Luteolin

Molecules of the tetra­hydroxy­flavone luteolin, C₁₅H₁₀O₆, are essentially planar and contain an intramolecular hydrogen bond. The crystal structure is stabilized by O—H...O, C—H...O and C—H...π interactions, and contains disordered water mol­ecules, probably corresponding to a hemihydrate.

Key indicators

• Single-crystal X-ray study
• T = 120 K
• Mean [sigma](C-C) = 0.010 Å
• R factor = 0.093
• wR factor = 0.190
• Data-to-parameter ratio = 7.2

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level B:



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           27.58
         From the CIF: _reflns_number_total               1471
         TEST2: Reflns within _diffrn_reflns_theta_max
         Count of symmetry unique reflns         1666
         Completeness (_total/calc)             88.30%
          Alert B: < 90% complete (theta max?)

PLAT_420  Alert B D-H Without Acceptor       O4     -   H4     ..           ?


 Alert Level C:



PLAT_601  Alert C Structure Contains Solvent Accessible VOIDS of .      34.00 A   3

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           27.58
         From the CIF: _reflns_number_total               1471
         Count of symmetry unique reflns         1666
         Completeness (_total/calc)             88.30%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured         0
         Fraction of Friedel pairs measured     0.000
         Are heavy atom types Z>Si present           no
          Please check that the estimate of the number of Friedel pairs is
          correct. If it is not, please give the correct count in the
          _publ_section_exptl_refinement section of the submitted CIF.


 0 Alert Level A = Potentially serious problem

 2 Alert Level B = Potential problem

 1 Alert Level C = Please check

---

S1. Comment

There is an extensive body of literature on the biological activity of luteolin (5,7,3',4'-tetrahydroxyflavone), (I), including a dedicated web site (luteolin.com). Many herbs containing luteolin have been used as traditional medicines to treat a wide variety of symptoms, and anti-inflammatory and anti-oxidant activity are particularly important features of this flavonoid. A recent example of its structure elucidation by spectroscopy has been published (Owen et al., 2003).

The atomic arrangement in (I) is shown in Fig. 1. The molecule is essentially planar, with a dihedral angle between the endocyclic atoms of the pyrone ring system and the phenyl ring of only 2.1 (3)°. The largest torsion angle [O6—C13—C14—O5 = 4.7 (9)°] involves hydroxy O atoms associated with intermolecular hydrogen bonding.

Within the crystal structure, hydrogen bonding is extensive (Table 2). An intramolecular hydrogen bond is present between the carbonyl and hydroxy groups at C4 and C5, respectively. The H12···O1 separation is also short at 2.31 Å, but the C12—H12···O1 angle is only 101°. The hydroxy group at C7 is believed to be linked with the solvent through hydrogen bonding, but the quality of the data cannot confirm this association. Apart from the classical hydrogen bonding, a C—H···O interaction and a C—H···π (Table 3) contact are also present. Crystal structures of related hydroxyflavones include cirsimaritin (Chou et al., 2002), pachypodol (Smith et al., 2001) and 5-hydroxy-3,7,4'-trimethoxyflavone (Gajhede et al., 1989).

S2. Experimental

The seeds of Daucus carota L. (family Apiaceae), commonly known as 'Wild Carrot', were purchased from B&T World Seeds, France. A voucher specimen (PH700 003) has been deposited in the herbarium of the Plant and Soil Science Department, University of Aberdeen, Scotland (ABD). Ground seeds were Soxhlet-extracted, successively, with n-hexane, dichloromethane and methanol (1.1 l each). The methanol extract was subjected to Sep-Pak (C₁₈, 10 g cartridge) fractionation using 30, 40, 60, 80 and 100% aqueous MeOH (200 ml each). The preparative HPLC analysis (A Luna C₁₈ preparative column 10 µ, 250 mm × 21.2 mm; mobile phase: 30–80% MeOH in water gradient over 50 min, flow rate = 20 ml min⁻¹) of the Sep-Pak 60% MeOH fraction yielded luteolin (19 mg, retention time = 26 min), the structure of which was preliminarily determined by UV, MS, ¹H and ¹³C NMR data analyses.

