Co-crystallization of a neutral molecule and its zwitterionic tautomer: structure and Hirshfeld surface analysis of 5-methyl-4-(5-methyl-1H-pyrazol-3-yl)-2-phenyl-2,3-dihydro-1H-pyrazol-3-one 5-methyl-4-(5-methyl-1H-pyrazol-2-ium-3-yl)-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-1-ide monohydrate

The title compound comprises a neutral molecule, its zwitterionic tautomer whereby the N-bound proton of the central ring is now resident on the pendant ring, and a water molecule of crystallization. Conventional hydrogen bonding leads to supramolecular layers in the crystal.

The title compound, 2C 14 H 14 N 4 OÁH 2 O, comprises a neutral molecule containing a central pyrazol-3-one ring flanked by an N-bound phenyl group and a C-bound 5-methyl-1H-pyrazol-3-yl group (at positions adjacent to the carbonyl substituent), its zwitterionic tautomer, whereby the N-bound proton of the central ring is now resident on the pendant ring, and a water molecule of crystallization. Besides systematic variations in geometric parameters, the two independent organic molecules have broadly similar conformations, as seen in the dihedral angle between the five-membered rings [9.72 (9) for the neutral molecule and 3.32 (9) for the zwitterionic tautomer] and in the dihedral angles between the central and pendant five-membered rings [28.19 (8) and 20.96 (8) (neutral molecule); 11.33 (9) and 11.81 (9) ]. In the crystal, pyrazolyl-N-HÁ Á ÁO(carbonyl) and pyrazolium-N-HÁ Á ÁN(pyrazolyl) hydrogen bonds between the independent organic molecules give rise to non-symmetric ninemembered {Á Á ÁHNNHÁ Á ÁNC 3 O} and {Á Á ÁHNNÁ Á ÁHNC 3 O} synthons, which differ in the positions of the N-bound H atoms. These aggregates are connected into a supramolecular layer in the bc plane by water-O-HÁ Á ÁN(pyrazolide), water-O-HÁ Á ÁO(carbonyl) and pyrazolyl-N-HÁ Á ÁO(water) hydrogen bonding. The layers are linked into a three-dimensional architecture by methyl-C-HÁ Á Á(phenyl) interactions. The different interactions, in particular the weaker contacts, formed by the organic molecules are clearly evident in the calculated Hirshfeld surfaces, and the calculated electrostatic potentials differentiate the tautomers.

Chemical context
Molecules related to the title compound, i.e. containing a pyrazolone ring, are of particular interest owing to their pharmaceutical potential. Applications in this context include their possible utilization as cardiovascular drugs (Higashi et al., 2006), as hypoglycemic agents (Das et al., 2008) and as antiinflammatory and analgesic agents (Badawey & El-Ashmawey, 1998). This class of compound has also been evaluated as anti-microbials (Sahu et al., 2007) and display fungicidal activities (Singh & Singh, 1991). In the course of ISSN 2056-9890 studies in this area, the title compound, which has been synthesized previously (Kumar et al., 1995), was characterized crystallographically on a crystal isolated from an ethanol solution and found to contain neutral and zwitterionic tautomers.
Tautomerism relates to a phenomenon whereby isomeric structures undergo inter-conversion by the migration of, typically, an atom, often a proton, or small group within the molecule. While different tautomers can co-exist in solution, in crystals usually only one form is found (Rubčić et al., 2012). Notable examples of tautomers crystallizing in the same crystal begin with biologically relevant isocytosine (Sharma & McConnell, 1965) and the histidine residue in the structure of l-His-Gly hemihydrate (Steiner & Koellner, 1997). Such behaviour has also been observed, for example, in a synthetic compound, namely, N-(3-hydroxysalicylidene)-4-methoxyaniline (Pizzala et al., 2000). Herein, the crystal and molecular structures of the title compound, (I), are described along with an analysis of the calculated Hirshfeld surfaces.

