Hydrogen bonding and π–π stacking in 6-hydroxy­biochanin A monohydrate

In the lattice of the title compound (systematic name: 5,6,7-trihydroxy-4′-meth­oxy­isoflavone monohydrate), C₁₆H₁₂O₆·H₂O, the isoflavone mol­ecules are linked into chains through R₄³(17) motifs composed via O—H...O and C—H...O hydrogen bonds. Centrosymmetric R₄²(14) motifs assemble the chains into sheets. Hydrogen-bonding and aromatic π–π stacking inter­actions lead to the formation of a three-dimensional network structure.

S1. Comment

Irisolidone (5,7-dihydroxy-6,4'-dimethoxyisoflavone), a kind of isoflavonoid, as one of the effective components in the flowers of Pueraia lobata, possesses potential inhibitory activity against Helicobacter pylori (HP), which is a risk factor for gastric cancer (Kim et al., 1998; Bae et al., 2001). Furthermore, various animal studies have indicated that irisolidone greatly reduces ethanol-induced mortality, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Both pre- and post-treatment with irisolidone have been found to reduce blood ethanol levels (Han et al., 2003; Yamazaki et al., 1997; Yamazaki et al., 2002). In this paper, using irisolidone as a starting compound, 6-hydroxybiochanin A (4'-methoxy-5,6,7-trihydroxyisoflavone), (II), was synthesized by demethylation. It has been reported that (II) was isolated from Serratula strangulata (Dai et al., 2001).

Klus & Barz (1998) found that tempe-derived bacterial strains identified as Micrococcus or Arthrobacter species were shown to transform biochanin A to (II) by a hydroxylation reaction at position C6. Additionally, compound (II) is one of the main extrahepatic metabolism constituents of biochanin A through recombinant human CYP1A1 or CYP1B1 (Roberts et al., 2004). Compound (II) has potential medical applications and we report here the crystal structure of 6-hydroxybiochanin A monohydrate, (I).

Compound (I) is composed of a benzopyranone moiety, a phenyl moiety, three hydroxyl groups, a methoxy group and a solvent water molecule (Fig. 1). The geometry of the bond lengths and angles of the isoflavone skeleton of (I) is similar to those in both 7-methoxy-4'-hydroxyisoflavone and 4',7-diethoxyl-5-hydroxyisoflavone (Zhang & Wang, 2005) and in 5-hydroxy-7,4'-dimethoxyisoflavone (Zhang et al., 2005). The atoms of the benzopyranone moiety including ring A (C1–C6) and ring C (O4/C5–C9) are nearly coplanar, the dihedral angle between the rings being 2.6 (1)°. To avoid steric conflicts, the two rigid ring systems, phenyl ring B (C10–C15) and the benzopyranone moiety, are rotated by 44.2 (1)° with respect to each other. The methoxy group at C13 is nearly coplanar with its attached ring B, as revealed by the C16—O6—C13—C12 torsion angle of 5.2 (4)°. Furthermore, an independent O1—H1···O5 intramolecular hydrogen bond forms a characteristic intramolecular S(6) motif (Bernstein et al., 1995).

As shown in Fig. 2, an R₄³(17) motif is determined by atoms O5, O6ⁱⁱ [symmetry code: (ii) 1/2 + x,1/2 − y, −1/2 + z] and O7, including C—H···O (entry 6 in Table 1) and O—H···O (entries 2 and 4 in Table 1) hydrogen bonds. These R₄³(17) motifs are generated via C—H···O and O—H···O hydrogen bonds and link the isoflavone molecules into chains. In addition, a centrosymmetric R₄²(14) motif is defined by paired O2—H2···O7 and O3—H3···O7ⁱⁱⁱ interactions [symmetry code: (iii) 1 − x, −y, 1 − z; entries 4 and 5 in Table 1]. Atom O7 interacts with atoms H2 and H3ⁱⁱⁱ to form a three-centred hydrogen bond. The isoflavone skeletons of (I) are assembled into (101) sheets via the R₄³(17)and R₄²(14) motifs. The solvent water molecules are involved in the formation of four O—H···O hydrogen bonds (entries 1, 2, 4 and 5 in Table 1).

