pH-triggered inclusion of bakuchiol in β-cyclodextrin: NMR insights, pKa determination and impact on antioxidant properties

Wanat, Karolina, Wallace, Matthew, Baj, Krzysztof, Wielgosz, Justyna and Brzezińska, Elżbieta (2026) pH-triggered inclusion of bakuchiol in β-cyclodextrin: NMR insights, pKa determination and impact on antioxidant properties. Journal of Molecular Liquids, 456. ISSN 0167-7322 (In Press)

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Abstract

Bakuchiol is a highly lipophilic phenolic compound with limited water solubility, which promotes aggregation and reduces its functionality in solution. In this study, we investigated the formation of an inclusion complex between bakuchiol and β-cyclodextrin (β-CD) and demonstrated that this process is strongly pH-dependent. Using 1H NMR and 2D NOESY spectroscopy, we confirmed that effective host-guest complexation occurs only after deprotonation of bakuchiol in an alkaline environment, which allows for deeper incorporation of the molecule into β-CD cavity. Under neutral conditions, bakuchiol tends to aggregate and does not interact with cyclodextrin, hence none of the standard complexation methods gave a positive result. The inclusion complex formed spontaneously in alkaline solution had a 1:1 stoichiometry and, most importantly remained stable after reprotonation, as confirmed by NOESY correlations. The acid-base properties of bakuchiol and its β-CD complex were investigated using chemical shift imaging, enabling the first experimental determination of their pK a values, which for both forms were higher than 10. The effect of complexation on functional properties was additionally assessed using the CUPRAC assay. The complex showed significantly increased antioxidant activity compared to free bakuchiol, with TEAC values increasing from 0.520 to 0.749 at the highest concentration tested. This effect is likely related to improved dispersibility of bakuchiol in aqueous media. These results reveal the mechanism of pH-induced inclusion complex formation of lipophilic phenolic structures and provide new insights into host-guest interactions involving compounds with different protonation states.

Item Type:	Article
Additional Information:	Data availability: The raw data have been deposited in the Zenodo repository and are available at https://doi.org/10.5281/zenodo.13969609 and https://doi.org/10.5281/zenodo.19233431.
Uncontrolled Keywords:	antioxidant activity,bakuchiol,inclusion complex,nmr spectroscopy,pk determination,β-cyclodextrin,electronic, optical and magnetic materials,atomic and molecular physics, and optics,condensed matter physics,spectroscopy,physical and theoretical chemistry,materials chemistry ,/dk/atira/pure/subjectarea/asjc/2500/2504
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Related URLs:	https://www.scopus.com/pages/publication...
Depositing User:	LivePure Connector
Date Deposited:	28 May 2026 11:35
Last Modified:	01 Jun 2026 07:47
URI:	https://ueaeprints.uea.ac.uk/id/eprint/103188
DOI:	10.1016/j.molliq.2026.129674

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