key: cord-1002155-vrnaad2e
authors: Douche, Dhaybia; Sert, Yusuf; Brandán, Silvia A.; Kawther, Ameed Ahmed; Bilmez, Bayram; Dege, Necmi; Louzi, Ahmed El; Bougrin, Khalid; Karrouchi, Khalid; Himmi, Banacer
title: 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol as potential antiviral SARS-CoV-2 candidate: Synthesis, crystal structure, Hirshfeld surface analysis, DFT and molecular docking studies
date: 2021-01-27
journal: J Mol Struct
DOI: 10.1016/j.molstruc.2021.130005
sha: 8369bf2af76d0bded6fe097461fe5c93cbcbdae5
doc_id: 1002155
cord_uid: vrnaad2e

A potential new drug to treat SARS-CoV-2 infections and chloroquine analogue, 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol (DD1) has been here synthesized and characterized by FT-IR, (1)H-NMR, (13)C-NMR, ultraviolet-visible, ESI-MS and single-crystal X-ray diffraction. DD1 was optimized in gas phase, aqueous and DMSO solutions using hybrid B3LYP/6-311++G(d,p) method. Comparisons between experimental and theoretical infrared spectra, (1)H and (13)C NMR chemical shifts and electronic spectrum in DMSO solution evidence good concordances. Higher solvation energy was observed in aqueous solution than in DMSO, showing in aqueous solution a higher value than antiviral brincidofovir and chloroquine. on Bond orders, atomic charges and topological studies suggest that imidazole ring play a very important role in the properties of DD1. NBO and AIM analyses support the intra-molecular O15-H16•••N17 bonds of DD1 in the three media. Low gap value supports the higher reactivity of DD1 than chloroquine justified by the higher electrophilicity and low nucleophilicity. Complete vibrational assignments of DD1 in gas phase and aqueous solution are reported together with the scaled force constants. In addition, better intermolecular interactions were observed by Hirshfeld surface analysis. Finally, the molecular docking mechanism between DD1 ligand and COVID-19/6WCF and COVID-19/6Y84 receptors were studied to explore the binding modes of these compounds at the active sites. Molecular docking results have shown that the DD1 molecule can be considered as a potential agent against COVID-19/6Y84-6WCF receptors.

Quinoline and its derivatives have always attracted both synthetic and biological chemist because of its diverse chemical and pharmacological properties [1] [2] [3] [4] [5] [6] . Literature survey revealed that quinoline derivatives had shown potency as antiviral agents against several viruses such as human immunodeficiency virus, Zika virus, H1N1 influenza virus, Hepatitis C virus, dengue virus, vaccinia virus and respiratory syncytial virus [7] [8] [9] [10] [11] [12] [13] . On the other hand, several authors report the antiviral potential of chloroquine as a therapeutic option against COVID-19, this quinoline derivative presented an EC 50 of 1.13 μM in vitro and it caused a negative conversion of the virus in more than 100 patients who participated in multicenter clinical trials conducted in China (in vivo) [14, 15] . In the in vitro study recently carried out by Liu et al. [16] have shown that chloroquine and hydroxychloroquine prevent the virus from entering the cell and block the transport of the virus between cell organelles at the later cellular stages of SARS-CoV-2 infection. However, chloroquine has been shown to have higher efficacy [16] . On the other hand, hydroxychloroquine ( Fig. 1 ) has been demonstrated to have an anti-SARS-CoV activity in vitro [17] . A clinical trial using hydroxychloroquine has been conducted in patients infected with SARS-CoV-2. The first results show a significant reduction in viral carriage and the use of hydroxychloroquine added to Azithromycin was significantly more efficient for virus elimination [18] .

In view of the therapeutic properties of quinoleine derivatives, the investigation of their molecular geometric structure, spectroscopic and electronic properties are fundamental to know the influence of different groups on structures in order to discover the relationship of these groups with their biological properties. In this context, DFT calculations have become a tool very reliable in predicting properties of molecules with great precision [19] [20] [21] [22] [23] [24] [25] .

