Hydrogen-bonded structures and inter­action energies in two forms of the SGLT-2 inhibitor sotagliflozin

The sotagliflozin mol­ecule exhibits two fundamentally different mol­ecular conformations in form 1 {systematic name: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-eth­oxy­benz­yl)phen­yl]-6-(methyl­sulfan­yl)tetra­hydro-2H-pyran-3,4,5-triol, C₂₁H₂₅ClO₅S, (I)} and the monohydrate [C₂₁H₂₅ClO₅S·H₂O, (II)]. Both crystals display hydrogen-bonded layers formed by inter­molecular inter­actions which involve the three –OH groups of the xyloside fragment of the mol­ecule. The layer architectures of (I) and (II) contain a non-hydrogen-bonded mol­ecule–mol­ecule inter­action along the short crystallographic axis (a axis) whose total PIXEL energy exceeds that of each hydrogen-bonded mol­ecule–mol­ecule pair. The hydrogen-bonded layer of (I) has the topology of the 4-connected sql net and that formed by the water and sotagliflozin mol­ecules of (II) has the topology of a 3,7-connected net.

Computing details

For both structures, data collection: CrysAlis PRO (Rigaku Oxford Diffraction, 2015); cell refinement: CrysAlis PRO (Rigaku Oxford Diffraction, 2015); data reduction: CrysAlis PRO (Rigaku Oxford Diffraction, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: XP (Bruker, 1998), Mercury (Macrae et al., 2006) and TOPOS (Blatov, 2006); software used to prepare material for publication: PLATON (Spek, 2009) and publCIF (Westrip, 2010).

(2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-6-(methylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol (I)

Crystal data

C21H25ClO5S	Dx = 1.314 Mg m^−3
Mr = 424.92	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, P212121	Cell parameters from 2082 reflections
a = 5.3945 (4) Å	θ = 4.0–67.4°
b = 9.1577 (5) Å	µ = 2.73 mm^−1
c = 43.475 (4) Å	T = 253 K
V = 2147.7 (3) Å^3	Prism, colourless
Z = 4	0.15 × 0.08 × 0.04 mm
F(000) = 896

Data collection

Rigaku Xcalibur Ruby (Gemini ultra) diffractometer	3849 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance Ultra (Cu) X-ray Source	3081 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.065
Detector resolution: 10.3575 pixels mm^-1	θmax = 68.1°, θmin = 4.1°
ω scans	h = −6→6
Absorption correction: multi-scan (CrysAlis PRO, Rigaku Oxford Diffraction, 2015)	k = −10→10
Tmin = 0.678, Tmax = 1.000	l = −49→51
12259 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.044	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.108	w = 1/[σ^2(Fo^2) + (0.0315P)^2 + 0.2004P] where P = (Fo^2 + 2Fc^2)/3
S = 1.07	(Δ/σ)max = 0.001
3849 reflections	Δρmax = 0.17 e Å^−3
269 parameters	Δρmin = −0.21 e Å^−3
3 restraints	Absolute structure: Flack x determined using 1021 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.031 (18)

