N,N′-Bis(pyridin-3-ylmethyl)ethanediamide monohydrate: crystal structure, Hirshfeld surface analysis and computational study

The organic molecule in the title bis-pyridyl-substituted diamide hydrate has a U-shape as the 3-pyridyl rings lie to the same side of the central plane. In the crystal, two supramolecular tapes, each sustained by amide-N—H⋯O(carbonyl) hydrogen bonds and ten-membered {⋯HNC2O}2 synthons, are connected by a helical chain of hydrogen-bonded water molecules.

The molecular structure of the title bis-pyridyl substituted diamide hydrate, C 14 H 14 N 4 O 2 ÁH 2 O, features a central C 2 N 2 O 2 residue (r.m.s. deviation = 0.0205 Å ) linked at each end to 3-pyridyl rings through methylene groups. The pyridyl rings lie to the same side of the plane, i.e. have a syn-periplanar relationship, and form dihedral angles of 59.71 (6) and 68.42 (6) with the central plane. An almost orthogonal relationship between the pyridyl rings is indicated by the dihedral angle between them [87. 86 (5) ]. Owing to an anti disposition between the carbonyl-O atoms in the core, two intramolecular amide-N-HÁ Á ÁO(carbonyl) hydrogen bonds are formed, each closing an S(5) loop. Supramolecular tapes are formed in the crystal via amide-N-HÁ Á ÁO(carbonyl) hydrogen bonds and ten-membered {Á Á ÁHNC 2 O} 2 synthons. Two symmetry-related tapes are linked by a helical chain of hydrogen-bonded water molecules via water-O-HÁ Á ÁN(pyridyl) hydrogen bonds. The resulting aggregate is parallel to the b-axis direction. Links between these, via methylene-C-HÁ Á ÁO(water) and methylene-C-HÁ Á Á(pyridyl) interactions, give rise to a layer parallel to (101); the layers stack without directional interactions between them. The analysis of the Hirshfeld surfaces point to the importance of the specified hydrogen-bonding interactions, and to the significant influence of the water molecule of crystallization upon the molecular packing. The analysis also indicates the contribution of methylene-C-HÁ Á ÁO(carbonyl) and pyridyl-C-HÁ Á ÁC(carbonyl) contacts to the stability of the inter-layer region. The calculated interaction energies are consistent with importance of significant electrostatic attractions in the crystal.

Chemical context
Having both amide and pyridyl functionality, bis(pyridin-nylmethyl)ethanediamide molecules of the general formula n-NC 5 H 4 CH 2 N(H)C( O)C( O)CH 2 C 5 H 4 N-n, for n = 2, 3 and 4, hereafter n LH 2 , are attractive co-crystal coformers via conventional hydrogen bonding. In the same way, complexation to metals may also be envisaged. It is therefore not surprising that there is now a wealth of structural information for these molecules occurring in co-crystals, salts and metal complexes, as has been reviewed recently (Tiekink, 2017). Complementing hydrogen-bonding interactions, the n LH 2 molecules, for n = 3 (Hursthouse et al., 2003;Goroff et al., 2005;Jin et al., 2013) and n = 4 (Goroff et al., 2005;Wilhelm et al., 2008;Tan & Tiekink, 2019c), are well-known to form NÁ Á ÁI halogen-bonding interactions and, indeed, some of the earliest studies were at the forefront of pioneering systematic investigations of halogen bonding. It was during the course of ongoing studies into co-crystal formation (Tan, Halcovitch et al.,

Supramolecular features
Significant conventional hydrogen bonding is noted in the crystal of (I) with the geometric parameters characterizing these included in Table 1. The most striking feature of the supramolecular association is the formation of tapes via amide-N-HÁ Á ÁO(carbonyl) hydrogen bonds leading to a sequence of inter-connected ten-membered {Á Á ÁHNC 2 O} 2 synthons. Two such tapes are connected by hydrogen bonds provided by the water molecule of crystallization. Thus, alternating water molecules in helical chains of hydrogenbonded water molecules, being aligned along the b-axis direction and propagated by 2 1 symmetry, connect to 3 LH 2 via water-O-HÁ Á ÁN(pyridyl) hydrogen bonds to form the onedimensional aggregate shown in Fig. 2(a). The presence of methylene-C-HÁ Á ÁO(water) and methylene-C-HÁ Á Á (pyridyl) contacts stabilizes a layer lying parallel to (101). The layers stack without directional interactions between them, Fig. 2 The molecular structure of the constituents of (I) showing the atomlabelling scheme and displacement ellipsoids at the 70% probability level. The water-O-HÁ Á ÁN(pyridyl) hydrogen bond is indicated by the dashed line.

