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

Ismail, A.Z.; Gunasekharan, M.; Karunakaran, T.; Mohd Faudzi, S.M.

doi:10.1107/S2056989023001925

research communications

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 79| Part 4| April 2023| Pages 287-291

https://doi.org/10.1107/S2056989023001925

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

Ahmad Zaidi Ismail,^a,^b Mohanapriya Gunasekharan,^b Thiruventhan Karunakaran ^c and Siti Munirah Mohd Faudzi ^b,^d ^*

^aSchool of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand, ^bDepartment of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia, ^cCentre for Drug Research, Universiti Sains Malaysia, 11800 USM, Pulau Pinang, Malaysia, and ^dNatural Medicines and Product Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
^*Correspondence e-mail: sitimunirah@upm.edu.my

Edited by C. Schulzke, Universität Greifswald, Germany (Received 20 September 2022; accepted 2 March 2023; online 10 March 2023)

High-quality single crystals of the title compound, 2C₁₃H₁₁NO₂·H₂O, were grown and a structural analysis was performed. The asymmetric unit comprises one molecule of 3-(3-hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (3HPPP), which was recently discovered to be a promising anti-MRSA candidate, and a half-molecule of water. The compound crystallizes in the monoclinic space group P2/c. The crystal structure features intermolecular pyrrole-N—H⋯O (water), carbonyl/keto-C—O⋯H—O-phenol and phenol-C—O⋯H (water) hydrogen bonds, which help to consolidate the crystal packing. A Hirshfeld surface analysis for the components in the asymmetric unit showed that H⋯H (40.9%) and H⋯C/C⋯H (32.4%) contacts make the largest contributions to the intermolecular interactions of 3HPPP. Considering the presence of water, in its vicinity H⋯O/O⋯H and H⋯C/C⋯H are the most significant contacts, contributing 48.7 and 29.8%, respectively.

Keywords: chalcone; pyrrole-derived chalcone; pyrrole; crystal structure; SCXRD.

CCDC reference: 2233979

1. Chemical context

Chalcones are 1,3-diphenyl-2-propen-1-ones with an α,β-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 ).

Chalcone analogues have been reported with a wide range of biological activities, including anti-inflammatory, antimicrobial, and anticancer properties (Kar Mahapatra et al., 2019 ; Lin et al., 2002 ; Nowakowska, 2007 ). Recently, we discovered a new promising anti-microbial candidate, 3-(3-hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (3HPPP), which showed remarkable inhibitory activity on methicillin-resistant Staphylococcus aureus (MRSA, ATCC 700699) with MIC and MBC values of 0.23 mg ml⁻¹ and 0.47 mg ml⁻¹, respectively (Gunasekharan et al., 2021 ). However, as yet the crystal structure of this compound has remained elusive. The molecular structure of its hydrate is analysed and discussed herein.

2. 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 α,β-unsaturated ketone linker, making dihedral angles of 0.91 (7) and 5.98 (7)°, respectively with the linker.

Figure 1
ORTEP (Burnett & Johnson, 1996

) diagram of compound 3HPPP plus the symmetry-completed water molecule with the atom-labelling scheme and 50% probability ellipsoids.

3. Supramolecular features

Fig. 2 illustrates the unit cell of 3HPPP viewed along the crystallographic b-axis and the supramolecular association within and around it. In the crystal, molecules are linked into dimers via multiple intermolecular hydrogen bonds (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—H13⋯O1ⁱ [symmetry code: (i) −x + 1, −y + 1, −z + 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—H3O⋯O2ⁱⁱ and N1—H1N⋯O3; symmetry code: (ii) x − 1, −y + 1, z − $[{1\over 2}]$ ; 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.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2O⋯O1ⁱ	0.901 (19)	1.828 (19)	2.7257 (11)	174.2 (16)
N1—H1N⋯O3	0.888 (17)	2.041 (17)	2.8722 (13)	155.4 (14)
C13—H13⋯O1ⁱ	0.95	2.51	3.2050 (13)	130
O3—H3O⋯O2ⁱⁱ	0.864 (18)	2.320 (18)	2.9430 (7)	129.2 (16)
Symmetry codes: (i) ; (ii) $[x-1, -y+1, z-{\script{1\over 2}}]$ .

Table 2
Percentage contribution of interatomic contacts to the calculated Hirshfeld surfaces for the individual constituents in the asymmetric unit of 3HPPP

Contact	Percentage contribution
	3HPPP	Water
H⋯H	40.9	16.2
H⋯O/O⋯H	19.4	48.7
H⋯C/C⋯H	32.4	29.8
H⋯N/N⋯H	2.0	4.6

Figure 2
The crystal packing of compound 3HPPP viewed along the b axis. The intermolecular interactions are indicated by dashed lines.