Since the quinoline derivatives have shown high potential for the development of new antiviral drugs, herein, we have designed novel 8-hydroxyquinoline derivative i.e, 5-((1Himidazol-1-yl)methyl)quinolin-8-ol (DD1) (Fig. 1) . This new 8-hydroxyquinoline derivative was synthesized and characterized by using FT-IR, UV-visible, 1 H-and 13 C-NMR, ESI-MS and single-crystal X-ray diffraction. Then, theoretical B3LYP/6-311++G** calculations were performed to explore its structural, electronic, topological and vibrational properties in gas phase and aqueous and DMSO solutions [26, 27] .

Thus, with the optimized structures in the different media additional calculations by using the same level of theory were carried out to calculate atomic charges, stabilization energies, bond orders, molecular electrostatic potentials, vibrational frequencies, 1 H and 13 C NMR chemical shifts and Hirshfeld surface analysis. Due to the importance of this derivative, calculations of frontier orbitals also were performed in order to predict the reactivities and behaviours of DD1 in the different studied media. Finally, the molecular docking mechanism between DD1 ligand and COVID-19/6WCF and COVID-19/6Y84 receptors were studied to explore the binding modes of these compounds at the active sites.

All organic solvents were purchased from commercial sources and used as received or dried using standard procedures; all chemicals were purchased from Aldrich, Merck or Alfa Aesar and used without further purification. Analytical thin layer-chromatographies (TLC) have been performed on pre-coated silica gel plates (Kieselgel 60 F 254 , Merck, Germany), and chromatograms were visualized by UV-light irradiation. NMR spectroscopies were recorded in dry deuterated DMSO on a Bruker AC spectrometer at 300 MHz for 1 H NMR and 75 MHz for 13 C NMR; δ is expressed in ppm related to TMS (0 ppm) as internal standard. Splitting patterns are designated as follow: s (singlet), d (doublet), t (triplet), m (multiplet). Coupling constants (J values) are listed in Hertz (Hz). Mass spectra were obtained using an API 3200 LC/MS/MS system equipped with an ESI source and the samples were diluted in methanol.

An equimolar mixture of the 5-(chloromethyl) quinolin-8-ol hydrochloride (0.57 g, 2.5 mmol), paraformaldehyde (0.075 g, 2.5 mmol), and 1H-imidazole (0.17 g, 2.5 mmol) in EtOH (30 mL) was refluxed for 4-5 h. After cooling, the solvent was evaporated under vacuum and the residue was purified through silica gel column chromatography using hexane/ethyl acetate (ratio 5:5). Green single crystals were obtained by slow evaporation at room temperature. 

The X-ray intensity data for DD1 were collected at 296 K on a STOE IPDS 2 diffractometer equipped with an X-ray generator operating at 50 kV and 1 mA, using Mo-Kα radiation of wavelength 1.54178 Å. The hemisphere of data was processed using SAINT [28] . The 3D structure was solved by direct methods and refined by full-matrix least squares method on F 2 using the SHELXL program [29, 30] . All the non-hydrogen atoms were revealed in the first difference Fourier map and were refined with isotropic displacement parameters. At the end of the refinement, the final difference Fourier map showed no peaks of chemical significance and the final residual was 0.0641. The molecular and packing diagrams were generated using DIAMOND [31] .

