4-Chloro­curcumin

Pham, P.-T.T.; Bader, M.M.

doi:10.1107/S2414314624012434

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 10| Part 1| January 2025| x241243

https://doi.org/10.1107/S2414314624012434

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4-Chlorocurcumin

Phuong-Truc T. Pham ^a and Mamoun M. Bader ^b ^*

^aDepartment of Chemistry, Pennsylvania State Scranton, Dunmore, PA 18512, USA, and ^bDepartment of Chemistry, Alfaisal University, Riyadh 11533, Saudi Arabia
^*Correspondence e-mail: mbader@alfaisal.edu

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 11 December 2024; accepted 24 December 2024; online 3 January 2025)

The title compound [systematic name: 4-chloro-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one], C₂₁H₁₉ClO₆, is close to planar, with a dihedral angle of 2.61 (7)° between the terminal phenyl groups and three intramolecular O—H⋯O hydrogen bonds occur. In the crystal, the molecules are linked into [201] chains by O—H⋯O hydrogen bonds and weak aromatic π–π stacking is also observed with a shortest centroid–centroid separation of 3.7279 (8) Å.

Keywords: crystal structure; curcumin derivative; hydrogen bonds.

CCDC reference: 2258982

Structure description

Curcumin, or 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (C₂₁H₂₀O₆), is a yellow–orange polyphenolic compound found in turmeric. Since the 1990s, extensive research has highlighted its antioxidant, anti-inflammatory, and anticancer properties (Dairam et al., 2008 ). Structurally, curcumin features an α,β-unsaturated β-diketone moiety. In neutral and acidic media, it predominantly adopts the diketo form, whereas the more stable keto–enol form is favored under alkaline conditions. The phenolic groups and the α,β-unsaturated diketone contribute to its antioxidant activity, while the α,β-unsaturated diketone unit is primarily linked to its anticancer effects (Priyadarsini, 2013 ). An examination of the Cambridge Structural Database (CSD; version2024.3, update of December 2024; Groom et al., 2016 ) indicates that curcumin exists in three polymorphs (I, II, and III), all displaying their keto–enol tautomeric forms in the solid-state. The most common form, polymorph I, crystallizes in the monoclinic space group P2/n [CSD refcodes BINMEQ (Tønnesen et al., 1982 ), BINMEQ01 (Ishigami et al., 1999 ), BINMEQ02 (Parimita et al., 2007 ), BINMEQ03 (Suo et al., 2006 ), BINMEQ04 (Fronczek, 2009 ), BINMEQ05 (Sanphui et al., 2011 ), BINMEQ09 (Reid et al., 2015 ), BINMEQ10 (Parveen et al., 2016 ), BINMEQ11 (Matlinska et al., 2018 ), BINMEQ13 (Lal et al., 2020 ) and BINMEQ14 (Kohnhorst & Saithong, 2019 )] while the less common forms II and III crystallize in the orthorhombic space groups Pca2₁ [BINMEQ06 (Sanphui et al., 2011), BINMEQ08 (Renuga Parameswari et al., 2012 ), BINMEQ12 (Matlinska et al., 2018) and BINMEQ15 (Zou, 2024 )] and Pbca (BINMEQ07; Sanphui et al., 2011), respectively.

This study presents the synthesis and crystal structure of the title compound, C₂₁H₁₉ClO₆ (I), where the hydrogen atom at the α-carbon atom (4-position) is replaced by a chlorine atom. The synthesis of the title compound was reported previously by two groups through multistep syntheses plagued with low yields and impurities (Ooko et al., 2016 ; Abood et al., 2021 ). Our method is a direct one-step halogenation reaction with a reasonable yield.

