Co-crystals of 3-de­oxy-3-fluoro-α-D-glucopyran­ose and 3-de­oxy-3-fluoro-β-D-glucopyran­ose

3-De­oxy-3-fluoro-D-glucopyran­ose crystallizes from acetone to give a unit cell containing two crystallographically independent mol­ecules. One of these mol­ecules (at site A) is structurally homogeneous and corresponds to 3-de­oxy-3-fluoro-β-D-glucopyran­ose, C₆H₁₁FO₅, (I). The second mol­ecule (at site B) is structurally heterogeneous and corresponds to a mixture of (I) and 3-de­oxy-3-fluoro-α-D-glucopyran­ose, (II); treatment of the diffraction data using partial-occupancy oxygen at the anomeric center gave a high-quality packing model with an occupancy ratio of 0.84:0.16 for (II):(I) at site B. The mixture of α- and β-anomers at site B appears to be accommodated in the lattice because hydrogen-bonding partners are present to hydrogen bond to the anomeric OH group in either an axial or equatorial orientation. Cremer–Pople analysis of (I) and (II) shows the pyranosyl ring of (II) to be slightly more distorted than that of (I) [θ_(I) = 3.85 (15)° and θ_(II) = 6.35 (16)°], but the general direction of distortion is similar in both structures [φ_(I) = 67 (2)° (B_C1,C4) and φ_(II) = 26.0 (15)° (^C3TB_C1); B = boat conformation and TB = twist-boat conformation]. The exocyclic hy­droxy­methyl (–CH₂OH) conformation is gg (gauche–gauche) (H5 anti to O6) in both (I) and (II). Structural comparisons of (I) and (II) to related unsubstituted, de­oxy and fluorine-substituted monosaccharides show that the gluco ring can assume a wide range of distorted chair structures in the crystalline state depending on ring substitution patterns.

S1. Comment

Fluorosugars (Taylor, 1988) are saccharide derivatives in which one or more of the hydroxyl groups or H atoms in the saccharide are substituted by fluorine. Substitution at the anomeric OH group, giving glycosyl fluorides, activates the anomeric center in chemical glycosylation reactions (Yokoyama, 2000). The altered internal electronic structure in fluorosugars relative to the parent (unsubstituted) saccharide renders them useful to investigate enzyme reaction mechanisms, since such substitution can be exploited to stabilize putative intermediates along a reaction trajectory (White et al., 1996). In addition, substitution of fluorine for OH groups or hydrogen alters the hydrogen-bonding character of saccharides, thus affecting their binding properties to various receptors (Buchini et al., 2008).

We have been preparing fluorosugars as tools to investigate the mechanisms of protein-bound saccharide rearrangements that accompany non-enzyme-catalyzed protein glycation (Chetyrkin et al., 2008). We reported recently the X-ray structure of 4-deoxy-4-fluoro-β-D-glucopyranose (4DFG) and showed that its packing and that of the parent β-D-glucopyranose are very similar (Zhang et al., 2010). Furthermore, we showed that the anomeric configuration of 4DFG molecules in the crystal lattice is not completely homogeneous; careful fitting of the electron density at O1 showed that a small percentage (<5%) of the α-anomer appears to be accommodated in the lattice.

Herein we report the X-ray structure of 3-deoxy-3-fluoro-D-glucopyranose (3DFG) crystallized from acetone (Fig. 1). The crystalline lattice contains two independent molecules at two distinct sites, sites A and B. Site A is occupied by a single structurally homogeneous form of 3DFG, namely, 3-deoxy-3-fluoro-β-D-glucopyranose, (I). Site B, however, is structurally heterogeneous, containing an 84:16 ratio of 3-deoxy-3-fluoro-α-D-glucopyranose, (II), and (I) based on a partial-occupancy fitting of the diffraction data. In comparison, ¹H and ¹³C NMR analyses of 3DFG in ²H₂O solvent show that the α- and β-pyranoses are present in an approximate 47:53 (α:β) ratio (Zhang & Serianni, private communication).