Structural commentary
The crystal of (I), Fig. 1, comprises a neutral molecule of 5-methyl-4-(5-methyl-1H-pyrazol-3-yl)-2-phenyl-2,3-dihydro-1H-pyrazol-3-one, its zwitterionic tautomer 5-methyl-4-(5methyl-1H-pyrazol-2-ium-3-yl)-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-1-ide and a molecule of water. Evidence of tautomerism is twofold. Firstly, in the nature of the hydrogenbonding interactions operating in the crystal; see Supramolecular features. Secondly, in small but systematic variations in key geometric parameters, Table 1. Thus, the N5-N6 bond in the zwitterion is longer than the equivalent N1-N2 bond in the neutral species with a concomitant shortening of the C16-N6 and lengthening of the C16-C17 bonds with respect to the bonds in the neutral species. The most notable changes in angles relate to protonation/deprotonation. Thus, the angle at the protonated N2 atom is greater than the angle at the deprotonated N6, and the same is true for the angles subtended at the N7 and N3 atoms. Molecules in (I) may also exhibit rotational isomerism about the C3-C5 and C17-C19 bonds. In the present case, the carbonyl group is syn with the pendent ring imine-N atom in the neutral molecule and is designated the NH-Z form (Kumar et al., 1995); the zwitterionic tautomer has a similar conformation.
The differences in geometric parameters characterizing the two independent organic molecules in (I) notwithstanding, the molecules present very similar conformations as highlighted in the overlay diagram, Fig. 2

Figure 2
Overlay diagram of the two organic molecules in (I): neutral molecule (blue image) and zwitterion (red). The molecules have been overlapped so that the five-membered rings are coincident.

Supramolecular features
The molecular packing of (I) features substantial conventional hydrogen-bonding interactions and the description of these can be conveniently divided by discussing interactions without the involvement of the water molecule of crystallization and then considering the role of the water molecule. Table 2 lists the geometric parameters of the specific intermolecular interactions in the crystal of (I). There are three hydrogen bonds formed between the two organic molecules comprising the asymmetric unit and these involve the three outer-ring amine-H atoms as donors and a ring-N and the two carbonyl-O atoms as acceptors. The resulting pyrazolyl-N4, N8-HÁ Á ÁO1, O2(carbonyl) and pyrazolium-N7-HÁ Á ÁN3(pyrazolyrazolyl) hydrogen bonds give rise to non-symmetric ninemembered {Á Á ÁHNNHÁ Á ÁNC 3 O} and {Á Á ÁHNNÁ Á ÁHNC 3 O} synthons, differing only in the relative placement of one of the ring-N-bound H atoms, Fig. 1. The two-molecule aggregates are assembled into a supramolecular layer in the bc plane by hydrogen bonding involving the water molecule, which functions as a donor to the pyrazolide-N6 and carbonyl-O1 atoms and as an acceptor from a pyrazolyl-N2 atom, Fig. 3a. Further consolidation of the layers is provided byinteractions with the shortest of these involving the N1-pyrazolyl and phenyl(C9-C14) i rings [inter-centroid separation = 3.5810 (9) Å , inter-planar angle = 6.29 (8) for symmetry operation: (i) 1 À x, 1 2 + y, 3 2 À z]. As shown in Fig. 3b, the points of contact between layers involve methyl-C8-HÁ Á Á interactions with the symmetry-related phenyl (C23-C28) ring, Table 2, resulting in a three-dimensional architecture.

Hirshfeld surface analysis
The Hirshfeld surface calculations for (I) were calculated employing Crystal Explorer (Turner et al., 2017) and were conducted in accord with recent studies (Tan et al., 2019) to investigate the influence of intermolecular interactions between the neutral and zwitterionic tautomers, along with the water molecule of crystallization, on the molecular packing.
The donors and acceptors of the hydrogen bonds summarized in Table 2 and discussed in the previous section are clearly evident as the broad and bright-red spots on the Hirshfeld surface mapped over d norm for the neutral tautomer in Fig. 4a and b and for the zwitterionic tautomer in Fig. 4c. In addition to these, a short intramolecular HÁ Á ÁH contact between symmetry-related pyrazolyl-H4N and H7N atoms (Table 3)  Supramolecular association in the crystal of (I): (a) a view of the supramolecular layer in the bc plane whereby the dimeric aggregates shown in Fig. 1 are connected by water-O1WÁ Á ÁO1(carbonyl), water-O1WÁ Á ÁN6(pyrazolide) (pink dashed lines) and pyrazolyl-N2-HÁ Á ÁO1W(water) hydrogen bonds (blue dashed lines) and (b) a view of the unit-cell contents shown in projection down the c axis. The C-HÁ Á Á interactions are shown as purple dashed lines. In both images, the nonparticipating and non-acidic H atoms are omitted. Table 2 Hydrogen-bond geometry (Å , ).

