Taxifolin tubes: crystal engineering and characteristics

Taxifolin, also known as di­hydro­quercetin, is the major flavonoid in larch wood. It is well known as an antioxidant and a bioactive substance. Taxifolin as an active pharmaceutical ingredient is produced industrially in crystalline form during the processing of larch wood. Some information is available on nano- and microstructured particles of taxifolin. This paper reports on the generation of a new form of taxifolin as microtubes. These self-assembled tubes were obtained from raw taxifolin by crystal engineering with urea at ambient temperature and pressure. The parameters of temperature, pH value, molar ratio of taxifolin and urea, and time duration were optimized for yield enhancement of the microtubes. The water solubility and melting point of the new form of taxifolin were established. The microtubes were characterized by X-ray diffraction, X-ray powder diffraction, microscopy, mass spectrometry, ¹H NMR spectroscopy, UV spectroscopy and Fourier transform infrared spectroscopy methods. The experimental results demonstrate that the microtubes and raw taxifolin both exist in crystalline form with the same structure of the crystal unit. However, they are characterized by different morphological and physicochemical properties. Computer simulation was performed to explain the mechanism of the self-assembly process.

Computing details

Program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997).

(I)

Crystal data

C30H24O19	F(000) = 1424
Mr = 688.49	Dx = 1.517 Mg m^−3
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
a = 23.2416 (14) Å	Cell parameters from 1657 reflections
b = 5.2305 (3) Å	θ = 3.3–28.7°
c = 25.4061 (14) Å	µ = 0.13 mm^−1
β = 102.634 (5)°	T = 150 K
V = 3013.7 (3) Å^3	Prism
Z = 4	0.40 × 0.37 × 0.32 mm

Data collection

Xcalibur diffractometer	Rint = 0.041
Radiation source: fine-focus sealed tube	θmax = 26.2°, θmin = 3.3°
Graphite monochromator	h = −28→18
5773 measured reflections	k = −6→6
4746 independent reflections	l = −23→31
2823 reflections with I > 2σ(I)

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)] = 0.071	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.190	w = 1/[σ^2(Fo^2) + (0.0938P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.056
4746 reflections	Δρmax = 0.35 e Å^−3
442 parameters	Δρmin = −0.37 e Å^−3
1 restraint	Absolute structure: Flack H D (1983), Acta Cryst. A39, 876-881
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 2 (2)

Special details

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.