In this paper, the X-ray structures of (I) and (II) are compared to those of related unsubstituted, deoxy and fluorine-substituted saccharides: β-D-glucopyranose, (III) (Kouwijzer et al., 1995); α-D-glucopyranose, (IV) (Mostad, 1994); 3-deoxy-β-D-ribo-hexopyranose, (V) (Zhang et al., 2007); 3-deoxy-3-fluoro-β-D-allopyranose, (VI) (Myers et al., 1997); 4-deoxy-4-fluoro-β-D-glucopyranose, (VII) (Zhang et al., 2010). While the diffraction data for (II) represent a weighted average of contributions made by both the α- and β-pyranose forms of 3DFG, the contribution from the α-anomer is highly dominant, thus justifying a comparison to α-D-glucopyranose, (IV).

A comparison of several structural parameters obtained from X-ray crystal structure analyses of (I)–(VII) is shown in Table 1. Corresponding C—C and C—O bond lengths in (I) and (II) are comparable, except for r_C1,O5, which is substantially longer in (II) [1.4383 (19) Å] than in (I) [1.4176 (19) Å]. Interestingly, r_C1,O1 in (I) and (II) are very similar. In contrast, both r_C1,O5 and r_C1,O1 are minimally affected by anomeric configuration in the unsubstituted D-glucopyranoses, (III) and (IV). The C—F bond length averages 1.400 (4) Å in (I), (II) and (VII), whereas r_C3,F is 1.414 (2) Å in (VI). Thus, axial C—F bonds appear elongated by ~0.01 Å relative to the same bond in an equatorial orientation.

The largest endocyclic bond angle in (I) and (II) is the C5—O5—C1 angle [112.66 (12) and 113.19 (11)°, respectively], thus mimicking behavior in (III) and (IV), where this angle is 112.0 (2) and 113.4 (1)°, respectively. A similar trend is observed in (V)–(VII), where the same angle averages 112.4 (5)°. The exocyclic C4—C5—C6 bond angles in (I)–(VII) are relatively large compared to endocyclic C—C—C bond angles; in (I)–(VII), the former angle averages 113.0 (12)° compared to the three endocyclic C—C—C bond angles, which average 110.6 (12)°.

Endocyclic torsion angles in (I)–(II) vary from 50 to 65° (absolute values), indicating the presence of rings distorted from idealized chair conformations. Similar deviations are observed in (III)–(VII). In addition, the C3—C4—C5—C6 torsion angle varies from 171 to 180° (absolute values), also indicating different degrees and/or types of ring distortion in (I)–(VII). Further insight into these distortions was obtained by calculating Cremer–Pople parameters in (I)–(VII) (Table 2, Cremer & Pople, 1975). The extent of ring distortion, embodied in the value of θ, is slightly greater for (II) [θ = 6.35 (16)°] than for (I) [θ = 3.85 (15)°]. Within (I)–(VII), the most significant ring distortion is observed in (III) [θ = 8.0 (3)°], followed by (VII) [θ = 7.16 (13)°]. The direction of ring distortion, embodied in the value of ϕ, varies widely in (I)–(VII). Average values of ϕ increase as follows: (II) and (VII), 18 (12)°; (I) and (V), 63 (6)°; (III) and (IV), 321 (3)°; and (VI), 358°. Thus, the pyranosyl rings of (II) and (VII) are distorted towards ^C3TB_C1, those of (I) and (V) towards B_C1,C4, those of (III) and (IV) towards ^O5TB_C2, and that of (VI) towards ^C3,O5B. The effect of anomeric configuration on 3DFG pyranose ring shape is small, mimicking the behavior of the unsubstituted D-glucopyranose anomers, (III) and (IV). Interestingly, both (I) and (V) show similar ring distortions, suggesting that C3 deoxygenation and C3 fluorine substitution exert similar effects of [on?] overall pyranose ring shape, at least in the crystalline state. Likewise, inversion of configuration at C3 of (I), giving (VI), induces a measurable but not radical change in ring distortion in that ϕ values for the two structures are within ~70° of one another; an ~60° shift in ϕ is also observed upon moving the fluorine atom in (I) from C3 to C4, giving (VII).

Exocyclic hydroxymethyl conformation in (I)–(VII) is either gg (H5 anti to O6) or gt (C4 anti to O6) [gg = gauche–gauche, gt = gauche–trans]. In gluco isomers (I)–(V) and (VII), this distribution is consistent with NMR findings in which both gg and gt conformers are detected in comparable proportions in solution, with tg [tg = trans–gauche?] present in very minor abundance (Thibaudeau et al., 2004).

