2,2′:4,4′′:4′,4′′′-Quaterpyridine: synthesis, crystal-structure description, and Hirshfeld surface analysis

The title compound, 2,2′:4,4′′:4′,4′′′-quaterpyridine (Qtpy), C20H14N4, crystallizes in the triclinic P space group and has half of the molecule in the asymmetric unit, corresponding to 4,4′-bipyridine (4,4′-bpy) that serves as the building block for the molecule.


Chemical context
2,2 0 :4,4 00 :4 0 ,4 000 -Quaterpyridine (Qtpy) is an important bridging ligand used in synthetic inorganic chemistry for the development of many transition-metal complexes (TMCs) employed as DNA-binding probes (Morgan et al., 1991;Pyle et al., 1989). Previously, bridging ligands that provide low inter-metal communication (due to the absence of conjugation between two ligands subunits connected by saturated carbon chains as experienced in bridging ligands that contain isolated bipyridine) have been obtained by the direct fusion of two bpy moieties. However, there has been a surge in interest in ligands that can electronically and coordinatively link two metal centres. In that context, Qtpy represents one of the only instances of a ligand formed from two fused bpy units whose coordination chemistry has been widely explored (Downard et al., 1991;Cooper et al., 1990).
In fact, the first report of Qtpy dates back to 1938 when Burstall and colleagues obtained the ligand as a by-product of the reaction between 4,4 0 -bipyridine (4,4 0 -bpy) and iodine (Burstall, 1938). However, since the 1990s, studies in the use of the ligand as a building block for the construction of oligonuclear supramolecular assemblies of photoactive and redoxactive chromophoric sites have multiplied (Gorczyń ski et al., 2016). Qtpy's suitability for such a role arises from its possession of both a bidentate diimine site that can coordinate through chelation to a metal centre, and also two monodentate imine sites, which can both coordinate to other metal centres (see scheme).
In a number of studies, we have employed Qtpy as a bridging ligand to synthesize novel luminescent TMCs towards therapeutic, diagnostic, theranostic and bioimaging ends. This work has mostly involved Ru II and other d 6 -metal ions (de Wolf et al., 2006;Ghosh et al., 2009;Ahmad et al., 2011Ahmad et al., , 2013Ahmad et al., , 2014aWalker et al., 2016) . Despite its structural simplicity and synthetic significance, there is no report of the singlecrystal structure of pure crystalline Qtpy.

Structural commentary and supramolecular Features
Qtpy ( Fig. 1) crystallizes in the triclinic space group P1. The asymmetric unit comprises of half of a single molecule, which sits on special position 1g (0.000, 1/2, 1/2). The 2,2 0 bipyridine rings are planar within 0.00 (12) and the mean torsion angle between the 4,4 0 -bipyridine rings is 34.7 (2) . Two types of weak intermolecular hydrogen bonds are observed between Qtpy and adjacent molecules (Table 1). A single linear contact between the sp 2 hydrogen atom H9 and atom N1 of an adjacent molecule (x + 1, y + 1, z) and a dimeric hydrogen bond between a pair of H11 and N10 atoms in a another adjacent molecule (Àx + 1, Ày + 2, Àz.). Both pyridine rings are engaged ininteractions (Fig. 2) between their symmetryequivalent rings in adjacent molecules, both above and below, packing in --stacked columns parallel to the (100) plane ( Fig. 3). The N1/C2-C6 rings pack with a distance between their centroids of 3.779 (1) Å with a shift of 1.629 Å and an angle of 0 . The C7-C9/N10/C11-C12 rings also pack with an intercentroid distance of 3.779 (1) Å , with a shorter shift distance of 1.385 Å and an angle of 0 .

