Computational methods for the interaction between cyclodextrins and natural compounds

Molecular interactions of Cannabidiol (CBD) and Delta-9-Tetrahydrocannabinol (THC9) with Beta-Cyclodextrins (BCD) are investigated by computer modelling methods. The results revealed that the interactions between BCD/CBD and BCD/THC9 are possible and form multiple hosts with one guest inclusion complexes (1:1) and (2:1). In one-to-one inclusion complex results suggested that there are two conformations for BCD/CBD and one conformation for BCD/THC9. It is also recommended that the more intermolecular hydrogen bonding between host and guest. The stability of the hosts (BCD and 2BCD) and guests (CBD and THC9) inclusion complexes are determined by the complexation energies and the HOMO and LUMO gaps which suggested that 2:1 inclusion complex (-83.53 to -135.36 kcal/mol) are more energy favorable than the 1:1 inclusion complex (-30.00 to -34.92 kcal/mol). However, the deformation energies of the host and the guest components in the 2:1 inclusion complex (37.47-96.91 kcal/mol) are much higher than those in the 1:1 inclusion complex (3.49-8.69 kcal/mol) which means the formation processes of the 2:1 inclusion complex are more difficult than 1:1 inclusion complex. The result of this study is supported by the experimental results that the complexation constant of 1:1 BCD/CBD (Ks = 300 M-1) is greater than that of 2:1 2BCD/CBD (Kss = 0.833 M-1).