2 research outputs found
Diastereomer Configurations from Joint Experimental–Computational Analysis
The potential of the approach combining nuclear magnetic
resonance
(NMR) spectroscopy, relaxed grid search (RGS), molecular dynamics
(MD) simulations, and quantum mechanical (QM) calculations for the
determination of diastereomer configurations is demonstrated using
four diastereomers of a trisubstituted epoxide. Since the change in
configuration of the chiral center is expected to change the distribution
of conformer populations (including those of side-chain rotamers),
changes in NMR parameters [chemical shifts, <i>J</i> couplings,
and nuclear Overhauser effects (NOEs)] are expected. The method therefore
relies on (1) identification of possible conformations in each diastereomer
using relaxed grid search analysis and MD simulations; (2) geometry
optimizations of conformers selected from step (1), followed by calculations
of their relative energies (populations) using QM methods; (3) calculations
of averaged NMR parameters using QM methods; (4) matching calculated
and experimental values of NMR parameters of diastereomers. The diastereomer
configurations are considered resolved, if three NMR parameters different
in nature, chemical shifts, <i>J</i> couplings, and NOEs,
are in agreement. A further advantage of this method is that full
structural and dynamics characterization of each of the diastereomers
is achieved based on the joint analysis of experimental and computational
data