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. 2023 Apr 28;13(1):6967.
doi: 10.1038/s41598-023-33815-7.

CBD hydroxyquinone photo-isomerises to a highly reactive intermediate

Brodie J Thomson  1 , Summer Hanna  2 , Adrian Schwarzenberg  2 , Pirouz Kiani  3 , Dan Bizzotto  1 , Pierre Kennepohl  3 , Ashley Davies  4 , Markus Roggen  5 , Glenn M Sammis  6
Affiliations

CBD hydroxyquinone photo-isomerises to a highly reactive intermediate

Brodie J Thomson et al. Sci Rep. .

Abstract

The legalisation of hemp has led to wide commercial availability of cannabidiol (CBD)-containing products. Here we show that the CBD-hydroxyquinone (HU-331), a readily formed oxidation product and common impurity in CBD isolates, undergoes a previously unknown photo-isomerisation to produce a highly reactive intermediate in solution. Studies supported by calculations indicate that this intermediate rapidly reacts with oxygen to form a multitude of cannabinoid products. The purple colour observed in light-aged CBD-containing solutions is largely due to the anions of these by-products and is not significantly due to the HU-331 anion. Our findings suggest that these uncharacterized cannabinoid derivatives can be present in CBD-containing e-liquids and solutions that have been stored under ambient light conditions, calling for quality control processes that manage HU-331 contamination.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Structures of cannabidiol (CBD) and its formed degradants in the Beam test. CBD (1), HU-331 (2), HU-331 anion (3) and HU-331 anion dimer (4).
Figure 2
Figure 2
Effect of visible light on HU-331 concentrations. (a) Changes in concentration of HU-331 (6 mM in DMSO-d6) stored in the dark (squares) or exposed to 6500 K fluorescence (circles) for up to 60 min. HU-331 concentration was measured by 1H-NMR. (b) 1H NMR of HU-331 samples degraded by white light over time.
Figure 3
Figure 3
Mechanism of the photo-induced HU-331 light isomerisation. Formation of highly reactive cannabinoid hydroxyquinol (5). (a) Photochemical synthesis of hydroxyquinol (5) from HU-331 (3). (b) Proposed mechanism of formation. (c) Energies of the ground state and key excited states of HU-331. (d) Molecular model showing the key distance between the hydroxyquinol radical and the C–H on the limonene moiety.
Figure 4
Figure 4
Formation and reaction of hydroxyquinol 5 and related products in CBD solutions.
Figure 5
Figure 5
Purple colour origin in 2-hydroxyquinone anions. (a) Electronic absorption spectra in molar absorptivity (ε) and TD-DFT-computed oscillator strengths (fosc) for 2 (orange) and its anion 3 (purple) in isopropanol. The simulated data were well matched to the experimental spectra by adding a small shift of + 1500 cm–1. (b) Effect of the limonene group on the electronic absorption spectra based on TD-DFT calculations for both the neutral species (2 vs 10) and their anions (3 vs 11); the limonene group has a significant impact on the spectra of the neutral species but not the anions. (c) Simplified representation of the dominant contributions to the most intense visible absorption bands in 2 and 3. Contours maps of the contributing canonical molecular orbitals (0.05 au isodensity) are shown for the neutral species.
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