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 > 2sigma(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	0.21443 (19)	0.1170 (8)	0.33401 (18)	0.0231 (11)
O3	0.31724 (19)	0.6288 (9)	0.32036 (19)	0.0286 (12)
H3B	0.3272	0.6868	0.2937	0.043*
O4	0.2607 (2)	0.5528 (9)	0.21473 (19)	0.0257 (11)
O5	0.1773 (2)	0.3147 (9)	0.14320 (18)	0.0299 (12)
H5	0.1995	0.4342	0.1542	0.045*
O7	0.07525 (19)	−0.3522 (9)	0.20816 (19)	0.0268 (12)
H7	0.0590	−0.3528	0.1761	0.040*
O3'	0.3971 (2)	0.0118 (9)	0.4942 (2)	0.0349 (13)
H3'A	0.3987	−0.0979	0.4715	0.052*
O4'	0.3812 (2)	0.3901 (10)	0.55885 (19)	0.0366 (13)
H4'A	0.3727	0.5145	0.5753	0.055*
C2	0.2435 (3)	0.3626 (12)	0.3458 (2)	0.0168 (14)
H2A	0.2136	0.4979	0.3409	0.020*
C3	0.2835 (3)	0.4049 (13)	0.3059 (3)	0.0198 (15)
H3A	0.3109	0.2601	0.3093	0.024*
C4	0.2474 (3)	0.4070 (12)	0.2490 (3)	0.0210 (16)
C5	0.1671 (3)	0.1794 (13)	0.1856 (3)	0.0187 (15)
C6	0.1252 (3)	−0.0142 (13)	0.1748 (3)	0.0230 (16)
H6A	0.1044	−0.0459	0.1398	0.028*
C7	0.1153 (3)	−0.1596 (12)	0.2180 (3)	0.0156 (14)
C8	0.1439 (3)	−0.1140 (12)	0.2703 (3)	0.0202 (15)
H8A	0.1350	−0.2097	0.2984	0.024*
C9	0.1868 (3)	0.0786 (13)	0.2811 (3)	0.0210 (16)
C10	0.1996 (3)	0.2279 (12)	0.2381 (3)	0.0226 (17)
C1'	0.2772 (3)	0.3617 (12)	0.4036 (3)	0.0204 (15)
C2'	0.3201 (3)	0.1759 (13)	0.4218 (3)	0.0228 (16)
H2'A	0.3260	0.0456	0.3987	0.027*
C3'	0.3537 (3)	0.1834 (12)	0.4736 (3)	0.0214 (16)
C4'	0.3447 (3)	0.3839 (13)	0.5067 (3)	0.0249 (17)
C5'	0.3019 (3)	0.5624 (12)	0.4907 (3)	0.0240 (16)
H5'A	0.2955	0.6888	0.5146	0.029*
C6'	0.2675 (3)	0.5545 (13)	0.4381 (3)	0.0226 (16)
H6'A	0.2385	0.6769	0.4265	0.027*
O1A	0.42206 (19)	1.4284 (9)	0.15135 (18)	0.0247 (11)
O3A	0.3063 (2)	0.9559 (9)	0.1548 (2)	0.0313 (13)
H3AB	0.3016	0.8681	0.1802	0.047*
O4A	0.36906 (19)	0.9534 (9)	0.25845 (18)	0.0254 (11)
O5A	0.4445 (2)	1.1812 (9)	0.33740 (19)	0.0313 (13)
H5A	0.4214	1.0698	0.3232	0.047*
O7A	0.55295 (18)	1.8702 (8)	0.28973 (18)	0.0250 (11)
H7A	0.5577	1.9480	0.2630	0.038*
O3'A	0.3819 (2)	0.9274 (10)	−0.0350 (2)	0.0397 (14)
H3"A	0.3617	0.9088	−0.0655	0.060*
O4'A	0.3052 (2)	1.2774 (9)	−0.09109 (19)	0.0298 (12)
H4"A	0.2782	1.3756	−0.1037	0.045*
C2A	0.3631 (3)	1.3118 (12)	0.1369 (3)	0.0227 (16)
H2AA	0.3351	1.4265	0.1488	0.027*
