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.