Two new polymorphic forms of combretastatin A-4, an anti­tumour agent

Two new polymorphic forms of combretastatin A-4 {systematic name: 2-meth­oxy-5-[(E)-2-(3,4,5-tri­meth­oxy­phen­yl)ethen­yl]phenol, C₁₈H₂₀O₅, CA-4}, an inhibitor of tubulin polymerization at the colchicine binding site, were identified. A number of crystallization attempts led to the ortho­rhom­bic form, with two mol­ecules in the asymmetric part of the unit cell; obtaining a different form required the experiment to be moved to another laboratory. None of the attempts resulted in the monoclinic form described earlier. The three different forms contain mol­ecules of significantly different geometries, which can be related to conformational freedom, postulated as the result of biological studies. In addition, the packing modes in all three forms are basically different. The structural differences at both the mol­ecular and the supra­molecular level have also been studied via calculations of energies and a topological analysis of the electron density. The results confirm the role of weak inter­actions in the determination of crystal architecture and additionally hint at an explanation for the results of crystallization attempts: the new monoclinic form has significantly lower energy than the form reported earlier.

Computing details

For both structures, data collection: CrysAlis PRO (Rigaku OD, 2015); cell refinement: CrysAlis PRO (Rigaku OD, 2015); data reduction: CrysAlis PRO (Rigaku OD, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: Mercury (Macrae et al., 2020).

2-Methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol (1)

Crystal data

C18H20O5	F(000) = 672
Mr = 316.34	Dx = 1.318 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 9.9167 (5) Å	Cell parameters from 1286 reflections
b = 6.9587 (5) Å	θ = 3.9–25.2°
c = 23.2803 (15) Å	µ = 0.10 mm^−1
β = 96.988 (6)°	T = 295 K
V = 1594.58 (17) Å^3	Block, colourless
Z = 4	0.25 × 0.2 × 0.1 mm

Data collection

Rigaku Xcalibur EosS2 diffractometer	3277 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source	1952 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.027
Detector resolution: 16.0338 pixels mm^-1	θmax = 27.7°, θmin = 3.4°
ω scans	h = −12→12
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2015)	k = −7→8
Tmin = 0.793, Tmax = 1.000	l = −30→12
5526 measured reflections

Refinement

Refinement on F^2	Hydrogen site location: difference Fourier map
Least-squares matrix: full	All H-atom parameters refined
R[F^2 > 2σ(F^2)] = 0.047	w = 1/[σ^2(Fo^2) + (0.0355P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.108	(Δ/σ)max = 0.001
S = 1.00	Δρmax = 0.15 e Å^−3
3277 reflections	Δρmin = −0.17 e Å^−3
289 parameters	Extinction correction: SHELXL2014 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0030 (6)

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.