4. 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°.

5. 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 −0.667 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 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-to-hydroxyl hydrogen bonds and are thereby mirrors of the interactions involving water described above.

Figure 3
Three-dimensional Hirshfeld surfaces plotted over d_norm in the range −0.667 to 1.118 a.u of (a) compound 3HPPP and (b) the water molecule, generated with Crystal Explorer (Spackman et al., 2021

The overall two-dimensional fingerprint plots of both molecules, water and 3HPPP, and those delineated into H⋯H, H⋯O/O⋯H, H⋯C/C⋯H and H⋯N/N⋯H 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 H⋯H and H⋯ C/C⋯ H are the most significant interatomic interactions in the crystal packing, contributing 40.9 and 32.4%, respectively, to the Hirshfeld surface. The H⋯O/O⋯H (19.4%) and other minor contacts (H⋯N/N⋯H = 2.0%) further contribute to the Hirshfeld surfaces. On the other hand, the most prominent interatomic contacts for the water molecule are H⋯O/O⋯H, as expected, with a 48.7% contribution while H⋯H and H⋯C/C⋯H contacts contribute 16.2 and 29.8%, respectively.

Figure 4
Overall two-dimensional fingerprint plots for compound 3HPPP and the water molecule together with those delineated into H⋯H, H⋯O/O⋯H, H⋯C/C⋯H and H⋯N/N⋯H interactions, generated with Crystal Explorer (Spackman et al., 2021

6. 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 × 10 ml). The organic layer was washed with distilled water (3 × 10 ml), filtered, dried over anhydrous MgSO₄ 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.

Figure 5
Synthetic route towards 3-(3-hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one (3HPPP).

7. 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).

Table 3
Experimental details

Crystal data
Chemical formula	2C₁₃H₁₁NO₂·H₂O
M_r	444.47
Crystal system, space group	Monoclinic, P2/c
Temperature (K)	100
a, b, c (Å)	11.9096 (1), 5.5836 (1), 16.8121 (2)
β (°)	105.356 (1)
V (Å³)	1078.07 (3)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	0.78
Crystal size (mm)	0.18 × 0.17 × 0.13

Data collection
Diffractometer	XtaLAB Synergy, Dualflex, AtlasS2
Absorption correction	Gaussian (CrysAlis PRO; Rigaku OD, 2021 $[Rigaku OD (2021). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.676, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	13888, 2221, 2067
R_int	0.028
(sin θ/λ)_max (Å⁻¹)	0.627

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.034, 0.095, 1.04
No. of reflections	2221
No. of parameters	163
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.30, −0.19
Computer programs: CrysAlis PRO (Rigaku OD, 2021 $[Rigaku OD (2021). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT2018/2 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ), OLEX2 1.3 (Dolomanov et al., 2009 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 2233979

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989023001925/yz2023sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989023001925/yz2023Isup2.hkl

checkCIF report

Computing details top

Data collection: CrysAlis PRO 1.171.41.121a (Rigaku OD, 2021); cell refinement: CrysAlis PRO 1.171.41.121a (Rigaku OD, 2021); data reduction: CrysAlis PRO 1.171.41.121a (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).

3-(3-Hydroxyphenyl)-1-(1H-pyrrol-2-yl)prop-2-en-1-one hemihydrate top

Crystal data top

2C₁₃H₁₁NO₂·H₂O	F(000) = 468
M_r = 444.47	D_x = 1.369 Mg m⁻³
Monoclinic, P2/c	Cu Kα radiation, λ = 1.54184 Å
a = 11.9096 (1) Å	Cell parameters from 9119 reflections
b = 5.5836 (1) Å	θ = 3.8–76.1°
c = 16.8121 (2) Å	µ = 0.78 mm⁻¹
β = 105.356 (1)°	T = 100 K
V = 1078.07 (3) Å³	Prism, colourless
Z = 2	0.18 × 0.17 × 0.13 mm

Data collection top

XtaLAB Synergy, Dualflex, AtlasS2 diffractometer	2067 reflections with I > 2σ(I)
Radiation source: micro-focus sealed X-ray tube	R_int = 0.028
ω scans	θ_max = 75.2°, θ_min = 3.9°
Absorption correction: gaussian (CrysAlisPro; Rigaku OD, 2021)	h = −14→14
T_min = 0.676, T_max = 1.000	k = −6→7
13888 measured reflections	l = −18→21
2221 independent reflections

