Crystal structure and molecular Hirshfeld surface analysis of acenaphthene derivatives obeying the chlorine–methyl exchange rule

The change of substituents viz. a chlorine atom in (I) replaced by a methyl group in (II) has not induced any differences in their respective crystal packing features, confirming the validity of the chlorine–methyl exchange rule.


Chemical context
The prediction of crystal structures has emerged as an exciting field involving researchers from diverse fields primarily because of its challenging complexity, which is considered analogous to that of the protein-folding problem. Attempts made in the field of crystal-structure prediction, its present status and the challenges ahead were discussed in detail in a recent article (Oganov, 2018). In this context, instances of crystal structures that remain isomorphous in spite of some minor changes in their respective molecules, such as a change in a substituent atom/group, are worthy of study as they might provide some insights regarding the subtle factors that govern the crystal packing.
The title compounds (I) and (II) are good examples of crystal structures that obey the Cl-Me exchange rule, ISSN 2056-9890 complying with the general conclusions arrived at in earlier studies (Jones et al., 1981;Gnanaguru et al., 1984;Desiraju & Sarma, 1986). In some recent studies carried out in our laboratory on molecules that showcase the validity of the Cl-Me exchange rule, it has been observed that factors such as the presence of disorder and minor conformational differences have not disturbed the tendency of molecules to remain as isomorphous pairs (Rajni Swamy, et al., 2013;Sribala et al., 2018). Interestingly, the validity of the Cl-Me exchange rule has also been observed in some regularly shaped planar molecules (Nath & Nangia, 2012).
From a pharmacological view point, the title compounds (I) and (II) are spiro compounds that consist of a methylpyrrole moiety with its 2-and 3-positions as spiro carbons linked, respectively, to acenapthene and methyl pyridinone ring systems. Each of these ring systems has a variety of associated biological properties. Studies on some 4-pyridone derivatives have shown them to be potent antimalarial agents (Bueno et al., 2011) and effective in the treatment and prophylaxis of the hepatitis B virus infection (Cheng et al., 2018). Acenaphthene is a pollutant known for its cytotoxicity (Jiang et al., 2019) but is also useful as a dye intermediate. Derivatives of acenaphthene are found to exhibit antitumor (El-Ayaan et al., 2007;Zhu et al., 2008) and fungistatic properties (McDavids & Daniels, 1951). Pyrrole derivatives belong to an important class of heterocycles owing to their potential applications as antimicrobial, antiviral, antimalarial, antitubercular, antiinflammatory and anticancer agents (Gholap, 2016).

Structural commentary
The molecular structures of (I) and (II) (Figs. 1 and 2, respectively) differ from each other only by a chlorine atom in (I) being replaced by a methyl group in (II). This replacement has not induced any significant change in their unit-cell parameters, lattice type or space group. Similarly, there are no substantial changes in the torsion angles of the title compounds (see Tables 1 and 2), as (I) and (II) are isomorphous.

Figure 1
Displacement ellipsoid plot drawn at 50% probability level for (I) showing the atom-labelling scheme. H atoms have been omitted for clarity.
acenaphthene ring system by 0.289 (2) Å in (I) and 0.311 (2) Å in (II), with the r.m.s. deviation of the fitted atoms being 0.043 and 0.044, respectively. This deviation is presumably due to the fact that the O2 atom is involved in two weak C-HÁ Á ÁO interactions that are characteristic of the molecular interaction patterns of both (I) and (II). The dihedral angle between the mean planes of the two chlorophenyl groups in (I) is 67.66 (9) , similarly the corresponding angle between the two methylphenyl groups in (II) is 66.78 (11) . The dihedral angles between the acenaphthene ring system and the chlorophenyl groups are 69.1 (1) and 49.4 (1) , respectively. The corresponding angles in the methyl-substituted analogue are 72.3 (1) and 47.8 (1) , respectively. Thus, it is clear that the minor differences observed in the conformation of the molecules are insufficient to disrupt the tendency of these molecules to remain isomorphous.