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

	x	y	z	Uiso*/Ueq
C1	0.64520 (19)	0.5250 (3)	0.66822 (8)	0.0417 (5)
C2	0.6923 (2)	0.3847 (3)	0.63298 (8)	0.0447 (5)
H2	0.6367 (19)	0.280 (3)	0.6220 (7)	0.046 (6)*
C3	0.8193 (2)	0.4025 (3)	0.61426 (8)	0.0444 (5)
O3	0.87314 (15)	0.2769 (2)	0.57784 (6)	0.0630 (4)
C31	0.7950 (3)	0.1154 (4)	0.55791 (13)	0.0676 (7)
H31A	0.851 (3)	0.051 (4)	0.5314 (10)	0.089 (8)*
H31B	0.708 (3)	0.155 (3)	0.5380 (10)	0.084 (9)*
H31C	0.779 (2)	0.034 (4)	0.5893 (10)	0.084 (9)*
C4	0.90185 (19)	0.5578 (3)	0.63217 (8)	0.0417 (5)
O4	1.03300 (13)	0.5646 (2)	0.61755 (6)	0.0521 (4)
C41	1.0506 (3)	0.6887 (4)	0.57004 (12)	0.0637 (7)
H41A	0.994 (3)	0.652 (4)	0.5350 (11)	0.104 (10)*
H41B	1.144 (3)	0.681 (4)	0.5616 (11)	0.109 (10)*
H41C	1.032 (2)	0.829 (4)	0.5808 (10)	0.092 (9)*
C5	0.85588 (19)	0.6977 (3)	0.66787 (8)	0.0408 (5)
O5	0.94493 (13)	0.8433 (2)	0.68289 (6)	0.0518 (4)
C51	0.9053 (3)	0.9916 (4)	0.71985 (11)	0.0559 (6)
H51A	0.818 (3)	1.057 (3)	0.7021 (10)	0.089 (8)*
H51B	0.983 (2)	1.080 (3)	0.7234 (9)	0.075 (7)*
H51C	0.890 (2)	0.939 (3)	0.7587 (9)	0.073 (7)*
C6	0.7269 (2)	0.6821 (3)	0.68547 (8)	0.0429 (5)
H6	0.6927 (19)	0.786 (3)	0.7105 (8)	0.059 (6)*
C7	0.5106 (2)	0.5001 (3)	0.68909 (9)	0.0492 (5)
H7	0.500 (2)	0.373 (3)	0.7085 (8)	0.060 (6)*
C8	0.4057 (2)	0.6211 (3)	0.68502 (9)	0.0487 (5)
H8	0.326 (2)	0.585 (3)	0.7048 (8)	0.057 (6)*
C9	0.38408 (18)	0.8059 (3)	0.65414 (8)	0.0409 (5)
C10	0.2861 (2)	0.9306 (3)	0.67065 (8)	0.0446 (5)
H10	0.2391 (18)	0.902 (3)	0.7030 (7)	0.046 (5)*
C11	0.25260 (19)	1.1000 (3)	0.64108 (8)	0.0439 (5)
O11	0.15689 (16)	1.2179 (2)	0.65950 (7)	0.0642 (5)
H11	0.140 (3)	1.323 (4)	0.6358 (10)	0.101 (10)*
C12	0.31594 (19)	1.1449 (3)	0.59253 (8)	0.0424 (5)
O12	0.27104 (14)	1.3122 (2)	0.56505 (6)	0.0598 (4)
C121	0.3414 (3)	1.3783 (5)	0.51988 (12)	0.0691 (8)
H12A	0.331 (3)	1.278 (4)	0.4871 (11)	0.101 (10)*
H12B	0.440 (3)	1.401 (4)	0.5346 (11)	0.109 (10)*
H12C	0.301 (2)	1.501 (4)	0.5090 (9)	0.083 (8)*
C13	0.4142 (2)	1.0231 (3)	0.57612 (8)	0.0464 (5)
H13	0.4551 (18)	1.055 (3)	0.5417 (7)	0.053 (6)*
C14	0.4478 (2)	0.8562 (3)	0.60633 (8)	0.0459 (5)
H14	0.513 (2)	0.774 (3)	0.5935 (8)	0.052 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0379 (11)	0.0417 (13)	0.0455 (11)	0.0045 (10)	0.0049 (9)	0.0074 (10)
C2	0.0387 (12)	0.0405 (13)	0.0535 (12)	−0.0002 (10)	0.0004 (10)	−0.0026 (11)
C3	0.0435 (12)	0.0426 (13)	0.0465 (11)	0.0101 (10)	0.0029 (9)	−0.0029 (10)
O3	0.0575 (10)	0.0585 (10)	0.0746 (10)	0.0022 (8)	0.0146 (8)	−0.0248 (8)
C31	0.083 (2)	0.0533 (18)	0.0665 (17)	0.0064 (16)	0.0074 (17)	−0.0138 (15)
C4	0.0326 (10)	0.0467 (13)	0.0457 (11)	0.0055 (10)	0.0050 (9)	0.0035 (10)
O4	0.0393 (8)	0.0574 (10)	0.0617 (9)	0.0074 (7)	0.0151 (7)	0.0053 (7)
C41	0.0594 (17)	0.074 (2)	0.0603 (16)	−0.0001 (16)	0.0178 (14)	0.0075 (15)
C5	0.0391 (11)	0.0383 (12)	0.0447 (11)	0.0001 (10)	0.0036 (9)	0.0005 (9)
O5	0.0440 (8)	0.0514 (9)	0.0620 (9)	−0.0086 (7)	0.0145 (7)	−0.0107 (7)
C51	0.0640 (16)	0.0519 (16)	0.0537 (14)	−0.0091 (14)	0.0146 (13)	−0.0105 (12)
C6	0.0404 (11)	0.0420 (13)	0.0474 (11)	0.0018 (10)	0.0096 (9)	0.0002 (10)
C7	0.0443 (12)	0.0456 (14)	0.0590 (13)	−0.0027 (11)	0.0118 (10)	0.0066 (11)
C8	0.0394 (12)	0.0539 (14)	0.0551 (12)	−0.0032 (11)	0.0150 (10)	0.0031 (11)
C9	0.0333 (10)	0.0465 (13)	0.0432 (10)	−0.0023 (10)	0.0061 (9)	−0.0026 (9)
C10	0.0373 (11)	0.0550 (14)	0.0438 (11)	−0.0001 (10)	0.0149 (9)	0.0008 (10)
C11	0.0369 (11)	0.0507 (13)	0.0462 (11)	0.0038 (10)	0.0130 (9)	−0.0030 (10)
O11	0.0664 (10)	0.0659 (11)	0.0672 (10)	0.0260 (9)	0.0356 (8)	0.0132 (9)
C12	0.0385 (11)	0.0493 (13)	0.0397 (10)	0.0024 (10)	0.0064 (9)	0.0017 (10)
O12	0.0615 (9)	0.0644 (10)	0.0577 (9)	0.0174 (8)	0.0241 (7)	0.0183 (8)
C121	0.073 (2)	0.069 (2)	0.0689 (17)	0.0104 (17)	0.0256 (15)	0.0271 (16)
C13	0.0421 (12)	0.0598 (15)	0.0395 (11)	0.0025 (11)	0.0139 (9)	0.0000 (11)
C14	0.0404 (12)	0.0530 (15)	0.0463 (12)	0.0073 (11)	0.0133 (10)	−0.0052 (10)

Geometric parameters (Å, º)