Database survey
Qtpy is a bridging ligand used in synthetic inorganic chemistry popular for the development of multinuclear TMCs. As such, a search in the Cambridge Structural Database (WebCSD, September 2022; Groom et al., 2016) shows there are 19 reported structures of Qtpy utilized as a ligand: in all cases, the 2,2 0 -bipyridine has the cis configuration and thus acts as a bidentate chelating ligand. In seven of these structures, the monodentate 4-pyridine coordinates to a different metal Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) x þ 1; y þ 1; z; (ii) Àx þ 1; Ày þ 2; Àz.

Figure 3
View along the a axis of the crystal packing showing the columnarstacking through the crystal structure. Hydrogen atoms are omitted for clarity.

Figure 2
Unit cell of Qtpy with completed fragments showing thestacking of the aromatic rings. Hydrogen atoms omitted for clarity.

Figure 1
The molecular structure of Qtpy showing 50% displacement ellipsoids.
centre. There are three crystal structures of modified Qtpy substrates, which are uncoordinated to metal centres. In each of these cases, as we see in our structure of Qtpy, the 2,2 0bipyridine is in the trans configuration, which is the lower energy conformation.

Hirshfeld Surface Analysis
A Hirshfeld surface analysis (HSA) was undertaken and fingerprint plots for Qtpy were generated using Crystal Explorer 21.5 (Spackman et al., 2021). HSA is an established technique to understand the various intermolecular interactions present in a compound and quantify weak interactions.
In mapping such interactions, internal consistency is highly crucial when comparing structures. As such, all reported Hirshfeld surfaces reported herein have their bond lengths set to hydrogen atoms are set to typical neutron values (C-H = 1.083 Å , N-H = 1.009 Å and O-H = 0.98 3Å ). A Hirshfeld surface is unique for a given crystal structure and a set of spherical atomic electron densities. It can help structural chemists gain additional insight into the intermolecular interactions present in molecular crystals (Spackman & McKinnon, 2002;Spackman & Jayatilaka, 2009 (Jayendran et al., 2019). The intermolecular interactions (Table 2)

Figure 6
Hirshfeld surfaces of Qtpy ligand mapped with shape index (left) and curvedness (right) for all the interactions.
complementary hollows (red) and bumps (blue) where two molecular surfaces touch one another. On the Hirshfeld surface mapped with the shape-index function, C-HÁ Á Á interactions appear as hollow orange areas (Á Á ÁH) and bulging blue areas (HÁ Á Á). On the Hirshfeld surface mapped with shape-index for the ligand, these interactions manifest as hollow orange areas and bulging blue areas. Curvedness is a function of the root-mean-square curvature of the surface, and maps of curvedness typically show large regions of green (relatively flat) separated by dark blue edges (large positive curvature). Thestacking interactions are further evidenced by the appearance of flat surfaces towards the bottom of the compound as clearly visible on the curvedness surface.

Synthesis and crystallization
Qtpy was synthesized ( Fig. 9) according to the published method given by Morgan & Baker (1990). 4,4 0 -bpy (20.42 g, 70.19 mmol) was weighed into a 500 mL two-neck roundbottom flask to which fresh Pd/C (2.20 g) was added. DMF (300 mL) that had been deaerated for ca 15 min was then transferred into the flask. The reaction was left to progress under an N 2 atmosphere while being refluxed at 426 K for ca 120 h. Once the reaction was complete and the mixture had cooled down to room temperature, DMF was removed by rotary evaporation to afford a mass of black residue. Chloroform (100 mL) was added to the black residue, and the mixture was allowed to reflux under stirring for a further ca 30 min. Once cooled, the Pd/C catalyst was filtered off through celite to yield a clear yellow solution. Afterwards, chloroform was removed in vacuo and the crude mass obtained was left to stir in acetone (60 mL) for ca 30 min to remove any unreacted 4,4 0 -bpy. The mixture was filtered under vacuum, and the residue was collected. The filtrate was concentrated by rotary evaporation to yield more portions of the desired product. There were several repetitions of this process, and the various portions of the product were reunited. The compound obtained was then recrystallized from EtOH to yield crystals of Qtpy ligand 6.84 g (33.7%) as a creamy solid but sometimes an off-white solid.