The theoretical initial structure of DD1 was taken from the CIF file determined in this work by X-ray diffraction. Then, the optimizations were performed in gas phase and aqueous and DMSO solutions by using the functional hybrid B3LYP and the 6-311++G** basis set with the Revision A.02 of Gaussian 09 program [26, 27, 32] . In this type of molecule the used method performs the better correlations in geometries and frequencies, as was observed by us for other species [19] [20] [21] [22] . The integral equation formalism variant polarised continuum model (IEFPCM) method and the solvation model were used for the optimizations in solution by using the same level of theory [33] [34] [35] . Atomic charges and topological properties were computed with natural bond orbital (NBO) and atoms in molecules (AIM) calculations [36] [37] [38] while the GaussView program was employed to graphic the mapped molecular electrostatic potentials (MEP) obtained from the Merz-Kollman (MK) charges [39, 40] . In the vibrational study, normal internal coordinates and transferable scaling factors were used to calculate the harmonic force fields in the different media with the scaled quantum mechanical force field (SQMFF) methodology and the Molvib program [41] [42] [43] . In the assignments only those potential energy distribution (PED) contributions  10% were considered while the correlations in the Raman spectra were improved transforming the predicted spectra in activities to intensities, as suggested in the literature [44, 45] . The 1 H-and 13 C-NMR spectra in aqueous and DMSO solutions were predicted with the Gauge-Independent Atomic Orbital (GIAO) method [46] with the hybrid B3LYP/6-311++G** method while the electronic spectra at the same level of theory were also predicted by using Time-dependent DFT calculations (TD-DFT) and the Gaussian 09 program [32] . The Moldraw program was used to calculate the volumes variations that experiment DD1 in aqueous and DMSO solutions [47] .

The gap values and the chemical potential (μ), electronegativity (χ), global hardness (η), global softness (S), global electrophilicity index (ω) and nucleophilicity indexes () descriptors were calculated from the frontier orbitals with the same level of theory and by using known equations [19] [20] [21] [22] . In this new derivative is useful to predict the reactivities and behaviours in the different media taking into account the presence of donor (OH) and acceptors (O and N) groups in the structure of DD1 [48, 49] . The molecular docking mechanism between DD1 ligand and COVID-19/6WCF and COVID-19/6Y84 receptors were studied by using AutoDock Vina free software program [50] .

The details of the X-ray crystal data and the structure solution as well as the refinement of the title compounds are given in Table 1 Table 2 ). 

The hybrid B3LYP/6-311++G** method has optimized the structures of 5-((1H-imidazol-1yl)methyl)quinolin-8-ol (DD1) in all media with C 1 symmetries where the structure in gas phase compared with the corresponding experimental determined by X-ray diffraction together with the definitions of rings can be seen in Figure 4 . R1 corresponds to pyridine ring, R2 to phenyl ring containing the OH group while the imidazol ring is defined as R3. In Table 3 are presented total energies uncorrected and corrected by zero point vibrational energy (ZPVE), dipole moments and volumes of DD1 in gas phase and aqueous and DMSO solutions by using the B3LYP/6-311++g(d,p) Method. The three calculations evidence a higher stability of structure in gas phase while in aqueous and DMSO solutions the energy values increase notably being slightly less stable in water than DMSO solvent. Perhaps, the higher dipole moment and volume values of DD1 in water justify its lower stability in this medium. In both solvents there is a contraction in the volume when dissolving is performed but, the value is higher in DMSO solution probably due to its higher stability and low dissolution (-1.6 Å 3 ). Thus, the solvent effect can be observed in graphics of orientations and directions of dipole moment vectors because the magnitude is higher in water ( Figure S1 ). Due to the difference observed in the properties of DD1 in both solvents it is necessary to calculate the solvation energies in the two solvents. Hence, the corrected and uncorrected solvation energies in both solvents calculated from the energies ZPVE can be seen in Table 4 . The results shown in Table 4 have evidenced most negative solvation energy of DD1 in water, as expected because this new derivative is most stable in DMSO. Hence, the G c value for the water was obtained from the difference between G un # and G ne, that is, -471. probably are protonated and charged because previous studies on some antiviral, antihistaminic and alkaloids species have evidenced that in aqueous solution the forms hydrated or cationic present a higher value as compared with the neutral free base or hydrochloride species [51] [52] [53] [54] [55] [56] [57] [58] [59] , as can be observed in Table S1 . If now the (G c ) values of DD1 in aqueous solution are compared with reported for antiviral species in aqueous solution from Table S2 [60] [61] [62] [63] [64] [65] we observed that DD1 has the lowest (G c ) value than the antiviral agents, perhaps due to the three rings present in its structure because the number of acceptors and donors is less than the other ones. From previous studies, we observed that the differences in the solvation energies with another smaller basis set do not present greater differences with those calculated with a higher level of theory [22, 61, 65] . Table 5 show comparisons of calculated geometrical parameters of 5-((1H-imidazol-1yl)methyl)quinolin-8-ol (DD1) in gas phase and aqueous and DMSO solutions with the corresponding experimental determined by X-ray diffraction by using root-mean-square deviation (RMSD) values. These calculations were performed at the same level of theory. The results shown in Table 5 

