NMR-guided refinement of crystal structures using 15N chemical shift tensors

Abstract

An NMR-guided procedure for refining crystal structures has recently been introduced and shown to produce unusually high resolution structures. Herein, this procedure, is modified to include ¹⁵N shift tensors instead of the ¹³C values employed previously. This refinement involves six benchmark structures and 45 ¹⁵N tensors. All refined structures show a statistically significant improvement in NMR fit over energy based refinements. Metrics other than NMR agreement indicate that NMR refinement does not introduce errors with no significant changes observed in atom positions or diffraction patterns. However, refinement does change bond lengths by more than experimental uncertainty with most bond types become shorter than diffraction values. Although this decrease is small (1–4 pm), it significantly alters computed ¹⁵N tensors. The NMR refinement was further evaluated by refining two tripeptides. These structures rapidly converged and achieved an NMR agreement equivalent to benchmark values. To ensure accurate comparisons, a complete atomic structure of the tripeptide AGG was determined by single crystal neutron diffraction at 0.58 Å resolution, allowing unambiguous determination of all hydrogen positions. To verify that all NMR refinements represent genuine improvements rather than artifacts of DFT methods, an independent approach was included to evaluate the final NMR refined coordinates. This analysis employs cluster methods and the PBE0 functional. The unusually small ¹⁵N NMR root-mean-square error of the final refined structures (3.6 ppm) supports the conclusion that the changes made represent improvements over both diffraction coordinates and lattice-including DFT energy refined coordinates.