In this work, the structural, electronic, topological and vibrational properties of potential antiviral to treatment of COVID-19, niclosamide (NCL) have been studied in different media together with its reactivities by combination of DFT calculations with molecular docking. Properties of two most stable conformers of niclosamide (C1 and C2) were reported in gas phase and water, ethanol and chloroform solvents. Calculations using the integral equation formalism variant polarised continuum (IEFPCM) and solvation methods in the different solutions have revealed solvation energy values for C1 and C2 in aqueous solution (GC= -78.43 and -64.53 kJ/mol, respectively) comparable with that observed for the antiviral agent zalcitabine (-78.92 kJ/mol). Probably, the high stability of C1, predicted by NBO studies, explains the experimental existence of C1 in the solid phase. Comparisons of frontier orbitals with eleven antiviral agents have evidenced the high reactivity of C2 slightly higher than brincidofovir, an antiviral agent used in the treatment to ebola disease. Possibly, the presence of deactivating groups (NO2 and Cl) in the chloro-4-nitrophenyl and hydroxybenzamide rings of both forms of NCL could explain the higher reactivities predicted in the different media. Here, the harmonic force fields and force constants for both forms are reported together with the assignments of 80 vibration modes expected in the experimental infrared spectrum of NCL. The predicted UV-Vis spectra in the different solvents suggest the presence of both forms of NCL in solution. Molecular docking results were discussed basing on the type of interaction between the ligands and several amino acid residues.

This research is a continuation of previously reported article on anhydrous freebase, cationic and hydrochloride tacrine. Here, structures and properties of di-hydrated species of cholinesterase inhibitor tacrine have been studied in gas phase and aqueous solution by using B3LYP/6-311G* and wB97XD/6-311G* levels of theory. Both methods show strong changes in the positions of two water molecules and similar solvation energies (−192.52 kJ/mol with the B3LYP method and −191.95 kJ/mol with the other one). The B3LYP method predicts low gap values for the anhydrous (2.4572 eV) and di-hydrated (3.2708 eV) species of tacrine in gas phase than the wB97XD/6-311G* method (7.2300 eV). Hence, higher reactivities are expected for the di-hydrated species in both media. Atoms in molecules (AIM) calculations support the lower stability of di-hydrated species in solution in agreement with its higher reactivity in this medium. Complete assignments of 104 vibration modes expected for di-hydrated hydrochloride by using the scaled mechanical force field (SQMFF) methodology have been reported. Both methods predict different assignments and scaled force constants presenting higher values those calculated with the wB97XD/6-311G* method. The predicted IR, Raman and ¹H NMR spectra with both methods show good correlations with the corresponding experimental ones, however, better concordances between the ¹³C NMR and UV spectra are observed with the wB97XD/6-311G* method.