The isoflavone skeletons of (I) are arranged in a parallel fashion and π–π stacking interactions exist between them (Fig. 3). Ring A of the isoflavone skeleton stacks with those of neighbouring isoflavone skeletons, with CgA···CgA^v = CgA···CgA^vi = 3.773 (2) Å, where CgA is the centroid of ring A [symmetry codes: (v) −1 + x, y, z; (vi) 1 + x, y, z], as do rings B and C. The offset distances of rings A and A^v, rings B and B^v, and rings C and C^v are 1.438, 1.424 and 1.430 Å, respectively. The centriod-to-centroid distances lie in the normal range of 3.3–3.8 Å (Janiak, 2000), indicative of π–π stacking interactions. These π–π stacking interactions result in the isoflavone skeletons forming columns along the a axis. These columns propagate via paired O2—H2···O7 and O7—H7A···O2ⁱ [symmetry code: (i) 2 − x, −y, 1 − z] hydrogen bonds (entries 1 and 4 in Table 1), which form centrosymmetric R₄⁴(8) motifs (Fig. 3). Hydrogen-bonding and aromatic π–π stacking interactions play a key role in the assembly of the three-dimensional network structure.

S2. Experimental

Irisolidone (1.0 g, 3.185 mmol) and anhydrous pyridine (15 ml) were placed into a 50 ml flask and dissolved by stirring at 313 K. Anhydrous aluminium chloride (3.0 g, 22.472 mmol) was added to the solution in three batches in order to control the reaction temperature. The mixture was stirred for 8 h at 353 K and excess pyridine was removed by a rotary evaporator under reduced-pressure distillation. The residue was cooled, hydrolyzed with 5% hydrochloric acid solution and extracted with ethyl acetate. The ethyl acetate layer was washed with water until the pH was 7 and finally dried overnight over anhydrous sodium sulfate. Evaporation of ethyl acetate gave 6-hydroxybiochanin A (0.85 g, yield 88.5%) as a pale-yellow powder. It was purified by 50% alcohol [Which alcohol? Mixed with which solvent?] and re-crystallized from 95% alcohol to give pale-yellow needles of (I) (m.p. 532 K). [Source of water to form monohydrate?]

S3. Refinement

Water H atoms were located in a difference Fourier map and refined with O—H restrained to 0.85 (1) Å, with U_iso(H) = 1.5U_eq(O). Phenol hydroxyl H atoms were placed in calculated positions, with O—H = ?.?? Å [Please complete], and refined using a riding model, with U_iso(H) = 1.5U_eq(O). H atoms bonded to C atoms were placed in calculated positions, with C—H = 0.93 and 0.96 Å, and refined as riding, allowing for free rotation of the rigid methyl groups; U_iso(H) = 1.2U_eq(C) or 1.5U_eq(C_methyl).

Computing details

Data collection: SMART (Bruker, 1999); cell refinement: SMART; data reduction: SMART; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997a); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997a); molecular graphics: SHELXTL (Sheldrick, 1997b); software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. A view of the molecule of (I), showing the atom-numbering scheme and with 50% probability displacement ellipsoids. Thin dashed lines represent the intramolecular hydrogen bond.
	Fig. 2. Part of the crystal structure of (I), showing the formation of the (101) sheets via the R4^3(17) and R4^2(14) motifs. For clarity, some H atoms have been omitted. Thin dashed lines indicate the hydrogen-bonding interactions. (See Table 1 for symmetry codes.)
	Fig. 3. Part of the crystal structure of (I), showing some of the hydrogen-bonding and π–π stacking interactions and the R4^4(8) motif. For clarity, some H atoms have been omitted. Thin dashed lines indicate the hydrogen bonding and π–π stacking interactions. CgA, CgB and CgC are the centroids of rings A, B and C, respectively, as defined in Fig. 1. [See Table 1 for symmetry codes. Additionally, (v) −1 + x, y, z; (vi) 1 + x, y, z.]

4'-methoxy-5,6,7-trihydroxyisoflavone monohydrate

Crystal data

C16H12O6·H2O	F(000) = 664
Mr = 318.27	Dx = 1.549 Mg m^−3
Monoclinic, P21/n	Melting point: 532 K
Hall symbol: -P 2yn	Mo Kα radiation, λ = 0.71073 Å
a = 3.7734 (5) Å	Cell parameters from 2432 reflections
b = 30.030 (4) Å	θ = 1.8–25.1°
c = 12.0750 (16) Å	µ = 0.12 mm^−1
β = 93.894 (2)°	T = 296 K
V = 1365.1 (3) Å^3	Needle, yellow
Z = 4	0.20 × 0.18 × 0.12 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2432 independent reflections
Radiation source: fine-focus sealed tube	1460 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.046
ϕ and ω scans	θmax = 25.1°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −4→4
Tmin = 0.976, Tmax = 0.985	k = −35→31
6841 measured reflections	l = −14→11

