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].