Abstract

CHALLAPA VELASQUEZ, Nancy Mariela  and  REBAZA OSORES, José Manuel. Optimization and validation of computational models: DFT, Ab Initio, and G3/G4 for the physicochemical characterization of neurotransmitters in the gas pase. e-Rev. Multidiscip. Saber [online]. 2025, vol.3, e-RMS05082025.  Epub Sep 23, 2025. ISSN 2960-2467.  https://doi.org/10.61286/e-rms.v3i.234.

The characterization of dopamine and its precursor, L-DOPA, in the gas phase constitutes an area of research with a marked scarcity of experimental data. Understanding the intrinsic physicochemical properties of these species is essential, given their central role in neurotransmission and their direct implication in neurodegenerative pathologies such as Parkinson's disease. To address this gap, an advanced computational methodology was employed, integrating Density Functional Theory (DFT), Ab Initio methods, and composite theories G3/G4. This approach allowed for the high-precision determination of the thermodynamic stability, molecular structure, and proton reactivity of both molecules. The calculations included an exhaustive conformational analysis aimed at identifying the most stable rotamers, which were optimized to obtain their electronic energies, enthalpies of formation, and Gibbs free energies. The results reveal that the G1a rotamer represents the most stable conformation of neutral dopamine. However, the energetic differences with other rotamers like G2 and T are marginal, oscillating between 2 and 5 kJ/mol depending on the method used. The application of isodesmic and atomization reactions proved key to improving the accuracy of the enthalpies of formation by mitigating systematic errors inherent to theoretical calculations. In summary, this study establishes a set of high-quality reference data, fundamental for the validation of future computational models and for advancing the understanding of the fundamental chemistry of neurotransmitters in solvent-free conditions. This knowledge not only strengthens basic research but also offers promising perspectives for the rational design of more effective therapeutic strategies.

Keywords : Dopamine; L-DOPA; gas phase; computational models; isodesmic reactions; neurodegenerative.

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