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
O1	0.5532 (6)	0.7137 (3)	0.67757 (6)	0.0416 (7)
C2	0.5324 (8)	0.8155 (4)	0.70215 (9)	0.0388 (9)
H2	0.3816	0.7912	0.7136	0.047*
C3	0.7474 (8)	0.7994 (4)	0.72382 (9)	0.0353 (8)
H3	0.9001	0.8289	0.7133	0.042*
C4	0.7747 (8)	0.6434 (4)	0.73522 (8)	0.0338 (8)
H4	0.6379	0.6224	0.7494	0.041*
C5	0.7656 (8)	0.5334 (4)	0.70900 (8)	0.0346 (8)
H5	0.9159	0.5446	0.6966	0.041*
C6	0.5402 (8)	0.5661 (4)	0.68863 (8)	0.0369 (8)
H6	0.3901	0.5559	0.7011	0.044*
S7	0.4926 (2)	0.99677 (11)	0.68675 (3)	0.0521 (3)
C8	0.7782 (13)	1.0243 (7)	0.66669 (16)	0.0871 (19)
H8A	0.9136	1.0195	0.6810	0.131*
H8B	0.7765	1.1185	0.6570	0.131*
H8C	0.7978	0.9498	0.6513	0.131*
O9	0.7144 (5)	0.8871 (3)	0.75063 (6)	0.0411 (6)
H9	0.807 (8)	0.960 (4)	0.7491 (12)	0.058 (15)*
O10	1.0025 (7)	0.6281 (3)	0.75158 (6)	0.0462 (6)
H10	1.015 (11)	0.699 (3)	0.7635 (9)	0.056 (13)*
O11	0.7565 (6)	0.3873 (3)	0.72033 (7)	0.0431 (7)
H11	0.618 (5)	0.376 (6)	0.7287 (12)	0.064 (17)*
C12	0.5191 (8)	0.4648 (4)	0.66126 (8)	0.0391 (9)
C13	0.6882 (9)	0.4738 (5)	0.63690 (9)	0.0468 (10)
H13	0.8096	0.5459	0.6373	0.056*
C14	0.6789 (9)	0.3773 (5)	0.61211 (9)	0.0493 (11)
C15	0.4919 (10)	0.2720 (4)	0.61243 (9)	0.0491 (10)
C16	0.3231 (10)	0.2630 (5)	0.63612 (10)	0.0491 (11)
H16	0.1994	0.1923	0.6356	0.059*
C17	0.3373 (9)	0.3583 (5)	0.66051 (9)	0.0434 (10)
H17	0.2241	0.3512	0.6766	0.052*
C18	0.8757 (10)	0.3829 (7)	0.58731 (10)	0.0629 (14)
H18A	0.9515	0.2870	0.5860	0.075*
H18B	1.0034	0.4504	0.5940	0.075*
C19	0.7951 (10)	0.4271 (6)	0.55509 (10)	0.0566 (12)
C20	0.5988 (11)	0.5178 (8)	0.54861 (11)	0.0737 (16)
H20	0.5002	0.5516	0.5646	0.088*
C21	0.5444 (12)	0.5601 (7)	0.51875 (12)	0.0758 (16)
H21	0.4097	0.6207	0.5149	0.091*
C22	0.6903 (12)	0.5121 (6)	0.49492 (11)	0.0654 (14)
C23	0.8842 (12)	0.4198 (7)	0.50102 (12)	0.0754 (17)
H23	0.9831	0.3861	0.4850	0.090*
C24	0.9329 (11)	0.3770 (7)	0.53060 (11)	0.0668 (14)
H24	1.0625	0.3124	0.5342	0.069 (17)*
Cl25	0.4717 (4)	0.14452 (15)	0.58310 (3)	0.0790 (5)
O26	0.6608 (10)	0.5511 (5)	0.46459 (8)	0.0909 (14)
C27	0.4644 (17)	0.6439 (8)	0.45612 (14)	0.094 (2)
H27A	0.4767	0.7358	0.4671	0.113*
H27B	0.3069	0.5989	0.4612	0.113*
C28	0.481 (2)	0.6698 (9)	0.42195 (14)	0.115 (3)
H28A	0.3348	0.7201	0.4151	0.173*
H28B	0.4938	0.5779	0.4115	0.173*
H28C	0.6244	0.7281	0.4175	0.173*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0534 (19)	0.0379 (13)	0.0336 (13)	0.0018 (13)	−0.0008 (13)	0.0029 (11)
C2	0.042 (2)	0.0351 (18)	0.0397 (19)	0.0028 (18)	−0.0013 (19)	0.0017 (15)
C3	0.035 (2)	0.0323 (18)	0.038 (2)	0.0004 (17)	0.0036 (17)	0.0003 (15)
C4	0.035 (2)	0.0309 (18)	0.0355 (19)	0.0024 (16)	−0.0036 (17)	−0.0010 (15)
C5	0.036 (2)	0.0311 (19)	0.0366 (19)	−0.0005 (16)	0.0008 (16)	−0.0009 (15)
C6	0.040 (2)	0.0355 (17)	0.0348 (18)	0.0016 (17)	0.0005 (18)	−0.0003 (15)
S7	0.0537 (6)	0.0399 (5)	0.0626 (6)	0.0086 (5)	−0.0028 (6)	0.0117 (5)
C8	0.077 (4)	0.089 (4)	0.096 (4)	0.008 (3)	0.011 (4)	0.048 (4)
O9	0.0440 (16)	0.0346 (14)	0.0446 (15)	−0.0014 (13)	−0.0011 (13)	−0.0072 (12)
O10	0.0509 (16)	0.0379 (13)	0.0497 (14)	0.0080 (15)	−0.0195 (15)	−0.0073 (12)
O11	0.048 (2)	0.0300 (13)	0.0515 (17)	0.0027 (14)	−0.0070 (15)	0.0022 (12)
C12	0.044 (2)	0.0401 (19)	0.0336 (18)	0.002 (2)	−0.0064 (19)	0.0009 (14)
C13	0.048 (2)	0.057 (3)	0.036 (2)	−0.005 (2)	−0.0033 (19)	−0.0002 (19)
C14	0.051 (3)	0.065 (3)	0.032 (2)	0.011 (2)	−0.0040 (19)	−0.001 (2)
C15	0.062 (3)	0.049 (2)	0.036 (2)	0.010 (2)	−0.010 (2)	−0.0060 (17)
C16	0.061 (3)	0.040 (2)	0.046 (2)	−0.005 (2)	−0.017 (2)	0.0011 (19)
C17	0.051 (3)	0.044 (2)	0.035 (2)	0.001 (2)	−0.0025 (18)	0.0004 (17)
C18	0.051 (3)	0.102 (4)	0.036 (2)	0.014 (3)	0.000 (2)	−0.007 (3)
C19	0.058 (3)	0.073 (3)	0.039 (2)	0.002 (3)	0.004 (2)	−0.008 (2)
C20	0.070 (4)	0.106 (4)	0.045 (3)	0.026 (3)	0.007 (2)	−0.004 (3)
C21	0.075 (4)	0.096 (4)	0.056 (3)	0.023 (3)	0.002 (3)	0.003 (3)
C22	0.085 (4)	0.073 (3)	0.039 (2)	−0.003 (3)	0.001 (2)	0.000 (2)
C23	0.091 (4)	0.095 (4)	0.039 (2)	0.021 (3)	0.012 (3)	−0.005 (3)
C24	0.069 (4)	0.087 (4)	0.045 (2)	0.016 (3)	0.002 (2)	−0.006 (3)
Cl25	0.1166 (13)	0.0693 (7)	0.0513 (6)	0.0050 (9)	−0.0106 (8)	−0.0229 (5)
O26	0.122 (4)	0.107 (3)	0.0438 (19)	0.027 (3)	−0.002 (2)	0.006 (2)
C27	0.118 (6)	0.096 (4)	0.068 (3)	0.016 (5)	−0.017 (4)	0.008 (3)
C28	0.170 (8)	0.110 (5)	0.064 (3)	0.019 (6)	−0.020 (5)	0.021 (3)