As was above mentioned, the high solvation energy values of DD1 in both media could be attributed to that the acceptors (N and O) and donor (OH) groups are protonated and charged and, for these reasons, the calculations related to involved charges on the atoms of those groups are important for this new species as drug candidate [48, 49] . Thus, three types of atomics charges, Merz-Kollman (MK), Mulliken and natural population analysis (NPA) charges were calculated on the O15, H16, N17, N21 and N28 atoms of DD1 in gas phase and aqueous and DMSO solutions by using the B3LYP/6-311++G** method [36, 39] . These results are summarized in Table S3 while comparisons among them can be observed in In Table S4 are shown the molecular electrostatic potentials (MEP) and bond orders (BO), expressed as Wiberg indexes for DD1 in gas phase and aqueous and DMSO solutions by using B3LYP/6-311++G** calculations. Regarding first the MEP values, there are not significant differences in the values on those five considered atoms of DD1 in the three media and, only the expected tendency in the values due to the electronegativities values are found, that is, O > N > H. But the higher MEP value is observed on N28, as compared with N17 and N21. When the mapped surface for DD1 in gas phase by using the B3LYP/6-311++G** method is graphed from the GaussView program in Figure S4 [40] the different colorations show clearly the nucleophilic and electrophilic regions that presents DD1. Thus, the region on N28 shows higher electronic density and strong red colour indicating nucleophilic sites while on the O15 and N17 weak orange colours are observed and, as a consequence, these places are weak nucleophilic sites. The strong blue colours is observed on the H16 linked to O15 of OH group. This region is a strong electrophilic site because the H16 is the most labile H atom than the other ones. The aromatic H atoms of pyridine, phenyl and imidazole rings shows ligth blue colours due to that these sites are weak electrophilic regions.

When the bond orders (BO), expressed as Wiberg indexes for DD1 in gas phase and aqueous and DMSO solutions are analyzed from Table S4 and Figure S5 , it is observed a low BO value for the H16 atom because this atoms is the most labile while the N21 atom is most strongly linked in DD1 in water than in gas phase and DMSO solution. Then, the BO values for the N17 and N28 atoms are practically the same in the three media. These parameters together with the NPA charges show that the N21 atom of imidazole ring play an important role in the properties of DD1 in the three media.

The NBO program allows examining all possible interactions between 'filled' (donor) Lewistype NBOs and 'empty' (acceptor) non-Lewis NBOs, and estimating their energetic importance by 2nd-order perturbation theory Analysis of Fock Matrix in NBO Basis [36] .