Figure 2
Molecular packing in the crystal of (I): (a) one-dimensional chain whereby tapes sustained by amide-N-HÁ Á ÁO(carbonyl) hydrogen bonds and ten-membered {Á Á ÁHNC 2 O} 2 synthons are connected, via water-O-HÁ Á ÁN(pyridyl) hydrogen bonds, by helical chains of hydrogen-bonded water molecules sustained by water-O-HÁ Á ÁO(water) hydrogen bonds and (b) a view of the unit-cell contents in projection down the b axis, highlighting the stacking of layers. The amide-N-HÁ Á ÁO(carbonyl) hydrogen bonds are shown as blue dashed lines and hydrogen bonds involving the water molecules, by orange dashed lines. The C-HÁ Á ÁO and C-HÁ Á Á interactions are shown as green and purple dashed lines, respectively.

Hirshfeld surface analysis
The calculations of the Hirshfeld surfaces and two-dimensional fingerprint plots were performed on the crystallographic asymmetric unit shown in Fig. 1, using Crystal Explorer 17 (Turner et al., 2017) and based on the procedures as described previously . The analysis identified a number of red spots on the d norm surface of 3 LH 2 with varying degrees of intensity indicating the presence of interactions with contact distances shorter than the sum of the respective van der Waals radii (Spackman & Jayatilaka, 2009). Referring to the images of Fig. 3, the most intense red spots stem from the amide-N-HÁ Á ÁO(carbonyl) and water-O-HÁ Á ÁN(pyridyl) hydrogen bonds, Table 1. Some additional contacts are detected through the Hirshfeld surface analysis for C1-H1Á Á ÁO1W, C5-H5Á Á ÁN4, C12-H12Á Á ÁC7, C6-H6AÁ Á ÁO2 and C7Á Á ÁO1 interactions with the red spots ranging from moderately to weakly intense. The data in Table 2 provide a succinct summary of interatomic contacts revealed in the above analysis; the O2Á Á ÁH6A and C7Á Á ÁH12 contacts occur in the inter-layer region.
To verify the nature of the aforementioned interactions, the 3 LH 2 molecule in (I) was subjected to electrostatic potential mapping. The results show that almost all of the interactions identified through the d norm mapping are electrostatic in nature as can be seen from the distinctive blue (electro- Symmetry codes: (i) Àx þ 3 2 ; y þ 1 2 ; Àz þ 3 2 ; (ii) x; y þ 1; z; (iii) x; y À 1; z; (iv) x À 1 2 ; Ày þ 1 2 ; z À 1 2 .

Figure 3
The d 1.83 x, y, z positive) and red (electronegative) regions on the surface, albeit with varying intensity, Fig. 4. A notable exception is found for the methylene-C-HÁ Á Á(pyridyl) interaction which is manifested in the pale regions in Fig. 4(a) and (b). This indicates no charge complementarity consistent with the interaction beings mainly dispersive in nature. The quantification of the close contacts to the Hirshfeld surface was performed through the analysis of the twodimensional fingerprint plots for (I) as well as for the individual molecular components. As shown in Fig. 5(a), the overall fingerprint plot of (I) exhibits a bug-like profile with a pair of symmetric spikes. This is in contrast to the asymmetric profile of 3 LH 2 , with splitting of the spike in the internal region due to the formation of the O-HÁ Á ÁN hydrogen bond, Fig. 5(e), suggesting a prominent role played by the water molecule in influencing the overall contacts in (I). The observation is very different to that of the benzene solvate of 4 LH 2 in which the overall surface contacts for 4 LH 2 are not very much influenced by the benzene molecule as demonstrated by the similar profiles for the solvate and individual 4 LH 2 molecule (Tan, Halcovitch et al., 2019). The decomposition of the overall profile of (I) shows that the most significant contacts are primarily HÁ Á ÁH contacts (43.5%), followed by OÁ Á ÁH/HÁ Á ÁO (21.1%), CÁ Á ÁH/HÁ Á ÁC (19.6%) and NÁ Á ÁH/HÁ Á ÁN (9.8%) contacts, with all of these interactions having d i + d e distances less than the respective sums of van der Waals radii (vdW), i.e.