Geometric parameters (Å, º)

O1—C2	1.423 (5)	C14—C18	1.514 (7)
O1—C6	1.436 (5)	C15—C16	1.377 (7)
C2—C3	1.501 (6)	C15—Cl25	1.732 (4)
C2—S7	1.803 (4)	C16—C17	1.376 (6)
C2—H2	0.9800	C16—H16	0.9300
C3—O9	1.427 (5)	C17—H17	0.9300
C3—C4	1.519 (5)	C18—C19	1.522 (7)
C3—H3	0.9800	C18—H18A	0.9700
C4—O10	1.427 (5)	C18—H18B	0.9700
C4—C5	1.522 (5)	C19—C20	1.375 (8)
C4—H4	0.9800	C19—C24	1.377 (7)
C5—O11	1.426 (5)	C20—C21	1.386 (8)
C5—C6	1.534 (6)	C20—H20	0.9300
C5—H5	0.9800	C21—C22	1.373 (8)
C6—C12	1.513 (5)	C21—H21	0.9300
C6—H6	0.9800	C22—C23	1.371 (9)
S7—C8	1.788 (7)	C22—O26	1.375 (6)
C8—H8A	0.9600	C23—C24	1.370 (8)
C8—H8B	0.9600	C23—H23	0.9300
C8—H8C	0.9600	C24—H24	0.9300
O9—H9	0.836 (14)	O26—C27	1.407 (9)
O10—H10	0.838 (14)	C27—C28	1.507 (9)
O11—H11	0.839 (14)	C27—H27A	0.9700
C12—C17	1.383 (6)	C27—H27B	0.9700
C12—C13	1.400 (6)	C28—H28A	0.9600
C13—C14	1.395 (6)	C28—H28B	0.9600
C13—H13	0.9300	C28—H28C	0.9600
C14—C15	1.396 (7)
C2—O1—C6	111.2 (3)	C13—C14—C18	120.2 (5)
O1—C2—C3	110.3 (3)	C15—C14—C18	122.5 (4)
O1—C2—S7	109.5 (2)	C16—C15—C14	121.8 (4)
C3—C2—S7	114.5 (3)	C16—C15—Cl25	117.9 (4)
O1—C2—H2	107.4	C14—C15—Cl25	120.3 (4)
C3—C2—H2	107.4	C17—C16—C15	120.1 (4)
S7—C2—H2	107.4	C17—C16—H16	120.0
O9—C3—C2	111.2 (3)	C15—C16—H16	120.0
O9—C3—C4	106.0 (3)	C16—C17—C12	120.3 (4)
C2—C3—C4	111.8 (3)	C16—C17—H17	119.8
O9—C3—H3	109.3	C12—C17—H17	119.8
C2—C3—H3	109.3	C14—C18—C19	117.7 (4)
C4—C3—H3	109.3	C14—C18—H18A	107.9
O10—C4—C3	109.8 (3)	C19—C18—H18A	107.9
O10—C4—C5	109.7 (3)	C14—C18—H18B	107.9
C3—C4—C5	112.0 (3)	C19—C18—H18B	107.9
O10—C4—H4	108.4	H18A—C18—H18B	107.2
C3—C4—H4	108.4	C20—C19—C24	117.3 (5)
C5—C4—H4	108.4	C20—C19—C18	124.7 (4)
O11—C5—C4	111.3 (3)	C24—C19—C18	117.9 (5)
O11—C5—C6	110.8 (3)	C19—C20—C21	121.6 (5)
C4—C5—C6	109.2 (3)	C19—C20—H20	119.2
O11—C5—H5	108.5	C21—C20—H20	119.2
C4—C5—H5	108.5	C22—C21—C20	119.7 (5)
C6—C5—H5	108.5	C22—C21—H21	120.1
O1—C6—C12	108.5 (3)	C20—C21—H21	120.1
O1—C6—C5	109.8 (3)	C23—C22—C21	119.3 (5)
C12—C6—C5	113.2 (3)	C23—C22—O26	115.7 (5)
O1—C6—H6	108.4	C21—C22—O26	125.0 (5)
C12—C6—H6	108.4	C24—C23—C22	120.3 (5)
C5—C6—H6	108.4	C24—C23—H23	119.9
C8—S7—C2	102.0 (3)	C22—C23—H23	119.9
S7—C8—H8A	109.5	C23—C24—C19	121.8 (5)