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.034	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.095	w = 1/[σ²(F_o²) + (0.0512P)² + 0.3933P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max < 0.001
2221 reflections	Δρ_max = 0.30 e Å⁻³
163 parameters	Δρ_min = −0.19 e Å⁻³
0 restraints	Extinction correction: SHELXL2018/3 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: dual	Extinction coefficient: 0.0039 (5)

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.27900 (7)	0.42189 (15)	0.33951 (5)	0.0268 (2)
O2	0.81284 (7)	0.95369 (15)	0.59533 (5)	0.0215 (2)
O3	0.000000	0.0526 (2)	0.250000	0.0208 (3)
N1	0.10566 (8)	0.45548 (17)	0.19188 (5)	0.0186 (2)
C1	0.17738 (9)	0.7925 (2)	0.15408 (6)	0.0178 (2)
H1A	0.225141	0.928386	0.153517	0.021*
C2	0.07695 (9)	0.7278 (2)	0.09255 (6)	0.0222 (3)
H2A	0.044033	0.812012	0.042726	0.027*
C3	0.03512 (9)	0.5190 (2)	0.11809 (6)	0.0222 (3)
H3	−0.032172	0.434067	0.088590	0.027*
C4	0.19382 (9)	0.62052 (19)	0.21594 (6)	0.0159 (2)
C5	0.28203 (9)	0.59293 (19)	0.29291 (6)	0.0177 (2)
C6	0.37555 (9)	0.7736 (2)	0.31381 (6)	0.0179 (2)
H6	0.376212	0.901776	0.276763	0.021*
C7	0.45937 (9)	0.75864 (19)	0.38443 (6)	0.0173 (2)
H7	0.455306	0.624717	0.418413	0.021*
C8	0.55672 (9)	0.92326 (19)	0.41588 (6)	0.0155 (2)
C9	0.56928 (9)	1.14020 (19)	0.37719 (6)	0.0174 (2)
H9	0.513693	1.186081	0.327786	0.021*
C10	0.66350 (9)	1.28752 (19)	0.41156 (6)	0.0184 (2)
H10	0.672229	1.433834	0.384975	0.022*
C11	0.74552 (9)	1.22472 (19)	0.48433 (6)	0.0181 (2)
H11	0.809769	1.326921	0.507080	0.022*
C12	0.73238 (9)	1.0110 (2)	0.52331 (6)	0.0166 (2)
C13	0.63891 (9)	0.86102 (19)	0.48899 (6)	0.0161 (2)
H13	0.630823	0.714363	0.515581	0.019*
H2O	0.7856 (15)	0.832 (3)	0.6202 (11)	0.050 (5)*
H1N	0.0948 (13)	0.324 (3)	0.2186 (9)	0.034 (4)*
H3O	−0.0335 (16)	−0.039 (4)	0.2091 (11)	0.062 (6)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0251 (4)	0.0272 (5)	0.0228 (4)	−0.0081 (3)	−0.0032 (3)	0.0089 (3)
O2	0.0178 (4)	0.0239 (4)	0.0194 (4)	−0.0044 (3)	−0.0012 (3)	0.0032 (3)
O3	0.0218 (5)	0.0193 (6)	0.0208 (5)	0.000	0.0046 (4)	0.000
N1	0.0170 (4)	0.0199 (5)	0.0176 (4)	−0.0025 (4)	0.0025 (3)	0.0010 (4)
C1	0.0176 (5)	0.0187 (5)	0.0171 (5)	0.0015 (4)	0.0044 (4)	0.0011 (4)
C2	0.0214 (5)	0.0256 (6)	0.0167 (5)	0.0024 (4)	0.0000 (4)	0.0025 (4)
C3	0.0172 (5)	0.0277 (6)	0.0182 (5)	−0.0011 (4)	−0.0015 (4)	−0.0008 (4)
C4	0.0145 (5)	0.0173 (5)	0.0163 (5)	−0.0006 (4)	0.0045 (4)	−0.0010 (4)
C5	0.0173 (5)	0.0189 (5)	0.0167 (5)	0.0002 (4)	0.0043 (4)	0.0013 (4)
C6	0.0183 (5)	0.0185 (5)	0.0166 (5)	−0.0009 (4)	0.0040 (4)	0.0019 (4)
C7	0.0176 (5)	0.0170 (5)	0.0176 (5)	0.0003 (4)	0.0051 (4)	0.0014 (4)
C8	0.0153 (5)	0.0165 (5)	0.0156 (5)	0.0011 (4)	0.0056 (4)	−0.0016 (4)
C9	0.0190 (5)	0.0180 (5)	0.0150 (5)	0.0017 (4)	0.0043 (4)	0.0002 (4)
C10	0.0232 (5)	0.0144 (5)	0.0191 (5)	−0.0002 (4)	0.0083 (4)	0.0007 (4)
C11	0.0176 (5)	0.0176 (5)	0.0195 (5)	−0.0038 (4)	0.0055 (4)	−0.0030 (4)
C12	0.0150 (5)	0.0196 (5)	0.0147 (5)	0.0017 (4)	0.0034 (4)	−0.0014 (4)
C13	0.0172 (5)	0.0147 (5)	0.0170 (5)	0.0005 (4)	0.0059 (4)	0.0008 (4)