The molecule of (I) adopts a near planar conformation, as indicated by the torsion angle of 2.61 (7)(7)° between the planes of the terminal C5–C10 and C15–C20 phenyl groups. Three intramolecular O—H⋯O hydrogen bonds occur (Fig. 1), with the central O1—H1⋯O2 bond notably shorter and closer to linearity than the terminal O3—H3⋯O4 and O5—H5⋯O6 bonds (Table 1). The supporting information provides a comparison of curcumin polymorph structural and physical data with those of (I).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2	0.82	1.70	2.4506 (16)	151
O3—H3⋯O4	0.82	2.18	2.6395 (15)	115
O5—H5⋯O6	0.82	2.28	2.7200 (15)	114
O3—H3⋯O6ⁱ	0.82	2.20	2.8398 (15)	135
O5—H5⋯O3ⁱⁱ	0.82	2.05	2.8439 (16)	164
C11—H11B⋯O2ⁱⁱⁱ	0.96	2.59	3.477 (2)	154
C17—H17⋯O2^iv	0.93	2.57	3.3206 (19)	138
Symmetry codes: (i) $[x-1, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ ; (ii) $[x+1, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ ; (iii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (iv) $[x, -y+{\script{3\over 2}}, z-{\script{1\over 2}}]$ .

Figure 1
The molecular structure of (I) showing 50% displacement ellipsoids. Hydrogen bonds are shown as dotted lines.

In the crystal of (I), the molecules are linked by O—H⋯O hydrogen bonds arising from O3 and O4 (both of which also form an intramolecular link) to generate infinite [20 $[\overline{1}]$ ] chains (Fig. 2). Aromatic π–π stacking also occurs, as indicated by the shortest centroid–centroid separation of 3.7279 (8) Å between inversion related C5–C10 and C15–C20 rings but no short Cl⋯Cl contacts occur.

Figure 2
Part of a [20 $[\overline{1}]$ ] hydrogen-bonded chain in the structure of (I).

Synthesis and crystallization

Curcumin (2.74 g, 7.45 mmol) was dissolved in anhydrous acetonitrile with heating. The solution was briefly cooled in an ice bath before N-chlorosuccinimide (1.21 g, 9.05 mmol) was added. Stirring was allowed to continue overnight at room temperature. The red crude powder was filtered and recrystallized from acetonitrile solution to give yellow needles of (I) (yield: 33%. Analysis calculated (C₂₁H₁₉ClO₆): C, 62.62; H, 4.75; Cl, 8.80. Found: C, 62.30; H, 4.77; Cl, 8.58. Exact mass: 402.0870, found (EI, M + 1): 403.0940. M.p. 197°C (lit. 190–191°C; Abood et al., 2021). Compared to curcumin, the solubility of (I) in water is slightly reduced, measuring approximately 5 g l⁻¹, compared to 6.6 g l⁻¹ for the former.

The UV/visible absorption spectrum of (I) dissolved in dichloromethane shows a bathochromic (red) shift of 35 nm, compared to the parent curcumin compound (Fig. 3), which might correlate with the electron-donating properties of the chlorine atom.

Figure 3
The UV/visible absorption spectrum of (I) dissolved in dichloromethane.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₂₁H₁₉ClO₆
M_r	402.81
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	298
a, b, c (Å)	16.7520 (3), 7.27831 (16), 15.9369 (3)
β (°)	100.0131 (17)
V (Å³)	1913.53 (7)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	2.08
Crystal size (mm)	0.2 × 0.17 × 0.13

Data collection
Diffractometer	Four-circle diffractometer
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2022 $[Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.765, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	13358, 3710, 3247
R_int	0.020
(sin θ/λ)_max (Å⁻¹)	0.623

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.108, 1.07
No. of reflections	3710
No. of parameters	259
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.27, −0.32
Computer programs: CrysAlis PRO (Rigaku OD, 2022 $[Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXT (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2258982

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314624012434/hb4501sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314624012434/hb4501Isup2.hkl

supporting information. DOI: https://doi.org/10.1107/S2414314624012434/hb4501sup3.doc

Supporting information file. DOI: https://doi.org/10.1107/S2414314624012434/hb4501Isup4.cml

checkCIF report

Computing details top

4-Chloro-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one top

Crystal data top

C₂₁H₁₉ClO₆	F(000) = 840
M_r = 402.81	D_x = 1.398 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 16.7520 (3) Å	Cell parameters from 8805 reflections
b = 7.27831 (16) Å	θ = 2.9–73.7°
c = 15.9369 (3) Å	µ = 2.08 mm⁻¹
β = 100.0131 (17)°	T = 298 K
V = 1913.53 (7) Å³	Block, clear orange
Z = 4	0.2 × 0.17 × 0.13 mm