Extensive hydrogen-bonding interactions are observed within the crystalline lattice containing (I) and (II) (Fig. 2). In (I), all of the hydroxyl groups serve as donors and all but O2A are mono-acceptors of hydrogen bonds. O2A accepts one `normal' hydrogen bond from O6B [2.7348 (16) Å] and a longer one from O4B [3.1417 (18) Å]. The ring oxygen in (I), O5A, and the fluorine are not involved in hydrogen bonding. In (II) the ordered hydroxyls, O2B, O4B and O6B serve as hydrogen-bond donors and mono-acceptors. O1B and O1B', the α- and β-anomer positions of this hydroxyl group, respectively, are both accomodated by hydrogen bonding to nearby hydroxyls. O1B forms a contact to O5B of a neighboring molecule (related by the screw axis along the a axis), and O1B' forms a contact to O6B of the same neighboring molecule (Fig. 3). Thus, both the α- and β-anomers in site B are accomodated in a `pocket' within the lattice in which they can reside with minimal distortion of the local environment.

S2. Experimental

3-Deoxy-3-fluoro-D-glucose was synthesized by a chemical route described in detail in the Supplementary material. The final purified product was dissolved in a minimal volume of hot acetone, and the solution was left at room temperature until clear, colorless crystals formed overnight. After recrystallization from acetone, the crystals were harvested for structure determination.

S3. Refinement

Of the two crystallographically independent molecules located, one was found to be ordered and is the β-anomer of the 3-deoxy-3-fluoro-D-glucose. The second molecule was found to contain a mixture of both the α- and β-anomers. The site occupancies were refined and summed to unity giving an approximately 0.84:0.16 ratio. The majority component was refined with anisotropic thermal motion parameters and the minor component with isotropic thermal parameters. The carbon to which the two hydroxyls are bonded was also split (but with positional and thermal parameters tied) allowing for modeling of the H-atom positions for both sites A and B.

Hydroxy H atoms were initially located from a difference Fourier map but were subsequently included in geometrically constrained positions with O—H distances of 0.84 Å. All other H atoms were included in calculated positions and constrained to ride on their parent atoms with C—H = 0.99 (methylene) or 1.00 Å (methine). For all H atoms, U_iso(H) values were constrained to 1.2U_eq(parent atom).

The absolute configuration was determined by the retention of the known configuration throughout the synthesis and the comparison of intensities of Freidel pairs of reflections [Flack parameter = 0.05 (12), Flack, 1983]. Further, an analysis of the Hooft y parameter [0.05 (5), Hooft et al., 2008] also agrees. The P2(true) and P3(true) values are both 1.000 (measures of enantiopurity of the crystal).

Computing details

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008) and POV-RAY (Cason, 2003); software used to prepare material for publication: XCIF (Sheldrick, 2008) and publCIF (Westrip, 2010).

Figures

	Fig. 1. Labelling scheme for compounds (I) and (II). Displacement ellipsoids are depicted at the 50% probability level.
	Fig. 2. Hydrogen-bonding scheme for (I) and (II), viewed along the a axis. Dashed lines represent hydrogen bonds.
	Fig. 3. Local hydrogen-bonding scheme for the α- and β-anomers present in the lattice. The light-colored O atoms (O1B') (pink in the electronic version of the paper) represent the minor component. Dashed lines represent hydrogen bonds. [Symmetry code: (i) x − 1/2, −y + 1/2, −z.]

3-deoxy-3-fluoro-β-D-glucopyranose

Crystal data

C6H11FO5	F(000) = 768
Mr = 182.15	Dx = 1.563 Mg m^−3
Orthorhombic, P212121	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2ab	Cell parameters from 8582 reflections
a = 5.1249 (2) Å	θ = 3.8–69.2°
b = 13.7748 (4) Å	µ = 1.33 mm^−1
c = 21.9297 (6) Å	T = 100 K
V = 1548.12 (9) Å^3	Tablet, colorless
Z = 8	0.27 × 0.13 × 0.08 mm

