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@ARTICLE{Buczek:1043732,
author = {Buczek, Aneta and Rzepiela, Kacper and Broda, Małgorzata
A. and Kupka, Teobald and Strodel, Birgit and Fatafta,
Hebah},
title = {{W}ater modulated influence of intramolecular
hydrogen-bonding on the conformational properties of
{C}annabidiol ({CBD})},
journal = {Journal of molecular liquids},
volume = {423},
issn = {0167-7322},
address = {New York, NY [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2025-03014},
pages = {127033 -},
year = {2025},
abstract = {Cannabidiol (CBD), a non-psychoactive phytocannabinoid from
Cannabis sativa, has gained significant attention due to its
diverse therapeutic properties, including anti-inflammatory,
antioxidant, and anxiolytic effects. However, its clinical
application is hindered by poor water solubility, which
limits its bioavailability. The aim of this study is to
deepen our understanding of the conformational properties of
CBD, and investigate how these properties affect its
solubility. Using Density Functional Theory (DFT)
calculations, we analyzed the axial and equatorial positions
of substituents on the limonene ring and the arrangement of
both hydroxyl groups. Our findings indicate that the most
stable conformation of CBD involves diequatorial
substitution on the limonene ring, stabilized by specific
–OH⋯π hydrogen bonding interactions. All-atom Molecular
Dynamics (MD) simulations in an aqueous environment revealed
that while single CBD molecules maintain their conformation,
multiple CBD molecules tend to cluster. These insights
provide a comprehensive understanding of the molecular
interactions that underlies CBD’s low aqueous solubility
and suggests potential strategies for enhancing its
bioavailability, which could optimize its therapeutic
potential.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
doi = {10.1016/j.molliq.2025.127033},
url = {https://juser.fz-juelich.de/record/1043732},
}