title: O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis.
abstract: α- and β-d-glucopyranose monoacetates 1-3 were prepared with selective13C enrichment in the O-acetyl side-chain, and ensembles of13C-1H and13C-13C NMR spin-couplings (J-couplings) were measured involving the labeled carbons. Density functional theory (DFT) was applied to a set of model structures to determine which J-couplings are sensitive to rotation of the ester bond θ. Eight J-couplings (1JCC,2JCH,2JCC,3JCH, and3JCC) were found to be sensitive to θ, and four equations were parametrized to allow quantitative interpretations of experimental J-values. Inspection of J-coupling ensembles in 1-3 showed that O-acetyl side-chain conformation depends on molecular context, with flanking groups playing a dominant role in determining the properties of θ in solution. To quantify these effects, ensembles of J-couplings containing four values were used to determine the precision and accuracy of several 2-parameter statistical models of rotamer distributions across θ in 1-3. The statistical method used to generate these models has been encoded in a newly developed program, MA'AT, which is available for public use. These models were compared to O-acetyl side-chain behavior observed in a representative sample of crystal structures, and in molecular dynamics (MD) simulations of O-acetylated model structures. While the functional form of the model had little effect on the precision of the calculated mean of θ in 1-3, platykurtic models were found to give more precise estimates of the width of the distribution about the mean (expressed as circular standard deviations). Validation of these 2-parameter models to interpret ensembles of redundant J-couplings using the O-acetyl system as a test case enables future extension of the approach to other flexible elements in saccharides, such as glycosidic linkage conformation.
authors.forename: Toby
authors.initials: T
authors.lastname: Turney
authors.affiliation: Omicron Biochemicals Inc. , South Bend, Indiana 46617-2701, United States.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Facebook Inc. , 1101 Dexter Ave. N, Seattle, Washington 98101, United States.
authors.forename: Luke
authors.initials: L
authors.lastname: Sernau
authors.forename: Ian
authors.initials: I
authors.lastname: Carmichael
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia , 315 Riverbend Rd, Athens, Georgia 30602, United States.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia , 315 Riverbend Rd, Athens, Georgia 30602, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Woods
authors.forename: Anthony S
authors.identifier: 0000-0001-6114-1446
authors.initials: AS
authors.lastname: Serianni
mesh_terms: D000085:Acetates / Q000737:chemistry*; D002236:Carbohydrate Conformation; D004952:Esters / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000592:standards; D015233:Models, Statistical; D009005:Monosaccharides / Q000737:chemistry*; D012015:Reference Standards
chemical_list: D000085:Acetates; D004952:Esters; D009005:Monosaccharides