6-[6-(Pyridin-2-yl)-1,2,4,5-tetrazin-3-yl]pyridin-3-amine monohydrate

The tetrazine derivative, as well as the water molecule, of C12H9N7·H2O are involved in a hydrogen-bond network accompanied by π-stacking.


Chemical context
Click chemistry is employed to label biological targets because of its highly selective reaction profile at ambient temperature in physiological media (Kolb et al., 2001). Several chemical reactions can be used for this purpose. Among the most popular are alkyne-azide [3 + 2]-pericyclic reactions, and enetetrazine Diels-Alder/retro-Diels-Alder (DA/rDA) reactions. If the biomolecule carries a clickable chemical unit, possibly installed by the introduction of unnatural amino acids, various label-bearing functionalities can be introduced efficiently (Hong et al., 2010;Tsai et al., 2015). Side-chain norbornenes have proven particularly successful as unnatural amino acids (Kaya et al., 2012). They undergo a DA/rDA reaction with tetrazines, resulting in the extrusion of nitrogen (Kaya et al., 2012;Vrabel et al., 2013). This reaction exhibits fast kinetics at ambient temperatures, making it particularly useful for biological labeling. To improve biological stability, more electron-deficient 2-pyridinyl-substituted tetrazines are employed as they display improved stability (Vrabel et al., 2013). In order to decorate tetrazines with functionalities, asymmetric bispyridyl tetrazine versions with a desired label are synthesized. For instance, an amine group can be introduced that reacts with activated esters. Herein, we describe the crystal structure of such an asymmetric tetrazine in its hydrate form, bearing pyridyl groups on each side, one of them exposing a free amine (Selvaraj & Fox, 2014).

Structural commentary
The asymmetric unit of the title compound, which is depicted in Fig. 1, comprises 6-[6-(pyridin-2-yl)-1,2,4,5-tetrazin-3-yl]pyridin-3-amin (1) and a water molecule. The three almost ISSN 2056-9890 planar six-membered rings of 1 deviate significantly from coplanarity. The plane of the central tetrazine ring forms angles of 5.33 (7) and 19.84 (8) with the adjacent 3-aminepyridine and pyridine rings, respectively. In two related structures of inversion-symmetric tetrazines these angles are 26.41 (10) (Liu et al., 2001) and 19.71 (5) (Klein et al., 1998). The latter two terminal rings enclose an angle of 14.60 (8) in the title compound. This observation deviates from two related structures in which the terminal pyridine rings are coplanar (Klein et al., 1998;Liu et al., 2001). The hydrogen atoms of the amine are almost parallel with the adjacent pyridine ring and form an angle of 120.7 (16) with amine N1. The H-O-H angle of the water molecule is 102.0 (17) .

Supramolecular features
Hydrogen bonding is the main feature of packing of the title compound. Both amine donor functions as well as both H atoms of the water molecule are involved in hydrogen bonds with the two pyridine ring N atoms and the water molecule acting as hydrogen-bond acceptors (Table 1). It shall be mentioned that the tetrazine N5 atom is acceptor in a bifurcated hydrogen bond with donor O1. However, the donor-Hacceptor angle O1-H14Á Á ÁN5 is rather acute at 124.9 (15) and the donor-acceptor distance rather long at 3.1934 (18) Å . Hence this hydrogen bond is not depicted in Figs. 2 and 3, and it is not considered in the following discussion of the hydrogen-bond network. Fig. 2 shows a part of the herringbone-pattern-like layer parallel to [010] of the title compound. In that figure, the four different hydrogen bonds are shown in different colours. The region with the blue water-pyridine-N hydrogen bonds contains no amine groups. By this hydrogen bond, the layer is linked to next layer on top of it. By the other three hydrogen bonds, the moieties of the title compound form a twodimensional network. According to graph set theory (Bernstein et al., 1995;Etter et al., 1990), the descriptor R 3 4 (11) can be assigned on the ternary level (three different hydrogen bonds) for the 11-membered rings formed by four hydrogen bonds involving two amine groups and two water molecules (two brown, one green and one red bond). In order to outline the chains along [101] formed by two different hydrogen bonds, the graph-set descriptor C 2 2 (7) may be assigned on the binary level. The seven-membered unit is formed by one N-HÁ Á ÁO (green) and one O-HÁ Á ÁN hydrogen bond (red). The molecular structure of the title compound, showing atom labels and anisotropic displacement ellipsoids (drawn at the 50% probability level) for non-H atoms.

Synthesis and crystallization
The title compound was synthesized according to a literature procedure (Selvaraj & Fox, 2014) and the analytical data matched that reported. Single crystals were obtained by recrystallization from hot acetone.

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