S7—C8—H8B	109.5	C23—C24—H24	119.1
H8A—C8—H8B	109.5	C19—C24—H24	119.1
S7—C8—H8C	109.5	C22—O26—C27	119.7 (5)
H8A—C8—H8C	109.5	O26—C27—C28	108.0 (7)
H8B—C8—H8C	109.5	O26—C27—H27A	110.1
C3—O9—H9	108 (4)	C28—C27—H27A	110.1
C4—O10—H10	108 (4)	O26—C27—H27B	110.1
C5—O11—H11	107 (4)	C28—C27—H27B	110.1
C17—C12—C13	119.1 (4)	H27A—C27—H27B	108.4
C17—C12—C6	120.3 (4)	C27—C28—H28A	109.5
C13—C12—C6	120.6 (4)	C27—C28—H28B	109.5
C14—C13—C12	121.6 (4)	H28A—C28—H28B	109.5
C14—C13—H13	119.2	C27—C28—H28C	109.5
C12—C13—H13	119.2	H28A—C28—H28C	109.5
C13—C14—C15	117.2 (4)	H28B—C28—H28C	109.5
C6—O1—C2—C3	63.6 (4)	C12—C13—C14—C15	0.6 (6)
C6—O1—C2—S7	−169.6 (3)	C12—C13—C14—C18	−175.5 (4)
O1—C2—C3—O9	−172.6 (3)	C13—C14—C15—C16	0.0 (6)
S7—C2—C3—O9	63.4 (4)	C18—C14—C15—C16	176.0 (4)
O1—C2—C3—C4	−54.4 (4)	C13—C14—C15—Cl25	−178.2 (4)
S7—C2—C3—C4	−178.4 (3)	C18—C14—C15—Cl25	−2.2 (6)
O9—C3—C4—O10	−68.1 (4)	C14—C15—C16—C17	−0.7 (7)
C2—C3—C4—O10	170.6 (3)	Cl25—C15—C16—C17	177.6 (4)
O9—C3—C4—C5	169.8 (3)	C15—C16—C17—C12	0.7 (6)
C2—C3—C4—C5	48.6 (4)	C13—C12—C17—C16	−0.1 (6)
O10—C4—C5—O11	66.0 (4)	C6—C12—C17—C16	−177.8 (4)
C3—C4—C5—O11	−171.9 (3)	C13—C14—C18—C19	−114.6 (6)
O10—C4—C5—C6	−171.3 (3)	C15—C14—C18—C19	69.4 (7)
C3—C4—C5—C6	−49.2 (4)	C14—C18—C19—C20	28.8 (9)
C2—O1—C6—C12	170.4 (3)	C14—C18—C19—C24	−153.5 (5)
C2—O1—C6—C5	−65.4 (4)	C24—C19—C20—C21	−1.4 (10)
O11—C5—C6—O1	179.9 (3)	C18—C19—C20—C21	176.3 (6)
C4—C5—C6—O1	56.9 (4)	C19—C20—C21—C22	−0.7 (10)
O11—C5—C6—C12	−58.7 (4)	C20—C21—C22—C23	1.7 (10)
C4—C5—C6—C12	178.3 (3)	C20—C21—C22—O26	−177.3 (6)
O1—C2—S7—C8	−63.5 (4)	C21—C22—C23—C24	−0.6 (10)
C3—C2—S7—C8	60.9 (4)	O26—C22—C23—C24	178.5 (6)
O1—C6—C12—C17	−130.3 (4)	C22—C23—C24—C19	−1.6 (10)
C5—C6—C12—C17	107.6 (4)	C20—C19—C24—C23	2.6 (10)
O1—C6—C12—C13	52.0 (5)	C18—C19—C24—C23	−175.3 (6)
C5—C6—C12—C13	−70.1 (5)	C23—C22—O26—C27	179.1 (6)
C17—C12—C13—C14	−0.6 (6)	C21—C22—O26—C27	−1.9 (10)
C6—C12—C13—C14	177.1 (4)	C22—O26—C27—C28	178.9 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···O10^i	0.84 (1)	1.85 (2)	2.686 (4)	175 (5)
O10—H10···O11^i	0.84 (1)	2.23 (3)	2.970 (4)	147 (5)
O11—H11···O9^ii	0.84 (1)	2.01 (2)	2.837 (5)	170 (6)

Symmetry codes: (i) −x+2, y+1/2, −z+3/2; (ii) −x+1, y−1/2, −z+3/2.