Data collection top

Four-circle diffractometer	3710 independent reflections
Radiation source: Rotating-anode X-ray tube, Rigaku (Cu) X-ray Source	3247 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.020
Detector resolution: 10.0000 pixels mm^-1	θ_max = 73.8°, θ_min = 2.7°
ω scans	h = −20→18
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2022)	k = −8→8
T_min = 0.765, T_max = 1.000	l = −18→19
13358 measured reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.036	w = 1/[σ²(F_o²) + (0.0595P)² + 0.3344P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.108	(Δ/σ)_max < 0.001
S = 1.07	Δρ_max = 0.27 e Å⁻³
3710 reflections	Δρ_min = −0.32 e Å⁻³
259 parameters	Extinction correction: SHELXL2018/3 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0016 (3)
Primary atom site location: dual

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
Cl1	0.43756 (2)	0.67682 (7)	0.37034 (2)	0.06172 (16)
O1	0.50652 (7)	0.79498 (18)	0.61198 (7)	0.0570 (3)
H1	0.550936	0.829843	0.603374	0.086*
O2	0.61937 (6)	0.85947 (18)	0.53705 (7)	0.0565 (3)
O3	0.04255 (6)	0.4600 (2)	0.66977 (7)	0.0641 (4)
H3	0.041337	0.463367	0.720969	0.096*
O4	0.15138 (7)	0.56430 (19)	0.80133 (6)	0.0581 (3)
O5	0.87723 (7)	0.9296 (2)	0.13546 (7)	0.0682 (4)
H5	0.922848	0.967388	0.154746	0.102*
O6	0.94585 (6)	1.00942 (19)	0.29885 (6)	0.0573 (3)
C1	0.49645 (8)	0.7455 (2)	0.46575 (9)	0.0434 (3)
C2	0.46339 (8)	0.7392 (2)	0.54077 (9)	0.0443 (3)
C3	0.38188 (9)	0.6737 (2)	0.54378 (10)	0.0477 (4)
H3A	0.349488	0.633170	0.493829	0.057*
C4	0.35239 (9)	0.6703 (2)	0.61630 (10)	0.0474 (4)
H4	0.387375	0.707950	0.665095	0.057*
C5	0.27120 (8)	0.6139 (2)	0.62761 (9)	0.0426 (3)
C6	0.21122 (9)	0.5600 (2)	0.56049 (9)	0.0476 (4)
H6	0.222603	0.557438	0.505431	0.057*
C7	0.13493 (9)	0.5102 (2)	0.57431 (9)	0.0508 (4)
H7	0.095275	0.475143	0.528788	0.061*
C8	0.11786 (8)	0.5126 (2)	0.65602 (9)	0.0459 (3)
C9	0.17684 (8)	0.5667 (2)	0.72415 (9)	0.0437 (3)
C10	0.25293 (9)	0.6168 (2)	0.71009 (9)	0.0451 (3)
H10	0.292303	0.652633	0.755702	0.054*
C11	0.20933 (11)	0.6084 (3)	0.87479 (10)	0.0649 (5)
H11A	0.229870	0.730055	0.868938	0.097*
H11B	0.253195	0.521893	0.880651	0.097*
H11C	0.184072	0.603208	0.924386	0.097*
C12	0.57657 (9)	0.8078 (2)	0.46588 (9)	0.0435 (3)
C13	0.61302 (9)	0.8162 (2)	0.38921 (10)	0.0464 (4)
H13	0.582583	0.783486	0.336848	0.056*
C14	0.68960 (9)	0.8704 (2)	0.39371 (10)	0.0453 (3)
H14	0.716934	0.901139	0.447769	0.054*
C15	0.73604 (8)	0.8876 (2)	0.32490 (9)	0.0423 (3)
C16	0.70374 (9)	0.8547 (2)	0.24003 (10)	0.0487 (4)
