Informing Saccharide Structural NMR Studies with Density Functional Theory Calculations

  • Thomas Klepach
  • Hongqiu Zhao
  • Xiaosong Hu
  • Wenhui Zhang
  • Roland Stenutz
  • Matthew J. Hadad
  • Ian Carmichael
  • Anthony S. Serianni
Part of the Methods in Molecular Biology book series (MIMB, volume 1273)


Density functional theory (DFT) is a powerful computational tool to enable structural interpretations of NMR spin–spin coupling constants ( J-couplings) in saccharides, including the abundant 1H–1H ( J HH), 13C–1H ( J CH), and 13C–13C ( J CC) values that exist for coupling pathways comprised of 1–4 bonds. The multiple hydroxyl groups in saccharides, with their attendant lone-pair orbitals, exert significant effects on J-couplings that can be difficult to decipher and quantify without input from theory. Oxygen substituent effects are configurational and conformational in origin (e.g., axial/equatorial orientation of an OH group in an aldopyranosyl ring; C–O bond conformation involving an exocyclic OH group). DFT studies shed light on these effects, and if conducted properly, yield quantitative relationships between a specific J-coupling and one or more conformational elements in the target molecule. These relationships assist studies of saccharide structure and conformation in solution, which are often challenged by the presence of conformational averaging. Redundant J-couplings, defined as an ensemble of J-couplings sensitive to the same conformational element, are particularly helpful when the element is flexible in solution (i.e., samples multiple conformational states on the NMR time scale), provided that algorithms are available to convert redundant J-values into meaningful conformational models. If the latter conversion is achievable, the data can serve as a means of testing, validating, and refining theoretical methods like molecular dynamics (MD) simulations, which are currently relied upon heavily to assign conformational models of saccharides in solution despite a paucity of experimental data needed to independently validate the method.

Key words

Density functional theory NMR spectroscopy Spin–spin coupling constants Scalar couplings J-couplings Saccharides Conformation Isotopic labeling JCH JCC Carbohydrate structure 


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Thomas Klepach
    • 1
    • 2
    • 3
  • Hongqiu Zhao
    • 1
    • 4
  • Xiaosong Hu
    • 1
    • 5
  • Wenhui Zhang
    • 1
  • Roland Stenutz
    • 1
    • 6
  • Matthew J. Hadad
    • 1
  • Ian Carmichael
    • 7
  • Anthony S. Serianni
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of Notre DameNotre DameUSA
  2. 2.Department of ChemistryColby CollegeWatervilleUSA
  3. 3.Department of BiologyColby CollegeWatervilleUSA
  4. 4.Department of Chemistry and Chemical BiologyIndiana University Purdue University Indianapolis (IUPUI)IndianapolisUSA
  5. 5.Department of Chemistry, School of ScienceWuhan University of TechnologyWuhanP.R. China
  6. 6.IsoSep ABTullingeSweden
  7. 7.Radiation LaboratoryUniversity of Notre DameNotre DameUSA

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