Análise computacional da solvatação do diclofenaco e interações da melatonina com radical hidroxila: abordagens via dinâmica molecular e teoria do funcional da densidade

Abstract

Computational chemistry represents an understanding of chemistry as the manifestation of the behavior of atoms and molecules. This active research field, spanning over a decade, employs mathematical techniques and algorithms to model and simulate chemical influences. The application of computational chemistry is crucial in material design, drug development, and the comprehension of biological processes. Analyzing solute-solvent interactions underscores the importance of physicochemical properties in chemical research, whereas the investigation of free radical elimination is essential for physiological balance. Within this context, the proposed study aims to comprehend the mechanisms of hydroxyl radical removal by melatonin and evaluate the aqueous solvation process of diclofenac through molecular modeling, employing Car-Parrinello and Born-Oppenheimer molecular dynamics, in addition to Density Functional Theory. Results from the dynamics of reactions between the •OH radical and melatonin provide a detailed understanding of various involved conditions, emphasizing the crucial influence of variables such as speed, temperature, and attack direction. The reaction with the hydrogen bonded to the nitrogen of the indole group (called H22) is the more favorable. Energy profiles and rate constants support H22 as the most likely path, providing comprehensive insights into the kinetic and thermodynamic characteristics of the interactions. Our findings regarding diclofenac solubility in water highlight the formation of important intermolecular hydrogen bonds between the atoms of diclofenac with water molecules (OH⋯Owater and CO⋯Hwater). The OH⋯Owater bond is exceptionally strong, similar a covalent bond. Additionally, we observe intramolecular hydrogen bonds in the diclofenac molecule (NH⋯OH e NH⋯Cl) and weaker interactions involving CH⋯Cl. Remarkably, diclofenac protonation contributes to molecular rigidity, hindering future hydrogen bonds with adjacent water molecules, directly impacting molecule solubility. Advancements in this field promise to enrich fundamental chemistry understanding and drive practical advancements in various areas, such as pharmacology, molecular biology, and industrial chemistry.