Hydrogen bonding and π-π stacking in dimethylgenistein

Article abstract of DOI:10.1107/S0108270104009758

The title compound, 5-hydroxy-4′,7-dimethoxyisoflavone, Q ₁₇H₁₄O₅, is composed of a benzopyranone moiety, a phenyl moiety and two methoxy groups. The benzopyranone ring is not coplanar with the phenyl ring, the dihedral an

Full text of DOI:10.1107/S0108270104009758

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
effective in inhibiting cardiovascular disease (Hwang et al.,
2001), tyrosine kinases (Nevala et al., 2002) and cancer cell
growth (Yuan et al., 2003; W. F. Chen et al., 2003), and in
accelerating the formation of bone cells (X. W. Chen et al.,
2003). The title compound, namely 5-hydroxy-40,7-di-
methoxyiso¯avone, (I), is a derivative of genistein and has
potential medical applications. We report here the crystal
structure of (I).
ISSN 0108-2701
Hydrogen bonding and p±p stacking in
dimethylgenistein
The title compound is composed of a benzopyranone
moiety, a phenyl moiety and two methoxy groups (Fig. 1). The
geometry of the iso¯avone skeleton of (I) is similar to that of
its analogue dalspinin (Lakshmi, et al., 1996) with respect to
most of the bond distances and angles. The atoms of the
benzopyranone moiety, composed of rings A (C1±C6) and C
(O1/C1/C6±C9), are almost coplanar, the dihedral angle
between the rings being 1.37 (8)ꢀ. To avoid steric con¯icts, the
two rigid ring systems, viz. benzene ring B (C10±C15) and the
benzopyranone moiety, are rotated by 56.28 (3)ꢀ with respect
to one another. The methoxy group at atom C3 is nearly
coplanar with ring A, as indicated by the C16ÐO4ÐC3ÐC2
torsion angle [2.9 (2)ꢀ]; the methoxy group at atom C13 is also
coplanar with the attached ring, the C17ÐO5ÐC13ÐC12
torsion angle being 5.9 (2)ꢀ.
Fig. 2 shows how a cyclic dimer is formed through a
supramolecular synthon, R22(8). Methoxy atom O4 acts as a
hydrogen-bond acceptor, via atom H4, to atom C4 of ring A.
In this manner, a centrosymmetric R22(8) ring is formed.
Hydroxy atoms O2 from the two molecules linked by the R22(8)
ring act as hydrogen-bond acceptors, via atoms H14, to atoms
C14 of rings B in adjacent molecules. The combination of the
C14ÐH14Á Á ÁO2 interaction and the R22(8) supramolecular
synthon generates a (101) sheet, which includes two A, two B
and two C rings from four molecules, and these six rings are
almost coplanar; furthermore, these dimers are also linked
into (100) chains by C11ÐH11Á Á ÁO3 interactions (Fig. 3). The
combination of the (101) sheets and the (100) chains generates
a three-dimensional framework. An independent O2Ð
H2OÁ Á ÁO3 intramolecular hydrogen bonds generates a char-
acteristic intramolecular S(6) motif. Details of the hydrogen
bonding are given in Table 1.
Zun-Ting Zhang,a* Xiao-Bing Wang,a Qian-Guang Liu,a
Jian-Bin Zhengb and Kai-Bai Yuc
aOrganoanalysis Research Laboratory, School of Chemistry and Materials Science,
Shaanxi Normal University, Xi'an 710062, People's Republic of China, bInstitute of
Electroanalitical Chemistry, Northwest University, Xi'an 710069, People's Republic
of China, and cAnalytical Centre, Chengdu Branch of Chinese Academy of Sciences,
Chengdu 610041, People's Republic of China
Correspondence e-mail: zhangzunting@sina.com
Received 25 February 2004
Accepted 21 April 2004
Online 11 December 2004
The title compound, 5-hydroxy-40,7-dimethoxyiso¯avone,
C17H14O5, is composed of a benzopyranone moiety, a phenyl
moiety and two methoxy groups. The benzopyranone ring is
not coplanar with the phenyl ring, the dihedral angle between
them being 56.28 (3)ꢀ. The two methoxy groups are nearly
coplanar with their corresponding rings, having CÐCÐOÐC
torsion angles of 2.9 (2) and 5.9 (2)ꢀ. The molecules are linked
by CÐHÁ Á ÁO hydrogen bonds into sheets containing classical
centrosymmetric R22(8) rings. The sheets are further linked by
aromatic ꢀ±ꢀ stacking interactions and CÐHÁ Á ÁO hydrogen
bonds into a supramolecular structure.
Comment
Hydrogen bonds and ꢀ±ꢀ stacking interactions are an
important research area in supramolecular chemistry and
crystal engineering (MacDonald & Whitesides, 1994). These
interactions play an important role in self-assembly and
recognition of aromatic compounds (Janiak, 2000; Hunter &
Sanders, 1990) as auxiliary stabilizing short contacts (William
et al., 1999; Luque et al., 2001; Kaafarani et al., 2001). In
biomacromolecular systems, stacking interactions and
hydrogen bonds are important for the double-helical DNA
structure (Hunter, 1993); they can direct the intercalation of
drugs into DNA (Wang et al., 1984) and they contribute to the
stability of the tertiary structure of proteins (Burley & Petsko,
1985).
Intermolecular stacking via aromatic ꢀ±ꢀ interactions is
also present (Fig. 3), the two molecules being offset by partial
overlap of rings B (ꢀ rich) and C (ꢀ de®cient). Ring B of one
Figure 1
Genistein, a natural soy iso¯avone, has potential phytoes-
trogen (Hua et al., 2003; Warren, 2002) and antioxidant
activities (Ian et al., 1995). Studies have also found genistein
A view of the molecule of (I), showing the atom-numbering scheme and
50% probability displacement ellipsoids. H atoms are shown as spheres of
arbitrary radii.
Acta Cryst. (2005). C61, o29±o31
DOI: 10.1107/S0108270104009758
# 2005 International Union of Crystallography o29