These energies values for DD1 in gas phase and aqueous and DMSO solutions were calculated by using the functional hybrid B3LYP method and two 6-311++G** and 6-31G* basis sets which are presented in Table S5 . Here, when the calculations were performed with the higher basis set only was obtained for DD1 in water while for DD1 in gas phase and in Table S6 . Whereas in Figure S6 is shown the molecular graphic only for DD1 in gas phase showing the intra-molecular O15-H16···N17 interaction. The same interaction is also observed in gas phase and in DMSO solution. The new RCP is named RCPN1 while RCP1, RCP2 and RCP3 correspond to the RCP of pyridine (R1), phenyl (R2) and imidazole (R3) rings.·Table S6 shows that the distance between the H16 and N17 atoms that forming those intra-molecular bonds is higher in water than the other ones, as expected because the permittivity of water is higher in this medium (78.355) than the corresponding to DMSO (46.826) and gas (vacuum). Higher parameters are observed in DMSO and lower in water confirming that the stability is higher in DMSO because DD1 has higher solvation energy in water.

Previous studies performed for DD1 in the different media have evidenced interesting properties for this new quinoline derivative and, probably its high solvation energy value in aqueous solution could support its use as antiviral drug candidate. For these reasons, calculations of frontier orbital, gap values and chemical potential (μ), electronegativity (χ), global hardness (η), global softness (S), global electrophilicity index (ω) and global nucleophilicity index (E) descriptors are very important to predict reactivities and behaviours of DD1 in the three studied media [19] [20] [21] [22] 51, [60] [61] [62] [63] [64] [65] . Table S7 shows those parameters for DD1 in gas phase and aqueous and DMSO solutions by using the B3LYP/6-311++G** method compared with the hydrochloride form of antiviral adamantadine in water and with both S and R forms of chloroquine in water by using the same level of theory. The differences between HOMO and LUMO, named gap, shows lower values in DD1 in the three media and, hence, a higher reactivity is expected for DD1 and, in particular, in DMSO solution while the R form of chloroquine is the less reactive than the other ones. A higher global electrophilicity index (ω) and a lower global nucleophilicity index (E) predicted for DD1 in DMSO could justify its higher reactivity in this medium. Comparisons of these parameters with reported for antiviral agents in the same medium and with the same basis set suggest that DD1 could be a very good antiviral drug candidate.

The experimental infrared spectra of the title compound DD1 in the solid state was recorded using reflectance (ATR) mode and its comparison with the corresponding predicted in the gas phase and aqueous and DMSO solutions by using the B3LYP/6-311++G** method are given in Figure 5 . The predicted Raman spectra of DD1 in the three media can be seen in Figure 6 .

Here, the theoretical Raman spectra were corrected from activities to intensities by using recommended equations [44, 45] . The optimized structures in the three media present C 1 symmetries and 28 atoms, hence, for this species are expected 78 vibration normal modes. All vibration modes present activity in the infrared and Raman spectra. The scaled quantum mechanical force field (SQMFF) methodology and the Molvib program were used, together with the normal internal coordinates and transferable scaling factors, to calculate the harmonic force fields of DD1 in the three media at the same level of theory [41] [42] [43] . Then, the vibrational assignments of bands observed in the experimental infrared spectrum to the vibration modes were performed considering potential energy distribution (PED) contributions  10 %. In Table 6 are summarized observed and calculated wavenumbers for DD1 in gas phase and aqueous solution by using B3LYP/6-311++G** calculations together with the corresponding assignments. In the region of higher wavenumbers the assignments in gas phase are practically the same than in aqueous solution and, only the C2-H7 and C1-H6 stretching modes corresponding to pyridine ring are predicted interchanged in solution in relation to the gas phase. Later, assignments for some groups are discussed below. The weak IR bands at 2794w, 2750w and 1890w could be attributed to the dimeric species because the calculations were performed in the gas phase to the isolated molecule where the forces packing in the solid phase were not considered. Figure S7 shows the predicted IR spectra in the three media and the increase in the intensities of some bands in solution.