C1—C6	1.391 (3)	C51—H51C	1.00 (2)
C1—C2	1.392 (3)	C6—H6	1.01 (2)
C1—C7	1.485 (3)	C7—C8	1.332 (3)
C2—C3	1.388 (3)	C7—H7	1.01 (2)
C2—H2	0.933 (19)	C8—C9	1.477 (3)
C3—O3	1.370 (2)	C8—H8	0.99 (2)
C3—C4	1.388 (3)	C9—C14	1.390 (3)
O3—C31	1.411 (3)	C9—C10	1.391 (3)
C31—H31A	0.99 (3)	C10—C11	1.385 (3)
C31—H31B	0.96 (2)	C10—H10	0.954 (18)
C31—H31C	0.95 (2)	C11—O11	1.363 (2)
C4—O4	1.385 (2)	C11—C12	1.394 (3)
C4—C5	1.392 (3)	O11—H11	0.92 (3)
O4—C41	1.431 (3)	C12—O12	1.376 (2)
C41—H41A	0.97 (3)	C12—C13	1.380 (3)
C41—H41B	0.97 (3)	O12—C121	1.408 (3)
C41—H41C	1.03 (3)	C121—H12A	1.03 (3)
C5—O5	1.361 (2)	C121—H12B	1.01 (3)
C5—C6	1.394 (3)	C121—H12C	0.97 (3)
O5—C51	1.429 (2)	C13—C14	1.377 (3)
C51—H51A	1.02 (2)	C13—H13	0.966 (18)
C51—H51B	0.98 (2)	C14—H14	0.94 (2)
C6—C1—C2	119.73 (19)	C1—C6—C5	119.97 (19)
C6—C1—C7	120.83 (18)	C1—C6—H6	120.2 (11)
C2—C1—C7	119.38 (19)	C5—C6—H6	119.8 (11)
C3—C2—C1	120.3 (2)	C8—C7—C1	128.9 (2)
C3—C2—H2	120.9 (12)	C8—C7—H7	117.6 (12)
C1—C2—H2	118.8 (12)	C1—C7—H7	113.5 (12)
O3—C3—C2	125.01 (19)	C7—C8—C9	130.6 (2)
O3—C3—C4	115.01 (18)	C7—C8—H8	117.8 (12)
C2—C3—C4	119.98 (19)	C9—C8—H8	111.6 (11)
C3—O3—C31	118.2 (2)	C14—C9—C10	117.71 (19)
O3—C31—H31A	104.0 (15)	C14—C9—C8	123.79 (19)
O3—C31—H31B	110.6 (15)	C10—C9—C8	118.28 (18)
H31A—C31—H31B	111 (2)	C11—C10—C9	121.79 (19)
O3—C31—H31C	111.0 (15)	C11—C10—H10	117.2 (11)
H31A—C31—H31C	111 (2)	C9—C10—H10	121.0 (11)
H31B—C31—H31C	108 (2)	O11—C11—C10	119.34 (18)
O4—C4—C3	119.29 (17)	O11—C11—C12	121.36 (19)
O4—C4—C5	120.57 (18)	C10—C11—C12	119.29 (19)
C3—C4—C5	119.98 (18)	C11—O11—H11	112.0 (17)
C4—O4—C41	114.67 (17)	O12—C12—C13	126.18 (18)
O4—C41—H41A	112.3 (16)	O12—C12—C11	114.47 (17)
O4—C41—H41B	109.5 (16)	C13—C12—C11	119.35 (19)
H41A—C41—H41B	107 (2)	C12—O12—C121	117.51 (18)
O4—C41—H41C	110.1 (13)	O12—C121—H12A	108.4 (15)
H41A—C41—H41C	111 (2)	O12—C121—H12B	110.2 (15)
H41B—C41—H41C	107 (2)	H12A—C121—H12B	111 (2)
O5—C5—C4	115.11 (17)	O12—C121—H12C	104.8 (14)
O5—C5—C6	124.91 (18)	H12A—C121—H12C	113.9 (19)
C4—C5—C6	119.98 (19)	H12B—C121—H12C	108 (2)
C5—O5—C51	118.36 (17)	C14—C13—C12	120.7 (2)
O5—C51—H51A	111.1 (13)	C14—C13—H13	121.0 (11)
O5—C51—H51B	103.6 (13)	C12—C13—H13	118.2 (11)
H51A—C51—H51B	111.9 (19)	C13—C14—C9	121.1 (2)
O5—C51—H51C	111.0 (13)	C13—C14—H14	119.1 (12)
H51A—C51—H51C	108.5 (19)	C9—C14—H14	119.8 (12)
H51B—C51—H51C	110.7 (17)
C6—C1—C2—C3	−1.0 (3)	C4—C5—C6—C1	1.2 (3)
C7—C1—C2—C3	−178.28 (18)	C6—C1—C7—C8	55.8 (3)
C1—C2—C3—O3	−177.42 (17)	C2—C1—C7—C8	−127.0 (2)
C1—C2—C3—C4	2.0 (3)	C1—C7—C8—C9	6.9 (4)
C2—C3—O3—C31	−0.6 (3)	C7—C8—C9—C14	24.8 (3)
C4—C3—O3—C31	179.9 (2)	C7—C8—C9—C10	−160.8 (2)
O3—C3—C4—O4	−6.4 (2)	C14—C9—C10—C11	−0.3 (3)
C2—C3—C4—O4	174.08 (16)	C8—C9—C10—C11	−175.11 (18)
O3—C3—C4—C5	178.08 (16)	C9—C10—C11—O11	−179.29 (18)
C2—C3—C4—C5	−1.4 (3)	C9—C10—C11—C12	1.7 (3)
C3—C4—O4—C41	101.4 (2)	O11—C11—C12—O12	−1.6 (3)
C5—C4—O4—C41	−83.1 (2)	C10—C11—C12—O12	177.38 (17)
O4—C4—C5—O5	4.4 (2)	O11—C11—C12—C13	178.74 (18)
C3—C4—C5—O5	179.88 (16)	C10—C11—C12—C13	−2.3 (3)
O4—C4—C5—C6	−175.62 (16)	C13—C12—O12—C121	−7.7 (3)
C3—C4—C5—C6	−0.2 (3)	C11—C12—O12—C121	172.7 (2)
C4—C5—O5—C51	−179.52 (18)	O12—C12—C13—C14	−178.10 (18)
C6—C5—O5—C51	0.5 (3)	C11—C12—C13—C14	1.6 (3)
C2—C1—C6—C5	−0.6 (3)	C12—C13—C14—C9	−0.2 (3)
C7—C1—C6—C5	176.64 (18)	C10—C9—C14—C13	−0.5 (3)
O5—C5—C6—C1	−178.89 (16)	C8—C9—C14—C13	174.00 (18)

2-Methoxy-5-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenol (2)

Crystal data

C18H20O5	Dx = 1.274 Mg m^−3
Mr = 316.34	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pca21	Cell parameters from 6871 reflections
a = 25.9293 (7) Å	θ = 3.7–26.0°
b = 8.8657 (3) Å	µ = 0.09 mm^−1
c = 14.3503 (5) Å	T = 295 K
V = 3298.87 (18) Å^3	Prism, colourless
Z = 8	0.3 × 0.2 × 0.2 mm
F(000) = 1344

Data collection

Xcalibur, Eos diffractometer	6241 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance (Mo) X-ray Source	5060 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.022
Detector resolution: 16.2413 pixels mm^-1	θmax = 27.0°, θmin = 3.1°
ω scans	h = −32→28
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2015)	k = −11→11
Tmin = 0.837, Tmax = 1.000	l = −16→18
19387 measured reflections

Refinement

Refinement on F^2	1 restraint
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.093	w = 1/[σ^2(Fo^2) + (0.0484P)^2 + 0.1541P] where P = (Fo^2 + 2Fc^2)/3
S = 1.04	(Δ/σ)max = 0.002
6241 reflections	Δρmax = 0.12 e Å^−3
431 parameters	Δρmin = −0.13 e Å^−3

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.

