Thermal Degradation Energy Landscapes of Fluorofentanyls: Probing the Mechanisms and Energetics of Bond Breaking

To aid in the detection of fluorofentanyls, which degrade with exposure to heat such as during consumption by smoking, it is essential to understand the potential degradation products. However, the degradation products of fluorofentanyls are not well characterized. In this study, we investigated the thermal degradation pathways of ortho-, para-, and meta-fluorofentanyl using a combination of ab initio molecular dynamics simulations and the enhanced sampling techniques of multiple walker metadynamics and umbrella sampling. We estimated the free energy profiles for each bond identified as a potential degradation site to elucidate the thermodynamic driving forces. Additionally, we predicted the forward attempt rate for each bond degradation reaction to assess its likelihood of breaking. Our findings indicate that, despite their structural similarities, fluorofentanyls differ in their degradation pathways.