Figure 4
Views of the Hirshfeld surface for (I) mapped over d norm in the range À0.527 to +1.288 arbitrary units for (a) and (b) the neutral tautomer and (c) in the range À0.527 to +1.367 arbitrary units for the zwitterion and a short intra-atomic HÁ Á ÁH contact by a yellow dashed line. Fig. 5a and b, and for the zwitterionic tautomer in Fig. 5c and d, that they have quite distinct charge distributions on their surfaces. The presence of non-protonated pyrazolyl-N3 and N6 atoms results in a pronounced electronegative regions adjacent to carbonyl-O1 atom in the neutral form and opposite to carbonyl-O2 atom in the zwitterion as shown by the intense-red regions in Fig. 5a-d; hence facilitating the chargeassisted hydrogen bonds with pyrazolyl-N7 and water-O1W atoms, respectively. The donors and acceptors of intermolecular water-O1W--HÁ Á ÁO1(carbonyl) and pyrazolyl-N2-HÁ Á ÁO1W(water) are also viewed as blue and red regions in Fig. 5e and f.
The short interatomic contacts characterizing weak intermolecular interactions in the crystal of (I) are viewed as characteristic red spots near the involved atoms on the Hirshfeld surface of the overall structure by modifying (making more sensitive) the d norm range, see Fig. 6 and Table 3. The short intra-and inter-layer CÁ Á ÁC contacts formed by the methyl-C22 atom with methyl-C8 and pyrazolyl-C15 atoms (Table 3) are viewed as small red spots near these atoms in Fig. 6a. The presence of faint-red spots near pyrazole-N2, C2, C17, C21 and phenyl-C13, C14 atoms in Fig. 6 represent their participation in short interatomic CÁ Á ÁC and CÁ Á ÁN contacts (Table 3) arising fromcontacts between the N1-pyrazolyl and phenyl (C9-C14), and pyrazolyl-N5 and pyrazolyl-N7 rings (Table 5). In addition to this, the influence of short interatomic HÁ Á ÁH and CÁ Á ÁH/HÁ Á ÁC contacts (Table 3) on the packing is also evident as the faint-red spots near methyl-H8B and phenyl-C28 atoms, and the spots near the methyl-H18A and phenyl-C14, H14 atoms in Fig. 6. The involvement of the methyl-H8A and H8B atoms as the donors and the phenyl (C23-C28) ring as the acceptor in the C-HÁ Á Á contacts are also confirmed from the Hirshfeld surface mapped with the shape-index property through blue and red regions, respectively, in Fig. 7 3.391 (3) 1 À x, 1 À y, 1 À z

Figure 5
Views of Hirshfeld surface mapped over the calculated electrostatic potential for (a) and (b) the neutral tautomer in the range À0.157 to +0.225 atomic units (a.u.), (c) and (d) zwitterionic tautomer in the range À0.152 to +0.259 a.u., and (e) and (f) for the overall structure in the range À0.166 to +0.250 a.u.. The red and blue regions represent negative and positive electrostatic potentials, respectively.

Figure 6
Views of Hirshfeld surfaces mapped over d norm for the overall structure in the range À0.031 to +1.343 arbitrary units.

Table 5
Geometric data (Å ) for additionalinteractions in the crystal of (I).

