Native plant cellulose has an intrinsic supramolecular structure. Consequently, it can be isolated as nanocellulose species, which can be utilized as building blocks for renewable nanomaterials. The structure of cellulose also permits its end‐wise modification, i.e., chemical reactions exclusively on one end of a cellulose chain or a nanocellulose particle. The premises for end‐wise modification have been known for decades. Nevertheless, different approaches for the reactions have emerged only recently, because of formidable synthetic and analytical challenges associated with the issue, including the adverse reactivity of the cellulose reducing end and the low abundance of newly introduced functionalities. This Review gives a full account of the scientific underpinnings and challenges related to end‐wise modification of cellulose nanocrystals. Furthermore, we present how the chemical modification of cellulose nanocrystal ends may be applied to directed assembly, resulting in numerous possibilities for the construction of new materials, such as responsive liquid crystal templates and composites with tailored interactions.
... [117,124,125] Es gibt verschiedene Hypothesen, wie genau Wasser der Mutarotation assistiert, inklusive der Theorie von Silva et al., welche die Beteiligung eines Wassermoleküls in einer konzertierten Reaktion vorschlugen (Abbildung 5). [126] Bei Abwesenheit weiterer Katalysatoren nimmt die Mutarotationsrate mit zunehmendem Anteil an nicht-wässrigem Lçsungsmittel ab, wie durch experimentelle Daten gezeigt wurde. [124,125] Die allgemeinen Auswirkungen von Säure-Base-Katalyse auf die Mutarotation wurden umfangreich untersucht, mit frühen Beiträgen von Lowry [21] sowie Brønsted und Guggenheim. ...
Native plant cellulose has an intrinsic supramolecular structure. Consequently, it can be isolated as nanocellulose species, which can be utilized as building blocks for renewable nanomaterials. The structure of cellulose also permits its end‐wise modification, i.e., chemical reactions exclusively on one end of a cellulose chain or a nanocellulose particle. The premises for end‐wise modification have been known for decades. Nevertheless, different approaches for the reactions have emerged only recently, because of formidable synthetic and analytical challenges involved with the issue, including the adverse reactivity of the cellulose reducing end and the low abundance of newly introduced functionalities. This review gives a full account of the scientific underpinnings and challenges related to end‐wise modification of cellulose nanocrystals. Furthermore, we present how the chemical modification of cellulose nanocrystal ends may be applied to directed assembly, resulting in numerous possibilities for construction of new materials, such as responsive liquid crystal templates or composites with tailored interactions.
... Two mechanisms are studied for the cyclic form of fructose (bpyranose and b-furanose as model substrate). In the first step, the conversion of the b-furanose and b-pyranose to the open chain form via an intramolecular proton migration (Scheme S2 and S4), and the other is solvent-assisted by one water molecule (Scheme S3 and S5) (Lewis et al., 2006;Silva et al., 2006;Yamabe and Ishikawa, 1999). The activation free energy via fourmembered transition states (Fig. 5, TS1 and TS2) for the formation of open chain fructose is calculated to be about 36 kcal/mol. ...
... Yamabe and Ishikawa 15 applied density functional theory to glucopyranose ring opening to calculate transition-state structures for the unimolecular and water-catalyzed reactions. Silva et al. 16 extended the understanding of the system with their own glucopyranose ring-opening transition states, including a calculation of overall rate constants for the conversion at 25°C ...
... This factor is offset in the presence of external hydrogenbonding species such as other monosaccharides or water, which would serve to stabilize other conformations and deemphasize preferences for internal hydrogen bonding. Hydrogen-bond stabilization seems to be one reason why computational treatments of the gas-phase anomerization of Dglucose, 5,16,65,66 including this work, predict α-D-glucopyranose as the preferred glucose anomer instead of β-D-glucopyranose as indicated in condensed-phase experiments. 6 In a condensed phase, effects of prereaction complexes in intermolecular reactions could also become significant. ...
Quantum-chemical calculations show how low barriers to anomerization and shifting equilibria cause significant presence of different monosaccharide isomers in high-temperature processes such as pyrolysis. The transition between isomeric forms of monosaccharides is long-studied, but examination has typically been limited to the solution phase and to pyranose isomers. Processes and rates of anomerization by reversible, gas-phase ring-opening and -closing reactions were predicted for the monosaccharides D-glucose, D-mannose, D-galactose, D-xylose, L-arabinose, and D-glucuronic acid. Structures and thermochemistry were computed for stable species and pericyclic transition states using CBS-QB3, and high-pressure-limit Arrhenius reaction parameters were predicted and fitted from 300 K to 1000 K. Activation energies for the ring-opening reactions were 162-217 kJ/mol for four-center pericyclic separation of the lactol group but were reduced by catalytic participation of a hydroxyl group within the monosaccharide or an external R-OH group represented by an explicit water molecule, reaching activation energies as low as 97 kJ/mol and 67 kJ/mol, respectively. Equilibrium constants implied increasing fractions of furanose and linear aldehyde anomers with increasing temperature.
... The mutarotation of lactose follows the same mechanics as the mutarotation of related sugars such as glucose (Silva et al., 2006) and has been described in detail elsewhere (Jawad et al., 2012). This occurs through the formation of a free aldehyde form from the glucose molecule in the lactose structure ( Figure 9). ...
