Crystal structure and Hirshfeld surface analysis of 3-(3-hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one hemihydrate

3-(3-Hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (3HPPP) crystallized as planar molecule together with half a molecule of water in the asymmetric unit in the monoclinic crystal system with space group P2/c. A Hirshfeld surface analysis for the chalcone component showed that H⋯H (40.9%) and H⋯C/C⋯H (32.4%) contacts make the largest contributions to the crystal packing of 3HPPP. In the vicinity of water, the H⋯O/O⋯H and H⋯C/C⋯H contacts are the most significant, at 48.7% and 29.8%, respectively.


Chemical context
Chalcones are 1,3-diphenyl-2-propen-1-ones with an ,unsaturated carbonyl system in between two aromatic rings (Zhuang et al., 2017;Attarde et al., 2010). Chalcones are widely used as precursors for the biosynthesis of compounds in the flavonoid class, and can be chemically synthesized by various reactions such as aldol condensation, and Suzuki and Wittig reactions (Zhuang et al., 2017). To date, chalcones have continued to attract great interest from researchers because of their simple chemistry and diverse applications in medicinal and synthetic chemistry (Zhuang et al., 2017), analytical chemistry (Sun et al., 2012), materials chemistry and lighting technology (Anandkumar et al., 2017;Danko et al., 2012).

Structural commentary
The molecular structure of the asymmetric unit of 3HPPP plus the symmetry-completed water molecule are shown in Fig. 1. The asymmetric unit consists of a molecule of 3HPPP in a neutral state plus half a water molecule of crystallization. The investigated bioactive compound crystallized in the monoclinic crystal system, space group P2/c, with the unit cell containing four molecules of 3HPPP together with two molecules of water. Four water molecules reside on four of the cell edges on the crystallographic c-axis and are shared between the unit and adjacent cells. Further analysis of the metrical parameters of the molecule showed no anomalies compared to the available literature data for related compounds. The planarity of 3HPPP is confirmed as both the aromatic pyrrole (N1/C1-C4) and phenyl (C8-C13) rings are aligned in the plane of the aliphatic ,-unsaturated ketone linker, making dihedral angles of 0.91 (7) and 5.98 (7) , respectively with the linker.  (Table 1). The dimers are arranged in planes with two distinct orientations and at an angle of roughly 61 to each other, while the water molecules act as hinges. This represents a zigzag pattern when viewed along the the ac diagonal. Furthermore, the 3HPPP dimers are arranged in a stair-like fashion, which ascends/descends roughly in the b-axis direction. Intermolecular hydrogen bonds C13-H13Á Á ÁO1 i [symmetry code: (i) Àx + 1, Ày + 1, Àz + 1) between two molecules of 3HPPP can be observed connecting these non-covalently. Molecules of 3HPPP are linked into inversion dimer-dimer chains through these weak interactions. Moreover, the lattice water molecules act as donors and acceptors in hydrogen bonds with the phenol and pyrrole moieties of 3HPPP [O3-H3OÁ Á ÁO2 ii and N1-H1NÁ Á ÁO3; symmetry code: (ii) x À 1, Ày + 1, z À 1 2 ; ORTEP (Burnett & Johnson, 1996) diagram of compound 3HPPP plus the symmetry-completed water molecule with the atom-labelling scheme and 50% probability ellipsoids.

Table 2
Percentage contribution of interatomic contacts to the calculated Hirshfeld surfaces for the individual constituents in the asymmetric unit of 3HPPP.  Table 2]. All hydrogen atoms and all lone pairs of the water molecule are engaged in hydrogen bonding (Fig. 2). These hydrogen bonds connect two of the 3HPPP dimers in different planes comparably strongly and further consolidate the crystal packing.

Database survey
A database survey of the Cambridge Structural Database (WEBCSD version 1.9.32, updated September 2022; Groom et al., 2016) revealed that no structure of a compound with a close similarity to the entire 3HPPP molecule as been reported. However, focusing on the pyrrole ene-one side yielded three [refcodes HIXGAW (Norsten et al., 1999); RICFEP (Camarillo et al., 2007) and RICFEP01 (Jones, 2013)] similar compounds with a 77-88% similarity score relative to the title compound. The title compound differs from those at the substituted ethyl-phenol (C6-C13) side. The overall conformation of the title compound and HIXGAW are very nearly planar and the other two (RICFEP and RICFEP01) are planar. A notable difference relates to the substitution on the keto side. The respective dihedral angles in the studied compound and in HIXGAW are in the range of 5.49-24.65 .