Supramolecular features
There are no classical hydrogen bonds in the structures of either (I) or (II). However, in both structures two weak C-HÁ Á ÁO-type intermolecular interactions, viz. C10-H10Á Á ÁO2 and C16-H16Á Á ÁO2, which are identical in nature and char-acteristic of similar fundamental molecular interaction patterns are present (Tables 3 and 4). The C16-H16Á Á ÁO2 interaction occurs between centrosymmetric pairs (Fig. 4), leading to the formation of R 2 2 (20) graph-set motifs along the b-axis direction in both (I) and (II). Similarly, in both (I) and (II) the C10-H10Á Á ÁO2 interaction links glide-related molecules along the b-axis direction (Fig. 5). The molecular aggregation pattern may be visualized as being composed of these two characteristic weak interactions in such a manner that centrosymmetric dimeric pairs are linked through glide-  Table 3 Hydrogen-bond geometry (Å , ) for (I).

Figure 3
An overlay diagram depicting the superimposition of molecule (I) and (II) showing no differences in the conformations.

Figure 5
Perspective view along the a axis showing the weak C10-H10Á Á ÁO2 intermolecular interactions between glide-related molecules in (I) and (II). Non-participating H atoms, methyl C atoms and Cl atoms have been omitted for clarity.

Figure 4
Perspective view along the a axis showing the weak C16-H16Á Á ÁO2 intermolecular interactions between centrosymmetric pairs of molecules in (I) and (II). Non-participating H atoms, methyl C atoms and Cl atoms have been omitted for clarity. related chains of molecules, forming a two-dimensional layer parallel to the bc plane in both structures, as shown in Figs. 6 and 7, respectively.
In (II), an additional intermolecular interaction is observed, viz. C36-H36AÁ Á ÁO1, that is stronger than the two characteristic weak intermolecular interactions and involves the replaced substituent methyl group (C36-H36A) as a donor and the piperidinone O1 atom as an acceptor (see Table 4). It may be concluded that the presence of this additional C-HÁ Á ÁO interaction in (II) has not disrupted the validity of the chloro-methyl exchange rule.

Hirshfeld surface analysis
Hirshfeld surface (HS) analysis was used to investigate and visualize the weak intermolecular interactions influential in the packing of the molecules in the crystal. The visual representation of molecular interactions on this isosurface is determined using two parameters, viz. d i and d e , which represent the distances from a given point on the surface to the nearest atom inside and outside the surface, respectively. The normalized contact distance, d norm is based on the values of d i and d e .
In the present work, the Hirshfeld surfaces (Spackman & Jayatilaka, 2009) and the associated two-dimensional fingerprint plots for title compounds (I) and (II) were generated using CrystalExplorer3.0 (Wolff et al., 2012). The Hirshfeld surfaces mapped over d norm together with decomposed finger print plots (  Hirshfeld surface of (I) mapped over shape-index and d norm and decomposed fingerprint plots of the dominant interactions.

Figure 9
Hirshfeld surface of (II) mapped over shape-index and d norm and decomposed fingerprint plots of the dominant interactions. display similar C-HÁ Á ÁO intermolecular interactions. The combined OÁ Á ÁH and HÁ Á ÁO interactions appear symmetrically as distinct spikes at the bottom of the fingerprint plot and contribute 7.5 and 6.9%, respectively, of the total surface in compounds (I) and (II).
The symmetrical internal wing-like projections correspond to CÁ Á ÁH/HÁ Á ÁC contacts, which account for 16% of the HS in (I) and 19.1% in (II). The dominant contribution is from the HÁ Á ÁH contacts [56.3% in (I) and 70.2% in (II)], as shown by the area occupied between the spikes. Such prominent differences may be accounted for by the presence of a ClÁ Á ÁH/ HÁ Á ÁCl contact in (I) (11.3% contribution) and its absence in (II).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5. C-bound H atoms were included in calculated positions and treated as riding, with C-H = 0.95-1.00 Å and U iso (H) = 1.5U eq (C) for methyl H atoms or 1.2U eq (C) otherwise. The H atoms of the methyl atoms C35 and C36 in (II) were refined as idealized and disordered over two positions since significant residual electron densities were noticed between the three hydrogen atoms of the respective methyl C atoms. The introduction of a disordered model for these two methyl groups had appreciable impact on the final structural parameters. Computer programs: APEX2 and SAINT (Bruker, 2012), SHELXS2013 (Sheldrick, 2008), SHELXL2018 (Sheldrick, 2015), PLATON (Spek, 2009) and publCIF (Westrip, 2010 For both structures, data collection: APEX2 (Bruker, 2012); cell refinement: SAINT (Bruker, 2012); data reduction: SAINT (Bruker, 2012); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018 (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: 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.