(2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-6-(methylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol monohydrate (II)

Crystal data

C21H25ClO5S·H2O	Dx = 1.384 Mg m^−3
Mr = 442.93	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, P212121	Cell parameters from 2038 reflections
a = 4.4659 (3) Å	θ = 4.6–67.2°
b = 9.8994 (8) Å	µ = 2.81 mm^−1
c = 48.073 (5) Å	T = 173 K
V = 2125.3 (3) Å^3	Prism, colourless
Z = 4	0.08 × 0.08 × 0.05 mm
F(000) = 936

Data collection

Rigaku Xcalibur Ruby (Gemini ultra) diffractometer	3737 independent reflections
Radiation source: fine-focus sealed X-ray tube, Enhance Ultra (Cu) X-ray Source	3253 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.083
Detector resolution: 10.3575 pixels mm^-1	θmax = 67.6°, θmin = 3.7°
ω scans	h = −5→5
Absorption correction: multi-scan (CrysAlis PRO; Rigaku Oxford Diffraction, 2015)	k = −7→11
Tmin = 0.560, Tmax = 1.000	l = −57→53
11848 measured reflections

Refinement

Refinement on F^2	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.073	w = 1/[σ^2(Fo^2) + (0.0183P)^2 + 2.0927P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.149	(Δ/σ)max < 0.001
S = 1.35	Δρmax = 0.71 e Å^−3
3737 reflections	Δρmin = −0.39 e Å^−3
279 parameters	Absolute structure: Flack x determined using 1099 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
8 restraints	Absolute structure parameter: 0.02 (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
O1	0.4138 (10)	0.2338 (4)	0.32594 (9)	0.0300 (10)
C2	0.2965 (17)	0.1227 (6)	0.31066 (14)	0.0292 (15)
H2	0.0739	0.1203	0.3129	0.035*
C3	0.3725 (15)	0.1378 (6)	0.27997 (13)	0.0273 (15)
H3	0.5946	0.1319	0.2776	0.033*
C4	0.2648 (16)	0.2740 (6)	0.26914 (12)	0.0282 (14)
H4	0.0427	0.2693	0.2666	0.034*
C5	0.3344 (17)	0.3897 (6)	0.28882 (14)	0.0296 (15)
H5	0.5530	0.4104	0.2874	0.036*
C6	0.2645 (17)	0.3581 (6)	0.31885 (13)	0.0277 (14)
H6	0.0435	0.3452	0.3209	0.033*
S7	0.4542 (4)	−0.02891 (17)	0.32496 (4)	0.0358 (4)
C8	0.282 (2)	−0.0248 (8)	0.35884 (14)	0.0448 (19)
H8A	0.3580	0.0531	0.3693	0.067*
H8B	0.3308	−0.1081	0.3689	0.067*
H8C	0.0646	−0.0172	0.3568	0.067*
O9	0.2341 (12)	0.0346 (4)	0.26364 (9)	0.0328 (11)
H9	0.361 (14)	−0.028 (6)	0.2639 (15)	0.039*
O10	0.3951 (12)	0.3081 (5)	0.24320 (10)	0.0342 (12)
H10	0.269 (8)	0.291 (8)	0.2308 (3)	0.041*
O11	0.1713 (13)	0.5085 (5)	0.28115 (10)	0.0392 (13)
H11	0.134 (17)	0.500 (4)	0.2640 (5)	0.047*
C12	0.3698 (15)	0.4589 (6)	0.34025 (13)	0.0260 (14)
C13	0.2978 (16)	0.4369 (7)	0.36771 (14)	0.0307 (15)
H13	0.1606	0.3664	0.3719	0.037*
C14	0.4143 (16)	0.5120 (7)	0.38983 (14)	0.0336 (16)
C15	0.6019 (17)	0.6201 (7)	0.38196 (15)	0.0330 (16)
C16	0.6726 (17)	0.6477 (7)	0.35477 (14)	0.0331 (16)
H16	0.7987	0.7219	0.3503	0.040*
C17	0.5577 (18)	0.5659 (6)	0.33381 (14)	0.0326 (16)
H17	0.6082	0.5835	0.3150	0.039*
C18	0.3475 (17)	0.4741 (7)	0.41914 (14)	0.0361 (16)
H18A	0.1416	0.4374	0.4201	0.043*
H18B	0.3543	0.5564	0.4308	0.043*
