Figure 3 . Individual contributions to the elimination score (SE), for the most promising rasagiline derivatives.
Contrarily, for the other indexes (PSA, HBA and HBD) larger SE values denote that the properties of the examined derivatives deviate from the reference average, although they still fulfill the Lipinski’s and Ghose’s rules, as well as the Veber criteria. Regarding PSA, the chosen rasagiline derivatives deviating the most from the reference set are dR-6, dR-7, dR-8, and RI, but their PSA values (12.03 for the first three and 26.02 Å2 for the last) are below the Veber’s limit: 140 Å2. The largest deviations for HBA and HBD correspond to R-6, R-7, R8 and RI with HBA = 1 and to RI-84 and RII-10, with HBD = 4, respectively. Once again, they do not represent violations of the Lipinski’s rule. Stand on what has been considered, none of the 16 rasagiline derivatives selected as the most promising candidates, following the selection score, was excluded after the exhaustive screening using the elimination scores. Hence, IE, EA, and electrophilicity were estimated and analyzed for all of them.
Since all the rasagiline derivatives selected in the subset may be involved in acid-base equilibria, and such equilibria frequently influences the antioxidant capability, their p Ka values were determined, as well as their molar fractions (Mf ) at physiological p H (Table 1). Their corresponding deprotonation routes and their distribution diagrams were also elucidated (Scheme S1 and Figure S1 in the Supporting Information). Ionization energies, electron affinities, and electrophilicities for the acid-base species with non-negligible population (Mf > 0.1%) atp H=7.4, are reported in Table 2.
Table 1 . Estimated p Ka values and molar fractions of the diprotonated (Mf diprot), protonated (Mf prot), neutral (Mf neutral), anionic (Mf anion) dianionic (Mf dian) and trianionic (Mf trian) species of rasagiline its derivatives, at p H=7.4.