Elucidation of the complex deprotonation routes of Changrolin, the antihypertensives LQM-303 and LQM-303b, and their derivatives

作者：Alejandro Hernandez Olivares Manuel; Ibarra Escutia Agustin; Mendoza Sarmiento Gabriela; Rojas Hernandez Alberto^*; Galano Annia^*

来源：Computational and Theoretical Chemistry, 2017, 1115: 229-238.

DOI：10.1016/j.comptc.2017.06.023

• Phenolic compounds
• Acid-base equilibrium
• Site acidity
• Hydrogen bonding
• Atoms in molecules

Elucidating the most likely deprotonation routes for polyprotic molecules is crucial in order to know the structures of the species prevailing under specific pH conditions. This is particularly important for molecules with potential applications as medical drugs, since different acid-base species, with the same deprotonation degree, may not interact in the same way with biological targets. The 19 polyprotic molecules investigated here are particularly challenging because they present phenolic and tertiary amino groups, which have similar ease of deprotonation, and also a high conformational complexity. Deprotonation energies in aqueous solution were estimated using the Density Functional Theory, and used as a quantitative criterion to identify the most likely deprotonation routes for the target molecules, which are proposed here for the first time. In addition, the LUMO and LUMO+1 distributions were also analyzed, and used as a qualitative criterion to support the proposed deprotonation routes. It is suggested that using both molecular orbitals combined for systems with small (LUMO+1) - LUMO energy gaps may provide a more useful picture in this context.

• 出版日期2017-9-1