1. Introduction
For a long time, Chloroquine (CQ) has been recognized because this
quinoline derivative was initially used in medicine to treat malaria and
because later its use was extended to also treat other diseases such as,
light-sensitive skin eruptions, hepatic amoebiasis, lupus erythematosus,
rheumatoid arthritis, including the cancer therapy [1-27]. The IUPAC
name is
4-N -(7-chloroquinolin-4-yl)-1-N ,1-N -diethylpentane-1,4-diamine.
From this year, CQ is used in experimental therapies together with its
hydroxychloroquine derivative as potential antiviral agent to treat
COVID-19 only in the context of a clinical trial [28]. Many adverse
effects appear after long time of using CQ, among which, retinopathy can
be mentioned [12,19,23].
So far, there are some studies on the infrared and Raman spectra of CQ
but the complete vibrational assignments have not been reported yet
[29-32]. Vibrational spectroscopy is not only one of the best tools
to identify all species quickly, easily and using a small amount of
sample, but it is also used to control the purity of the samples. A
study of CQ under physiological conditions by using UV resonance Raman
spectroscopy has shown that the rocking CH2 mode
assigned to chloroquine side chain is apparently influenced by
protonation of chloroquine [29] while in other study by using
surface-enhanced Raman scattering (SERS), CQ was analyzed to recognize
substandard and falsified antimalarial drugs present in commercially
available tablets [32]. In this context, the structural and
vibrational studies of CQ are valuable to characterize in complete form
its structure and properties and, besides, to understand the connection
between the structure and its mechanism of action. Particularly,
structural studies are important to determine which the most stable
structure is and, in this way, to produce the complete assignments of
all the normal modes of vibration of the compound. Hence, the objectives
of this work are: (i) to perform DFT calculations of CQ in gas phase and
aqueous solution by using the B3LYP/6-311++G** method [33,34] where
the calculations in solution were performed by using the IEFPCM and
universal solvation methods [35-37], (ii) to calculate atomic
charges, bond orders, molecular electrostatic potentials, stabilization
energies, solvation energy and, topological properties of CQ in both
media, (iii) carry out the complete assignments of the normal modes of
vibration to the bands observed in the experimental available IR and
Raman spectra by using the scaled mechanical force field (SQMFF)
methodology, scaling factors, the corresponding normal internal
coordinates and the Molvib program [38-40] and, (iv) to predict
reactivities and the behaviour of CQ in both media at the same level of
theory by using the frontier orbitals and know descriptors [41-46].
Later, the predicted 1H- and 13C-NMR
and ultra-visible spectra were compared with the corresponding available
ones while the harmonic force constants were also reported. All
properties here predicted were compared with the corresponding reported
for other antiviral agents [42-47]. Finally, the antiviral activity
of CQ and its therapeutic capacity was evaluated against a set of
COVID-19-related proteins using docking calculations because it is a
very convenient tool for the examination of biological activity
[48-53].