Data collection

Bruker APEXII diffractometer	2847 independent reflections
Radiation source: fine-focus sealed tube	2755 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.026
Detector resolution: 8.33 pixels mm^-1	θmax = 69.7°, θmin = 3.8°
combination of ω and ϕ scans	h = −5→4
Absorption correction: numerical (SADABS; Sheldrick, 2003)	k = −16→16
Tmin = 0.718, Tmax = 0.900	l = −26→25
15073 measured reflections

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)] = 0.027	H-atom parameters constrained
wR(F^2) = 0.070	w = 1/[σ^2(Fo^2) + (0.0374P)^2 + 0.5403P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max < 0.001
2847 reflections	Δρmax = 0.24 e Å^−3
236 parameters	Δρmin = −0.18 e Å^−3
0 restraints	Absolute structure: Flack (1983), 1117 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.05 (12)

Special details

Experimental. 1,2;5,6-Di-O-isopropylidene-α-D-allofuranose. A solution of dimethyl sulfoxide (1.68 ml, 23.64 mmol) in dry CH₂Cl₂ (5 ml) was added to a solution of oxalyl chloride (1.00 ml, 11.82 mmol) in dry CH₂Cl₂ (20 ml) with stirring in a dry ice-acetone bath. The reaction mixture was stirred for 15 min, and 1,2;5,6-di-O-isopropylidene-α-D-glucofuranose (1.00 g, 3.85 mmol, in 30 ml of dry CH₂Cl₂) was added dropwise. After stirring for 2 h, triethylamine (4.00 ml, 28.70 mmol) was added dropwise. Finally, the reaction was quenched by adding a solution of NaBH₄ (0.29 g, 7.67 mmol) in EtOH/H₂O (4:1, 20 ml). All of the above steps were conducted in a dry ice-acetone bath. After warming to room temperature, the reaction mixture was extracted with ethyl acetate (3 × 40 ml), dried over Na₂SO₄, and concentrated in vacuo to give the product, 1,2;5,6-di-O-isopropylidene-α-D-allofuranose (0.90 g; white solid; 90%) (Cruz-Gregorio et al., 2005).

1,2;5,6-Di-O-isopropylidene-3-O-p-tolylsulfonyl-α-D-allofuranose. 1,2;5,6-Di-O-isopropylidene-α-D-allofuranose (0.60 g, 2.31 mmol) was dissolved in dry pyridine (15 ml), and a solution of p-toluenesulfonyl chloride (0.60 g, 3.15 mmol) in CH₂Cl₂ (3 ml) was added dropwise with efficient stirring in a dry ice-acetone bath. The reaction mixture was warmed to room temperature and was stirred for an additional 16 h. Ice water (100 ml) was then added to the reaction mixture, and the mixture was extracted with CH₂Cl₂ (2 × 50 ml). After drying the organic phase over Na₂SO₄, the solution was concentrated in vacuo to a small volume, and the latter was applied to a column of silica gel (30 cm × 2.5 cm) and eluted with ethyl acetate/ hexanes solvent (3:1) to afford pure 1,2;5,6-di-O-isopropylidene-3-O-p-tolylsulfonyl-α-D-allofuranose (0.87 g, 91%).

1,2;5,6-Di-O-isopropylidene-3-deoxy-3-fluoro-α-D-glucofuranose. 1,2;5,6-Di-O-isopropylidene-3-O-p-tolylsulfonyl-α-D-allofuranose (0.80 g, 1.93 mmol) was added to 20 ml of tetra-n-butylammonium fluoride in tetrahydrofuran (1 M). After refluxing for 24 h, the solution was cooled and H₂O (40 ml) was added. The mixture was extracted with CH₂Cl₂ (2 × 40 ml), and the organic phase was dried over Na₂SO₄ and concentrated in vacuo to a small volume. The latter solution was applied to a column of silica gel (30 cm × 2.0 cm) and eluted with ethyl acetate/hexanes solvent (5:1) to afford pure 1,2;5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-glucofuranose (0.39 g, 77%) (Podlasek & Serianni, 1994).