H16	0.649540	0.821538	0.224812	0.058*
C17	0.75172 (9)	0.8709 (2)	0.17775 (10)	0.0521 (4)
H17	0.729421	0.848662	0.121046	0.063*
C18	0.83262 (9)	0.9199 (2)	0.19931 (9)	0.0471 (3)
C19	0.86553 (8)	0.9572 (2)	0.28391 (9)	0.0434 (3)
C20	0.81761 (8)	0.9398 (2)	0.34580 (9)	0.0442 (3)
H20	0.839899	0.963208	0.402395	0.053*
C21	0.98395 (10)	1.0319 (3)	0.38498 (10)	0.0639 (5)
H21A	1.038542	1.074016	0.386889	0.096*
H21B	0.984627	0.916388	0.414174	0.096*
H21C	0.954454	1.120490	0.412132	0.096*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0402 (2)	0.0935 (4)	0.0527 (2)	−0.01305 (19)	0.01165 (17)	−0.00591 (19)
O1	0.0407 (6)	0.0814 (8)	0.0512 (6)	−0.0087 (6)	0.0141 (5)	0.0033 (5)
O2	0.0340 (5)	0.0848 (8)	0.0516 (6)	−0.0076 (5)	0.0097 (4)	0.0013 (6)
O3	0.0334 (6)	0.1104 (10)	0.0526 (6)	−0.0065 (6)	0.0187 (5)	−0.0016 (7)
O4	0.0452 (6)	0.0933 (9)	0.0395 (5)	−0.0025 (6)	0.0175 (4)	−0.0007 (5)
O5	0.0469 (6)	0.1209 (11)	0.0400 (6)	−0.0127 (7)	0.0165 (5)	0.0010 (6)
O6	0.0313 (5)	0.1007 (10)	0.0419 (5)	−0.0091 (5)	0.0118 (4)	0.0003 (5)
C1	0.0314 (7)	0.0511 (8)	0.0493 (7)	0.0004 (6)	0.0113 (6)	0.0058 (6)
C2	0.0343 (7)	0.0491 (8)	0.0514 (8)	0.0015 (6)	0.0124 (6)	0.0067 (6)
C3	0.0354 (7)	0.0552 (9)	0.0553 (8)	−0.0011 (6)	0.0163 (6)	0.0049 (7)
C4	0.0391 (8)	0.0542 (9)	0.0514 (8)	−0.0025 (6)	0.0151 (6)	0.0035 (6)
C5	0.0371 (7)	0.0481 (8)	0.0456 (7)	0.0016 (6)	0.0151 (6)	0.0043 (6)
C6	0.0417 (8)	0.0636 (9)	0.0415 (7)	0.0011 (7)	0.0179 (6)	0.0032 (6)
C7	0.0367 (7)	0.0748 (11)	0.0420 (7)	−0.0007 (7)	0.0100 (6)	−0.0012 (7)
C8	0.0310 (7)	0.0631 (9)	0.0464 (7)	0.0014 (6)	0.0144 (6)	0.0019 (7)
C9	0.0378 (7)	0.0563 (9)	0.0399 (7)	0.0045 (6)	0.0145 (6)	0.0032 (6)
C10	0.0377 (7)	0.0554 (8)	0.0439 (7)	−0.0017 (6)	0.0116 (6)	0.0001 (6)
C11	0.0625 (11)	0.0925 (14)	0.0404 (8)	0.0013 (10)	0.0106 (7)	−0.0003 (8)
C12	0.0323 (7)	0.0490 (8)	0.0505 (8)	0.0029 (6)	0.0109 (6)	0.0071 (6)
C13	0.0354 (7)	0.0542 (9)	0.0521 (8)	0.0003 (6)	0.0147 (6)	0.0036 (6)
C14	0.0354 (7)	0.0538 (9)	0.0493 (8)	0.0007 (6)	0.0145 (6)	0.0014 (6)
C15	0.0334 (7)	0.0470 (8)	0.0488 (8)	0.0012 (6)	0.0131 (6)	0.0034 (6)
C16	0.0337 (7)	0.0605 (9)	0.0519 (8)	−0.0048 (6)	0.0076 (6)	0.0048 (7)
C17	0.0434 (8)	0.0711 (10)	0.0407 (7)	−0.0062 (7)	0.0041 (6)	0.0037 (7)
C18	0.0405 (7)	0.0633 (9)	0.0397 (7)	0.0007 (7)	0.0136 (6)	0.0057 (6)
C19	0.0300 (7)	0.0587 (9)	0.0427 (7)	0.0003 (6)	0.0099 (5)	0.0043 (6)
C20	0.0340 (7)	0.0596 (9)	0.0403 (7)	−0.0007 (6)	0.0098 (5)	0.0003 (6)
C21	0.0372 (8)	0.1081 (15)	0.0465 (8)	−0.0085 (9)	0.0072 (6)	−0.0080 (9)