S3. Refinement

Data were collected on a weakly diffracting thin plate over 46 h. H atoms were placed in calculated positions (O—H = 0.84 Å and C—H= 0.95 Å) and allowed to ride on their parent atoms with freely refined U_{iso(H). The structure contains disordered solvent, which was treated with the SQUEEZE procedure in PLATON (Spek, 2002). There are two solvent cavities per unit cell, at positions (0, 0.261, 0) and (1/2, 0.761, 0), each with a volume of 35 ų and each containing approximately 13 electrons. At least two diffuse peaks could be seen in each cavity in a difference map, but the small volume indicates the presence of a single water molecule (10 electrons) disordered in each cavity.}

In the absence of elements heavier than oxygen, Friedel pairs were merged prior to refinement. The absolute polarity of the crystal was assigned arbitrarily (for a planar molecule, absolute configuration is meaningless).

The high value of R relates to the difficulty in obtaining suitable data from a small, thin plate of diffracting material containing diffuse solvent.

Computing details

Data collection: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); cell refinement: DENZO and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2002); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

Fig. 1. The molecular structure of (I). Displacement ellipsoids are drawn at the 50% probability level.

(I)

Crystal data

C15H10O6	F(000) = 592
Mr = 286.23	Dx = 1.463 Mg m^−3
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: C 2y	Cell parameters from 8254 reflections
a = 35.327 (5) Å	θ = 2.9–27.5°
b = 5.618 (1) Å	µ = 0.12 mm^−1
c = 6.682 (1) Å	T = 120 K
β = 101.554 (5)°	Plate, light brown
V = 1299.3 (4) Å^3	0.4 × 0.1 × 0.01 mm
Z = 4

Data collection

Nonius KappaCCD area-detector diffractometer	1262 reflections with I > 2σ(I)
ϕ and ω scans	Rint = 0.087
Absorption correction: multi-scan (SORTAV; Blessing, 1995, 1997)	θmax = 27.6°, θmin = 3.1°
Tmin = 0.911, Tmax = 1.000	h = −45→45
8254 measured reflections	k = −7→7
1471 independent reflections	l = −8→8

Refinement

Refinement on F^2	1 restraint
Least-squares matrix: full	Only H-atom displacement parameters refined
R[F^2 > 2σ(F^2)] = 0.093	w = 1/[σ^2(Fo^2) + (0.0452P)^2 + 6.6344P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.190	(Δ/σ)max < 0.001
S = 1.18	Δρmax = 0.35 e Å^−3
1471 reflections	Δρmin = −0.34 e Å^−3
204 parameters

