Crystal structure, Hirshfeld surface analysis, DFT and molecular docking investigation of 2-(2-oxo-1,3-oxazolidin-3-yl)ethyl 2-[2-(2-oxo-1,3-oxazolidin-3-yl)ethoxy]quinoline-4-carboxylate

In the crystal of the title compound, corrugated layers of molecules extending along the ab plane are generated by C—H⋯O hydrogen bonds.


Figure 1
The molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The intramolecular hydrogen bond is indicated by a dashed line.
forming an S(6) graph-set motif. Weak intermolecularinteractions are observed in this crystal structure.

Hirshfeld surface analysis
Hirshfeld surface analysis was used to quantify the intermolecular contacts of the title compound, using Crystal Explorer (Turner et al., 2017). The Hirshfeld surface was generated with a standard (high) surface resolution and with the three-dimensional d norm surface plotted over a fixed colour scale of À0.1538 (red) to 1.1337 (blue) a.u. (Fig. 3a). The palered spots symbolize short contacts and negative d norm values on the surface and correspond to the C-HÁ Á ÁO interactions ( Table 1). The shape-index map of the title molecule was generated in the range À1 to 1 Å (Fig. 3b). The convex blue regions symbolize hydrogen-donor groups and the concave red regions hydrogen-acceptor groups. The absence of adjacent red and blue triangles in the shape-index map, which generally indicateinteractions, reveals that this kind of interaction is not present in the title compound. The curvedness map was generated in the range À4.0 to 4.0 Å (Fig. 3c). It shows large regions of green with a relatively flat (i.e. planar) surface area while the blue regions demonstrate areas of curvature. The overall two-dimensional fingerprint plot is illustrated in Fig. 4a

Frontier molecular orbital analyses
The energy levels for the title compound were computed on basis of density functional theory (DFT) using the standard B3LYP functional and 6-311G++ (d,p) basis-set calculations (Becke, 1993) as implemented in GAUSSIAN 09 (Frisch et al., 2009). The HOMO (highest occupied molecular orbital) acts as an electron donor and the LUMO (lowest occupied molecular orbital) as an electron acceptor. The energy levels, energy gaps, the ionization potential (IP), electron affinity (EA), the chemical potential (), the electronegativity (), chemical hardness (), chemical softness (), and the electrophilicity index (!) are given in Table 2. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 5. If a molecule has a large HOMO-LUMO energy gap, it can be considered as hard with a low polarizability and a low chemical reactivity. Based on the numerical values collated in Table 2, the title compound can be classified as a hard material with a HOMO-LUMO energy gap of 4.2907 eV.

Molecular electrostatic potentials
The molecular electrostatic potential (MEP) map ( Fig. 6) was calculated at the B3LYP/6-311G++ (d,p) level of theory. In the MEP diagram, the molecular electrostatic potential is in the range À7.122 e À2 to 7.122 e À2 , and the different electrostatic potentials at the surface of the molecule are represented by different colours. Electrostatic potentials increase in the order of red < yellow < green < blue, and red indicates the electronrich region and blue indicates the electron-deficient region. As shown in Fig. 6, the carbonyl groups are surrounded by negative charges, indicating some possible nucleophilic attack sites. In addition, the positive charge regions are located on the H atoms.

Molecular docking study
A molecular docking study was performed to determine possible intermolecular interactions between the COVID-19 main protease (PDB ID: 6LU7) and the title molecule. Theoretical molecular electrostatic potential surface calculated at the DFT/B3LYP/6-311 G++ (d,p) basis set level.

Figure 5
Molecular orbital energy levels of the title compound. study was carried out using PyRx AutoDock Vina Wizard. The intermolecular interactions between the title compound and the target protein were visualized by using the Discovery Studio 2020 Client program (Biovia, 2017 Table 3. According to the affinity binding energies, the best binding was determined with À6.3 (kcal mol À1 ) energy and nine active hydrogen-bonding sites. The 2D and 3D visuals of the intermolecular interactions for the best binding pose of the title compound docked into macromolecule 6LU7 can be seen in Fig. 7. Table 4 lists details of intermolecular hydrogen-bonding interactions between the title molecule and the macromolecule 6LU7. Additionally in Fig. 7,and alkyl interactions and their bonding distances are shown. The title molecule appears to be a good agent because of its affinity and ability to adhere to the active sites of the protein.
The organic phase was dried over Na 2 SO 4 and then concentrated in vacuo. The resulting mixture was chromatographed on a silica gel column [eluent: ethyl acetate/hexane (2/8 v/v)].
Colourless single crystals of the title compound were obtained by slow evaporation of an ethanol solution.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5. Hydrogen atoms were discernible from difference Fourier maps and were refined freely.

Funding information
The support of NSF-MRI grant No. 1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged. research communications Table 4 The intermolecular hydrogen-bonding interactions with the distances (Å ) between the title molecule and the macromolecule 6LU7.