NMR crystallography methods to probe complex hydrogen bonding networks: application to structure elucidation of anhydrous quercetin

Abstract

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.