3-Deoxy-3-fluoro-D-glucose. To 0.35 g of 1,2;5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-glucofuranose (1.34 mmol) were added distilled water (20 ml) and Dowex 50 × 8 (200–400 mesh, H⁺) ion-exchange resin (0.6 g). The suspension was refluxed for 3 h. After cooling, the resin was removed by filtration, and the solution was concentrated at 30 °C in vacuo to a small volume. The latter solution was then applied to a column (110 × 2.5 cm) containing Dowex 50 × 8 (200–400 mesh) ion-exchange resin in the Ca²⁺ form (Angyal et al., 1979). The column was eluted with distilled, decarbonated water at ~1.5 ml/min, and fractions (10 ml) were collected and assayed by TLC (silica gel; spots detected by charring after spraying with 1% (w/v) CeSO₄ − 2.5% (w/v) (NH₄)₆Mo₇O₂₄ − 10% aq H₂SO₄ reagent) (Tropper et al.,1992). Fractions 16–19 were pooled and concentrated at 30 °C in vacuo to give pure 3-deoxy-3-fluoro-D-glucose (0.20 g. 82%).

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.

There are two molecules of the fluorinated sugar in the asymmetric unit. One of the molecules is ordered. The other exhibits a mixture of the α- and β-anomers. The site occupancies for the α and β-anomers were refined and summed to unity yielding an approximately 0.84:0.16 ratio of α:β.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
F1	0.1826 (2)	0.71907 (7)	0.03444 (4)	0.0233 (2)
O1A	−0.3845 (3)	0.65910 (8)	0.20127 (5)	0.0196 (2)
H1'	−0.4002	0.6637	0.2393	0.023*
O2A	−0.0724 (2)	0.58012 (8)	0.10888 (5)	0.0186 (2)
H2'	0.0714	0.5630	0.1238	0.022*
O4A	0.3238 (2)	0.89918 (9)	0.09197 (5)	0.0203 (3)
H4'	0.3053	0.9326	0.0602	0.024*
O5A	−0.2138 (2)	0.80927 (8)	0.18628 (5)	0.0177 (2)
O6A	−0.2802 (2)	1.00240 (9)	0.14243 (6)	0.0208 (3)
H6'	−0.3898	0.9574	0.1389	0.025*
C1A	−0.1619 (3)	0.70835 (11)	0.18269 (7)	0.0166 (3)
H1AA	−0.0106	0.6909	0.2093	0.020*
C2A	−0.1044 (3)	0.68196 (11)	0.11632 (7)	0.0152 (3)
H2AA	−0.2565	0.7029	0.0910	0.018*
C3A	0.1336 (3)	0.73931 (12)	0.09576 (7)	0.0171 (3)
H3AA	0.2878	0.7190	0.1206	0.021*
C4A	0.0892 (3)	0.84755 (11)	0.10407 (7)	0.0165 (3)
H4AA	−0.0513	0.8701	0.0757	0.020*
C5A	0.0083 (3)	0.86748 (11)	0.17023 (7)	0.0171 (3)
H5AA	0.1569	0.8507	0.1978	0.021*
C6A	−0.0718 (4)	0.97148 (12)	0.18160 (8)	0.0212 (4)
H6AA	−0.1275	0.9784	0.2246	0.025*
H6AB	0.0810	1.0143	0.1752	0.025*
F2	0.6060 (2)	0.34553 (7)	0.21767 (4)	0.0232 (2)
O1B	0.1269 (3)	0.22215 (10)	0.08123 (6)	0.0187 (4)	0.836 (4)
H1"	0.0565	0.2142	0.0470	0.022*	0.836 (4)
O1B'	0.4827 (16)	0.1498 (5)	0.0468 (3)	0.022 (2)	0.164 (4)
H1B"	0.3610	0.1234	0.0272	0.026*	0.164 (4)
O2B	0.4505 (2)	0.15979 (8)	0.17617 (5)	0.0188 (3)
H2"	0.5298	0.1089	0.1661	0.023*
