Despite the simple molecular structure of quercetin, the exact conformation of the hydroxyl groups and the induced hydrogen bonding network in its anhydrous form could not be determined if starting from crystal structure models provided by X-ray powder diffraction (XRPD) alone. If instead a multi-technique approach that combines XRPD data analysis with information from ¹³C and ¹H solid-state Nuclear Magnetic Resonance (ss-NMR) and molecular modeling is employed the ambiguities could be largely reduced. A conformational analysis was performed on the isolated molecule at the molecular mechanics (MM) level of theory, whereas quantum chemical computations of the full crystal were employed for geometry optimization and chemical shift calculation based on the Gauge Including Projector Augmented-Wave (GIPAW) method. ¹³C and ultra-fast MAS (60 kHz) ¹H ss-NMR data were used at 11.75 T to assess the reliability of the derived structure solutions, and to obtain important insights into the relationship between the hydrogen bonding network and the induced supra-molecular architectures/crystal packing patterns. A direct comparison with the data recorded on quercetin dihydrate, of which single-crystal X-ray structure is known, proved useful for increasing the confidence level in the derived conclusions. Also, an ultra-fast MAS ¹H double-quantum (DQ) excitation scheme is employed, which has the advantage of providing better resolution at long DQ excitation times compared with conventional multiple-pulse homonuclear decoupling: this may be relevant for further methodological development in NMR crystallography, especially when dealing with the effects of increased lattice disorder.

A protocol is presented for correcting the effect of non-specific cross-polarization in CHHC solid-state MAS NMR experiments, thus allowing the recovery of the ¹H–¹H magnetization exchange functions from the mixing-time dependent buildup of experimental CHHC peak intensity. The presented protocol also incorporates a scaling procedure to take into account the effect of multiplicity of a CH₂ or CH₃ moiety. Experimental CHHC buildup curves are presented for l-tyrosine·HCl samples where either all or only one in 10 molecules are U–¹³C labeled. Good agreement between experiment and 11-spin SPINEVOLUTION simulation (including only isotropic ¹H chemical shifts) is demonstrated for the initial buildup (t_mix < 100 μs) of CHHC peak intensity corresponding to an intramolecular close (2.5 Å) H–H proximity. Differences in the initial CHHC buildup are observed between the one in 10 dilute and 100% samples for cases where there is a close intermolecular H–H proximity in addition to a close intramolecular H–H proximity. For the dilute sample, CHHC cross-peak intensities tended to significantly lower values for long mixing times (500 μs) as compared to the 100% sample. This difference is explained as being due to the dependence of the limiting total magnetization on the ratio N_obs/N_tot between the number of protons that are directly attached to a ¹³C nucleus and hence contribute significantly to the observed ¹³C CHHC NMR signal, and the total number of ¹H spins into the system. ¹H–¹H magnetization exchange curves extracted from CHHC spectra for the 100% l-tyrosine·HCl sample exhibit a clear sensitivity to the root sum squared dipolar coupling, with fast buildup being observed for the shortest intramolecular distances (2.5 Å) and slower, yet observable buildup for the longer intermolecular distances (up to 5 Å).

A new analytical method is presented for studying in a uniform way the spin dynamics in NMR experiments performed under the conditions of magic angle spinning. It was derived on the basis of the formalized Floquet theory and consists in transforming the Fourier-state representation of the NMR signal into an integral one. The integral representation proves to be well suited in combination with Rayleigh-Schrodinger perturbation theory for both the fast and the slow spinning regimes. The corresponding perturbation expansions can be readily extended to higher-order correction terms, which also allows the inclusion of more moderate spinning speeds. Explicit expressions of the perturbation series were derived for both spinning regimes and applied to the case of isolated dipolar-coupled spin-1/2 pairs for which the results can be compared with those obtained by the exact evaluation of the equation of motion.