Computational Modeling of Cocaine Degradation by Esterases: A Theoretical Approach Applied to Forensic Chemistry.

This study investigates the structural, electronic, and intermolecular properties of cocaine and its major metabolites through computational methods. Density Functional Theory (DFT) calculations were performed using FHI-aims at the PBE+TS/light-tier2 level to evaluate electronic reactivity based on the frontier orbital energy gap (Egap). Molecular docking simulations were conducted to investigate the interactions between cocaine, its metabolites, and cocaine esterase (CocE). Neutral cocaine exhibited the lowest energy gap, indicating higher chemical reactivity, whereas protonated cocaine and methylecgonine showed greater electronic stability. Docking results revealed that protonation enhances enzyme recognition and that benzoylecgonine forms the most stable enzyme–ligand complex. Overall, these results contribute to a better understanding of cocaine degradation and the recognition of its metabolites by CocE, providing a foundation for future detoxification strategies and forensic applications, including molecularly imprinted polymers (MIPs) and sensing devices.