STRUCTURE-ACTIVITY RELATIONSHIP OF PSYCHOACTIVE CANNABINOIDS: A CHEMOMETRIC EXPERIMENT FOR UNDERGRADUATE AND POSTGRADUATE STUDENTS IN CHEMICAL EDUCATION

Abstract

Undergraduate and postgraduate Chemistry Education students had to develop the experiment in four (4) stages. Twenty-two (22) cannabinoids (Δ9-THC and derivatives) with different degrees of psychoactivity, previously scrutinized by our research group with the approaches: molecular electrostatic potential (MEP) and interaction with the CB1 receptor (CARDOSO-FILHO et al., 2004), are investigated through Chemometrics. Exploratory Analysis: Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA). E Classification Methods: K-Nearest Neighbor (KNN) method, Soft Independent Modeling Class Analogy (SIMCA) method, and Stepwise Discriminant Analysis (SDA) were employed to reduce the dimensionality of the data matrix and investigate which descriptors are responsible for the classification between the most active cannabinoids (mac), pKi ≥ 6.72, and the least active cannabinoids (lac), pKi < 6.72, according to the hypothesis previously reported (Cardoso-Filho et al., 2024). The investigation with PCA, HCA, KNN, SIMCA, and SDA showed that the descriptors LUMO+1 energy, Geary autocorrelation of lag 6 weighted by van der Waals volumes (GATS6V), hydration energy (EH), atomic charge on the atom of C4 (qC4), and molecular representation of structure based on the electron diffraction, code of signal 3, unweighted (MOR03u) are responsible for separating cannabinoids according to their degrees of psychoactivity. The insights accumulated and the models built in the research – PCA chemometric model, HCA chemometric model, KNN chemometric model, SIMCA chemometric model, and SDA chemometric model – will be able to support the design of new potentially psychoactive Δ9-THC derivatives.