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.12646 (13)	0.1650 (9)	0.1071 (7)	0.0257 (11)
O2	0.13361 (12)	0.6547 (9)	−0.3352 (7)	0.0258 (11)
O3	0.07851 (13)	0.4290 (10)	−0.5823 (8)	0.0325 (13)
H3	0.1009	0.4848	−0.5707	0.03 (2)*
O4	0.02586 (14)	−0.2521 (10)	−0.3174 (9)	0.0360 (14)
H4	0.026	−0.3208	−0.2055	0.10 (5)*
O5	0.24217 (13)	0.2814 (9)	0.9362 (7)	0.0271 (12)
H5	0.2574	0.3965	0.9671	0.03 (2)*
O6	0.18886 (13)	−0.0343 (9)	0.8124 (8)	0.0289 (12)
H6	0.1686	−0.1116	0.7667	0.02 (2)*
C2	0.15262 (16)	0.3495 (12)	0.1438 (11)	0.0206 (16)
C3	0.1546 (2)	0.5170 (13)	−0.0009 (12)	0.0297 (17)
H3A	0.1724	0.6447	0.0307	0.03 (2)*
C4	0.13032 (17)	0.5045 (12)	−0.1998 (11)	0.0201 (14)
C5	0.07756 (18)	0.2764 (13)	−0.4265 (11)	0.0254 (16)
C6	0.0527 (2)	0.0894 (14)	−0.4540 (13)	0.0320 (18)
H6A	0.0359	0.0658	−0.5825	0.11 (4)*
C7	0.05183 (17)	−0.0730 (13)	−0.2886 (13)	0.0311 (19)
C8	0.07567 (19)	−0.0374 (14)	−0.1021 (13)	0.0319 (18)
H8	0.0744	−0.1394	0.0098	0.05 (3)*
C9	0.10104 (19)	0.1464 (14)	−0.0807 (11)	0.0253 (15)
C10	0.1032 (2)	0.3133 (14)	−0.2351 (12)	0.0272 (17)
C11	0.17618 (18)	0.3345 (13)	0.3490 (11)	0.0230 (15)
C12	0.17082 (19)	0.1511 (14)	0.4789 (11)	0.0267 (16)
H12	0.1517	0.0333	0.4346	0.03 (2)*
C13	0.1936 (2)	0.1398 (12)	0.6749 (11)	0.0252 (16)
C14	0.22093 (17)	0.3136 (13)	0.7433 (11)	0.0234 (16)
C15	0.22675 (18)	0.4970 (13)	0.6154 (11)	0.0241 (16)
H15	0.246	0.6136	0.6613	0.03 (2)*
C16	0.20440 (18)	0.5109 (13)	0.4191 (11)	0.0260 (16)
H16	0.2081	0.6388	0.3319	0.04 (2)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.030 (2)	0.028 (3)	0.018 (3)	−0.001 (2)	0.0024 (19)	0.002 (2)
O2	0.031 (2)	0.025 (3)	0.022 (3)	−0.007 (2)	0.005 (2)	0.002 (2)
O3	0.032 (3)	0.039 (3)	0.025 (3)	−0.004 (2)	0.002 (2)	0.002 (3)
O4	0.036 (3)	0.033 (3)	0.032 (3)	−0.004 (2)	−0.009 (2)	0.006 (3)
O5	0.028 (2)	0.024 (3)	0.025 (3)	−0.007 (2)	−0.0040 (19)	−0.003 (2)
O6	0.035 (3)	0.027 (3)	0.022 (3)	−0.003 (2)	−0.001 (2)	0.006 (2)
C2	0.013 (3)	0.023 (3)	0.024 (4)	−0.001 (2)	0.000 (2)	−0.003 (3)
C3	0.046 (4)	0.015 (3)	0.028 (5)	−0.005 (3)	0.009 (3)	−0.008 (3)
C4	0.019 (3)	0.024 (3)	0.018 (4)	−0.002 (3)	0.006 (2)	−0.001 (3)
C5	0.028 (3)	0.018 (3)	0.031 (5)	−0.003 (3)	0.007 (3)	0.009 (3)
C6	0.036 (4)	0.034 (4)	0.024 (5)	0.001 (3)	0.002 (3)	0.000 (3)
C7	0.017 (3)	0.024 (4)	0.049 (6)	−0.002 (3)	−0.002 (3)	−0.005 (4)
C8	0.034 (3)	0.032 (4)	0.029 (5)	0.002 (3)	0.003 (3)	0.011 (3)
C9	0.030 (3)	0.027 (4)	0.019 (4)	−0.003 (3)	0.006 (3)	−0.004 (3)
C10	0.030 (3)	0.033 (4)	0.017 (4)	0.002 (3)	0.003 (3)	0.002 (3)
C11	0.025 (3)	0.025 (4)	0.021 (4)	0.001 (3)	0.010 (3)	0.003 (3)
C12	0.032 (3)	0.030 (4)	0.016 (4)	−0.002 (3)	0.000 (3)	−0.005 (3)
C13	0.044 (4)	0.018 (3)	0.014 (4)	0.005 (3)	0.005 (3)	0.001 (3)
C14	0.021 (3)	0.029 (4)	0.018 (4)	0.007 (3)	−0.002 (3)	−0.005 (3)
C15	0.025 (3)	0.023 (3)	0.024 (4)	−0.004 (3)	0.007 (3)	0.003 (3)
C16	0.029 (3)	0.022 (3)	0.028 (5)	0.003 (3)	0.007 (3)	0.009 (3)

Geometric parameters (Å, º)