Geometric parameters (Å, º) top

Cl1—C1	1.7359 (15)	C7—C8	1.381 (2)
O1—H1	0.8200	C8—C9	1.392 (2)
O1—C2	1.2999 (18)	C9—C10	1.381 (2)
O2—C12	1.2881 (19)	C10—H10	0.9300
O3—H3	0.8200	C11—H11A	0.9600
O3—C8	1.3718 (17)	C11—H11B	0.9600
O4—C9	1.3703 (16)	C11—H11C	0.9600
O4—C11	1.422 (2)	C12—C13	1.459 (2)
O5—H5	0.8200	C13—H13	0.9300
O5—C18	1.3650 (17)	C13—C14	1.332 (2)
O6—C19	1.3785 (16)	C14—H14	0.9300
O6—C21	1.4190 (18)	C14—C15	1.4561 (19)
C1—C2	1.4030 (19)	C15—C16	1.387 (2)
C1—C12	1.4164 (19)	C15—C20	1.4016 (19)
C2—C3	1.4550 (19)	C16—H16	0.9300
C3—H3A	0.9300	C16—C17	1.387 (2)
C3—C4	1.334 (2)	C17—H17	0.9300
C4—H4	0.9300	C17—C18	1.386 (2)
C4—C5	1.4614 (19)	C18—C19	1.392 (2)
C5—C6	1.391 (2)	C19—C20	1.3814 (19)
C5—C10	1.4007 (19)	C20—H20	0.9300
C6—H6	0.9300	C21—H21A	0.9600
C6—C7	1.383 (2)	C21—H21B	0.9600
C7—H7	0.9300	C21—H21C	0.9600

C2—O1—H1	109.5	O4—C11—H11C	109.5
C8—O3—H3	109.5	H11A—C11—H11B	109.5
C9—O4—C11	117.50 (12)	H11A—C11—H11C	109.5
C18—O5—H5	109.5	H11B—C11—H11C	109.5
C19—O6—C21	117.40 (11)	O2—C12—C1	118.50 (13)
C2—C1—Cl1	119.25 (11)	O2—C12—C13	118.38 (13)
C2—C1—C12	121.57 (13)	C1—C12—C13	123.13 (14)
C12—C1—Cl1	119.18 (11)	C12—C13—H13	119.8
O1—C2—C1	119.47 (13)	C14—C13—C12	120.44 (14)
O1—C2—C3	117.12 (13)	C14—C13—H13	119.8
C1—C2—C3	123.41 (14)	C13—C14—H14	115.8
C2—C3—H3A	119.1	C13—C14—C15	128.36 (15)
C4—C3—C2	121.73 (15)	C15—C14—H14	115.8
C4—C3—H3A	119.1	C16—C15—C14	123.40 (13)
C3—C4—H4	116.4	C16—C15—C20	118.51 (12)
C3—C4—C5	127.22 (15)	C20—C15—C14	118.09 (13)
C5—C4—H4	116.4	C15—C16—H16	119.8
C6—C5—C4	123.22 (13)	C17—C16—C15	120.45 (14)
C6—C5—C10	118.65 (13)	C17—C16—H16	119.8
C10—C5—C4	118.13 (13)	C16—C17—H17	119.7
C5—C6—H6	119.5	C18—C17—C16	120.54 (14)
C7—C6—C5	121.05 (13)	C18—C17—H17	119.7
C7—C6—H6	119.5	O5—C18—C17	117.85 (13)
C6—C7—H7	120.1	O5—C18—C19	122.41 (13)
C8—C7—C6	119.71 (14)	C17—C18—C19	119.74 (13)
C8—C7—H7	120.1	O6—C19—C18	115.56 (12)
O3—C8—C7	119.61 (13)	O6—C19—C20	124.95 (13)
O3—C8—C9	120.14 (12)	C20—C19—C18	119.49 (13)
C7—C8—C9	120.26 (13)	C15—C20—H20	119.4
O4—C9—C8	114.02 (12)	C19—C20—C15	121.25 (13)
O4—C9—C10	126.09 (13)	C19—C20—H20	119.4
C10—C9—C8	119.89 (13)	O6—C21—H21A	109.5
C5—C10—H10	119.8	O6—C21—H21B	109.5
C9—C10—C5	120.45 (14)	O6—C21—H21C	109.5
C9—C10—H10	119.8	H21A—C21—H21B	109.5
O4—C11—H11A	109.5	H21A—C21—H21C	109.5
O4—C11—H11B	109.5	H21B—C21—H21C	109.5