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

	x	y	z	Uiso*/Ueq
C1A	0.37378 (10)	0.0390 (3)	0.4398 (2)	0.0472 (6)
C2A	0.41006 (10)	0.0977 (3)	0.50153 (19)	0.0475 (6)
H2A	0.4230	0.0375	0.5492	0.057*
C3A	0.42693 (10)	0.2454 (3)	0.4922 (2)	0.0473 (6)
O3A	0.46376 (8)	0.3119 (2)	0.54636 (15)	0.0620 (5)
C31A	0.48146 (14)	0.2328 (5)	0.6256 (3)	0.0835 (11)
H31A	0.4526	0.2047	0.6637	0.125*
H31B	0.5043	0.2961	0.6607	0.125*
H31C	0.4995	0.1437	0.6061	0.125*
C4A	0.40716 (10)	0.3364 (3)	0.42173 (19)	0.0440 (6)
O4A	0.42370 (8)	0.48385 (19)	0.41356 (14)	0.0532 (5)
C41A	0.45741 (14)	0.5132 (4)	0.3367 (2)	0.0696 (9)
H41A	0.4888	0.4573	0.3446	0.104*
H41B	0.4651	0.6191	0.3342	0.104*
H41C	0.4409	0.4830	0.2798	0.104*
C5A	0.36913 (10)	0.2801 (3)	0.36276 (19)	0.0462 (6)
O5A	0.35117 (8)	0.3797 (2)	0.29787 (15)	0.0589 (5)
C51A	0.31995 (13)	0.3229 (4)	0.2244 (2)	0.0696 (9)
H51A	0.3371	0.2396	0.1951	0.104*
H51B	0.3141	0.4011	0.1794	0.104*
H51C	0.2875	0.2896	0.2492	0.104*
C6A	0.35230 (10)	0.1325 (3)	0.3724 (2)	0.0477 (6)
H6A	0.3265	0.0958	0.3336	0.057*
C7A	0.36021 (10)	−0.1226 (3)	0.4482 (2)	0.0551 (7)
H7A	0.3618	−0.1622	0.5081	0.066*
C8A	0.34598 (10)	−0.2192 (3)	0.3818 (2)	0.0566 (7)
H8A	0.3375	−0.3155	0.4026	0.068*
C9A	0.34163 (10)	−0.1962 (3)	0.2804 (2)	0.0508 (7)
C10A	0.37862 (11)	−0.1136 (3)	0.2305 (2)	0.0554 (7)
H10A	0.4077	−0.0777	0.2612	0.067*
C11A	0.37257 (11)	−0.0853 (3)	0.1379 (2)	0.0570 (7)
O11A	0.40896 (10)	0.0001 (3)	0.0928 (2)	0.0841 (8)
H11A	0.396 (2)	0.011 (6)	0.034 (4)	0.14 (2)*
C12A	0.33059 (11)	−0.1421 (4)	0.0899 (2)	0.0591 (7)
O12A	0.32956 (9)	−0.1045 (3)	−0.00288 (18)	0.0832 (7)
C121	0.28899 (17)	−0.1595 (7)	−0.0572 (3)	0.1145 (16)
H12D	0.2867	−0.2669	−0.0500	0.172*
H12E	0.2952	−0.1356	−0.1215	0.172*
H12F	0.2573	−0.1138	−0.0375	0.172*
C13A	0.29515 (11)	−0.2296 (4)	0.1363 (2)	0.0650 (8)
H13A	0.2673	−0.2708	0.1043	0.078*
C14A	0.30097 (11)	−0.2564 (3)	0.2316 (2)	0.0598 (8)
H14A	0.2769	−0.3160	0.2625	0.072*
C1B	0.42763 (9)	0.1464 (3)	0.87618 (19)	0.0430 (5)
C2B	0.38647 (10)	0.1113 (3)	0.81668 (19)	0.0469 (6)
H2B	0.3895	0.0319	0.7747	0.056*
C3B	0.34166 (9)	0.1937 (3)	0.82019 (19)	0.0460 (6)
O3B	0.29932 (7)	0.1659 (2)	0.76591 (15)	0.0600 (5)
C31B	0.30430 (13)	0.0570 (4)	0.6937 (3)	0.0731 (10)
H31D	0.3325	0.0842	0.6538	0.110*
H31E	0.2730	0.0537	0.6579	0.110*
H31F	0.3107	−0.0404	0.7205	0.110*
C4B	0.33683 (9)	0.3157 (3)	0.8817 (2)	0.0482 (6)
O4B	0.29291 (7)	0.4038 (2)	0.87813 (16)	0.0634 (5)
C41B	0.25780 (13)	0.3781 (5)	0.9519 (3)	0.0887 (12)
H41D	0.2491	0.2730	0.9541	0.133*
H41E	0.2271	0.4365	0.9418	0.133*
H41F	0.2734	0.4074	1.0098	0.133*
C5B	0.37766 (10)	0.3509 (3)	0.9396 (2)	0.0476 (6)
O5B	0.36984 (7)	0.4737 (2)	0.99656 (16)	0.0641 (6)
C51B	0.41135 (13)	0.5169 (4)	1.0551 (3)	0.0841 (12)
H51D	0.4215	0.4327	1.0929	0.126*
H51E	0.4006	0.5986	1.0945	0.126*
H51F	0.4400	0.5487	1.0175	0.126*
C6B	0.42259 (10)	0.2677 (3)	0.93711 (19)	0.0458 (6)
H6B	0.4497	0.2928	0.9765	0.055*
C7B	0.47708 (9)	0.0655 (3)	0.8765 (2)	0.0490 (6)
H7B	0.5028	0.1112	0.9119	0.059*
C8B	0.49146 (10)	−0.0625 (3)	0.83475 (19)	0.0496 (6)
H8B	0.5260	−0.0882	0.8417	0.059*
C9B	0.46040 (9)	−0.1688 (3)	0.77915 (18)	0.0439 (6)
C10B	0.47509 (10)	−0.2003 (3)	0.68782 (19)	0.0464 (6)
H10B	0.5046	−0.1553	0.6634	0.056*
C11B	0.44673 (10)	−0.2968 (3)	0.63325 (19)	0.0468 (6)
O11B	0.46226 (8)	−0.3222 (3)	0.54421 (15)	0.0660 (6)
H11B	0.4434 (19)	−0.401 (6)	0.525 (4)	0.129 (17)*
C12B	0.40256 (10)	−0.3655 (3)	0.6695 (2)	0.0477 (6)
O12B	0.37597 (8)	−0.4529 (3)	0.60644 (16)	0.0677 (6)
C122	0.33565 (14)	−0.5404 (5)	0.6377 (3)	0.0877 (12)
H12A	0.3476	−0.6055	0.6867	0.132*
H12B	0.3226	−0.6003	0.5873	0.132*
H12C	0.3087	−0.4765	0.6611	0.132*
C13B	0.38878 (11)	−0.3395 (3)	0.7603 (2)	0.0536 (7)