O4B	0.3781 (2)	0.50293 (8)	0.14995 (5)	0.0183 (2)
H4"	0.4954	0.5395	0.1637	0.022*
O5B	0.4705 (2)	0.31000 (8)	0.03780 (5)	0.0162 (2)
O6B	0.7232 (3)	0.49087 (9)	0.00825 (5)	0.0197 (3)
H6"	0.7837	0.5221	0.0380	0.024*
C1B	0.3945 (4)	0.22782 (11)	0.07416 (7)	0.0163 (3)
H1BA	0.4577	0.1672	0.0539	0.020*	0.836 (4)
H1B'	0.2004	0.2249	0.0784	0.020*	0.164 (4)
C2B	0.5244 (3)	0.23678 (11)	0.13666 (7)	0.0159 (3)
H2BA	0.7181	0.2356	0.1313	0.019*
C3B	0.4467 (3)	0.33221 (11)	0.16632 (7)	0.0157 (3)
H3BA	0.2592	0.3301	0.1788	0.019*
C4B	0.4945 (3)	0.41804 (11)	0.12446 (7)	0.0146 (3)
H4BA	0.6866	0.4286	0.1202	0.018*
C5B	0.3760 (3)	0.40066 (11)	0.06136 (7)	0.0151 (3)
H5BA	0.1818	0.3973	0.0652	0.018*
C6B	0.4469 (4)	0.47928 (11)	0.01570 (7)	0.0186 (4)
H6BC	0.3684	0.4630	−0.0243	0.022*
H6BA	0.3711	0.5417	0.0294	0.022*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
F1	0.0260 (6)	0.0243 (5)	0.0197 (5)	−0.0001 (4)	0.0075 (4)	−0.0020 (4)
O1A	0.0227 (6)	0.0209 (6)	0.0150 (5)	−0.0051 (5)	0.0032 (5)	−0.0017 (5)
O2A	0.0181 (6)	0.0152 (5)	0.0225 (6)	−0.0003 (4)	−0.0006 (5)	−0.0021 (5)
O4A	0.0190 (7)	0.0220 (6)	0.0200 (6)	−0.0053 (5)	−0.0029 (5)	0.0071 (5)
O5A	0.0196 (6)	0.0162 (6)	0.0174 (5)	−0.0008 (4)	0.0009 (4)	−0.0009 (4)
O6A	0.0201 (7)	0.0138 (5)	0.0287 (6)	−0.0011 (5)	−0.0021 (5)	−0.0008 (5)
C1A	0.0182 (9)	0.0153 (8)	0.0165 (7)	−0.0024 (6)	−0.0019 (6)	0.0002 (6)
C2A	0.0152 (8)	0.0136 (7)	0.0168 (8)	0.0011 (6)	−0.0019 (6)	0.0006 (6)
C3A	0.0160 (9)	0.0197 (8)	0.0157 (7)	0.0016 (6)	0.0000 (6)	0.0008 (6)
C4A	0.0154 (8)	0.0171 (7)	0.0169 (7)	−0.0010 (6)	−0.0028 (6)	0.0015 (6)
C5A	0.0184 (9)	0.0162 (8)	0.0166 (8)	−0.0036 (6)	−0.0035 (6)	0.0008 (6)
C6A	0.0236 (10)	0.0194 (8)	0.0206 (8)	−0.0022 (7)	−0.0028 (7)	−0.0030 (6)
F2	0.0311 (6)	0.0239 (5)	0.0148 (4)	−0.0053 (4)	−0.0078 (4)	0.0002 (4)
O1B	0.0204 (8)	0.0222 (7)	0.0135 (6)	−0.0051 (6)	−0.0025 (5)	−0.0014 (5)
O1B'	0.030 (5)	0.020 (4)	0.016 (4)	0.002 (3)	0.001 (3)	−0.001 (3)
O2B	0.0263 (7)	0.0138 (5)	0.0162 (5)	0.0020 (5)	0.0031 (5)	0.0015 (4)
O4B	0.0215 (6)	0.0143 (5)	0.0191 (6)	−0.0008 (5)	−0.0014 (5)	−0.0047 (5)
O5B	0.0219 (6)	0.0154 (5)	0.0113 (5)	0.0000 (4)	0.0029 (4)	−0.0008 (4)
O6B	0.0244 (7)	0.0192 (6)	0.0154 (6)	−0.0037 (5)	0.0009 (5)	0.0008 (5)
C1B	0.0202 (9)	0.0143 (7)	0.0144 (7)	−0.0005 (6)	0.0019 (6)	−0.0008 (6)
C2B	0.0166 (8)	0.0162 (7)	0.0150 (8)	0.0009 (6)	0.0003 (6)	0.0023 (6)
C3B	0.0181 (9)	0.0177 (8)	0.0111 (7)	−0.0016 (6)	−0.0013 (6)	−0.0014 (6)
C4B	0.0159 (8)	0.0130 (7)	0.0150 (7)	−0.0010 (6)	0.0009 (6)	−0.0021 (6)
C5B	0.0164 (8)	0.0140 (7)	0.0149 (7)	0.0011 (6)	−0.0009 (6)	−0.0006 (6)
C6B	0.0228 (10)	0.0179 (8)	0.0150 (7)	0.0009 (7)	−0.0017 (6)	0.0019 (6)

