Correlated C−C and C−O Bond Conformations in Saccharide Hydroxymethyl Groups:  Parametrization and Application of Redundant 1H−1H, 13C−1H, and 13C−13C NMR J-Couplings

• Published in: Journal of the American Chemical Society Vol. 126; no. 48; pp. 15668 - 15685
• Main Authors: Thibaudeau, Christophe, Stenutz, Roland, Hertz, Brian, Klepach, Thomas, Zhao, Shikai, Wu, Qingquan, Carmichael, Ian, Serianni, Anthony S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 08.12.2004
• Subjects: Biological and medical sciences; Carbohydrate Conformation; Carbohydrate Sequence; Carbon Isotopes; Conformational dynamics in molecular biology; Fundamental and applied biological sciences. Psychology; Galactose - analogs & derivatives; Galactose - chemical synthesis; Galactose - chemistry; Glucose - analogs & derivatives; Glucose - chemical synthesis; Glucose - chemistry; Isotope Labeling; Models, Chemical; Molecular biophysics; Molecular Sequence Data; Nuclear Magnetic Resonance, Biomolecular - methods; Polysaccharides - chemistry; Protons; Pyrans - chemical synthesis; Pyrans - chemistry; Spin spin coupling constant; Monte Carlo method; NMR parameter; Conformational dynamics; Oligosaccharide; Conformational analysis; Theoretical study; Density functional method; NMR spectrometry; Experimental study; Carbon 13
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0306718

Methyl α- and β-pyranosides of d-glucose and d-galactose 1 − 4 were prepared containing single sites of 13C-enrichment at C4, C5, and C6 (12 compounds), and 1H and 13C{1H} NMR spectra were obtained to determine a complete set of J-couplings (1 J, 2 J, and 3 J) involving the labeled carbon and nearby protons and carbons within the exocyclic hydroxymethyl group (CH2OH) of each compound. In parallel theoretical studies, the dependencies of 1 J, 2 J, and 3 J involving 1H and 13C on the C5−C6 (ω) and C6−O6 (θ) torsion angles in aldohexopyranoside model compounds were computed using density functional theory (DFT) and a special basis set designed to reliably recover the Fermi contact contribution to the coupling. Complete hypersurfaces for 1 J C5,C6, 2 J C5,H6 R , 2 J C5,H6 S , 2 J C6,H5, 2 J C4,C6, 3 J C4,H6 R , 3 J C4,H6 S , and 3 J C6,H4, as well as 2 J H6 R ,H6 S , 3 J H5,H6 R , and 3 J H5,H6 S , were obtained and used to parametrize new equations correlating these couplings to ω and/or θ. DFT-computed couplings were also tested for accuracy by measuring J-couplings in 13C-labeled 4,6-O-ethylidene derivatives of d-glucose and d-galactose in which values of ω and θ were constrained. Using a new computer program, Chymesa, designed to utilize multiple J-couplings sensitive to exocyclic CH2OH conformation, the ensemble of experimental couplings observed in 1 − 4 were analyzed to yield preferred rotamer populations about ω and θ. Importantly, due to the sensitivity of some couplings, most notably 2 J H6 R ,H6 S , 2 J C5,H6 R , and 2 J C5,H6 S , to both ω and θ, unique information on correlated conformation about both torsion angles was obtained. The latter treatment represents a means of evaluating correlated conformation in 1,6-linked oligosaccharides, since ψ and θ are redundant in these linkages. In the latter regard, multiple, redundant scalar couplings originating from both sides of the glycosidic linkage can be used collectively to evaluate conformational correlations between ψ/θ and C5−C6 bond rotamers.