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Determination of Complex Small‐Molecule Structures Using Molecular Alignment Simulation
Author(s) -
Ibáñez de Opakua Alain,
Klama Frederik,
Ndukwe Ikenna E.,
Martin Gary E.,
Williamson R. Thomas,
Zweckstetter Markus
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202000311
Subject(s) - molecule , chemistry , small molecule , nuclear magnetic resonance spectroscopy , molecular dynamics , organic molecules , anisotropy , computational chemistry , chemical physics , isotropy , stereochemistry , organic chemistry , physics , biochemistry , quantum mechanics
Correct structural assignment of small molecules and natural products is critical for drug discovery and organic chemistry. Anisotropy‐based NMR spectroscopy is a powerful tool for the structural assignment of organic molecules, but it relies on the utilization of a medium that disrupts the isotropic motion of molecules in organic solvents. Here, we establish a quantitative correlation between the atomic structure of the alignment medium, the molecular structure of the small molecule, and molecule‐specific anisotropic NMR parameters. The quantitative correlation uses an accurate three‐dimensional molecular alignment model that predicts residual dipolar couplings of small molecules aligned by poly(γ‐benzyl‐ l ‐glutamate). The technique facilitates reliable determination of the correct stereoisomer and enables unequivocal, rapid determination of complex molecular structures from extremely sparse NMR data.