Assignments O-H group. The OH stretching vibrations are generally observed around 3500-3300 cm -1 [63] . This absorption is strongly influenced by the chemical environment, in particular when OH group are involved in the intramolecular or intermolecular hydrogen bond [66] [67] [68] . De Freitas et al. [66] reported the OH stretching vibration of the 8-hydroxyquinoline-2-carboxaldehyde isonicotinoylhydrazone at 3396 cm -1 . On the other hand, Benković et al. [69] reported the stretching of the OH groups, involved in the intramolecular hydrogen bond with the nitrogen atom of the group C=N, of hydrazones with hydroxyl group in position 2 of phenyl ring at 3142 cm -1 . In the present study, the broad and very weak IR band at 3490 cm −1 have been assigned to stretching modes of OH involved in the intramolecular hydrogen bond for DD1 (Figs. 5 and 6 ). Note that in solution this mode is predicted to lower wavenumbers due to the hydration. In general, the OH in-plane deformation vibration for phenols lies in the region 1440-1260 cm -1 [70] , Arunagiri et al. [71] reported the in-plane deformation vibrations of two OH at 1242 and 1220 cm -1 . In this work, the observed in-plane deformation vibrations of OH for DD1 in gas phase and aqueous solution are predicted at 1180 and 1172 cm -1 , respectively while the out-of-plane deformation or torsion mode of OH for DD1 in gas phase is predicted at 569 cm -1 and, in solution it is predicted shifted at 492 cm -1 due to the hydration, as observed in similar compounds containing this group [58] [59] [60] [61] [62] [63] [64] [65] .

in the region 3100-3000 cm -1 in aromatic compounds [55] [56] [57] [58] 60, 72] . For the title molecule, a series of infrared absorptions between 3168 and 2989 cm -1 were assigned as CH stretching modes of the quinolone, imidazole and benzotriazole rings. The C-H in-plane deformation vibrations are observed in the region 1500-1058 cm -1 and are usually of medium to weak intensity [55] [56] [57] [58] 60, 65, 72] . In the present work, the bands due to C-H in-plane bending vibration interact somewhat with C-C stretching vibrations, hence, they are assigned to IR bands between 1472 and 1054 cm −1 . The out-of-plane CH deformations are predicted and assigned between 999 and 715 cm -1 [55] [56] [57] [58] 60, 65, 72] . The assignments of these vibration modes in solution are slightly different from those predicted in gas phase, as can be seen in Table 6 . In our case, the strong IR bands at 823, 791 and 696 cm -1 together with the band of medium intensity at 927 cm -1 are assigned to CH out-of-plane deformation vibrations.

Assignments CH 2 groups. These vibration modes are influenced by the medium because in solution are predicted at higher wavenumbers than in gas phase. Thus, the anti-symmetric and symmetric stretching modes are predicted in gas phase at 2943 and 2911 cm -1 while in solution are predicted at 3004 and 2962 cm -1 , respectively. The remaining deformation, wagging, rocking and twisting modes are observed at higher wavenumbers in aqueous solution. Probably, the proximity of this group with the imidazole ring justifies these differences.

Assignments skeletal groups. The C=N stretching vibration is reported at 1613 cm -1 by Sheeja et al. [72] . Here, the C5=N17 and C23=N28 stretching modes are predicted in gas phase at 1563 and 1474 cm -1 while in solution at 1578 and 1333 cm -1 . Note that the C23=N28 stretching mode in solution is predicted coupled with the C23-N21 stretching mode. The aromatic C=C-C stretching vibrations of aromatic ring are very much important and occur in the region 1200-1650 cm -1 [19] [20] [21] [22] [55] [56] [57] [58] 60] . In DD1, the IR bands in the range 1687-1457 cm -1 are assigned to C=C stretching mode in aromatic rings while the C-C stretching modes are predicted by SQM calculation between 1367 and 1001 cm -1 . Then, these modes are assigned in those regions, as predicted by calculations. Here, the C18-N21 stretching modes in both media are predicted couples with one of torsion modes of pyridine ring between 728 and 725 cm -1 , that is, practically in the same region. Hence, we can see that that mode is not influenced by the medium. The assignments of other groups in the 360 and 25 cm -1 region such as, deformations and torsions of three rings were not performed because the infrared spectrum was recorded only until 400 cm -1 .

