The structure and conformational behavior of sulfonium salt glycosidase inhibitors in solution: a combined quantum mechanical NMR approach

J Am Chem Soc. 2004 Jun 9;126(22):6866-7. doi: 10.1021/ja049700k.

Abstract

We present the conformational analysis of an inhibitor of alpha-mannosidase, based on a novel sulfonium salt structure (1) that mimics the mannosyl cation intermediate. Because of the number of possible isomeric structures for 1, as well as its complex molecular structure, traditional conformational analysis by NMR was not applicable. Instead, a single experimentally consistent structure was obtained from finite perturbation quantum mechanical calculations of the NMR J-couplings at the B3LYP/6-311G** level. Using a full relaxation matrix analysis, we showed that the quantum-predicted NMR structure was the only isomer that was consistent with the experimental NOE intensities. The results illustrate the potential for finite perturbation calculations to be useful in the analysis of complex charged molecules.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Molecular Structure
  • Quantum Theory
  • Sulfonium Compounds / chemistry*
  • Sulfonium Compounds / pharmacology

Substances

  • Enzyme Inhibitors
  • Sulfonium Compounds
  • Glycoside Hydrolases