Geometric parameters (Å, º)

F1—C3A	1.3960 (18)	O1A—H1'	0.8400
O1A—C1A	1.388 (2)	O2A—H2'	0.8400
O2A—C2A	1.4218 (18)	O4A—H4'	0.8400
O4A—C4A	1.422 (2)	O6A—H6'	0.8400
O5A—C1A	1.4175 (19)	C1A—H1AA	1.0000
O5A—C5A	1.436 (2)	C2A—H2AA	1.0000
O6A—C6A	1.435 (2)	C3A—H3AA	1.0000
C1A—C2A	1.529 (2)	C4A—H4AA	1.0000
C2A—C3A	1.521 (2)	C5A—H5AA	1.0000
C3A—C4A	1.519 (2)	C6A—H6AA	0.9900
C4A—C5A	1.534 (2)	C6A—H6AB	0.9900
C5A—C6A	1.511 (2)	O1B—H1"	0.8400
F2—C3B	1.4030 (18)	O1B'—H1B"	0.8400
O1B—C1B	1.382 (2)	O2B—H2"	0.8400
O1B'—C1B	1.312 (7)	O4B—H4"	0.8400
O2B—C2B	1.4208 (19)	O6B—H6"	0.8400
O4B—C4B	1.4265 (19)	C1B—H1BA	1.0000
O5B—C5B	1.4357 (19)	C1B—H1B'	1.0000
O5B—C1B	1.4383 (19)	C2B—H2BA	1.0000
O6B—C6B	1.434 (2)	C3B—H3BA	1.0000
C1B—C2B	1.529 (2)	C4B—H4BA	1.0000
C2B—C3B	1.520 (2)	C5B—H5BA	1.0000
C3B—C4B	1.517 (2)	C6B—H6BC	0.9900
C4B—C5B	1.530 (2)	C6B—H6BA	0.9900
C5B—C6B	1.519 (2)
C1A—O5A—C5A	112.67 (13)	C1A—C2A—H2AA	108.1
O1A—C1A—O5A	107.99 (13)	F1—C3A—H3AA	109.1
O1A—C1A—C2A	108.78 (13)	C4A—C3A—H3AA	109.1
O5A—C1A—C2A	108.80 (12)	C2A—C3A—H3AA	109.1
O2A—C2A—C3A	112.71 (13)	O4A—C4A—H4AA	109.7
O2A—C2A—C1A	111.46 (12)	C3A—C4A—H4AA	109.7
C3A—C2A—C1A	108.27 (13)	C5A—C4A—H4AA	109.7
F1—C3A—C4A	109.79 (13)	O5A—C5A—H5AA	109.0
F1—C3A—C2A	109.03 (13)	C6A—C5A—H5AA	109.0
C4A—C3A—C2A	110.73 (14)	C4A—C5A—H5AA	109.0
O4A—C4A—C3A	109.98 (14)	O6A—C6A—H6AA	109.1
O4A—C4A—C5A	108.38 (13)	C5A—C6A—H6AA	109.1
C3A—C4A—C5A	109.24 (13)	O6A—C6A—H6AB	109.1
O5A—C5A—C6A	105.88 (14)	C5A—C6A—H6AB	109.1
O5A—C5A—C4A	110.25 (13)	H6AA—C6A—H6AB	107.8
C6A—C5A—C4A	113.52 (13)	C1B—O1B—H1"	109.5
O6A—C6A—C5A	112.63 (13)	C1B—O1B'—H1B"	109.5
C5B—O5B—C1B	113.19 (11)	C2B—O2B—H2"	109.5
O1B'—C1B—O1B	110.3 (4)	C4B—O4B—H4"	109.5
O1B'—C1B—O5B	107.3 (3)	C6B—O6B—H6"	109.5
O1B—C1B—O5B	112.05 (14)	O1B'—C1B—H1BA	1.7
O1B'—C1B—C2B	109.1 (4)	O1B—C1B—H1BA	108.9
O1B—C1B—C2B	109.63 (13)	O5B—C1B—H1BA	108.9