C19	0.5647 (18)	0.3699 (7)	0.43105 (15)	0.0354 (17)
C20	0.6680 (18)	0.2602 (7)	0.41556 (15)	0.0394 (18)
H20	0.6121	0.2528	0.3966	0.047*
C21	0.8488 (19)	0.1624 (8)	0.42711 (16)	0.0401 (19)
H21	0.9159	0.0886	0.4161	0.048*
C22	0.932 (2)	0.1719 (7)	0.45475 (15)	0.0407 (19)
C23	0.8321 (18)	0.2803 (8)	0.47028 (16)	0.0406 (18)
H23	0.8905	0.2885	0.4892	0.049*
C24	0.6489 (18)	0.3762 (7)	0.45862 (15)	0.0372 (18)
H24	0.5784	0.4486	0.4698	0.045*
Cl25	0.7588 (5)	0.72261 (18)	0.40774 (4)	0.0463 (5)
O26	1.1092 (13)	0.0793 (5)	0.46841 (11)	0.0449 (14)
C27	1.212 (2)	−0.0365 (8)	0.45391 (16)	0.049 (2)
H27A	1.3441	−0.0095	0.4384	0.059*
H27B	1.0398	−0.0874	0.4462	0.059*
C28	1.381 (3)	−0.1227 (9)	0.47430 (19)	0.066 (3)
H28A	1.5540	−0.0725	0.4813	0.099*
H28B	1.4491	−0.2053	0.4650	0.099*
H28C	1.2491	−0.1466	0.4899	0.099*
O1W	0.0159 (12)	0.2555 (5)	0.20304 (11)	0.0376 (12)
H1W	−0.104 (13)	0.314 (5)	0.1982 (17)	0.056*
H2W	−0.073 (15)	0.184 (4)	0.2055 (17)	0.056*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.029 (3)	0.024 (2)	0.036 (2)	−0.001 (2)	−0.004 (2)	−0.0004 (19)
C2	0.023 (4)	0.019 (3)	0.046 (4)	−0.001 (3)	−0.007 (3)	0.000 (3)
C3	0.014 (3)	0.026 (3)	0.041 (4)	−0.001 (3)	−0.001 (3)	−0.005 (3)
C4	0.027 (4)	0.025 (3)	0.033 (3)	0.007 (3)	−0.001 (3)	0.000 (3)
C5	0.027 (4)	0.019 (3)	0.043 (4)	0.000 (3)	−0.003 (3)	−0.002 (3)
C6	0.024 (4)	0.022 (3)	0.038 (4)	0.001 (3)	0.000 (3)	−0.001 (2)
S7	0.0382 (11)	0.0249 (8)	0.0443 (10)	0.0028 (8)	−0.0045 (8)	0.0024 (7)
C8	0.058 (6)	0.038 (4)	0.038 (4)	0.001 (5)	−0.003 (4)	0.009 (3)
O9	0.032 (3)	0.025 (2)	0.041 (3)	0.001 (2)	−0.005 (2)	−0.005 (2)
O10	0.038 (3)	0.031 (3)	0.033 (3)	−0.005 (2)	−0.001 (2)	0.0011 (19)
O11	0.049 (3)	0.028 (3)	0.041 (3)	0.008 (2)	−0.006 (2)	−0.0025 (19)
C12	0.020 (3)	0.019 (3)	0.040 (4)	0.005 (3)	−0.004 (3)	−0.002 (3)
C13	0.020 (4)	0.028 (3)	0.045 (4)	0.008 (3)	−0.004 (3)	−0.005 (3)
C14	0.026 (4)	0.033 (4)	0.042 (4)	0.011 (3)	−0.002 (3)	−0.006 (3)
C15	0.026 (4)	0.028 (4)	0.045 (4)	0.000 (3)	−0.008 (3)	−0.013 (3)
C16	0.027 (4)	0.028 (4)	0.044 (4)	0.004 (3)	0.001 (3)	0.000 (3)
C17	0.032 (4)	0.027 (4)	0.039 (4)	0.009 (3)	−0.003 (3)	0.001 (3)
C18	0.030 (4)	0.038 (4)	0.040 (4)	0.002 (4)	0.001 (3)	−0.006 (3)
C19	0.033 (4)	0.031 (4)	0.043 (4)	−0.006 (3)	0.006 (3)	0.001 (3)
C20	0.039 (5)	0.043 (4)	0.036 (4)	−0.009 (4)	−0.001 (3)	−0.002 (3)
C21	0.038 (5)	0.037 (4)	0.046 (5)	−0.003 (4)	0.005 (3)	−0.003 (3)
C22	0.047 (5)	0.034 (4)	0.042 (4)	−0.002 (4)	0.000 (4)	0.001 (3)
C23	0.037 (5)	0.047 (4)	0.038 (4)	−0.003 (4)	0.003 (3)	0.000 (3)
C24	0.041 (5)	0.033 (4)	0.038 (4)	−0.004 (4)	0.004 (3)	−0.006 (3)
Cl25	0.0522 (12)	0.0413 (10)	0.0453 (10)	−0.0086 (10)	−0.0066 (9)	−0.0098 (8)
O26	0.049 (4)	0.038 (3)	0.048 (3)	0.007 (3)	−0.004 (2)	−0.003 (2)
C27	0.051 (6)	0.041 (4)	0.056 (5)	0.002 (5)	0.001 (4)	−0.001 (4)
C28	0.077 (8)	0.056 (5)	0.064 (6)	0.011 (6)	0.012 (5)	0.006 (4)
O1W	0.037 (3)	0.025 (2)	0.050 (3)	−0.002 (2)	−0.003 (2)	0.002 (2)