H13B	0.3600	−0.3875	0.7853	0.064*
C14B	0.41767 (10)	−0.2415 (3)	0.8152 (2)	0.0531 (7)
H14B	0.4081	−0.2248	0.8768	0.064*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1A	0.0491 (14)	0.0432 (14)	0.0492 (16)	0.0015 (12)	0.0059 (12)	0.0023 (12)
C2A	0.0525 (14)	0.0475 (15)	0.0427 (15)	0.0012 (12)	0.0032 (12)	0.0047 (12)
C3A	0.0501 (14)	0.0499 (15)	0.0419 (15)	−0.0001 (12)	0.0015 (12)	−0.0016 (12)
O3A	0.0728 (12)	0.0598 (13)	0.0533 (12)	−0.0116 (10)	−0.0167 (10)	0.0052 (9)
C31A	0.091 (2)	0.097 (3)	0.063 (2)	−0.025 (2)	−0.027 (2)	0.021 (2)
C4A	0.0542 (14)	0.0351 (13)	0.0426 (14)	0.0004 (11)	0.0040 (12)	−0.0039 (11)
O4A	0.0709 (11)	0.0407 (10)	0.0480 (11)	−0.0042 (9)	0.0027 (9)	−0.0042 (8)
C41A	0.086 (2)	0.0601 (19)	0.063 (2)	−0.0154 (16)	0.0132 (17)	0.0016 (15)
C5A	0.0526 (14)	0.0402 (14)	0.0458 (16)	0.0064 (11)	−0.0003 (12)	0.0017 (11)
O5A	0.0712 (12)	0.0427 (10)	0.0628 (13)	−0.0001 (9)	−0.0200 (10)	0.0044 (9)
C51A	0.083 (2)	0.065 (2)	0.062 (2)	−0.0056 (17)	−0.0217 (17)	0.0086 (16)
C6A	0.0483 (13)	0.0427 (13)	0.0521 (16)	−0.0009 (11)	−0.0028 (13)	−0.0031 (12)
C7A	0.0593 (16)	0.0469 (17)	0.0590 (19)	−0.0049 (13)	0.0030 (14)	0.0082 (14)
C8A	0.0576 (15)	0.0396 (14)	0.072 (2)	−0.0050 (12)	0.0058 (15)	0.0082 (14)
C9A	0.0507 (15)	0.0368 (14)	0.0648 (19)	0.0015 (11)	0.0062 (13)	−0.0027 (13)
C10A	0.0516 (15)	0.0530 (17)	0.062 (2)	−0.0059 (13)	0.0045 (13)	−0.0050 (14)
C11A	0.0545 (15)	0.0520 (17)	0.064 (2)	−0.0048 (13)	0.0102 (14)	−0.0046 (14)
O11A	0.0778 (16)	0.107 (2)	0.0674 (17)	−0.0348 (14)	0.0092 (13)	0.0084 (14)
C12A	0.0558 (16)	0.0620 (18)	0.0594 (19)	0.0025 (14)	0.0056 (15)	−0.0078 (15)
O12A	0.0787 (14)	0.109 (2)	0.0617 (16)	−0.0134 (14)	−0.0012 (12)	−0.0011 (14)
C121	0.102 (3)	0.168 (5)	0.074 (3)	−0.032 (3)	−0.022 (2)	0.004 (3)
C13A	0.0535 (16)	0.067 (2)	0.074 (2)	−0.0096 (14)	−0.0038 (15)	−0.0146 (17)
C14A	0.0598 (17)	0.0480 (16)	0.071 (2)	−0.0106 (14)	0.0084 (15)	−0.0032 (15)
C1B	0.0458 (12)	0.0419 (13)	0.0412 (14)	−0.0018 (10)	−0.0050 (12)	−0.0021 (11)
C2B	0.0486 (14)	0.0457 (14)	0.0463 (16)	−0.0015 (11)	−0.0051 (11)	−0.0064 (12)
C3B	0.0431 (13)	0.0489 (15)	0.0462 (15)	−0.0045 (11)	−0.0057 (12)	−0.0022 (12)
O3B	0.0483 (10)	0.0689 (13)	0.0628 (13)	0.0001 (9)	−0.0137 (9)	−0.0130 (10)
C31B	0.0688 (19)	0.077 (2)	0.073 (2)	−0.0023 (17)	−0.0217 (17)	−0.0240 (18)
C4B	0.0439 (13)	0.0514 (15)	0.0492 (16)	0.0019 (11)	0.0020 (12)	−0.0016 (13)
O4B	0.0513 (10)	0.0742 (14)	0.0648 (13)	0.0136 (9)	0.0008 (10)	−0.0094 (11)
C41B	0.0528 (17)	0.122 (3)	0.092 (3)	0.002 (2)	0.0125 (18)	−0.020 (2)
C5B	0.0509 (14)	0.0452 (15)	0.0465 (15)	−0.0028 (12)	−0.0002 (12)	−0.0087 (12)
O5B	0.0588 (11)	0.0631 (13)	0.0704 (15)	0.0048 (10)	−0.0053 (11)	−0.0291 (11)
C51B	0.074 (2)	0.078 (2)	0.101 (3)	0.0065 (18)	−0.020 (2)	−0.050 (2)
C6B	0.0454 (13)	0.0473 (15)	0.0446 (15)	−0.0040 (12)	−0.0061 (11)	−0.0064 (12)
C7B	0.0476 (13)	0.0523 (15)	0.0472 (15)	−0.0025 (12)	−0.0106 (13)	−0.0078 (12)
C8B	0.0478 (13)	0.0515 (15)	0.0494 (16)	0.0036 (12)	−0.0096 (12)	−0.0039 (13)
C9B	0.0477 (13)	0.0400 (14)	0.0440 (15)	0.0050 (11)	−0.0016 (11)	−0.0003 (11)
C10B	0.0489 (14)	0.0418 (14)	0.0484 (16)	−0.0026 (12)	0.0014 (12)	−0.0013 (11)
C11B	0.0546 (14)	0.0443 (15)	0.0415 (15)	−0.0049 (12)	0.0038 (12)	−0.0044 (11)
O11B	0.0718 (13)	0.0760 (16)	0.0503 (12)	−0.0270 (12)	0.0151 (10)	−0.0173 (11)
C12B	0.0508 (14)	0.0412 (14)	0.0510 (16)	−0.0075 (12)	0.0029 (12)	−0.0058 (12)
O12B	0.0720 (12)	0.0715 (14)	0.0596 (14)	−0.0302 (11)	0.0081 (10)	−0.0132 (11)
C122	0.084 (2)	0.106 (3)	0.074 (2)	−0.050 (2)	−0.001 (2)	−0.003 (2)
C13B	0.0580 (15)	0.0469 (16)	0.0560 (18)	−0.0075 (13)	0.0120 (14)	−0.0008 (13)
C14B	0.0644 (16)	0.0510 (16)	0.0439 (16)	−0.0009 (13)	0.0057 (13)	−0.0057 (13)

