Isotope Effect-Mapping of the Ionization of Glucose Demonstrates Unusual Charge Sharing

Abstract

Isotopic substitution is known to affect kinetic rate constants and equilibrium constants in chemistry. In this study, we have used tritium substitution and high pH to probe the glucose left harpoon over right harpoon glucose(-) + H(+) equilibrium. Passing partially ionized mixtures of [(3)H]- and [(14)C]glucose over anionic exchange resin has permitted the detection of subtle differences in pK(a). We have found that, at pH 11.7 in an anionic exchange system, [(3)H]glucose always elutes ahead of the [(14)C]glucose, and we report isotope effects of 1.051 +/- 0.0007, 1.012 +/- 1.0005, 1.014 +/- 0.0004, 1.024 +/- 0.0003, 1.014 +/- 0.0004, and 1.015 +/- 0.0014 for [1-(3)H]-, [2-(3)H]-, [3-(3)H]-, [4-(3)H]-, [5-(3)H]-, and [6,6-(3)H(2)]glucose, respectively, as compared to either [2-(14)C]-or [6-(14)C]glucose. The elevated isotope effects at H1 and H4 imply unusual charge sharing in anionic aqueous glucose. Base titration of (13)C-chemical shift changes demonstrates the dominance of pyranose forms at elevated pH, and ab initio isotope effect computations on gas-phase glucose anions are presented.

Following in Emil Fischer’s Footsteps: A Site-Selective Probe of Glucose Acid–Base Chemistry

“…Considering additional uncertainties in the pH values when preparing the solutions, a precision of 0.2, yielding 12.2 ± 0.2, is reasonable. This result is in excellent agreement with the value reported from titration-based methods (p K a1 values in the 12.1 to 12.5 range 36 , 37 , 39 − 41 ). The novelty of our LJ-PES approach is the simultaneous determination of the actual deprotonation site, which allows us to associate site-selective spectral changes with a particular acid-ionization constant.…”

“…This latter finding is in contradiction with the report by Feng et al, 85 who found p K a1 values for C4 and C6 sites to vary between the anomeric forms by more than 2 and 4 p K a units, respectively. Whereas charge sharing between the two most acidic (C1 and C4) sites has been suggested by Lewis and Schramm 39 and cannot be completely excluded based on the C 1s PES experimental data, the present calculations show that C4-deprotonation contributions to the p K a1 equilibrium would be negligibly small. The second acid dissociation constant (p K a2 ) of glucose, assuming deprotonation at C1 followed by deprotonation at C4, was also calculated, yielding a value of 20.8, which is well-separated from the p K a1 value.…”

“…Glucose is a weak acid with at least two reported acid-ionization ( i.e ., deprotonation) equilibria and acidity constants (p K a ) of 12.1 (p K a1 ) and 13.9 (p K a2 ), , which highlight its enhanced reactivity in alkaline media. , Previous determinations of glucose p K a values involved the use of site-insensitive high-performance liquid chromatography and titration-based methods. ,, Consequently, ambiguity remains regarding the extent to which the transition defined at p K a1 involves charge sharing with C–OH groups beyond the C1 site . Schematic representations of both the neutral (glucose 0 (aq) ) and deprotonated (glucose – (aq) ) forms , of aqueous glucose are shown in Figure .…”

Monoglucosyldiacylglycerol, a Foreign Lipid, Can Substitute for Phosphatidylethanolamine in Essential Membrane-associated Functions in Escherichia coli

“…Both PE and MGlcDAG may also partly phase separate from their lipid environment under certain conditions (62,63), and PE is potentially enriched around membrane proteins in E. coli (64). Likewise, they can both become ionized and engage in hydrogen bonding (65,66), in contrast to phosphatidylcholine, which does not substitute for PE in supporting LacY function (67,68). Finally, the chemical differences between the zwitterionic PE headgroup, and the uncharged, stiff, ring-shaped glucose of MGlcDAG are substantial, although both would dampen the negative charge density of a bilayer composed of only anionic lipids.…”

Gas phase acidities and associated equilibrium isotope effects for selected main group mono- and polyhydrides, carbon acids, and oxyacids: A G4 and W1BD study

“…In general, secondary hydrogen-deuterium equilibrium isotope effects (EIEs) on gas phase acidities are much smaller (typically $<1 kJ/mol for the a-position, and $<0.5 kJ/mol for the b-position) than primary EIEs [10], for which the experimental database [11] shows an effect typically on the order of $5 to 10 kJ/mol. However, despite the broad interest in isotope effects across all disciplines of chemistry, it appears relatively few experimental or theoretical studies have investigated EIEs on gas phase acidities [10] (of interest, we also note the following EIE solution phase studies on acidity constants [12][13][14][15][16][17][18][19][20][21]). Consequently, in the current work we examine the gas phase acidities of various main group hydrides, carbon acids, and oxyacids and representative isotopologues using high-level theoretical methods, providing comparison to experimental data where possible, and investigating potential periodic trends and other structure-property relationships.…”