A theoretical study on the influence of the frontier orbitals HOMO and LUMO and the size of C4 and C2 substituents in the psychoactivity of cannabinoid compounds

摘要

A theoretical study on the influence of the frontier orbitals HOMO and LUMO and on substitutions at the C4 and C2 regions, with known psychoactive and psychoinactive cannabinoid molecules, showed that the size (volume) of C4 substituents may have an important role to explain the presence or absence of psychoactivity in cannabinoid compounds. The calculated E_(LUMO) values showed that this descriptor could be important for the separation between the psychoactive and psychoinactive compounds only when there is no substitution at the C4 position. The results indicate that there is a relationship between the volume of the C4 substituent and the activity of the compound. C4 substituents with a volume bigger than 83 A~3 will always cause psychoinactivity.