Geometric parameters (Å, º)

C1A—C6A	1.390 (4)	C1B—C6B	1.392 (4)
C1A—C2A	1.393 (4)	C1B—C2B	1.402 (3)
C1A—C7A	1.480 (4)	C1B—C7B	1.469 (3)
C2A—C3A	1.387 (4)	C2B—C3B	1.374 (4)
C2A—H2A	0.9300	C2B—H2B	0.9300
C3A—O3A	1.365 (3)	C3B—O3B	1.369 (3)
C3A—C4A	1.392 (4)	C3B—C4B	1.401 (4)
O3A—C31A	1.412 (4)	O3B—C31B	1.423 (4)
C31A—H31A	0.9600	C31B—H31D	0.9600
C31A—H31B	0.9600	C31B—H31E	0.9600
C31A—H31C	0.9600	C31B—H31F	0.9600
C4A—O4A	1.381 (3)	C4B—C5B	1.382 (4)
C4A—C5A	1.392 (4)	C4B—O4B	1.382 (3)
O4A—C41A	1.431 (4)	O4B—C41B	1.415 (4)
C41A—H41A	0.9600	C41B—H41D	0.9600
C41A—H41B	0.9600	C41B—H41E	0.9600
C41A—H41C	0.9600	C41B—H41F	0.9600
C5A—O5A	1.365 (3)	C5B—O5B	1.376 (3)
C5A—C6A	1.386 (4)	C5B—C6B	1.380 (4)
O5A—C51A	1.421 (4)	O5B—C51B	1.418 (4)
C51A—H51A	0.9600	C51B—H51D	0.9600
C51A—H51B	0.9600	C51B—H51E	0.9600
C51A—H51C	0.9600	C51B—H51F	0.9600
C6A—H6A	0.9300	C6B—H6B	0.9300
C7A—C8A	1.333 (4)	C7B—C8B	1.337 (4)
C7A—H7A	0.9300	C7B—H7B	0.9300
C8A—C9A	1.474 (4)	C8B—C9B	1.474 (4)
C8A—H8A	0.9300	C8B—H8B	0.9300
C9A—C14A	1.374 (4)	C9B—C14B	1.382 (4)
C9A—C10A	1.403 (4)	C9B—C10B	1.393 (4)
C10A—C11A	1.361 (4)	C10B—C11B	1.374 (4)
C10A—H10A	0.9300	C10B—H10B	0.9300
C11A—O11A	1.372 (4)	C11B—O11B	1.359 (3)
C11A—C12A	1.384 (4)	C11B—C12B	1.397 (4)
O11A—H11A	0.92 (6)	O11B—H11B	0.89 (5)
C12A—O12A	1.373 (4)	C12B—C13B	1.371 (4)
C12A—C13A	1.374 (4)	C12B—O12B	1.376 (3)
O12A—C121	1.398 (4)	O12B—C122	1.377 (4)
C121—H12D	0.9600	C122—H12A	0.9600
C121—H12E	0.9600	C122—H12B	0.9600
C121—H12F	0.9600	C122—H12C	0.9600
C13A—C14A	1.396 (5)	C13B—C14B	1.391 (4)
C13A—H13A	0.9300	C13B—H13B	0.9300
C14A—H14A	0.9300	C14B—H14B	0.9300
C6A—C1A—C2A	119.4 (2)	C6B—C1B—C2B	118.9 (2)
C6A—C1A—C7A	122.6 (3)	C6B—C1B—C7B	117.2 (2)
C2A—C1A—C7A	118.0 (2)	C2B—C1B—C7B	123.9 (2)
C3A—C2A—C1A	120.3 (3)	C3B—C2B—C1B	120.2 (2)
C3A—C2A—H2A	119.9	C3B—C2B—H2B	119.9
C1A—C2A—H2A	119.9	C1B—C2B—H2B	119.9
O3A—C3A—C2A	125.0 (3)	O3B—C3B—C2B	124.2 (2)
O3A—C3A—C4A	114.9 (2)	O3B—C3B—C4B	115.2 (2)
C2A—C3A—C4A	120.1 (2)	C2B—C3B—C4B	120.6 (2)
C3A—O3A—C31A	118.1 (2)	C3B—O3B—C31B	117.7 (2)
O3A—C31A—H31A	109.5	O3B—C31B—H31D	109.5
O3A—C31A—H31B	109.5	O3B—C31B—H31E	109.5
H31A—C31A—H31B	109.5	H31D—C31B—H31E	109.5
O3A—C31A—H31C	109.5	O3B—C31B—H31F	109.5
H31A—C31A—H31C	109.5	H31D—C31B—H31F	109.5
H31B—C31A—H31C	109.5	H31E—C31B—H31F	109.5
O4A—C4A—C3A	119.7 (2)	C5B—C4B—O4B	121.7 (2)
