Hydration of Sugars in the Gas Phase: Regioselectivity and Conformational Choice in N‐Acetyl Glucosamine and Glucose

Abstract

The influence of an acetamido group in directing the preferred choice of hydration sites in glucosamine and a consequent extension of the working rules governing regioselective hydration and conformational choice, have been revealed through comparisons between the conformations and structures of "free" and multiply hydrated phenyl N-acetyl-beta-D-glucosamine (betapGlcNAc) and phenyl beta-D-glucopyranoside (betapGlc), isolated in the gas phase at low temperatures. The structures have been assigned through infrared ion depletion spectroscopy conducted in a supersonic jet expansion, coupled with computational methods. The acetamido motif provides a hydration focus that overwhelms the directing role of the hydroxymethyl group; in multiply hydrated betapGlcNAc the water molecules are all located around the acetamido motif, on the "axial" faces of the pyranose ring rather than around its edge, despite the equatorial disposition of all the hydrophilic groups in the ring. The striking and unprecedented role of the C-2 acetamido group in controlling hydration structures may, in part, explain the differing and widespread roles of GlcNAc, and perhaps GalNAc, in nature.

Carbohydrate hydration: heavy water complexes of α and β anomers of glucose, galactose, fucose and xylose

“…The choice of preferred hydration sites is now governed solely by the gain in cooperative hydrogen bonding achieved by selection of the weakest links in the original hydrogen bond chains. 20,21,23,25 The new data for the heavy water hydrated carbohydrate complexes confirm this 'working rule' in the mono-hydrates and reveal its continued operation when a second water molecule is introduced. In every case the two molecules insert as a dimer rather than separately, occupying the same preferred sites, (3,2) in fucose and (2,1) in xylose, as before.…”

“…In the latter case, it has shown how water binding can change the conformation of the substrate and helped to establish a set of 'working rules' governing the preferred binding sites in a representative series of biologically important monosaccharides. 23,25 Very recently, the differing OH vibrational signatures of doubly hydrated O-phenyl aand b-D-mannopyranoside 26 (and also carbohydrate-peptide complexes 27 ) have exposed small structural differences arising from the stereoelectronic changes associated with the anomeric effect. The two water molecules were bound separately between OH4 and O6, and OH6 and the (axial) O2 sites, see Scheme 1, located on either side of the exocyclic hydroxymethyl group, crucially with the second one lying above the key endocyclic oxygen atom, O5.…”

“…In each case, a bound water molecule would be expected to be located close to the anomeric site. The scope of the new investigations was subsequently extended by expanding the earlier studies of carbohydrate hydration (by H 2 O) [20][21][22][23][24][25] to include heavy water complexes of the a and b anomers of the pentose carbohydrate, O-phenyl D-xylopyranoside (a/b-PhXylÁ(D 2 O) 1,2 ) and the deoxy carbohydrate, O-phenyl a-L-fucopyranoside (a-PhFucÁ(D 2 O) 1,2 ):(the choice of L-rather than D-fucose reflects its biological relevance). Unlike glucose or galactose however, neither xylose (an analogue of glucose) nor fucose (6-deoxy galactose) incorporates an exocyclic hydroxymethyl group, see Scheme 1.…”

Phenyl-β-D-glucopyranoside and Phenyl-β-D-galactopyranoside Dimers: Small Structural Differences but Very Different Interactions

“…Note that the only difference between both monosacharides is the relative position of the O4H hydroxyl group. such as amino acids or peptides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], neurotransmitters [22][23][24][25][26][27][28], anesthetics [29,30], several mono-, di-and poly-saccharides [4,6,[31][32][33][34][35][36][37][38][39] or even micelles [40][41][42]. In these systems, the addition of a chromophore with an optically accessible excited electronic state is required to probe the molecules.…”

The structural determination and skeletal ring modes of tetrahydropyran

“…The spectroscopic investigations of cyclic ethers in the gas phase have been mostly centered on the exploration of the conformational landscape. [3][4][5][6] Important contributions come from microwave spectroscopic studies, in which many of the conformeric properties were determined. 6 Infrared spectroscopy was also used to identify the low frequency vibrational modes of these molecules.…”