organic compounds
Figure 2
Part of the crystal structure of (I), showing the formation of the (101) sheets via hydrogen bonds. Atoms marked with an asterisk (*), hash (#) or
1
2
1
2
ampersand (&) are at the symmetry positions (1 x, 1 y, 1 z), (x
have been omitted.
,
y, z 12 ) and (23 x, 21 + y, 32 z), respectively. For clarity, some H atoms
mixture was stirred for 4 h at room temperature and a colourless
precipitate began to appear. The precipitate was ®ltered off and
washed with water until the pH of the ®ltrate was 8. After recrys-
tallization from ethyl acetate, the product had a melting point of
428 K. Crystals of (I) suitable for X-ray analysis were obtained by
slow evaporation from ethyl acetate after 7 d at room temperature.
Crystal data
3
C17H14O5
Mr = 298.28
Dx = 1.441 Mg m
Mo Kꢂ radiation
Cell parameters from 34
re¯ections
Monoclinic, P21=n
Ê
a = 5.7754 (8) A
ꢃ = 2.7±15.9ꢀ
ꢄ = 0.11 mm
T = 296 (2) K
Ê
b = 7.9446 (12) A
1
Ê
c = 30.044 (5) A
ꢁ = 93.807 (12)ꢀ
3
Ê
V = 1375.4 (4) A
Z = 4
Prism, colourless
0.58 Â 0.54 Â 0.50 mm
Data collection
Siemens P4 diffractometer
! scans
h = Ð6 ! 6
k = 0 ! 9
3089 measured re¯ections
2485 independent re¯ections
1673 re¯ections with I > 2ꢅ(I)
Rint = 0.010
l = 36 ! 36
3 standard re¯ections
every 97 re¯ections
intensity decay: 0.4%
ꢃ
max = 25.3ꢀ
Figure 3
Re®nement
Part of the crystal structure of (I), showing the formation of the (100)
chains via hydrogen bonds and ꢀ±ꢀ stacking interactions. Labels Cg
represent the centroids of rings A and C. Atoms marked with an asterisk
(*), hash (#) or ampersand (&) are at the symmetry positions (1 x, y, z),
Re®nement on F2
R[F2 > 2ꢅ(F2)] = 0.035
wR(F2) = 0.087
S = 0.90
2485 re¯ections
w = 1/[ꢅ2(F2o) + (0.0522P)2]
where P = (F2o + 2Fc2)/3
(Á/ꢅ)max = 0.001
3
Ê
Áꢆmax = 0.19 e A
1
3
(
atoms have been omitted.
x, 12 + y,
z) and (1 + x, y, z), respectively. For clarity, some H
3
Ê
0.15 e A
2
2
Áꢆmin
Extinction correction: SHELXL97
=
203 parameters
H-atom parameters constrained
Extinction coef®cient: 0.0233 (18)
molecule and ring C of a neighbouring molecule are almost
parallel, with a dihedral angle between them of 8.02 (7)ꢀ. The
perpendicular plane-to-plane distance between the rings is
Table 1
Hydrogen-bonding geometry (A, ).
ꢀ
Ê
Ê
Ê
3.311 A, and the corresponding CgÁ Á ÁCg# distance is 3.693 A
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
[Cg represents the centroids of rings A and C; symmetry code:
1
O2ÐH2OÁ Á ÁO3
C4ÐH4Á Á ÁO4i
0.82
0.93
0.93
0.93
1.86
2.54
2.56
2.58
2.590 (2)
3.459 (2)
3.464 (2)
3.399 (2)
148
171
164
147
3
(#)
x, 12 + y,
z], indicating that a strong ꢀ±ꢀ stacking
2
2
C11ÐH11Á Á ÁO3ii
C14ÐH14Á Á ÁO2iii
interaction exists in the title compound. Hydrogen bonds and
aromatic ꢀ±ꢀ stacking interactions play a key role in assem-
bling the supramolecular structure.
3
2
1 3
Symmetry codes: (i) 1 x; 1 y; 1 z; (ii) x 1; y; z; (iii)
x; y
;
2 2
z.
Experimental
H atoms were placed at calculated positions and treated as riding,
Ê
with CÐH distances in the range 0.93±0.96 A and Uiso(H) values of
1.2Ueq of the attached C atom [1.5Ueq(C) for methyl H atoms].
Genistein (1.0 g) was dissolved in Na2CO3 (20 ml, 5%) and dimethyl
sulfate (0.5 ml) was added dropwise to the solution with stirring. The
ꢁ
o30 Zun-Ting Zhang et al.
C17H14O5
Acta Cryst. (2005). C61, o29±o31