C3A	0.3637 (3)	1.0601 (12)	0.1664 (3)	0.0204 (15)
H3AA	0.3898	0.9421	0.1529	0.024*
C4A	0.3876 (3)	1.0946 (13)	0.2270 (3)	0.0249 (17)
C5A	0.4577 (3)	1.3339 (13)	0.2988 (3)	0.0239 (16)
C6A	0.4982 (3)	1.5253 (12)	0.3130 (3)	0.0202 (16)
H6AA	0.5157	1.5515	0.3491	0.024*
C7A	0.5132 (3)	1.6792 (12)	0.2744 (3)	0.0237 (17)
C8A	0.4877 (3)	1.6451 (12)	0.2197 (3)	0.0178 (15)
H8AA	0.4987	1.7482	0.1937	0.021*
C9A	0.4459 (3)	1.4559 (12)	0.2049 (3)	0.0210 (16)
C1OA	0.4297 (3)	1.2959 (12)	0.2435 (3)	0.0154 (14)
C1'A	0.3475 (3)	1.2991 (12)	0.0766 (3)	0.0252 (17)
C2'A	0.3704 (3)	1.1134 (13)	0.0478 (3)	0.0264 (17)
H2'B	0.3953	0.9883	0.0664	0.032*
C3'A	0.3568 (3)	1.1118 (13)	−0.0082 (3)	0.0250 (17)
C4'A	0.3187 (3)	1.2979 (13)	−0.0358 (3)	0.0254 (17)
C5'A	0.2965 (3)	1.4846 (13)	−0.0076 (3)	0.0300 (19)
H5'B	0.2717	1.6101	−0.0261	0.036*
C6'A	0.3111 (3)	1.4859 (12)	0.0487 (3)	0.0221 (16)
H6'B	0.2963	1.6133	0.0676	0.027*
OW1	0.4182 (2)	−0.2752 (9)	0.4121 (2)	0.0331 (13)
OW2	0.6149 (2)	1.8651 (12)	0.3912 (2)	0.0542 (17)
OW3	0.4988 (2)	1.3164 (11)	0.4451 (2)	0.0487 (16)
OW4	0.0212 (3)	−0.455 (2)	0.1040 (3)	0.114 (3)
OW5	−0.0123 (4)	0.046 (2)	0.0485 (4)	0.139 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.024 (2)	0.024 (3)	0.021 (3)	−0.005 (2)	0.003 (2)	−0.002 (2)
O3	0.032 (3)	0.030 (3)	0.026 (3)	−0.015 (2)	0.011 (2)	0.001 (2)
O4	0.029 (2)	0.027 (3)	0.022 (3)	−0.010 (2)	0.009 (2)	0.000 (2)
O5	0.042 (3)	0.040 (3)	0.008 (3)	−0.014 (3)	0.006 (2)	0.002 (2)
O7	0.030 (3)	0.026 (3)	0.023 (3)	−0.013 (2)	0.003 (2)	−0.006 (2)
O3'	0.038 (3)	0.030 (3)	0.033 (4)	0.005 (2)	0.000 (2)	−0.001 (2)
O4'	0.039 (3)	0.057 (4)	0.012 (3)	0.003 (3)	0.001 (2)	−0.002 (3)
C2	0.018 (3)	0.022 (4)	0.008 (4)	−0.003 (3)	−0.002 (3)	0.003 (3)
C3	0.018 (3)	0.025 (4)	0.017 (4)	−0.006 (3)	0.003 (3)	−0.002 (3)
C4	0.020 (3)	0.018 (4)	0.026 (5)	0.002 (3)	0.008 (3)	0.004 (3)
C5	0.024 (3)	0.030 (4)	0.002 (4)	0.006 (3)	0.003 (3)	−0.001 (3)
C6	0.028 (4)	0.026 (4)	0.015 (4)	−0.002 (3)	0.005 (3)	−0.009 (3)
C7	0.016 (3)	0.019 (3)	0.012 (4)	−0.001 (3)	0.004 (3)	−0.002 (3)
C8	0.025 (3)	0.018 (3)	0.020 (4)	0.000 (3)	0.010 (3)	0.003 (3)
C9	0.020 (3)	0.027 (4)	0.017 (4)	0.005 (3)	0.007 (3)	0.000 (3)