Cl1—C1—C2—O1	−178.22 (12)	C6—C7—C8—C9	0.6 (2)
Cl1—C1—C2—C3	1.4 (2)	C7—C8—C9—O4	179.38 (15)
Cl1—C1—C12—O2	179.55 (11)	C7—C8—C9—C10	−0.5 (2)
Cl1—C1—C12—C13	−0.5 (2)	C8—C9—C10—C5	0.1 (2)
O1—C2—C3—C4	−0.2 (2)	C10—C5—C6—C7	0.0 (2)
O2—C12—C13—C14	2.2 (2)	C11—O4—C9—C8	176.77 (15)
O3—C8—C9—O4	−1.1 (2)	C11—O4—C9—C10	−3.4 (2)
O3—C8—C9—C10	179.02 (15)	C12—C1—C2—O1	1.3 (2)
O4—C9—C10—C5	−179.74 (14)	C12—C1—C2—C3	−179.07 (14)
O5—C18—C19—O6	1.6 (2)	C12—C13—C14—C15	−179.93 (14)
O5—C18—C19—C20	−178.20 (16)	C13—C14—C15—C16	2.7 (3)
O6—C19—C20—C15	179.36 (15)	C13—C14—C15—C20	−177.12 (16)
C1—C2—C3—C4	−179.78 (15)	C14—C15—C16—C17	−178.99 (15)
C1—C12—C13—C14	−177.78 (15)	C14—C15—C20—C19	179.38 (15)
C2—C1—C12—O2	0.0 (2)	C15—C16—C17—C18	0.1 (3)
C2—C1—C12—C13	179.96 (14)	C16—C15—C20—C19	−0.5 (2)
C2—C3—C4—C5	177.85 (15)	C16—C17—C18—O5	178.57 (16)
C3—C4—C5—C6	−2.2 (3)	C16—C17—C18—C19	−1.5 (3)
C3—C4—C5—C10	178.62 (16)	C17—C18—C19—O6	−178.37 (15)
C4—C5—C6—C7	−179.12 (15)	C17—C18—C19—C20	1.8 (2)
C4—C5—C10—C9	179.31 (14)	C18—C19—C20—C15	−0.9 (2)
C5—C6—C7—C8	−0.4 (3)	C20—C15—C16—C17	0.9 (2)
C6—C5—C10—C9	0.1 (2)	C21—O6—C19—C18	−174.18 (16)
C6—C7—C8—O3	−178.88 (15)	C21—O6—C19—C20	5.6 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2	0.82	1.70	2.4506 (16)	151
O3—H3···O4	0.82	2.18	2.6395 (15)	115
O5—H5···O6	0.82	2.28	2.7200 (15)	114
O3—H3···O6ⁱ	0.82	2.20	2.8398 (15)	135
O5—H5···O3ⁱⁱ	0.82	2.05	2.8439 (16)	164
C11—H11B···O2ⁱⁱⁱ	0.96	2.59	3.477 (2)	154
C17—H17···O2^iv	0.93	2.57	3.3206 (19)	138

Symmetry codes: (i) x−1, −y+3/2, z+1/2; (ii) x+1, −y+3/2, z−1/2; (iii) −x+1, y−1/2, −z+3/2; (iv) x, −y+3/2, z−1/2.