Hirshfeld surface analysis
Crystal Explorer 21 (Spackman et al., 2021) was used to calculate the Hirshfeld surfaces to obtain further insight into the intermolecular interactions in the crystal structure of the title compound. The three-dimensional Hirshfeld surfaces plotted over d norm ranging from À0.667 to 1.118 a.u. are shown in Fig. 3. For compound 3HPPP (Fig. 3a), the most prominent interactions in the crystal packing are the hydrogen bonds, which are represented by four bright-red spots on the mapped d norm surface. The bright-red spots around O1 and O2 correspond to the hydrogen bonding between hydroxyl and carbonyl/keto functional groups of two molecules of 3HPPP.
The other two bright-red spots are due to hydrogen bonding between the pyrrole-N-H functional group and the water molecule, and between the water molecule and the hydroxyl group of 3HPPP. In addition to these four spots, two faint-red spots appear around O1 and H13, representing the non-classical hydrogen-bond interaction of an aromatic C-H and the carbonyl/keto functional group. The intensities of all these red spots indicate the relative strengths of the interactions, as well Three-dimensional Hirshfeld surfaces plotted over d norm in the range À0.667 to 1.118 a.u of (a) compound 3HPPP and (b) the water molecule, generated with Crystal Explorer (Spackman et al., 2021).
as the distances of the contacts. The d norm Hirshfeld surface for the water molecules present in the crystal lattice was also calculated and mapped (Fig. 3b). Four bright-red spots are observed, which are due to the pyrrole-to-water and water-tohydroxyl hydrogen bonds and are thereby mirrors of the interactions involving water described above. The overall two-dimensional fingerprint plots of both molecules, water and 3HPPP, and those delineated into HÁ Á ÁH, HÁ Á ÁO/OÁ Á ÁH, HÁ Á ÁC/CÁ Á ÁH and HÁ Á ÁN/NÁ Á ÁH interactions are shown in Fig. 4, while the percentage contributions are listed in Table 2. The two-dimensional fingerprint plots for compound 3HPPP show that HÁ Á ÁH and HÁ Á Á C/CÁ Á Á H are the most significant interatomic interactions in the crystal packing, contributing 40.9 and 32.4%, respectively, to the Hirshfeld surface. The HÁ Á ÁO/OÁ Á ÁH (19.4%) and other minor contacts (HÁ Á ÁN/NÁ Á ÁH = 2.0%) further contribute to the Hirshfeld surfaces. On the other hand, the most prominent interatomic contacts for the water molecule are HÁ Á ÁO/OÁ Á ÁH, as expected, with a 48.7% contribution while HÁ Á ÁH and HÁ Á ÁC/CÁ Á ÁH contacts contribute 16.2 and 29.8%, respectively.

Synthesis and crystallization
The 3-hydroxypyrrolylated chalcone 3HPPP was synthesized by a Claisen-Schmidt condensation reaction between 2-acetylpyrrole (2 mmol) and 3-hydroxybenzaldehyde (2 mmol) under ethanolic (10 ml) conditions. The resulting mixture was stirred for 5 min followed by the dropwise addition of 3 ml of a 40% aqueous NaOH solution (Fig. 5). The mixture was stirred overnight at room temperature. After the reaction was essentially complete, it was quenched by pouring the resultant solution onto crushed ice and extraction with ethyl acetate (3 Â 10 ml). The organic layer was washed with distilled water (3 Â 10 ml), filtered, dried over anhydrous MgSO 4 and concentrated in vacuo. Finally, the collected crudes were purified by gravity column chromatography using hexane:ethyl acetate (ratio of 7:3) as solvent system. Multiple spectroscopic analyses confirmed the chemical structure (Mohd Faudzi et al., 2020). The obtained pure 3HPPP was then recrystallized by slow evaporation of an ethanol solution, giving crystals suitable for X-ray diffraction analysis.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The hydrogen atoms bound to oxygen or nitrogen were found in difference maps and refined freely. The carbon-bound hydrogen atoms, which are all aromatic, were geometrically placed and refined using a riding model with C-H = 0.95 Å and U iso (H) = 1.2U eq (C).   (Rigaku OD, 2021); program(s) used to solve structure: SHELXT2018/2 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: Olex2 1.3 (Dolomanov et al., 2009); software used to prepare material for publication: publCIF (Westrip, 2010).