Powder NMRcrystallography of thymol

Abstract

A protocol for the structure determination of powdered solids at natural abundance by NMR is presented and illustrated for the case of the small drug molecule thymol. The procedure uses proton spin-diffusion data from two-dimensional NMR experiments in combination with periodic DFT refinements incorporating ¹H and ¹³C NMR chemical shifts. For thymol, the method yields a crystal structure for the powdered sample, which differs by an atomic root-mean-square-deviation (all atoms except methyl group protons) of only 0.07 Å from the single crystal X-ray diffraction structure with DFT-optimized proton positions.