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.046	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.122	w = 1/[σ^2(Fo^2) + (0.0493P)^2 + ] where P = (Fo^2 + 2Fc^2)/3
S = 1.09	(Δ/σ)max < 0.001
2422 reflections	Δρmax = 0.22 e Å^−3
219 parameters	Δρmin = −0.19 e Å^−3
2 restraints	Extinction correction: SHELXL97 (Sheldrick, 1997a), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0077 (16)

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
O1	0.8274 (5)	0.12824 (6)	0.50834 (14)	0.0453 (5)
H1	0.8538	0.1549	0.4970	0.068*
O2	0.6803 (6)	0.04315 (6)	0.57556 (16)	0.0569 (6)
H2	0.7392	0.0516	0.5149	0.085*
O3	0.4547 (7)	0.02950 (6)	0.78304 (16)	0.0611 (6)
H3	0.4008	0.0136	0.7293	0.092*
O4	0.4684 (5)	0.18214 (6)	0.85916 (14)	0.0440 (5)
O5	0.8158 (5)	0.21336 (6)	0.55423 (14)	0.0458 (5)
O6	0.6437 (5)	0.42496 (6)	0.67724 (15)	0.0517 (6)
O7	0.8753 (7)	0.03205 (7)	0.36564 (18)	0.0628 (7)
H7A	1.051 (7)	0.0145 (10)	0.380 (3)	0.094*
H7B	0.964 (9)	0.0490 (9)	0.317 (2)	0.094*
C1	0.7066 (7)	0.12230 (8)	0.6103 (2)	0.0347 (6)
C2	0.6371 (7)	0.07958 (9)	0.6430 (2)	0.0392 (7)
C3	0.5180 (7)	0.07144 (9)	0.7481 (2)	0.0399 (7)
C4	0.4705 (7)	0.10630 (9)	0.8203 (2)	0.0415 (7)
H4	0.3975	0.1010	0.8911	0.050*
C5	0.5330 (7)	0.14883 (9)	0.7856 (2)	0.0364 (7)
C6	0.6508 (6)	0.15870 (8)	0.68090 (19)	0.0324 (6)
C7	0.7028 (7)	0.20437 (9)	0.6472 (2)	0.0356 (6)
C8	0.6242 (7)	0.23834 (8)	0.7286 (2)	0.0347 (6)
C9	0.5126 (7)	0.22463 (9)	0.8269 (2)	0.0410 (7)
H9	0.4611	0.2467	0.8774	0.049*
C10	0.6519 (7)	0.28656 (8)	0.7082 (2)	0.0361 (7)
C11	0.5154 (7)	0.30598 (9)	0.6098 (2)	0.0409 (7)
H11	0.4261	0.2878	0.5522	0.049*
C12	0.5091 (7)	0.35177 (9)	0.5955 (2)	0.0408 (7)
H12	0.4152	0.3641	0.5291	0.049*
C13	0.6432 (7)	0.37889 (8)	0.6803 (2)	0.0392 (7)
C14	0.7894 (7)	0.36043 (9)	0.7776 (2)	0.0419 (7)
H14	0.8857	0.3787	0.8340	0.050*
C15	0.7927 (7)	0.31499 (9)	0.7911 (2)	0.0415 (7)
H15	0.8913	0.3029	0.8572	0.050*