O4A—C4A—C5A	120.6 (2)	C5B—C4B—C3B	119.0 (2)
C3A—C4A—C5A	119.6 (2)	O4B—C4B—C3B	119.1 (2)
C4A—O4A—C41A	115.3 (2)	C4B—O4B—C41B	114.3 (3)
O4A—C41A—H41A	109.5	O4B—C41B—H41D	109.5
O4A—C41A—H41B	109.5	O4B—C41B—H41E	109.5
H41A—C41A—H41B	109.5	H41D—C41B—H41E	109.5
O4A—C41A—H41C	109.5	O4B—C41B—H41F	109.5
H41A—C41A—H41C	109.5	H41D—C41B—H41F	109.5
H41B—C41A—H41C	109.5	H41E—C41B—H41F	109.5
O5A—C5A—C6A	124.8 (2)	O5B—C5B—C6B	124.3 (2)
O5A—C5A—C4A	115.1 (2)	O5B—C5B—C4B	115.0 (2)
C6A—C5A—C4A	120.1 (2)	C6B—C5B—C4B	120.7 (2)
C5A—O5A—C51A	118.1 (2)	C5B—O5B—C51B	117.0 (2)
O5A—C51A—H51A	109.5	O5B—C51B—H51D	109.5
O5A—C51A—H51B	109.5	O5B—C51B—H51E	109.5
H51A—C51A—H51B	109.5	H51D—C51B—H51E	109.5
O5A—C51A—H51C	109.5	O5B—C51B—H51F	109.5
H51A—C51A—H51C	109.5	H51D—C51B—H51F	109.5
H51B—C51A—H51C	109.5	H51E—C51B—H51F	109.5
C5A—C6A—C1A	120.4 (2)	C5B—C6B—C1B	120.6 (2)
C5A—C6A—H6A	119.8	C5B—C6B—H6B	119.7
C1A—C6A—H6A	119.8	C1B—C6B—H6B	119.7
C8A—C7A—C1A	129.0 (3)	C8B—C7B—C1B	131.0 (2)
C8A—C7A—H7A	115.5	C8B—C7B—H7B	114.5
C1A—C7A—H7A	115.5	C1B—C7B—H7B	114.5
C7A—C8A—C9A	129.6 (3)	C7B—C8B—C9B	129.3 (2)
C7A—C8A—H8A	115.2	C7B—C8B—H8B	115.4
C9A—C8A—H8A	115.2	C9B—C8B—H8B	115.4
C14A—C9A—C10A	117.8 (3)	C14B—C9B—C10B	118.5 (2)
C14A—C9A—C8A	120.6 (3)	C14B—C9B—C8B	122.2 (2)
C10A—C9A—C8A	121.6 (3)	C10B—C9B—C8B	119.2 (2)
C11A—C10A—C9A	121.0 (3)	C11B—C10B—C9B	121.0 (2)
C11A—C10A—H10A	119.5	C11B—C10B—H10B	119.5
C9A—C10A—H10A	119.5	C9B—C10B—H10B	119.5
C10A—C11A—O11A	118.9 (3)	O11B—C11B—C10B	118.7 (2)
C10A—C11A—C12A	120.7 (3)	O11B—C11B—C12B	121.4 (2)
O11A—C11A—C12A	120.4 (3)	C10B—C11B—C12B	119.9 (3)
C11A—O11A—H11A	104 (3)	C11B—O11B—H11B	105 (3)
O12A—C12A—C13A	126.4 (3)	C13B—C12B—O12B	126.1 (2)
O12A—C12A—C11A	114.2 (3)	C13B—C12B—C11B	119.6 (2)
C13A—C12A—C11A	119.3 (3)	O12B—C12B—C11B	114.3 (2)
C12A—O12A—C121	118.1 (3)	C12B—O12B—C122	118.9 (3)
O12A—C121—H12D	109.5	O12B—C122—H12A	109.5
O12A—C121—H12E	109.5	O12B—C122—H12B	109.5
H12D—C121—H12E	109.5	H12A—C122—H12B	109.5
O12A—C121—H12F	109.5	O12B—C122—H12C	109.5
H12D—C121—H12F	109.5	H12A—C122—H12C	109.5
H12E—C121—H12F	109.5	H12B—C122—H12C	109.5
C12A—C13A—C14A	119.9 (3)	C12B—C13B—C14B	120.2 (3)
C12A—C13A—H13A	120.1	C12B—C13B—H13B	119.9
C14A—C13A—H13A	120.1	C14B—C13B—H13B	119.9
C9A—C14A—C13A	121.1 (3)	C9B—C14B—C13B	120.7 (3)
C9A—C14A—H14A	119.5	C9B—C14B—H14B	119.6