Geometric parameters (Å, º)

O1—C2	1.423 (8)	C15—C16	1.372 (10)
O1—C6	1.440 (8)	C15—Cl25	1.748 (6)
C2—C3	1.521 (10)	C16—C17	1.391 (10)
C2—S7	1.795 (6)	C16—H16	0.9500
C2—H2	1.0000	C17—H17	0.9500
C3—O9	1.428 (8)	C18—C19	1.528 (11)
C3—C4	1.524 (9)	C18—H18A	0.9900
C3—H3	1.0000	C18—H18B	0.9900
C4—O10	1.417 (8)	C19—C24	1.379 (10)
C4—C5	1.518 (9)	C19—C20	1.395 (10)
C4—H4	1.0000	C20—C21	1.377 (11)
C5—O11	1.431 (8)	C20—H20	0.9500
C5—C6	1.510 (9)	C21—C22	1.383 (11)
C5—H5	1.0000	C21—H21	0.9500
C6—C12	1.508 (9)	C22—O26	1.377 (9)
C6—H6	1.0000	C22—C23	1.382 (11)
S7—C8	1.801 (8)	C23—C24	1.373 (11)
C8—H8A	0.9800	C23—H23	0.9500
C8—H8B	0.9800	C24—H24	0.9500
C8—H8C	0.9800	O26—C27	1.417 (9)
O9—H9	0.837 (13)	C27—C28	1.503 (12)
O10—H10	0.836 (14)	C27—H27A	0.9900
O11—H11	0.843 (13)	C27—H27B	0.9900
C12—C13	1.376 (10)	C28—H28A	0.9800
C12—C17	1.387 (10)	C28—H28B	0.9800
C13—C14	1.398 (10)	C28—H28C	0.9800
C13—H13	0.9500	O1W—H1W	0.821 (13)
C14—C15	1.411 (10)	O1W—H2W	0.820 (14)
C14—C18	1.488 (10)
C2—O1—C6	111.6 (5)	C15—C14—C18	124.3 (6)
O1—C2—C3	110.0 (5)	C16—C15—C14	122.9 (6)
O1—C2—S7	107.7 (4)	C16—C15—Cl25	117.9 (6)
C3—C2—S7	111.5 (5)	C14—C15—Cl25	119.2 (5)
O1—C2—H2	109.2	C15—C16—C17	119.3 (7)
C3—C2—H2	109.2	C15—C16—H16	120.3
S7—C2—H2	109.2	C17—C16—H16	120.3
O9—C3—C2	111.5 (5)	C12—C17—C16	120.4 (7)
O9—C3—C4	107.9 (5)	C12—C17—H17	119.8
C2—C3—C4	110.3 (5)	C16—C17—H17	119.8
O9—C3—H3	109.0	C14—C18—C19	113.4 (6)
C2—C3—H3	109.0	C14—C18—H18A	108.9
C4—C3—H3	109.0	C19—C18—H18A	108.9
O10—C4—C5	106.5 (5)	C14—C18—H18B	108.9
O10—C4—C3	112.4 (5)	C19—C18—H18B	108.9
C5—C4—C3	113.0 (5)	H18A—C18—H18B	107.7
O10—C4—H4	108.2	C24—C19—C20	117.3 (7)
C5—C4—H4	108.2	C24—C19—C18	120.2 (6)
C3—C4—H4	108.2	C20—C19—C18	122.4 (7)
O11—C5—C6	108.1 (5)	C21—C20—C19	121.7 (7)
O11—C5—C4	110.8 (5)	C21—C20—H20	119.1
C6—C5—C4	113.4 (5)	C19—C20—H20	119.1
O11—C5—H5	108.1	C20—C21—C22	119.8 (7)
C6—C5—H5	108.1	C20—C21—H21	120.1
C4—C5—H5	108.1	C22—C21—H21	120.1
O1—C6—C12	105.0 (5)	O26—C22—C23	116.4 (7)
O1—C6—C5	107.9 (5)	O26—C22—C21	124.6 (7)
C12—C6—C5	116.8 (5)	C23—C22—C21	119.0 (7)
O1—C6—H6	109.0	C24—C23—C22	120.6 (7)
C12—C6—H6	109.0	C24—C23—H23	119.7
C5—C6—H6	109.0	C22—C23—H23	119.7
C2—S7—C8	99.2 (3)	C23—C24—C19	121.6 (7)
S7—C8—H8A	109.5	C23—C24—H24	119.2
S7—C8—H8B	109.5	C19—C24—H24	119.2
H8A—C8—H8B	109.5	C22—O26—C27	119.3 (6)
