Structural Investigation of Beta-Cyclodextrin Complexes with Cannabidiol and Delta-9-Tetrahydrocannabinol in 1:1 and 2:1 Host-Guest Stoichiometry: Molecular Docking and Density Functional Calculations

Abstract

The complexation of β-cyclodextrin (β-CD) with cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) was investigated using molecular docking and M062X/6-31G(d,p) calculations. The calculations suggested two possible complex formations of 1:1 and 2:1 host-guest molecular ratio of β-CD with CBD and THC. The preferred orientation of all complexes in this study exhibited the hydrogen bonding between hydroxy-substituted benzene ring of CBD and THC with the β-CD’s secondary hydroxy groups at the wide rim. The calculated complexation energies indicate that formation of the 2:1 complexes (−83.53 to −135.36 kcal/mol) was more energetically favorable and chemically stable than the 1:1 complexes (−30.00 to −34.92 kcal/mol). However, the deformation energies of the host and the guest components in the 2:1 complexes (37.47–96.91 kcal/mol) are much higher than those in the 1:1 complexes (3.49–8.69 kcal/mol), which means the formation processes of the 2:1 complexes are more difficult due to the rigidity of the dimeric β-CDs. Therefore, the inclusion complexes of β-CD with CBD and THC are more likely to be in 1:1 host-guest ratio than in 2:1 molecular ratio. The results of this study supported the experimental results that the complexation constant of 1:1 β-CD/CBD (Ks = 300 M−1) is greater than that of 2:1 β-CDs/CBD (Kss = 0.833 M−1). Altogether, this study introduced the fitting parameters that could indicate the stability of the molecular fits in complex formation of each stoichiometry host-guest ratio, which are important for the assessment of the inclusion mechanisms as well as the relationships of reactants and products in chemical reactions.

In Vitro Wound Healing Potential of a Fibroin Film Incorporating a Cannabidiol/2-Hydroxypropyl-β-cyclodextrin Complex

“…However, the peak of -C-H stretching of the aromatic rings of CBD at 3080 cm −1 disappeared in the complex. These findings suggest that CBD, particularly the hydrophobic characteristic of its aromatic rings, was entirely entrapped by HP-β-CD [ 24 ], thereby restricting the vibration of functional groups within CBD molecules. Once again, the observed changes in the appearance, XRD pattern, and FTIR spectrum provide strong evidence of significant structural alterations and molecular interactions between CBD and HP-β-CD, supporting the formation of the inclusion complex and its potential application in enhancing CBD’s solubility [ 21 , 24 ].…”

How areN-methylcarbamates encapsulated by β-cyclodextrin: insight into the binding mechanism

“…[1][2][3][4] Recently, there has been a surge in pure theoretical studies that have provided new insights into the binding mode and interaction mechanism of host-guest systems. [5][6][7][8][9][10][11][12][13][14][15][16] b-Cyclodextrin (b-CD) is one of the most common and significant host molecules and is internally hydrophobic and externally hydrophilic, and is often used to encapsulate guest molecules containing a phenyl group. Due to its flexible nature and asymmetric shape, the conformational space of b-CD inclusion complexes is rather complicated.…”

“…1–4 Recently, there has been a surge in pure theoretical studies that have provided new insights into the binding mode and interaction mechanism of host–guest systems. 5–16…”