C16	0.4691 (9)	0.44675 (9)	0.5838 (2)	0.0560 (9)
H16A	0.5889	0.4398	0.5183	0.084*
H16B	0.4737	0.4784	0.5956	0.084*
H16C	0.2272	0.4368	0.5745	0.084*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0650 (14)	0.0381 (11)	0.0346 (11)	−0.0019 (11)	0.0154 (9)	0.0027 (9)
O2	0.0906 (17)	0.0372 (12)	0.0448 (13)	−0.0021 (11)	0.0179 (12)	0.0004 (9)
O3	0.0935 (18)	0.0405 (13)	0.0508 (13)	−0.0130 (12)	0.0174 (13)	0.0067 (10)
O4	0.0593 (13)	0.0404 (12)	0.0335 (11)	−0.0023 (9)	0.0127 (9)	0.0011 (9)
O5	0.0640 (14)	0.0410 (12)	0.0339 (11)	−0.0023 (9)	0.0148 (10)	0.0044 (9)
O6	0.0724 (15)	0.0349 (12)	0.0479 (12)	0.0019 (10)	0.0053 (11)	−0.0016 (10)
O7	0.093 (2)	0.0443 (14)	0.0528 (15)	0.0029 (12)	0.0210 (13)	0.0089 (11)
C1	0.0375 (16)	0.0404 (17)	0.0264 (14)	0.0009 (12)	0.0052 (12)	0.0034 (12)
C2	0.0485 (18)	0.0320 (15)	0.0369 (16)	−0.0011 (13)	0.0021 (13)	−0.0011 (13)
C3	0.0479 (18)	0.0344 (17)	0.0378 (16)	−0.0053 (13)	0.0056 (13)	0.0084 (13)
C4	0.0520 (18)	0.0415 (17)	0.0317 (15)	−0.0034 (13)	0.0084 (13)	0.0056 (13)
C5	0.0397 (16)	0.0387 (16)	0.0310 (15)	0.0010 (13)	0.0037 (12)	−0.0012 (13)
C6	0.0332 (15)	0.0356 (15)	0.0285 (14)	0.0027 (12)	0.0034 (12)	0.0021 (12)
C7	0.0356 (16)	0.0378 (16)	0.0332 (16)	0.0004 (12)	0.0001 (12)	0.0038 (12)
C8	0.0378 (16)	0.0357 (16)	0.0303 (15)	0.0020 (12)	0.0012 (12)	−0.0030 (12)
C9	0.0461 (17)	0.0405 (18)	0.0366 (16)	0.0016 (13)	0.0051 (13)	−0.0044 (13)
C10	0.0355 (16)	0.0385 (16)	0.0346 (15)	0.0019 (12)	0.0054 (12)	−0.0016 (13)
C11	0.0467 (18)	0.0389 (17)	0.0370 (16)	−0.0013 (13)	0.0023 (13)	−0.0048 (13)
C12	0.0473 (18)	0.0411 (17)	0.0340 (16)	0.0024 (13)	0.0018 (13)	0.0010 (13)
C13	0.0413 (17)	0.0337 (17)	0.0434 (17)	0.0017 (12)	0.0080 (14)	−0.0009 (13)
C14	0.0424 (17)	0.0422 (18)	0.0404 (17)	−0.0010 (13)	−0.0011 (13)	−0.0083 (13)
C15	0.0451 (18)	0.0432 (18)	0.0355 (16)	0.0044 (13)	−0.0014 (13)	−0.0020 (13)
C16	0.071 (2)	0.0419 (18)	0.056 (2)	0.0157 (16)	0.0116 (17)	0.0069 (15)

