Journal Article

FZJ-2025-03014

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Water modulated influence of intramolecular hydrogen-bonding on the conformational properties of Cannabidiol (CBD)

Buczek, A. (Corresponding author) ; Rzepiela, K. ; Broda, M. A. ; Kupka, T. ; Strodel, B.FZJ* ; Fatafta, H. (Corresponding author)

2025
Elsevier New York, NY [u.a.]

This record in other databases:

Please use a persistent id in citations: doi:10.1016/j.molliq.2025.127033  doi:10.34734/FZJ-2025-03014

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.

---

Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2025

---

Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---