Figure 7
Views of Hirshfeld surfaces mapped with the shape-index property highlighting the donors (labelled '1 0 ) and acceptors ('2 0 ) of C-HÁ Á Á contacts through blue and red regions, respectively.
In the fingerprint plot delineated into HÁ Á ÁH contacts, Fig. 8b, the short contact involving the methyl-H18A and phenyl-H14 atoms, Table 3, are viewed as the pair of two adjacent short peaks at d e + d i $2.1 Å while the points corresponding to the H13Á Á ÁH18A contact are merged within the plot. The involvement of the water molecule in the N-HÁ Á ÁO hydrogen bond results in a pair of long spikes at d e + d i $1.8 Å in the fingerprint plot delineated into OÁ Á ÁH/HÁ Á ÁO contacts, Fig. 8c; these encompass the pair of spikes corresponding to the O-HÁ Á ÁO hydrogen bond involving carbonyl-O1 atom. The percentage contribution from these contacts to the Hirshfeld surface of the overall structure is less than the individual tautomers (Table 4) as the atoms of the organic components comprising the asymmetric unit are selfassociated by hydrogen bonds as well as participating in hydrogen bonding with the water molecule.
The fingerprint plot delineated into NÁ Á ÁH/HÁ Á ÁN contacts in Fig. 8d shows interatomic distances are at van der Waals separations or longer in the crystal. The significant 19.9% contribution from CÁ Á ÁH/HÁ Á ÁC contacts to the Hirshfeld surface of (I), Table 4, arises from a significant number of methyl-C-HÁ Á Á(phenyl) interactions (Tables 2 and 3) and short phenyl-, pyrazolyl-CÁ Á ÁH(water, methyl) contacts (Table 3). The presence of C-HÁ Á Á interactions are viewed as the pair of characteristic wings in Fig. 8e with the shortest CÁ Á ÁH contact represented as the pair of peaks at d e + d i $2.7 Å , Table 3. It is evident from the fingerprint plots delineated into CÁ Á ÁC and CÁ Á ÁN/NÁ Á ÁC contacts in Fig. 8f and g, arise from the presence of inter-layercontacts between pyrazolyl and phenyl rings whereas the other short CÁ Á ÁC contacts summarized in Table 3 are intra-layer, i.e. methyl-C8Á Á ÁC22(methyl). The small contribution from CÁ Á ÁO/OÁ Á ÁC contacts appears to have a negligible effect on the molecular packing.

Database survey
There are no direct precedents for the neutral molecule found in (I) in the crystallographic literature. Arguably, the most closely related species is the compound whereby the nitrogenbound proton in the pendant five-membered ring has been substituted by a phenyl ring to give (II) -this structure has been reported three times [Bertolasi et al., 1995 (ZILJIN); Kumar et al., 1995 (ZILJIN01); Ghandour et al., 2017 (ZILJIN02)]. Here, owing to the presence of the phenyl ring, there is a significant twist between the five-membered rings as seen in the C carbonyl -C-C-N external ring torsion angle of 57.1 (3) . In two other derivatives, a similar situation pertains. In the derivative where the original phenyl ring of the neutral molecule in (I) is substituted with a benzenesulfonamide group (EXIJEB; Asiri et al., 2011), the equivalent torsion angle is 132.9 (2) . Finally, when both phenyl groups of (II) are substituted with 4-chlorobenzene rings (KUZPIF; Rabnawaz et al., 2010), C carbonyl -C-C-N external ring torsion angles of À57 (1) and 56 (1) are found for the two crystallographically independent molecules comprising the asymmetric unit.    (2001), DIAMOND (Brandenburg, 2006) and publCIF (Westrip, 2010).

Refinement details
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 = 0.95-0.98 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 O-and N-bound H atoms were refined with distance restraints of 0.84AE0.01 and 0.86AE0.01 Å , respectively, and with U iso (H) = 1.5U eq (O) and 1.2U eq (N).  (2001) and DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

Refinement
Refinement on F 2 Least-squares matrix: full R[F 2 > 2σ(F 2 )] = 0.052 wR(F 2 ) = 0.137 S = 1.06 5838 reflections 374 parameters 6 restraints Primary atom site location: structure-invariant direct methods Hydrogen site location: mixed H atoms treated by a mixture of independent and constrained refinement w = 1/[σ 2 (F o 2 ) + (0.0593P) 2 + 0.7451P] where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.27 e Å −3 Δρ min = −0.40 e Å −3 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.