O1—C2	1.377 (8)	C5—C10	1.426 (9)
O1—C9	1.393 (8)	C6—C7	1.438 (11)
O2—C4	1.260 (8)	C6—H6A	0.95
O3—C5	1.354 (8)	C7—C8	1.372 (10)
O3—H3	0.84	C8—C9	1.356 (10)
O4—C7	1.349 (8)	C8—H8	0.95
O4—H4	0.84	C9—C10	1.408 (10)
O5—C14	1.367 (7)	C11—C12	1.384 (10)
O5—H5	0.84	C11—C16	1.417 (10)
O6—C13	1.375 (8)	C12—C13	1.394 (9)
O6—H6	0.84	C12—H12	0.95
C2—C3	1.361 (10)	C13—C14	1.385 (9)
C2—C11	1.457 (9)	C14—C15	1.380 (10)
C3—C4	1.432 (9)	C15—C16	1.391 (9)
C3—H3A	0.95	C15—H15	0.95
C4—C10	1.428 (10)	C16—H16	0.95
C5—C6	1.358 (10)
C2—O1—C9	120.3 (5)	C7—C8—H8	120.7
C5—O3—H3	109.5	C8—C9—O1	116.4 (7)
C7—O4—H4	109.5	C8—C9—C10	124.1 (7)
C14—O5—H5	109.5	O1—C9—C10	119.4 (6)
C13—O6—H6	109.5	C9—C10—C5	116.3 (6)
C3—C2—O1	121.5 (6)	C9—C10—C4	120.8 (6)
C3—C2—C11	127.4 (6)	C5—C10—C4	122.8 (7)
O1—C2—C11	111.1 (6)	C12—C11—C16	119.3 (6)
C2—C3—C4	121.2 (6)	C12—C11—C2	120.6 (6)
C2—C3—H3A	119.4	C16—C11—C2	120.1 (6)
C4—C3—H3A	119.4	C11—C12—C13	119.8 (7)
O2—C4—C10	122.7 (6)	C11—C12—H12	120.1
O2—C4—C3	120.6 (6)	C13—C12—H12	120.1
C10—C4—C3	116.6 (6)	O6—C13—C14	116.8 (6)
O3—C5—C6	120.1 (6)	O6—C13—C12	122.4 (7)
O3—C5—C10	119.2 (6)	C14—C13—C12	120.7 (7)
C6—C5—C10	120.7 (7)	O5—C14—C15	124.1 (6)
C5—C6—C7	120.0 (7)	O5—C14—C13	115.6 (6)
C5—C6—H6A	120	C15—C14—C13	120.1 (6)
C7—C6—H6A	120	C14—C15—C16	120.0 (6)
O4—C7—C8	121.0 (7)	C14—C15—H15	120
O4—C7—C6	118.9 (6)	C16—C15—H15	120
C8—C7—C6	120.1 (7)	C15—C16—C11	120.1 (7)
C9—C8—C7	118.7 (7)	C15—C16—H16	120
C9—C8—H8	120.7	C11—C16—H16	120
C9—O1—C2—C3	−0.3 (9)	C6—C5—C10—C4	178.8 (7)
C9—O1—C2—C11	179.9 (6)	O2—C4—C10—C9	178.6 (7)
O1—C2—C3—C4	−1.9 (10)	C3—C4—C10—C9	−0.5 (10)
C11—C2—C3—C4	177.8 (6)	O2—C4—C10—C5	0.1 (11)
C2—C3—C4—O2	−176.9 (6)	C3—C4—C10—C5	−179.0 (7)
C2—C3—C4—C10	2.2 (10)	C3—C2—C11—C12	−179.6 (7)
O3—C5—C6—C7	179.8 (6)	O1—C2—C11—C12	0.2 (8)
C10—C5—C6—C7	0.5 (11)	C3—C2—C11—C16	1.6 (10)
C5—C6—C7—O4	177.5 (7)	O1—C2—C11—C16	−178.6 (6)
C5—C6—C7—C8	0.9 (11)	C16—C11—C12—C13	−1.1 (10)
O4—C7—C8—C9	−179.4 (7)	C2—C11—C12—C13	−179.9 (7)
C6—C7—C8—C9	−3.0 (11)	C11—C12—C13—O6	178.2 (6)
C7—C8—C9—O1	−175.6 (7)	C11—C12—C13—C14	1.7 (10)
C7—C8—C9—C10	3.8 (11)	O6—C13—C14—O5	4.7 (9)
C2—O1—C9—C8	−178.5 (6)	C12—C13—C14—O5	−178.6 (6)
C2—O1—C9—C10	2.1 (9)	O6—C13—C14—C15	−178.7 (6)
C8—C9—C10—C5	−2.4 (10)	C12—C13—C14—C15	−2.0 (10)
O1—C9—C10—C5	177.0 (7)	O5—C14—C15—C16	178.0 (7)
C8—C9—C10—C4	179.0 (7)	C13—C14—C15—C16	1.7 (10)
O1—C9—C10—C4	−1.6 (10)	C14—C15—C16—C11	−1.2 (10)
O3—C5—C10—C9	−179.2 (6)	C12—C11—C16—C15	0.9 (10)
C6—C5—C10—C9	0.2 (10)	C2—C11—C16—C15	179.7 (6)
O3—C5—C10—C4	−0.6 (10)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O2	0.84	2.00	2.614 (7)	130
O5—H5···O5^i	0.84	2.26	2.955 (7)	141
O5—H5···O6^i	0.84	2.19	2.862 (7)	137
O6—H6···O2^ii	0.84	1.84	2.658 (7)	165
C3—H3A···O6^iii	0.95	2.46	3.159 (9)	130

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