Calculations of harmonic force fields for DD1 in the three media by using the B3LYP/6-311++G** method have allowed to compute the scaled force constants which are very important parameters that explain the forces of different bonds. Thus, these constants are obtained when the harmonic force fields are transformed from Cartesian coordinates to normal internal coordinates with the SQMFF methodology and the Molvib program [41] [42] [43] .

The results for DD1 in the three media are presented in Table 7 . Thus, due to the proximity of CH 2 group to ring R3 the stretching modes are influenced by the medium because in solution are observed higher force constants values than in gas phase.

However, the deformations of those groups practically are practically similar in the three media.

The experimental ultraviolet-visible spectrum of DD1 in DMSO solution recorded between 200 and 400 nm region can be seen in Figure S8 

The experimental 1 H-and 13 C -NMR spectra of DD1 were obtained by using TMS as an internal standard and DMSO-d 6 as solvent (Figs. S9 and S10) . In Tables 

The (Fig. S11) . These values are in good agreement with the proposed composition for the title compound.

In this section, the Hirshfeld surface analysis of the DD1 molecule were carried out with the help of Crystal Explorer 3.1 program [73] . 

In this section, the molecular docking analysis of 5-((1H-imidazol-1-yl) methyl) quinolin-8-ol Table 8 , also between DD1-6Y84 docking mechanism as 2D and 3D were shown in Fig. 9 . In addition, the positions of DD1 within the receptor (6Y84) were shown in Fig. 10 . The best binding was determined with -7.2 (kcal/mol) energy between DD1 ligand and 6Y84 receptor according to the affinity energies with two hydrogen bonding. But one active hydrogen bonding was observed GLN127 active residue and H2 atom with 2.33 Å bond distance as seen Fig. 9 . Furthermore, from the Fig. 9 van der Waals, π-cation, π-donor hydrogen bond and π-alkyl interactions could be easily seen. At the last of the tables, the obtained inhibition constants and the number of hydrogen bonding for DD1-6Y84 interactions were given. Secondly, the molecular docking mechanism between DD1 ligands and the 6WCF receptor was investigated and evaluated. 6WCF is Crystal Structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES [82] . The active sites of PDB:6WCF were detected as PHE132, ILE131, GLY130, ALA129, ASN72, THR71, SER128, LYS55, ALA52, GLY51, GLY47, GLY46, LYS44, ASN40, and ALA38. As mentioned before, the grid parameters were determined to include the active region as follows : centre_x=-4.969, centre_y=8.796, centre_z=-5.972, size_x=62, size_y=84, size_z=42, spacing=0.375. The same grids were used in both ligands and the docking scores were tabulated in Table 9 and additionally between DD1-6WCF docking mechanism were indicated as 2D and 3D in Fig.   11 . Figure 11 . The molecular docking results of the DD1 compound with 6WCF protein, surfaces around ligand (a) and 2D forms (b).

Furthermore, the positions of DD1 within the 6WCF receptor were indicated in Fig. 11 . As seen from the Table 9 , the best binding was determined with -6.2 (kcal/mol) energy between DD1 ligand and 6WCF receptor with two active hydrogen bonding (Fig. 10) . The bond distances between ALA129-N5 and SER128-N6 were determined as 2.35 and 2.70 Å, respectively. Additionally, from the Fig. 12 van der Waals, carbon hydrogen bond, π-π-T shaped and π-alkyl interactions could be easily observed and at the last of the tables, the inhibition constants and the number of hydrogen bonding for DD1-6WCF interactions were

given. The inhibition constants were computed with the help of Ki=exp(ΔG/RT) equation,

where, ΔG, R and T are the docking binding energy, gas constant (1.9872036×10 -3 kcal/mol) and room temperature (298.15 K), respectively. From the molecular docking results, it is concluded that DD1 molecule can be considered as potential agent against COVID-19/6Y84-6WCF receptors.

