Estudo teórico do mecanismo de interação da dopamina e o radical hidroxila usando dinâmica molecular de Born-Oppenheimer

Abstract

Dopamine is a neurotransmitter synthesized by dopaminergic neurons located in the substantia nigra. It plays a fundamental role in functions such as motor control and cognition. Its dysregulation is associated with various conditions, including neurodegenerative diseases such as Parkinson's and Alzheimer's, as well as disorders like schizophrenia. Oxidative stress, resulting from excessive free radical production and/or deficiencies in antioxidant systems, is recognized as a key factor in the development of neurodegenerative diseases, as it can cause cellular damage and neuroinflammation. There are several experimental studies on dopamine and the hydroxyl radical; however, there is a scarcity of theoretical research exploring the molecular interactions involved in these processes. In this context, the present study employed Born-Oppenheimer Molecular Dynamics in conjunction with Density Functional Theory to investigate the interaction mechanism between dopamine and the hydroxyl radical. To achieve this, Fukui indices were calculated, and simulations were performed using Born-Oppenheimer Molecular Dynamics combined with Density Functional Theory. The Fukui indices indicated that the two hydrogen atoms bonded to the nitrogen (amine group) and the hydrogen bonded to the oxygen (phenolic group) are the most susceptible to radical attack. Simulations were carried out by varying the approach velocity of the hydroxyl radical, revealing that higher velocities result in molecular degradation, whereas lower velocities favor specific interactions, such as water formation. These findings enhance the understanding of the molecular-level interactions between the hydroxyl radical and dopamine.