Geometric parameters (Å, º) top

O1—C5	1.2417 (13)	C5—C6	1.4748 (14)
O2—C12	1.3683 (12)	C6—C7	1.3362 (14)
O2—H2O	0.901 (19)	C6—H6	0.9500
O3—H3O	0.864 (18)	C7—C8	1.4642 (14)
O3—H3Oⁱ	0.864 (18)	C7—H7	0.9500
N1—C3	1.3484 (13)	C8—C13	1.3973 (14)
N1—C4	1.3749 (13)	C8—C9	1.4015 (15)
N1—H1N	0.888 (17)	C9—C10	1.3879 (15)
C1—C4	1.3906 (14)	C9—H9	0.9500
C1—C2	1.4056 (14)	C10—C11	1.3932 (14)
C1—H1A	0.9500	C10—H10	0.9500
C2—C3	1.3804 (17)	C11—C12	1.3902 (15)
C2—H2A	0.9500	C11—H11	0.9500
C3—H3	0.9500	C12—C13	1.3903 (15)
C4—C5	1.4429 (14)	C13—H13	0.9500

C12—O2—H2O	109.4 (11)	C5—C6—H6	119.7
H3O—O3—H3Oⁱ	108 (3)	C6—C7—C8	127.97 (10)
C3—N1—C4	109.61 (9)	C6—C7—H7	116.0
C3—N1—H1N	122.9 (10)	C8—C7—H7	116.0
C4—N1—H1N	127.4 (10)	C13—C8—C9	119.15 (9)
C4—C1—C2	107.27 (10)	C13—C8—C7	117.69 (9)
C4—C1—H1A	126.4	C9—C8—C7	123.14 (9)
C2—C1—H1A	126.4	C10—C9—C8	119.53 (9)
C3—C2—C1	107.15 (9)	C10—C9—H9	120.2
C3—C2—H2A	126.4	C8—C9—H9	120.2
C1—C2—H2A	126.4	C9—C10—C11	121.19 (10)
N1—C3—C2	108.67 (10)	C9—C10—H10	119.4
N1—C3—H3	125.7	C11—C10—H10	119.4
C2—C3—H3	125.7	C12—C11—C10	119.33 (10)
N1—C4—C1	107.30 (9)	C12—C11—H11	120.3
N1—C4—C5	120.68 (9)	C10—C11—H11	120.3
C1—C4—C5	132.01 (10)	O2—C12—C11	118.55 (9)
O1—C5—C4	120.80 (10)	O2—C12—C13	121.51 (10)
O1—C5—C6	121.48 (9)	C11—C12—C13	119.94 (9)
C4—C5—C6	117.73 (9)	C12—C13—C8	120.84 (10)
C7—C6—C5	120.54 (10)	C12—C13—H13	119.6
C7—C6—H6	119.7	C8—C13—H13	119.6

C4—C1—C2—C3	−0.20 (12)	C5—C6—C7—C8	−178.53 (9)
C4—N1—C3—C2	0.25 (13)	C6—C7—C8—C13	−175.38 (10)
C1—C2—C3—N1	−0.03 (13)	C6—C7—C8—C9	6.06 (17)
C3—N1—C4—C1	−0.38 (12)	C13—C8—C9—C10	0.72 (14)
C3—N1—C4—C5	−179.58 (9)	C7—C8—C9—C10	179.26 (9)
C2—C1—C4—N1	0.35 (12)	C8—C9—C10—C11	−0.54 (15)
C2—C1—C4—C5	179.42 (11)	C9—C10—C11—C12	−0.24 (16)
N1—C4—C5—O1	−1.17 (16)	C10—C11—C12—O2	−179.10 (9)
C1—C4—C5—O1	179.86 (11)	C10—C11—C12—C13	0.84 (15)
N1—C4—C5—C6	178.55 (9)	O2—C12—C13—C8	179.27 (9)
C1—C4—C5—C6	−0.42 (17)	C11—C12—C13—C8	−0.67 (15)
O1—C5—C6—C7	−0.66 (16)	C9—C8—C13—C12	−0.12 (15)
C4—C5—C6—C7	179.62 (10)	C7—C8—C13—C12	−178.74 (9)