organic compounds
Hwang, J. L., Hodis, H. N. & Sevanian, A. (2001). J. Agric. Food Chem. 49,
308±314.
Ian, R. R., Ivor, D. E. & Jennifer, K. M. (1995). J. Nutr. Biochem. 6, 481±485.
Janiak, C. (2000). J. Chem. Soc. Dalton Trans. pp. 3885±3896.
Kaafarani, B. R., Pinkerton, A. A. & Neckers, D. C. (2001). Tetrahedron Lett.
42, 8137±8139.
Data collection: XSCANS (Siemens, 1996); cell re®nement:
XSCANS; data reduction: SHELXTL (Siemens, 1997); program(s)
used to solve structure: SHELXS97 (Sheldrick, 1990); program(s)
used to re®ne structure: SHELXL97 (Sheldrick, 1997); molecular
graphics: SHELXTL; software used to prepare material for publi-
cation: SHELXTL.
Lakshmi, S., Kumar, S., Senthilselvan, J. & Subramanian, K. (1996). Acta Cryst.
C52, 2873±2875.
Luque, A., Sertucha, J., Castillo, O. & Roman, P. (2001). New J. Chem.
pp. 1208±1214.
MacDonald, J. C. & Whitesides, G. M. (1994). Chem. Rev. 94, 2383±2420.
Nevala, R., Lassila, M., Finckenberg, P., Paukku, K., Korpela, R. & Vapaatalo,
H. (2002). Eur. J. Pharmacol. 452, 87±96.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: FR1473). Services for accessing these data are
described at the back of the journal.
Sheldrick, G. M. (1990). Acta Cryst. A46, 467±473.
Sheldrick, G. M. (1997). SHELXL97. University of Gottingen, Germany.
È
Siemens (1996). XSCANS. Version 2.21. Siemens Analytical X-ray Instru-
ments Inc., Madison, Wisconsin, USA.
References
Burley, S. K. & Petsko, G. A. (1985). Science, 229, 23±28.
Chen, W. F., Huang, M. H., Tzang, C. H., Yang, M. S. & Wong, M. S. (2003).
Biochim. Biophys. Acta, 1638, 187±196.
Chen, X. W., Sanford, C. G. L., Quarles, D. & Anderson, J. B. (2003). J. Nutr.
Biochem. 14, 342±349.
Siemens (1997). SHELXTL. Version 5.10. Bruker AXS Inc., Madison,
Wisconsin, USA.
Wang, A. H., Ughetto, G., Quigley, G. J., Hakoshima, T., van der Marel, G. A.,
van Boom, J. H. & Rich, A. (1984). Science, 225, 1115±1121.
Warren, N. R. (2002). Life Sci. 71, 865±877.
Hua, P., Tsai, W. J. & Kuo, S. M. (2003). Biochim. Biophys. Acta, 1627, 63±70.
Hunter, C. A. (1993). J. Mol. Biol. 230, 1025±1054.
Hunter, C. A. & Sanders, J. K. (1990). J. Am. Chem. Soc. 112, 5525±5534.
William, O. G., Barbour, L. J. & Atwood, J. L. (1999). Science, 285, 1049±1051.
Yuan, L., Wagatsuma, C., Yoshida, M., Miura, T., Mukoda, T., Fujii, H., Sun,
B. X., Kim, J. H. & Surh, Y. J. (2003). Mutat. Res. 523±524, 55±62.
ꢁ
Acta Cryst. (2005). C61, o29±o31
Zun-Ting Zhang et al. C17H14O5 o31