3.5. Frontier orbitals and global descriptors studies
Taking into account the widely-known antiviral properties reported for
CQ [1-27] and, particularly, its potential use to treat COVID-19
[28] the reactivities and behaviour of both S(-) and R(+) forms in
the two media should be investigated. Hence, calculations of frontier
orbitals HOMO and LUMO were used to compute the gap values and chemical
potential (μ ), electronegativity (χ ), global hardness
(η ), global softness (S ), global electrophilicity index
(ω ) and global nucleophilicity index (E ) descriptors by
using known equations [41-47]. Therefore, the results of those
properties for both S(-) and R(+) forms in gas phase are presented inTable S7 by using the B3LYP/6-311++G** method while the values
for these forms of CQ are compared with the corresponding to antiviral
isothiazol, thymidine, cidofovir, brincidofovir, foscarnet, niclosamide
and amantadine agents in Table S8 [42-47]. The structures
of all compared antiviral agents are presented in Figure S2 .
The analyses of results for both S(-) and R(+) forms of CQ show that the
S(-) forms (4.3729 and 4.2994 eV) in both media are slightly more
reactive than the R(+) ones (4.3924 and 4.3021 eV) because there are
little differences between the values in gas phase and in aqueous
solution. Both forms are more reactive in solution. When those gap
values are compared with other antiviral agents from Table S8
brincidofovir (3.7715 eV) and niclosamide (4.2205 eV) they are the more
reactive than the other ones. Note that the value for brincidofovir was
calculated by using B3LYP/6-31G* method while niclosamide was calculated
with the same method than both forms of chloroquine. Hence, it is
observed that potential antiviral to COVID-19 niclosamide is better than
both forms of chloroquine and, therefore, both forms of CQ could be used
to treatment of COVID-19. These differences are justified by the two Cl
atoms present in niclosamide in addition to NO2 group
and to the nine acceptors and donors groups different from both forms of
CQ because these only have a Cl atom and 4 acceptors and donors groups.
In relation to the descriptors, the S(-) form has lower electrophilicity
index in gas phase but a higher value in solution than the R(+) one
while a same tendency it is observed for the S(-) form in the
nucleophilicity index. If now these two electrophilicity and
nucleophilicity indexes are compared with the predicted for other
antiviral agents we observe that niclosamide presents a higher
electrophilicity index value while foscarnet presents the highest
nucleophilicity index. The presence of 19 acceptors and donors groups in
addition to three Na atoms and phosphate group in foscarnet could
justify that high value predicted for the nucleophilicity index.