Structural methods in solid-state NMR

New solid-state NMR experiments for measuring internuclear distances are designed using symmetry principles. The “recoupling” sequences described here are intended to reintroduce the MAS-averaged heteronuclear dipole-dipole coupling between a spin-1/2 nucleus (e.g. 1H) and a half-integer quadrupolar nucleus (e.g. 17O, I = 5/2). The magnitude of the dipolar interaction depends on the separation between the coupled nuclei, so the evolution of the spin system under the recoupled Hamiltonian can be used to measure the internuclear distance. Simulations of the spin dynamics are used initially to select candidate sequences and these are subsequently employed to measure both long-range and direct O–H distances in powdered L-Tyrosine.HCl (isotopically enriched with 17O at 20%to 30% at the O$^\eta$ site). Improvements to existing methods for the data analysis for this type of NMR experiment are also discussed, including the restriction and/or removal of certain fit parameters and the explicit inclusion of inhomogeneous radio-frequency fields as part of the fitting procedure. The effects of processing on the uncertainty of experimentally determined distances are considered, and a new analysis method which circumvents several of these effects is presented. Similar recoupling sequences can be used to measure the anisotropy of proton chemical shifts, and some preliminary results are also presented for this application. A systematic method for the assignment of congested spin-1/2 spectra resulting from molecules with large numbers of chemically similar sites is also described. This makes use of a comparison between the chemical shift tensor measured as usual by the 2D-PASS experiment and its principal components calculated from first principles using the density functional theory package CASTEP. The initial peak assignment is generated randomly and then varied using a steepest-ascent hill climbing algorithm with the square sum of the difference between the experimental and calculated principal values of the chemical shift tensor as the target function. The new method is tested on the 13C spectrum of the anti-inflammatory drug flufenamic acid and found to be superior to simple assignments using only the isotropic chemical shift