Issue 19, 2024

1H and 13C chemical shift–structure effects in anhydrous β-caffeine and four caffeine–diacid cocrystals probed by solid-state NMR experiments and DFT calculations

Abstract

By using density functional theory (DFT) calculations, we refined the H atom positions in the structures of β-caffeine (C), α-oxalic acid (OA; (COOH)2), α-(COOH)2·2H2O, β-malonic acid (MA), β-glutaric acid (GA), and I-maleic acid (ME), along with their corresponding cocrystals of 2 : 1 (2C–OA, 2C–MA) or 1 : 1 (C–GA, C–ME) stoichiometry. The corresponding 13C/1H chemical shifts obtained by gauge including projector augmented wave (GIPAW) calculations agreed overall very well with results from magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy experiments. Chemical-shift/structure trends of the precursors and cocrystals were examined, where good linear correlations resulted for all COO1H sites against the H⋯O and/or H⋯N H-bond distance, whereas a general correlation was neither found for the aliphatic/caffeine-stemming 1H sites nor any 13C chemical shift against either the intermolecular hydrogen- or tetrel-bond distance, except for the 13COOH sites of the 2C–OA, 2C–MA, and C–GA cocrystals, which are involved in a strong COOHN bond with caffeine that is responsible for the main supramolecular stabilization of the cocrystal. We provide the first complete 13C NMR spectral assignment of the structurally disordered anhydrous β-caffeine polymorph. The results are discussed in relation to previous literature on the disordered α-caffeine polymorph and the ordered hydrated counterpart, along with recommendations for NMR experimentation that will secure sufficient 13C signal-resolution for reliable resonance/site assignments.

Graphical abstract: 1H and 13C chemical shift–structure effects in anhydrous β-caffeine and four caffeine–diacid cocrystals probed by solid-state NMR experiments and DFT calculations

Supplementary files

Article information

Article type
Paper
Submitted
20 Dec 2023
Accepted
08 Apr 2024
First published
08 Apr 2024
This article is Open Access
Creative Commons BY license

Phys. Chem. Chem. Phys., 2024,26, 14345-14363

1H and 13C chemical shift–structure effects in anhydrous β-caffeine and four caffeine–diacid cocrystals probed by solid-state NMR experiments and DFT calculations

D. Majhi, B. Stevensson, T. M. Nguyen and M. Edén, Phys. Chem. Chem. Phys., 2024, 26, 14345 DOI: 10.1039/D3CP06197C

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