In this work, a new chloroquine analogue, 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol (DD1)

with potential antiviral agent against COVID-19/6Y84-6WCF receptors has been synthesized and characterized by FT-IR, 1 H-NMR, 13 

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Scaling of ab-initio force fields by MOLVIB

Vibrational spectra of monothiocarbamates-II. IR and Raman spectra, vibrational assignment, conformational analysis and ab initio calculations of S-methyl-N,N-dimethylthiocarbamate

The prediction of Raman spectra of platinum(II) anticancer drugs by density functional theory

Self-consistent perturbation theory of diamagnetism. I. A gage-invariant LCAO (linear combination of atomic orbitals) method for NMR chemical shifts

Molecular Properties that influence the oral bioavailability of drug candidates

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development setting

AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading

Normal internal coordinates, Force fields and vibrational study of Species Derived from Antiviral adamantadine

DFT study of Species Derived from the Narcotic Antagonist Naloxone

S(-) and R(+) Species Derived from Antihistaminic Promethazine Agent: Structural and Vibrational Studies

Ab-initio and Vibrational studies on Free Base, Cationic and Hydrochloride Species Derived from Antihistaminic Cyclizine agent

Why morphine is a molecule chemically powerful. Their comparison with cocaine

Vibrational analyses of alkaloid cocaine as free base, cationic and hydrochloride species based on their internal coordinates and force fields, Paripex A

Structural, FT-IR, FT-Raman and ECD studies on the free base, cationic and hydrobromide species of scopolamine alkaloid

Understanding the potency of heroin against to morphine and cocaine

Force field, internal coordinates and vibrational study of alkaloid tropane hydrochloride by using their infrared spectrum and DFT calculations

Structural, topological and vibrational properties of an isothiazole derivatives series with antiviral activities

Properties, Reactivities and Molecular docking of Potential Antiviral to Treatment of COVID-19 Niclosamide in different media

A structural and vibrational investigation on the antiviral deoxyribonucleoside thymidine agent in gas and aqueous solution phases

Structural and vibrational properties of the antiviral ribavirin drug in gas and aqueous environmental. A complete assignment of their vibrational spectra

Effect of the side chain on the properties from cidofovir to brincidofovir, an experimental antiviral drug against to Ebola virus disease

Structural and vibrational study on the acid, hexa-hydrated and anhydrous trisodic salts of antiviral drug Foscarnet

Structural and vibrational study of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoylhydrazone-A potential metalprotein attenuating compound (MPAC) for the treatment of Alzheimer's disease

Anharmonic effects on theoretical IR line shapes of medium strong H (D) bonds

Theoretical infrared line shapes of H-bonds within the strong anharmonic coupling theory and Fermi resonances effects

Aromatic hydrazones derived from nicotinic acid hydrazide as fluorimetric pH sensing molecules: Structural analysis by computational and spectroscopic methods in solid phase and in solution

Density functional, Hartree− Fock, and MP2 studies on the vibrational spectrum of phenol

Synthesis, X-ray crystal structure, vibrational spectroscopy, DFT calculations, electronic properties and Hirshfeld analysis of (E)-4-Bromo-N'-(2, 4-dihydroxy-benzylidene) benzohydrazide

Vibrational spectroscopic studies and computational study of quinoline-2-carbaldehyde benzoyl hydrazone

Bonded-atom fragments for describing molecular charge densities

Hirshfeld surface analysis

The process of structure-based drug design

Bioinformatics software resources

The Molecular Docking Study of Potential Drug Candidates Showing Anti-COVID-19 Activity by Exploring of Therapeutic Targets of SARS-CoV-2, screening

COVID-19 main protease with unliganded active site

Center for Structural Genomics of Infectious Diseases (CSGID), Crystal Structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES