Racemic crystals of trolox derivatives compared to their chiral counterparts: Structural studies using solid-state NMR, DFT calculations and X-ray diffraction

摘要

Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) is a water-soluble vitamin E analogue that is available in enantiomeric forms R or S. Enantiomerically pure Trolox 1, its derivatives 2, 3 (R and S enantiomers) and racemic forms 1-3 were studied using solid-state C-13 cross-polarisation (CP) magic angle spinning (MAS) NMR (C-13 CPMAS NMR). Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations of the shielding constants supported the assignment of C-13 resonances in the solid-state NMR spectra. For the C-13 CPMAS NMR spectra of 1, resonances of pure enantiomers were significantly broader than those of the racemic R/S form. In order to explain these effects, five of the available crystal structures were analysed (1R/S, 3R/S, 2S and the newly measured 2R/S and 3S). Cyclic dimers with one R and one S enantiomer linked by two OH-O=C2b hydrogen bonds were formed in 1R/S. Similar hydrogen-bonded dimers were present in 3S but not in 3R/S, in which interactions are water-mediated. A comparison of X-ray diffraction, CPMAS NMR data and the OFT GIPAW calculations of racemic forms and pure enantiomers was conducted for the first time. Our results, particularly the solid-state NMR data, were discussed in relation to Wallach's rule, that the racemic crystal appears as more ordered than its chiral counterpart. (C) 2017 Elsevier B.V. All rights reserved.