Acknowledgements

The authors acknowledge partial support from the SIG S10 of the National Institute of Health under awards 1S10OD028589–01 and 1S10RR023439–01 to Dr Neela Yennawar for the X-ray instrumentation. The authors also acknowledge Dr Hemant P. Yennawar of the X-ray facility at Penn State University, University Park. We would also like to thank Dr E. Alsharaeh, Dr Mohan C. and undergraduate students Sarah Younas and Samar Al Rifai for help with the DSC and UV measurements. MMB acknowledges the support of the Office of Research at Alfaisal University for financial support (IRG-2020 and 2024).

Funding information

Funding for this research was provided by: Penn State Scranton (grant No. RDG-Pham to P.-T. T. Pham); Office of the VP for Research at Alfaisal University (grant No. IRG-2024 to M. M. Bader).

References

Abood, R. G., Alsalim, T. A. & Abood, E. A. (2021). Egypt. J. Chem. 64, 2173–2183. Google Scholar
Dairam, A., Fogel, R., Daya, S. & Limson, J. L. (2008). J. Agric. Food Chem. 56, 3350–3356. CrossRef PubMed 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
Fronczek, F. R. (2009). CSD Communication (refcode BINMEQ04). CCDC, Cambridge, England. 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
Ishigami, Y., Goto, M., Masuda, T., Takizawa, Y. & Suzuki, S. (1999). Shikizai Kyokaishi, 72, 71–77. CAS Google Scholar
Kohnhorst, S. A. & Saithong, S. (2019). J. Curr. Sci. Technol. 9, 77–87. Google Scholar
Lal, S., Prakash, K., Khera, N. & Hooda, S. (2020). CSD Communication (refcode BINMEQ13). CCDC, Cambridge, England. Google Scholar
Matlinska, M. A., Wasylishen, R. E., Bernard, G. M., Terskikh, V. V., Brinkmann, A. & Michaelis, V. K. (2018). Cryst. Growth Des. 18, 5556–5563. CrossRef CAS Google Scholar
Ooko, E., Alsalim, T., Saeed, B., Saeed, M. E. M., Kadioglu, O., Abbo, H. S., Titinchi, S. J. J. & Efferth, T. (2016). Toxicol. Appl. Pharmacol. 305, 216–233. CrossRef CAS PubMed Google Scholar
Parimita, S. P., Ramshankar, Y. V., Suresh, S. & Guru Row, T. N. (2007). Acta Cryst. E63, o860–o862. CrossRef IUCr Journals Google Scholar
Parveen, M., Ahmad, F., Malla, A. M., Azaz, S., Alam, M., Basudan, O. A., Silva, M. R. & Pereira Silva, P. S. (2016). Nat. Prod. Bioprospect. 6, 267–278. CrossRef PubMed Google Scholar
Priyadarsini, K. I. (2013). Curr. Pharm. Des. 19, 2093–2100. CAS PubMed Google Scholar
Reid, J. W., Kaduk, J. A., Garimella, S. V. & Tse, J. S. (2015). Powder Diffr. 30, 67–75. CrossRef CAS Google Scholar
Renuga Parameswari, A., Devipriya, B., Jenniefer, S. J., Thomas Muthiah, P. & Kumaradhas, P. (2012). J. Chem. Crystallogr. 42, 227–231. CrossRef Google Scholar
Rigaku OD (2022). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England. Google Scholar
Sanphui, P., Goud, N. R., Khandavilli, U. B. R., Bhanoth, S. & Nangia, A. (2011). Chem. Commun. 47, 5013. CrossRef 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
Suo, Q., Huang, Y., Weng, L., He, W., Li, C., Li, Y. & Hong, H. (2006). Shipin Kexue (Beijing), 27, 27. Google Scholar
Tønnesen, H. H., Karlsen, J., Mostad, A., Samuelsson, B., Enzell, C. R. & Berg, J. (1982). Acta Chem. Scand. 36b, 475–479. Google Scholar
Zou, H. (2024). CSD Communication (refcode BINMEQ15). CCDC, Cambridge, England. Google Scholar