C10	0.020 (3)	0.017 (4)	0.032 (5)	0.000 (3)	0.010 (3)	0.001 (3)
C1'	0.022 (3)	0.020 (4)	0.020 (4)	−0.004 (3)	0.008 (3)	0.000 (3)
C2'	0.027 (4)	0.021 (4)	0.019 (4)	−0.004 (3)	0.002 (3)	−0.003 (3)
C3'	0.019 (3)	0.018 (3)	0.025 (5)	−0.002 (3)	0.000 (3)	0.004 (3)
C4'	0.025 (4)	0.031 (4)	0.019 (5)	−0.008 (3)	0.005 (3)	0.001 (3)
C5'	0.028 (4)	0.023 (4)	0.021 (5)	−0.004 (3)	0.007 (3)	0.002 (3)
C6'	0.023 (3)	0.027 (4)	0.018 (4)	0.000 (3)	0.005 (3)	0.000 (3)
O1A	0.026 (2)	0.034 (3)	0.012 (3)	−0.010 (2)	−0.001 (2)	0.001 (2)
O3A	0.029 (3)	0.032 (3)	0.030 (3)	−0.014 (2)	0.001 (2)	0.002 (2)
O4A	0.026 (2)	0.031 (3)	0.018 (3)	−0.012 (2)	0.000 (2)	−0.001 (2)
O5A	0.038 (3)	0.033 (3)	0.020 (3)	−0.017 (2)	0.000 (2)	0.002 (2)
O7A	0.030 (3)	0.024 (3)	0.020 (3)	−0.009 (2)	0.004 (2)	0.004 (2)
O3'A	0.043 (3)	0.039 (3)	0.034 (4)	0.013 (3)	0.003 (3)	−0.005 (3)
O4'A	0.040 (3)	0.036 (3)	0.013 (3)	0.011 (2)	0.005 (2)	0.009 (2)
C2A	0.023 (3)	0.019 (4)	0.025 (5)	−0.004 (3)	0.003 (3)	−0.005 (3)
C3A	0.018 (3)	0.023 (4)	0.018 (4)	−0.006 (3)	−0.002 (3)	−0.004 (3)
C4A	0.019 (3)	0.016 (4)	0.041 (5)	−0.001 (3)	0.011 (3)	−0.003 (3)
C5A	0.019 (3)	0.025 (4)	0.028 (5)	−0.001 (3)	0.008 (3)	0.004 (3)
C6A	0.019 (3)	0.025 (4)	0.015 (4)	−0.002 (3)	0.001 (3)	−0.002 (3)
C7A	0.015 (3)	0.018 (4)	0.038 (5)	−0.004 (3)	0.006 (3)	−0.003 (3)
C8A	0.023 (3)	0.018 (3)	0.012 (4)	−0.002 (3)	0.003 (3)	0.000 (3)
C9A	0.021 (3)	0.020 (4)	0.022 (5)	0.001 (3)	0.005 (3)	−0.002 (3)
C1OA	0.016 (3)	0.022 (3)	0.005 (4)	0.000 (3)	−0.005 (3)	0.000 (3)
C1'A	0.024 (3)	0.017 (4)	0.036 (5)	−0.004 (3)	0.008 (3)	0.003 (3)
C2'A	0.022 (3)	0.022 (4)	0.030 (5)	0.004 (3)	−0.005 (3)	0.003 (3)
C3'A	0.024 (3)	0.029 (4)	0.021 (5)	0.003 (3)	0.005 (3)	0.000 (3)
C4'A	0.024 (4)	0.024 (4)	0.025 (5)	−0.002 (3)	−0.004 (3)	0.000 (3)
C5'A	0.026 (4)	0.023 (4)	0.041 (6)	0.004 (3)	0.009 (4)	0.007 (3)
C6'A	0.028 (4)	0.024 (4)	0.013 (4)	−0.003 (3)	0.002 (3)	−0.005 (3)
OW1	0.036 (3)	0.043 (3)	0.020 (3)	0.001 (2)	0.007 (2)	−0.001 (2)
OW2	0.050 (3)	0.065 (4)	0.049 (4)	−0.020 (3)	0.014 (3)	−0.029 (3)
OW3	0.042 (3)	0.066 (4)	0.031 (4)	0.013 (3)	−0.004 (3)	−0.009 (3)
OW4	0.073 (5)	0.170 (9)	0.093 (7)	−0.013 (6)	0.007 (5)	0.008 (6)
OW5	0.112 (7)	0.174 (11)	0.139 (9)	−0.039 (7)	0.041 (7)	−0.031 (8)