Computational chemistry
All associations between molecules in (I), as described in Hirshfeld surface analysis, were subjected to the calculation of the interaction energy using Crystal Explorer 17 (Turner et al., 2017) based on the method described previously  to evaluate the strength of each interaction,    Table 3 Summary of interaction energies (kJ mol À1 ) calculated for (I).
The crystal of (I) is mainly sustained by electrostatic forces owing to the strong N2-H2NÁ Á ÁO1/ N3-H3NÁ Á ÁO2, O1W-H1WÁ Á ÁN1 and O1W-H2WÁ Á ÁO1W hydrogen bonding leading to a barricade-like electrostatic energy framework parallel to (101), as shown in Fig. 6(a). This is further stabilized by the dispersion forces arising from other supporting interactions which result in another barricade-like dispersion energy framework parallel to (100), Fig. 6(b). The overall energy framework for (I) is shown in Fig. 6(c).
A comparison of the distribution of contacts on the Hirshfeld surfaces between the 3 LH 2 molecule in (I) and in its two polymorphic forms, i.e. Form I and Form II , with latter having two independent molecules, was performed. This analysis returned the data shown in Table 4 and indicates that 3 LH 2 in (I) is relatively closer to Form I as compared to the independent molecules comprising Form II.
This conclusion is consistent with the analysis of the packing similarity in which a comparison of (I) and Form I exhibits an r.m.s. deviation of 0.895 Å while a comparison with Form II exhibits an r.m.s. deviation of 1.581 Å , despite only one out of 20 molecules displaying some similarity with the reference 3 LH 2 molecule in (I), Fig. 7. The packing analysis was performed using Mercury (Macrae et al., 2006), with the analysis criteria being set that only molecules within the 20% Perspective views of the energy framework of (I), showing the (a) electrostatic force, (b) dispersion force and (c) total energy diagram. The cylindrical radius is proportional to the relative strength of the corresponding energies and they were adjusted to the same scale factor of 100 with a cut-off value of 8 kJ mol À1 within 2 Â 1 Â 2 unit cells.

Figure 7
A comparison of the molecular packing of 3 LH 2 : (a) (I) (red) and Form I (green) and (b) (I) (red) and Form II (blue), showing the differences in terms of molecular connectivity of 3 LH 2 with r.m.s. deviations of 0.895 and 1.581 Å , respectively. tolerance for both distances and angles were included in the calculation while molecules with a variation >20% were discarded, and that molecular inversions were allowed during calculation. It is therefore also apparent through this analysis that the water molecules in (I) play a crucial role in influencing the packing of 3 LH 2 in (I).

Database survey
The 3 LH 2 molecule has been characterized in two polymorphs  and in a number of (neutral) co-crystals. A characteristic of these structures is a long central C-C bond and conformational flexibility in terms of the relative disposition of the 3-pyridyl substituents with respect to the central C 2 N 2 O 2 chromophore (Tiekink, 2017). Indeed, the relatively long length of the central C-C bonds often attracts a level C alert in PLATON (Spek, 2009). Of the data included in Table 5 [for the chemical diagrams of (II) and (III), see Scheme 2], the shorter of the C-C bonds is 1.515 (3) Å , found in the cocrystal of 3 LH 2 with HO 2 CCH 2 N(H)C( O)N(H)CH 2 CO 2 H (Nguyen et al., 2001) and the longest bond of 1.550 (17) Å is found in the co-crystal of 3 LH 2 with (III) (Jin et al., 2013). In terms of conformational flexibility, the two polymorphs of 3 LH 2 highlight this characteristic of these molecules . In Form I, the pyridyl rings lie to the same side of the central C 2 N 2 O 2 and therefore, have a syn-periplanar relationship, or, more simply, a U-shape. In Form II, comprising two independent molecules, each is disposed about a centre of inversion so the relationship is anti-periplanar, or S-shaped. DFT calculations revealed that the difference in energy between the two conformations is less than 1 kcal À1 . Despite this result, most of the 3 LH 2 molecules are centrosymmetric, S-shaped. For the U-shaped molecules, the dihedral angles between the central plane and pyridyl rings range from 59.71 (6) to 84.61 (9) . The comparable range for the S-shaped molecules, for which both dihedral angles are identical from symmetry, is 64.2 (3) to 84.79 (18) .

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 6. The carbon-bound H atoms were placed in calculated positions (C-H = 0.95-0.99 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2-1.5U eq (C). The oxygen-and nitrogenbound H atoms were located in a difference-Fourier map and refined with O-H = 0.84AE0.01 Å and N-H = 0.88AE0.01 Å , respectively, and with U iso (H) set to 1.5U eq (O) or 1.2U eq (N).
Owing to poor agreement, one reflection, i.e. (551), was omitted from the final cycles of refinement. Table 6 Experimental details.

N,N′-Bis(pyridin-3-ylmethyl)ethanediamide monohydrate
Crystal data 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.