Lactose, a disaccharide is a ubiquitous excipient in many pharmaceutical formulations which exists in two anomeric forms; either as α- or β-lactose. The anomers have different properties which can affect their application. Nevertheless, batches of lactose products are widely produced by many manufacturers, and is available in many grades. However, the anomeric content of these batches has not been accurately characterized and reported previously. Therefore, the aim of this study was to analyse a set of 19 commercially available samples of lactose using a novel H¹-NMR technique to establish a library showing the anomeric content of a large range of lactose products. The lactose samples were also analysed by DSC. The anomeric content of the α-lactose monohydrate samples were found to vary by more than 10%, which might influence bioavailability from final formulations. The data showed that there is a need to determine and monitor the anomeric content of lactose and this should be a priority to both the manufacturers and the formulators of medicines.
... Each of the reducing sugars will undergo mutarotation when dissolved in water prior to lyophilization, forming a mixture of α and β anomers. The anomeric mixture is expected to persist in the lyophilized matrix (Silva, da Silva, & da Silva, 2006;Taylor, York, Williams, & Mehta, 1997). It can be noted that the reducing disaccharide sugars were more effective than the Figure 6-Structural overlays of sucrose with different crystalline saccharide additives, generated using Mercury 3.9 software, with the sucrose structure shown in blue and the saccharide additive structure shown in red. ...
Amorphous sucrose is a component of many food products but is prone to crystallize over time, thereby altering product quality and limiting shelf‐life. A systematic investigation was conducted to determine the effects of two monosaccharides (glucose and fructose), five disaccharides (lactose, maltose, trehalose, isomaltulose, and cellobiose), and two trisaccharides (maltotriose and raffinose) on the stability of amorphous sucrose in lyophilized two‐component sucrose‐saccharide blends exposed to different relative humidity (RH) and temperature environmental conditions relevant for food product storage. Analyses included X‐ray diffraction, differential scanning calorimetry, microscopy, and moisture content determination, as well as crystal structure overlays. All lyophiles were initially amorphous, but during storage the presence of an additional saccharide tended to delay sucrose crystallization. All samples remained amorphous when stored at 11% and 23% RH at 22 °C, but increasing the RH to 33% RH and/or increasing the temperature to 40 °C resulted in variations in crystallization onset times. Monosaccharide additives were less effective sucrose crystallization inhibitors relative to di‐ and tri‐saccharides. Within the group of di‐ and tri‐saccharides, effectiveness depended on the specific saccharide added, and no clear trends were observed with saccharide molecular weight and other commonly studied factors such as system glass transition temperature. Molecular level interactions, as evident in crystal structure overlays of the added saccharides and sucrose and morphological differences in crystals formed, appeared to contribute to the effectiveness of a di‐ or tri‐saccharide in delaying sucrose crystallization. In conclusion, several di‐ and tri‐saccharides show promise for use as additives to delay the crystallization kinetics of amorphous sucrose during storage at moderate temperatures and low RH conditions.
Practical Application
Amorphous sucrose is desirable in a variety of food products, wherein crystallization can be problematic for texture and shelf‐life. This study documents how different mono‐, di‐, and tri‐saccharides influence the crystallization of sucrose. Monosaccharide additives were less effective sucrose crystallization inhibitors relative to di‐ and tri‐saccharides. These findings increase the understanding of how different mono‐, di‐, and tri‐saccharide structures and their solid‐state properties influence the crystallization of amorphous sucrose and show that several di‐ and tri‐saccharides have potential for use as sucrose crystallization inhibitors.
... Each of the glucopyranose isomers (1) are predicted to bridge with either mono-or dianionic Pi. Moreover, this mechanism is analogous to that proposed for the mutarotation of glucose in aqueous solution at physiological pH in which water is the bridging agent (Silva, da Silva, & da Silva, 2006). ...
Nonenzymatic glycation (NEG) begins with the non-covalent binding of a glucopyranose to a protein. The bound glucopyranose must then undergo structural modification to generate a bound electrophile that can reversibly form a Schiff base, which can then lead to Amadori intermediates, and ultimately to glycated proteins. Inorganic phosphate (Pi) is known to accelerate the glycation of human hemoglobin (HbA), although the specific mechanism(s) of Pi as an effector reagent have not been determined. The aim of this study was to determine whether Pi and a glucopyranose can concomitantly bind to HbA and react while bound within the early, noncovalent stages to generate electrophilic species capable of progress in NEG. 31P and 1HNMR of model reactions confirm that bimolecular reactions between Pi and glucopyranose occur generating modified glucose electrophiles. Computations of protein/substrate interactions predict that Pi can concomitantly bind with a glucopyranose in HbA pockets with geometries suitable for multiple acid/base mechanisms that can generate any of four transient electrophiles. Pi-facilitated mechanisms in the noncovalent stages predict that the glycation of β-Val1 of HbA to HbA1c is a “hot spot” because the β-Val1 pocket facilitates many more mechanisms than any other site. The mechanistic diversity of the Pi effect within the early noncovalent stages of NEG predicts well the overall site selectivity observed from the in vivo glycation of HbA in the presence of Pi. These insights extend our basic understanding of the NEG process and may have clinical implications for diabetes mellitus and even normal aging.