Geometric parameters (Å, º)

O1—C9	1.372 (8)	O1A—C9A	1.359 (8)
O1—C2	1.452 (7)	O1A—C2A	1.471 (7)
O3—C3	1.412 (7)	O3A—C3A	1.410 (7)
O4—C4	1.247 (8)	O4A—C4A	1.233 (8)
O5—C5	1.353 (8)	O5A—C5A	1.351 (8)
O7—C7	1.357 (7)	O7A—C7A	1.359 (7)
O3'—C3'	1.366 (7)	O3'A—C3'A	1.382 (8)
O4'—C4'	1.408 (8)	O4'A—C4'A	1.374 (8)
C2—C1'	1.505 (9)	C2A—C1'A	1.498 (10)
C2—C3	1.534 (8)	C2A—C3A	1.514 (9)
C3—C4	1.504 (9)	C3A—C4A	1.528 (10)
C4—C10	1.434 (9)	C4A—C1OA	1.437 (9)
C5—C6	1.390 (9)	C5A—C6A	1.367 (9)
C5—C10	1.403 (9)	C5A—C1OA	1.427 (9)
C6—C7	1.396 (9)	C6A—C7A	1.372 (9)
C7—C8	1.371 (9)	C7A—C8A	1.398 (10)
C8—C9	1.401 (9)	C8A—C9A	1.379 (9)
C9—C10	1.427 (9)	C9A—C1OA	1.403 (9)
C1'—C6'	1.388 (9)	C1'A—C6'A	1.380 (9)
C1'—C2'	1.397 (9)	C1'A—C2'A	1.390 (10)
C2'—C3'	1.376 (9)	C2'A—C3'A	1.389 (10)
C3'—C4'	1.389 (10)	C3'A—C4'A	1.397 (9)
C4'—C5'	1.360 (9)	C4'A—C5'A	1.377 (10)
C5'—C6'	1.400 (9)	C5'A—C6'A	1.397 (10)
C9—O1—C2	115.4 (5)	C9A—O1A—C2A	116.6 (5)
O1—C2—C1'	108.5 (5)	O1A—C2A—C1'A	106.1 (5)
O1—C2—C3	108.2 (5)	O1A—C2A—C3A	109.3 (5)
C1'—C2—C3	112.4 (5)	C1'A—C2A—C3A	116.3 (6)
O3—C3—C4	113.9 (6)	O3A—C3A—C2A	109.1 (5)
O3—C3—C2	109.3 (5)	O3A—C3A—C4A	112.1 (6)
C4—C3—C2	110.1 (5)	C2A—C3A—C4A	111.0 (5)
O4—C4—C10	124.3 (7)	O4A—C4A—C1OA	124.2 (7)
O4—C4—C3	120.3 (6)	O4A—C4A—C3A	118.7 (6)
C10—C4—C3	115.3 (6)	C1OA—C4A—C3A	117.1 (6)
O5—C5—C6	117.4 (6)	O5A—C5A—C6A	119.7 (6)
O5—C5—C10	120.7 (6)	O5A—C5A—C1OA	120.3 (6)
C6—C5—C10	121.8 (6)	C6A—C5A—C1OA	120.0 (6)
C5—C6—C7	118.1 (6)	C5A—C6A—C7A	120.6 (7)
O7—C7—C8	118.4 (6)	O7A—C7A—C6A	119.3 (6)
O7—C7—C6	119.0 (6)	O7A—C7A—C8A	119.5 (6)
C8—C7—C6	122.6 (6)	C6A—C7A—C8A	121.2 (6)
C7—C8—C9	119.2 (6)	C9A—C8A—C7A	118.8 (6)
O1—C9—C8	117.2 (6)	O1A—C9A—C8A	117.2 (6)
O1—C9—C10	122.6 (6)	O1A—C9A—C1OA	121.6 (6)
C8—C9—C10	120.2 (6)	C8A—C9A—C1OA	121.2 (6)
C5—C10—C9	118.0 (6)	C9A—C1OA—C5A	118.2 (6)
C5—C10—C4	122.4 (6)	C9A—C1OA—C4A	120.2 (6)
C9—C10—C4	119.4 (7)	C5A—C1OA—C4A	121.6 (6)
C6'—C1'—C2'	119.9 (6)	C6'A—C1'A—C2'A	119.2 (7)
C6'—C1'—C2	119.5 (6)	C6'A—C1'A—C2A	118.5 (6)
C2'—C1'—C2	120.5 (6)	C2'A—C1'A—C2A	122.2 (6)
C3'—C2'—C1'	120.8 (7)	C3'A—C2'A—C1'A	121.0 (7)
O3'—C3'—C2'	124.4 (6)	O3'A—C3'A—C4'A	121.9 (6)
O3'—C3'—C4'	117.4 (6)	O3'A—C3'A—C2'A	118.8 (6)
C2'—C3'—C4'	118.1 (6)	C4'A—C3'A—C2'A	119.3 (6)
C5'—C4'—C3'	122.3 (7)	O4'A—C4'A—C5'A	124.0 (6)
C5'—C4'—O4'	121.1 (6)	O4'A—C4'A—C3'A	115.9 (6)
C3'—C4'—O4'	116.6 (6)	C5'A—C4'A—C3'A	120.0 (7)
C4'—C5'—C6'	119.5 (7)	C4'A—C5'A—C6'A	120.1 (7)
C1'—C6'—C5'	119.2 (7)	C1'A—C6'A—C5'A	120.4 (6)