Implicit and Explicit Solvent Effects on the Global Reactivity and the Density Topological Parameters of the Preferred Conformers of Caespitate

• Published in: Computation 2024-01, Vol.12 (1), p.5
• Main Authors: Moreno-Ceballos, Andrea, Castro, María Eugenia, Caballero, Norma A, Mammino, Liliana, Melendez, Francisco J
• Format: Article
• Language: English
• Subjects: Acetonitrile; Analysis; Biological activity; caespitate; Care and treatment; Chloroform; Compositae; Composition; conceptual-DFT; conformational search; Density functional theory; explicit solvent effect; Hydrogen; Hydrogen bonding; Hydrogen bonds; implicit solvent effect; Infectious diseases; Materia medica, Vegetable; Natural products; NMR; Nuclear magnetic resonance; ONIOM-DFT; Phytochemicals; Plant extracts; Solvent effect; Solvents; Tuberculosis; Vapor phases
• ISSN: 2079-3197; 2079-3197
• DOI: 10.3390/computation12010005

In the search to cover the urgent need to combat infectious diseases, natural products have gained attention in recent years. The caespitate molecule, isolated from the plant Helichrysum caespititium of the Asteraceae family, is used in traditional African medicine. Caespitate is an acylphloroglucinol with biological activity. Acylphloroglucinols have attracted attention for treating tuberculosis due to their structural characteristics, highlighting the stabilizing effect of their intramolecular hydrogen bonds (IHBs). In this work, a conformational search for the caespitate was performed using the MM method. Posteriorly, DFT calculations with the APFD functional were used for full optimization and vibrational frequencies, obtaining stable structures. A population analysis was performed to predict the distribution of the most probable conformers. The calculations were performed in the gas phase and solution using the implicit SMD model for water, chloroform, acetonitrile, and DMSO solvents. Additionally, the multiscale ONIOM QM1/QM2 model was used to simulate the explicit solvent. The implicit and explicit solvent effects were evaluated on the global reactivity indexes using the conceptual-DFT approach. In addition, the QTAIM approach was applied to analyze the properties of the IHBs of the most energetically and populated conformers. The obtained results indicated that the most stable and populated conformer is in the gas phase, and chloroform has an extended conformation. However, water, acetonitrile, and DMSO have a hairpin shape. The optimized structures are well preserved in explicit solvent and the interaction energies for the IHBs were lower in explicit than implicit solvents due to non-covalent interactions formed between the solvent molecules. Finally, both methodologies, with implicit and explicit solvents, were validated with 1H and 13C NMR experimental data. In both cases, the results agreed with the experimental data reported in the CDCl3 solvent.