Geometric parameters (Å, º)

O1—C1	1.354 (3)	C5—C6	1.400 (3)
O1—H1	0.8200	C6—C7	1.448 (3)
O2—C2	1.380 (3)	C7—C8	1.461 (3)
O2—H2	0.8200	C8—C9	1.351 (3)
O3—C3	1.355 (3)	C8—C10	1.474 (3)
O3—H3	0.8200	C9—H9	0.9300
O4—C9	1.348 (3)	C10—C11	1.391 (4)
O4—C5	1.370 (3)	C10—C15	1.393 (3)
O5—C7	1.257 (3)	C11—C12	1.386 (3)
O6—C13	1.384 (3)	C11—H11	0.9300
O6—C16	1.426 (3)	C12—C13	1.377 (3)
O7—H7A	0.86 (3)	C12—H12	0.9300
O7—H7B	0.86 (3)	C13—C14	1.380 (3)
C1—C2	1.373 (3)	C14—C15	1.374 (3)
C1—C6	1.411 (3)	C14—H14	0.9300
C2—C3	1.396 (3)	C15—H15	0.9300
C3—C4	1.382 (3)	C16—H16A	0.9600
C4—C5	1.369 (3)	C16—H16B	0.9600
C4—H4	0.9300	C16—H16C	0.9600
C1—O1—H1	109.5	C7—C8—C10	123.6 (2)
C2—O2—H2	109.5	O4—C9—C8	126.5 (2)
C3—O3—H3	109.5	O4—C9—H9	116.8
C9—O4—C5	118.2 (2)	C8—C9—H9	116.8
C13—O6—C16	118.6 (2)	C11—C10—C15	117.3 (2)
H7A—O7—H7B	100 (3)	C11—C10—C8	121.9 (2)
O1—C1—C2	117.9 (2)	C15—C10—C8	120.7 (2)
O1—C1—C6	121.4 (2)	C12—C11—C10	121.7 (2)
C2—C1—C6	120.7 (2)	C12—C11—H11	119.2
C1—C2—O2	122.6 (2)	C10—C11—H11	119.2
C1—C2—C3	120.3 (2)	C13—C12—C11	119.4 (3)
O2—C2—C3	117.1 (2)	C13—C12—H12	120.3
O3—C3—C4	118.3 (2)	C11—C12—H12	120.3
O3—C3—C2	121.4 (2)	C12—C13—C14	120.1 (3)
C4—C3—C2	120.3 (2)	C12—C13—O6	124.9 (2)
C5—C4—C3	118.8 (2)	C14—C13—O6	115.0 (2)
C5—C4—H4	120.6	C15—C14—C13	120.0 (3)
C3—C4—H4	120.6	C15—C14—H14	120.0
C4—C5—O4	116.2 (2)	C13—C14—H14	120.0
C4—C5—C6	123.0 (2)	C14—C15—C10	121.5 (3)
O4—C5—C6	120.8 (2)	C14—C15—H15	119.2
C5—C6—C1	116.8 (2)	C10—C15—H15	119.2
C5—C6—C7	120.8 (2)	O6—C16—H16A	109.5
C1—C6—C7	122.4 (2)	O6—C16—H16B	109.5
O5—C7—C6	121.0 (2)	H16A—C16—H16B	109.5
O5—C7—C8	123.2 (2)	O6—C16—H16C	109.5
C6—C7—C8	115.7 (2)	H16A—C16—H16C	109.5
C9—C8—C7	117.9 (2)	H16B—C16—H16C	109.5
C9—C8—C10	118.4 (2)
O1—C1—C2—O2	−1.1 (4)	C1—C6—C7—C8	178.3 (2)
C6—C1—C2—O2	178.5 (2)	O5—C7—C8—C9	−178.4 (2)
O1—C1—C2—C3	178.9 (2)	C6—C7—C8—C9	0.2 (3)
C6—C1—C2—C3	−1.6 (4)	O5—C7—C8—C10	3.2 (4)
C1—C2—C3—O3	−178.6 (2)	C6—C7—C8—C10	−178.3 (2)
O2—C2—C3—O3	1.3 (4)	C5—O4—C9—C8	−1.7 (4)
C1—C2—C3—C4	−0.3 (4)	C7—C8—C9—O4	0.7 (4)
O2—C2—C3—C4	179.7 (2)	C10—C8—C9—O4	179.3 (2)
O3—C3—C4—C5	−179.8 (2)	C9—C8—C10—C11	−132.9 (3)
C2—C3—C4—C5	1.8 (4)	C7—C8—C10—C11	45.6 (4)
C3—C4—C5—O4	177.6 (2)	C9—C8—C10—C15	42.1 (4)
C3—C4—C5—C6	−1.5 (4)	C7—C8—C10—C15	−139.4 (3)
C9—O4—C5—C4	−177.4 (2)	C15—C10—C11—C12	−1.9 (4)
C9—O4—C5—C6	1.7 (3)	C8—C10—C11—C12	173.3 (2)
C4—C5—C6—C1	−0.3 (4)	C10—C11—C12—C13	0.4 (4)
O4—C5—C6—C1	−179.3 (2)	C11—C12—C13—C14	1.4 (4)
C4—C5—C6—C7	178.2 (2)	C11—C12—C13—O6	−178.2 (2)
O4—C5—C6—C7	−0.8 (4)	C16—O6—C13—C12	5.2 (4)
O1—C1—C6—C5	−178.6 (2)	C16—O6—C13—C14	−174.5 (2)
C2—C1—C6—C5	1.9 (4)	C12—C13—C14—C15	−1.7 (4)
O1—C1—C6—C7	2.9 (4)	O6—C13—C14—C15	177.9 (2)
C2—C1—C6—C7	−176.6 (2)	C13—C14—C15—C10	0.2 (4)
C5—C6—C7—O5	178.5 (2)	C11—C10—C15—C14	1.6 (4)
C1—C6—C7—O5	−3.1 (4)	C8—C10—C15—C14	−173.6 (2)
C5—C6—C7—C8	−0.1 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O7—H7A···O2^i	0.86 (3)	2.06 (2)	2.874 (3)	160 (3)
O7—H7B···O6^ii	0.86 (3)	2.02 (3)	2.861 (3)	166 (3)
O1—H1···O5	0.82	1.90	2.616 (3)	146
O2—H2···O7	0.82	1.99	2.706 (3)	145
O3—H3···O7^iii	0.82	2.03	2.810 (3)	160 (3)
C9—H9···O5^iv	0.93	2.54	3.439 (3)	163

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