Crystal structure, Hirshfeld surface analysis, DFT and the molecular docking studies of 3-(2-chloroacetyl)-2,4,6,8-tetraphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one

In the bicyclic title compound, C33H29ClN2O2, the two piperidine rings of the diazabicylco moiety adopt distorted-chair conformations.


Structural commentary
The molecular structure of (I) is displayed in Fig. 1.The chloroacetyl group (C8/O1/C9/Cl1) and the phenyl ring (C10-C15) are perpendicular with each other and make a dihedral angle of 89.8 (1) � .The chloroacetyl group is planar with a maximum deviation of 0.080 (1) A ˚for atom C8.

Figure 2
The crystal packing of (I).The intra-and intermolecular C-H� � �� interactions are shown as dashed lines.For clarity, H atoms not involved in these interactions have been omitted.(McKinnon et al., 2007) were generated.The HS mapped over d norm in the range À 0.0876 to +1.5105 a.u. is illustrated in Fig. 3, using colours to indicate contacts that are shorter (red areas), equal to (white areas), or longer than (blue areas) the sum of the van der Waals radii (Ashfaq et al., 2021).
The two-dimensional fingerprint plots provide quantitative information about the non-covalent interactions and the crystal packing in terms of the percentage contribution of the interatomic contacts (Spackman & McKinnon, 2002;Ashfaq et al., 2021).The overall two-dimensional fingerprint plot, Fig. 4a, and those delineated into H� � �H interactions (52.3%),H� � �C/C� � �H (23.7%),H� � �Cl/Cl� � �H (11.3%),H� � �O/O� � �H (10.8%),Cl� � �C/C� � �Cl (1.1%) and C� � �C (0.7%) interactions are illustrated in Fig. 4b-g, respectively.The most important interaction is H� � �H, which is reflected in Fig. 4b as widely scattered points of high density due to the large hydrogen content of the molecule with the tip at d e = d i = 1.10A ˚.The large number of H� � �H, H� � �C/C� � �H, H� � �Cl/Cl� � �H, H� � �O/ O� � �H and Cl� � �C/C� � �Cl interactions suggest that van der Waals and hydrogen-bonding interactions play the major roles in the crystal packing (Hathwar et al., 2015).The fragment patches on the HS provide an easy way to investigate the nearest neighbour coordination environment of a molecule, which is 15 in the present case.

DFT Studies
The optimized structure of (I) in the gas phase was computed with Gaussian 09W (Frisch et al., 2009)

Figure 5
The DFT-optimized structure of (I).theoretical ones obtained from the optimized structure revealed that they are in good agreement (Table 2).The optimized structure of (I) is shown in Fig. 5.
The HOMO and LUMO (Fig. 6) were generated and their energies were evaluated from the optimized structure.The electron density in the HOMO mainly resides on the amidic carbonyl (N-C O) group and the bicyclic ring system and at the phenyl groups to a lesser extent.In the LUMO, the electronic charge densities are delocalized to reside on the bicyclic ring and the phenyl groups.The energies of HOMO and LUMO are À 6.361 eV and À 0.1.056eV, respectively, resulting in an energy gap (�E) of 5.305 eV.
The molecular electrostatic potential surface (MEPS; Fig. 7) is used to find the positive and negative electrostatic potential of the molecule, which provides possible information about the reactive sites of (I).The electron-rich part with a partial negative charge is shown by red regions on the MEPS over the carbonyl oxygen atom of the chloroacetyl moiety, which is expected to undergo electrophilic attack.The pale-yellow colour spread over the chlorine atom and the secondary amine (-NH) shows lower electron density regions.The faint blue colour spread all over the molecule implies less electrondeficient parts.The absence of a bright-blue region on the MEPS reveals that there are no possible sites on the molecule for nucleophile attack.

Molecular Docking Studies
Molecules with ester and acetyl moieties are expected to have enhanced bioavailability and biological activity.Hence, it is interesting to evaluate the biological activity of (I) through molecular docking studies.To examine the binding affinity of the title compound, a molecular docking study was performed with ER� protein (PDB ID: 3ERT).The molecular docking was carried out using the AutoDock tool (Huey et al., 2012)

Figure 6
The HOMO/LUMO energy diagram of (I).

Figure 7
The molecular electrostatic potential surface of (I).

Figure 8
Molecular docking analysis of (I) against 3ERT.
and the results were visualized using Discovery Studio-Visualizer software (v21.1.0.20298:Biovia, 2017).The results showed a good binding affinity to the target receptor 3ERT protein with a docking score of À 9.56 kcal mol À 1 .The threeand two-dimensional views of the docking interactions are shown in Fig. 8.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Atom H2 was located from a difference-Fourier map and other H atoms were placed in idealized positions and allowed to ride on their parent atoms with C-H = 0.93-0.98A ˚and U iso (H) = 1.2U eq of the parent atom.Reflections 134, 043, 102 and 210 were obstructed from the beam stop and thus were omitted from the refinement.(Sheldrick, 2015a), SHELXL (Sheldrick, 2015b), ORTEP-3 for Windows (Farrugia, 2012), PLATON (Spek, 2020) and publCIF (Westrip, 2010).

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

Fractional atomic coordinates and isotropic
Figure 1 A view of the molecular structure of (I), showing the atom labelling.Displacement ellipsoids are drawn at the 30% probability level.Intramolecular hydrogen bonds are shown as dashed lines.

Figure 3 A
Figure 3A view of the Hirshfeld surface mapped over d norm for (I).

Table 2
Comparison (X-ray and DFT) of selected bond lengths, bond angles and torsion angles (A ˚, � ).

Table 3
Experimental details.