Estudo teórico de opioides sintéticos no contexto das novas substâncias psicoativas

Abstract

Synthetic fentanyl analog substances that have not been approved for medical use are known as Non-Pharmaceutical Fentanyls (NPF). Its clandestine synthesis involves the chemical modification of an existing drug, which can lead to unpredictable pharmacological effects. These changes also make chemical identification difficult. As new structures are emerging at a rapid rate, the experimental methods used to characterize these substances cannot keep pace. In this scenario, in silico methods have become an alternative to study these systems. In this work we apply factorial planning to decide the best conditions related to Density Functional Theory (DFT) to perform the calculations.The method that presented the best results was the B3LYP, 6-311G **, LooseSCF and NormalOpt set, as it reproduced in a satisfactory way the experimental structures used for comparison. These conditions were used to calculate the infrared spectrum of 45 apprehended NPF reported in the literature. The calculated spectra were validated by comparison with experimental data and therefore have the potential to serve as a reference for unknown compounds. Chemometric methods were used to establish the main characteristics of these substances according to the structural variation. In silico methods were also used to study the tendency of biological behavior of these substances. In this sense, we use molecular docking methods, which give an idea about the interaction of these drugs with its receptors. The metabolites of these substances were also studied by computational methodology and could be compared with results reported in the literature.In conclusion, in silico methods provided valuable information on illegal substances. In addition, these methods are useful for predicting the spectroscopic and biological properties of NPF and for improving the quality of available information about them.