Enhancing NMR Prediction for Organic Compounds Using Molecular Dynamics.

NMR spectroscopy is a crucial tool in organic chemistry for the routine characterization of small molecules, structural elucidation of natural products, and study of reaction mechanisms. Although there is evidence that thermal motions strongly affect observed resonances, conventional predictions are performed only on stationary structures. Here we show that quasiclassical molecular dynamics provides a highly accurate and broadly applicable method for improving shielding predictions. Gas-phase values of the absolute shieldings of protons and carbons are predicted to nearly within experimental uncertainty, while the chemical shifts of large systems such as natural products are closely reproduced. Importantly, these results are obtained without the use of any empirical corrections. Our analysis suggests that the linear scaling factors currently employed are primarily a correction for vibrational effects. As a result, our method extends the reach of prediction methods to the study of molecules with unusual dynamics such as the iconic and controversial [18]annulene. Our predictions agree closely with experiment at both low and high temperatures and provide strong evidence that the equilibrium structure of [18]annulene is planar and aromatic.