S7—C8—H8C	109.5	O26—C27—C28	107.5 (7)
H8A—C8—H8C	109.5	O26—C27—H27A	110.2
H8B—C8—H8C	109.5	C28—C27—H27A	110.2
C3—O9—H9	103 (5)	O26—C27—H27B	110.2
C4—O10—H10	107.6 (17)	C28—C27—H27B	110.2
C5—O11—H11	105.9 (16)	H27A—C27—H27B	108.5
C13—C12—C17	118.5 (6)	C27—C28—H28A	109.5
C13—C12—C6	118.5 (6)	C27—C28—H28B	109.5
C17—C12—C6	122.8 (6)	H28A—C28—H28B	109.5
C12—C13—C14	124.0 (7)	C27—C28—H28C	109.5
C12—C13—H13	118.0	H28A—C28—H28C	109.5
C14—C13—H13	118.0	H28B—C28—H28C	109.5
C13—C14—C15	114.9 (6)	H1W—O1W—H2W	109 (2)
C13—C14—C18	120.8 (7)
C6—O1—C2—C3	67.4 (7)	C12—C13—C14—C15	3.7 (10)
C6—O1—C2—S7	−170.9 (4)	C12—C13—C14—C18	−174.4 (6)
O1—C2—C3—O9	−174.5 (5)	C13—C14—C15—C16	−1.8 (10)
S7—C2—C3—O9	66.1 (6)	C18—C14—C15—C16	176.2 (7)
O1—C2—C3—C4	−54.6 (7)	C13—C14—C15—Cl25	179.4 (5)
S7—C2—C3—C4	−174.0 (5)	C18—C14—C15—Cl25	−2.6 (10)
O9—C3—C4—O10	−73.3 (7)	C14—C15—C16—C17	−0.4 (11)
C2—C3—C4—O10	164.7 (6)	Cl25—C15—C16—C17	178.4 (6)
O9—C3—C4—C5	166.1 (6)	C13—C12—C17—C16	0.8 (10)
C2—C3—C4—C5	44.1 (8)	C6—C12—C17—C16	−173.4 (6)
O10—C4—C5—O11	69.5 (7)	C15—C16—C17—C12	1.0 (10)
C3—C4—C5—O11	−166.6 (6)	C13—C14—C18—C19	87.0 (8)
O10—C4—C5—C6	−168.7 (6)	C15—C14—C18—C19	−90.9 (9)
C3—C4—C5—C6	−44.8 (8)	C14—C18—C19—C24	144.3 (7)
C2—O1—C6—C12	169.5 (5)	C14—C18—C19—C20	−40.6 (10)
C2—O1—C6—C5	−65.3 (7)	C24—C19—C20—C21	−0.6 (11)
O11—C5—C6—O1	176.4 (5)	C18—C19—C20—C21	−175.8 (7)
C4—C5—C6—O1	53.1 (8)	C19—C20—C21—C22	−0.1 (12)
O11—C5—C6—C12	−65.7 (8)	C20—C21—C22—O26	179.2 (8)
C4—C5—C6—C12	171.0 (6)	C20—C21—C22—C23	−0.1 (12)
O1—C2—S7—C8	66.4 (5)	O26—C22—C23—C24	−178.5 (7)
C3—C2—S7—C8	−172.8 (5)	C21—C22—C23—C24	0.9 (12)
O1—C6—C12—C13	−63.6 (8)	C22—C23—C24—C19	−1.6 (12)
C5—C6—C12—C13	176.9 (6)	C20—C19—C24—C23	1.4 (11)
O1—C6—C12—C17	110.6 (7)	C18—C19—C24—C23	176.8 (7)
C5—C6—C12—C17	−8.9 (10)	C23—C22—O26—C27	178.0 (7)
C17—C12—C13—C14	−3.3 (10)	C21—C22—O26—C27	−1.3 (12)
C6—C12—C13—C14	171.1 (7)	C22—O26—C27—C28	−176.5 (8)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···O10^i	0.84 (1)	1.99 (2)	2.807 (7)	166 (7)
O10—H10···O1W	0.84 (1)	1.79 (2)	2.621 (7)	177 (3)
O11—H11···O9^ii	0.84 (1)	2.14 (4)	2.825 (7)	138 (5)
O1W—H1W···S7^ii	0.82 (1)	2.47 (2)	3.282 (5)	170 (8)
O1W—H2W···O11^iii	0.82 (1)	1.90 (3)	2.694 (6)	162 (7)

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