C13A—C14A—H14A	119.5	C13B—C14B—H14B	119.6
C6A—C1A—C2A—C3A	−3.9 (4)	C6B—C1B—C2B—C3B	−1.3 (4)
C7A—C1A—C2A—C3A	175.2 (2)	C7B—C1B—C2B—C3B	−179.3 (3)
C1A—C2A—C3A—O3A	−177.2 (2)	C1B—C2B—C3B—O3B	−178.9 (3)
C1A—C2A—C3A—C4A	0.8 (4)	C1B—C2B—C3B—C4B	1.3 (4)
C2A—C3A—O3A—C31A	−8.9 (4)	C2B—C3B—O3B—C31B	−8.0 (4)
C4A—C3A—O3A—C31A	173.1 (3)	C4B—C3B—O3B—C31B	171.7 (3)
O3A—C3A—C4A—O4A	−2.6 (4)	O3B—C3B—C4B—C5B	179.5 (3)
C2A—C3A—C4A—O4A	179.3 (2)	C2B—C3B—C4B—C5B	−0.7 (4)
O3A—C3A—C4A—C5A	−179.6 (2)	O3B—C3B—C4B—O4B	−5.1 (4)
C2A—C3A—C4A—C5A	2.2 (4)	C2B—C3B—C4B—O4B	174.7 (2)
C3A—C4A—O4A—C41A	106.9 (3)	C5B—C4B—O4B—C41B	−79.8 (4)
C5A—C4A—O4A—C41A	−76.0 (3)	C3B—C4B—O4B—C41B	104.9 (3)
O4A—C4A—C5A—O5A	1.0 (4)	O4B—C4B—C5B—O5B	3.7 (4)
C3A—C4A—C5A—O5A	178.0 (2)	C3B—C4B—C5B—O5B	179.0 (2)
O4A—C4A—C5A—C6A	−179.1 (2)	O4B—C4B—C5B—C6B	−175.3 (3)
C3A—C4A—C5A—C6A	−2.1 (4)	C3B—C4B—C5B—C6B	0.0 (4)
C6A—C5A—O5A—C51A	−11.8 (4)	C6B—C5B—O5B—C51B	0.8 (5)
C4A—C5A—O5A—C51A	168.1 (3)	C4B—C5B—O5B—C51B	−178.1 (3)
O5A—C5A—C6A—C1A	178.8 (3)	O5B—C5B—C6B—C1B	−178.9 (3)
C4A—C5A—C6A—C1A	−1.1 (4)	C4B—C5B—C6B—C1B	0.0 (4)
C2A—C1A—C6A—C5A	4.1 (4)	C2B—C1B—C6B—C5B	0.7 (4)
C7A—C1A—C6A—C5A	−175.0 (3)	C7B—C1B—C6B—C5B	178.8 (3)
C6A—C1A—C7A—C8A	30.6 (4)	C6B—C1B—C7B—C8B	171.6 (3)
C2A—C1A—C7A—C8A	−148.6 (3)	C2B—C1B—C7B—C8B	−10.3 (5)
C1A—C7A—C8A—C9A	2.9 (5)	C1B—C7B—C8B—C9B	−4.4 (6)
C7A—C8A—C9A—C14A	−139.2 (3)	C7B—C8B—C9B—C14B	−59.4 (4)
C7A—C8A—C9A—C10A	41.2 (4)	C7B—C8B—C9B—C10B	122.2 (3)
C14A—C9A—C10A—C11A	4.4 (4)	C14B—C9B—C10B—C11B	2.6 (4)
C8A—C9A—C10A—C11A	−175.9 (3)	C8B—C9B—C10B—C11B	−179.0 (2)
C9A—C10A—C11A—O11A	177.9 (3)	C9B—C10B—C11B—O11B	179.1 (2)
C9A—C10A—C11A—C12A	−2.4 (4)	C9B—C10B—C11B—C12B	−0.3 (4)
C10A—C11A—C12A—O12A	−180.0 (3)	O11B—C11B—C12B—C13B	178.6 (3)
O11A—C11A—C12A—O12A	−0.3 (4)	C10B—C11B—C12B—C13B	−2.0 (4)
C10A—C11A—C12A—C13A	−0.8 (4)	O11B—C11B—C12B—O12B	−2.8 (4)
O11A—C11A—C12A—C13A	178.8 (3)	C10B—C11B—C12B—O12B	176.5 (3)
C13A—C12A—O12A—C121	−0.3 (5)	C13B—C12B—O12B—C122	−9.6 (5)
C11A—C12A—O12A—C121	178.8 (4)	C11B—C12B—O12B—C122	171.9 (3)
O12A—C12A—C13A—C14A	−179.0 (3)	O12B—C12B—C13B—C14B	−176.3 (3)
C11A—C12A—C13A—C14A	1.9 (5)	C11B—C12B—C13B—C14B	2.1 (4)
C10A—C9A—C14A—C13A	−3.3 (4)	C10B—C9B—C14B—C13B	−2.5 (4)
C8A—C9A—C14A—C13A	177.0 (3)	C8B—C9B—C14B—C13B	179.1 (3)
C12A—C13A—C14A—C9A	0.2 (5)	C12B—C13B—C14B—C9B	0.2 (4)