Symmetry code: (i) −x, y, −z+1/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2O···O1ⁱⁱ	0.901 (19)	1.828 (19)	2.7257 (11)	174.2 (16)
N1—H1N···O3	0.888 (17)	2.041 (17)	2.8722 (13)	155.4 (14)
C13—H13···O1ⁱⁱ	0.95	2.51	3.2050 (13)	130
O3—H3O···O2ⁱⁱⁱ	0.864 (18)	2.320 (18)	2.9430 (7)	129.2 (16)

Symmetry codes: (ii) −x+1, −y+1, −z+1; (iii) x−1, −y+1, z−1/2.

Percentage contribution of interatomic contacts to the calculated Hirshfeld surfaces for the individual constituents in the asymmetric unit of 3HPPP top

Contact	Percentage contribution
	3HPPP	Water
H···H	40.9	16.2
H···O/O···H	19.4	48.7
H···C/C···H	32.4	29.8
H···N/N···H	2.0	4.6

Funding information

The authors acknowledge the Ministry of Higher Education, Malaysia under the Fundamental Research Grant Scheme (FRGS) (grant No. FRGS/1/2018/STG01/UPM/02/8; vote number of 55401477) and Universiti Putra Malaysia under the Putra grant – Putra Graduates Initiative (IPS)(GP-IPS/2018/9618500) for their financial support.

References

Anandkumar, D., Ganesan, S., Rajakumar, P. & Maruthamuthu, P. (2017). New J. Chem. 41, 11238–11249. Web of Science CrossRef CAS Google Scholar
Attarde, M., Vora, A., Varghese, A. & Kachwala, Y. (2010). Org. Chem. Ind. J. 10(5), 192–204. Google Scholar
Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Camarillo, E. A., Flores, H., Amador, P. & Bernès, S. (2007). Acta Cryst. E63, o2593–o2594. Web of Science CSD CrossRef IUCr Journals Google Scholar
Danko, M., Andics, A., Kosa, C., Hrdlovic, P. & Vegh, D. (2012). Dyes Pigments, 92, 1257–1265. Web of Science CrossRef CAS Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Gunasekharan, M., Choi, T. I., Rukayadi, Y., Mohammad Latif, M. A., Karunakaran, T., Mohd Faudzi, S. M. & Kim, C. H. (2021). Molecules, 26, 5314. Web of Science CrossRef PubMed Google Scholar
Jones, P. (2013). Private communication (refcode RICFEP01, CCDC 969887). CCDC, Cambridge, England. Google Scholar
Kar Mahapatra, D., Asati, V. & Bharti, S. K. (2019). Expert Opin. Ther. Pat. 29, 385–406. Web of Science CrossRef CAS PubMed Google Scholar
Lin, Y. M., Zhou, Y., Flavin, M. T., Zhou, L. M., Nie, W. & Chen, F. C. (2002). Bioorg. Med. Chem. 10, 2795–2802. Web of Science CrossRef PubMed CAS Google Scholar
Mohd Faudzi, S. M., Abdullah, M. A., Abdull Manap, M. R., Ismail, A. Z., Rullah, K., Mohd Aluwi, M. F. F., Mazila Ramli, A. N., Abas, F. & Lajis, N. H. (2020). Bioorg. Chem. 94, 103376. Web of Science CSD CrossRef PubMed Google Scholar
Norsten, T. B., McDonald, R. & Branda, N. R. (1999). Chem. Commun. pp. 719–720. Web of Science CSD CrossRef Google Scholar
Nowakowska, Z. (2007). Eur. J. Med. Chem. 42, 125–137. Web of Science CrossRef PubMed CAS Google Scholar
Rigaku OD (2021). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England. Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spackman, P. R., Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Jayatilaka, D. & Spackman, M. A. (2021). J. Appl. Cryst. 54, 1006–1011. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sun, Y., Chen, H., Cao, D., Liu, Z., Chen, H., Deng, Y. & Fang, Q. (2012). J. Photochem. Photobiol. Chem. 244, 65–70. Web of Science CrossRef CAS Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Zhuang, C., Zhang, W., Sheng, C., Zhang, W., Xing, C. & Miao, Z. (2017). Chem. Rev. 117, 7762–7810. Web of Science CrossRef CAS PubMed Google Scholar

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