O5B—C1B—C2B	108.39 (13)	C2B—C1B—H1BA	108.9
O2B—C2B—C3B	108.36 (12)	O1B'—C1B—H1B'	110.7
O2B—C2B—C1B	111.74 (13)	O1B—C1B—H1B'	1.4
C3B—C2B—C1B	109.85 (13)	O5B—C1B—H1B'	110.7
F2—C3B—C4B	106.86 (12)	C2B—C1B—H1B'	110.7
F2—C3B—C2B	107.73 (12)	H1BA—C1B—H1B'	109.3
C4B—C3B—C2B	111.91 (13)	O2B—C2B—H2BA	108.9
O4B—C4B—C3B	109.53 (13)	C3B—C2B—H2BA	108.9
O4B—C4B—C5B	108.48 (13)	C1B—C2B—H2BA	108.9
C3B—C4B—C5B	111.19 (12)	F2—C3B—H3BA	110.1
O5B—C5B—C6B	107.60 (12)	C4B—C3B—H3BA	110.1
O5B—C5B—C4B	109.14 (12)	C2B—C3B—H3BA	110.1
C6B—C5B—C4B	112.94 (13)	O4B—C4B—H4BA	109.2
O6B—C6B—C5B	112.98 (14)	C3B—C4B—H4BA	109.2
C1A—O1A—H1'	109.5	C5B—C4B—H4BA	109.2
C2A—O2A—H2'	109.5	O5B—C5B—H5BA	109.0
C4A—O4A—H4'	109.5	C6B—C5B—H5BA	109.0
C6A—O6A—H6'	109.5	C4B—C5B—H5BA	109.0
O1A—C1A—H1AA	110.4	O6B—C6B—H6BC	109.0
O5A—C1A—H1AA	110.4	C5B—C6B—H6BC	109.0
C2A—C1A—H1AA	110.4	O6B—C6B—H6BA	109.0
O2A—C2A—H2AA	108.1	C5B—C6B—H6BA	109.0
C3A—C2A—H2AA	108.1	H6BC—C6B—H6BA	107.8
C5A—O5A—C1A—O1A	177.72 (12)	C5B—O5B—C1B—C2B	−64.88 (17)
C5A—O5A—C1A—C2A	−64.37 (16)	O1B'—C1B—C2B—O2B	−65.7 (4)
O1A—C1A—C2A—O2A	−57.64 (17)	O1B—C1B—C2B—O2B	55.19 (18)
O5A—C1A—C2A—O2A	−175.05 (13)	O5B—C1B—C2B—O2B	177.78 (12)
O1A—C1A—C2A—C3A	177.85 (13)	O1B'—C1B—C2B—C3B	174.0 (4)
O5A—C1A—C2A—C3A	60.44 (16)	O1B—C1B—C2B—C3B	−65.11 (17)
O2A—C2A—C3A—F1	58.62 (17)	O5B—C1B—C2B—C3B	57.48 (17)
C1A—C2A—C3A—F1	−177.61 (12)	O2B—C2B—C3B—F2	68.41 (16)
O2A—C2A—C3A—C4A	179.51 (12)	C1B—C2B—C3B—F2	−169.26 (12)
C1A—C2A—C3A—C4A	−56.72 (17)	O2B—C2B—C3B—C4B	−174.41 (13)
F1—C3A—C4A—O4A	−66.85 (17)	C1B—C2B—C3B—C4B	−52.08 (18)
C2A—C3A—C4A—O4A	172.71 (12)	F2—C3B—C4B—O4B	−72.20 (16)
F1—C3A—C4A—C5A	174.31 (13)	C2B—C3B—C4B—O4B	170.11 (13)
C2A—C3A—C4A—C5A	53.87 (18)	F2—C3B—C4B—C5B	167.91 (12)
C1A—O5A—C5A—C6A	−175.25 (13)	C2B—C3B—C4B—C5B	50.22 (18)
C1A—O5A—C5A—C4A	61.57 (16)	C1B—O5B—C5B—C6B	−174.53 (13)
O4A—C4A—C5A—O5A	−174.37 (12)	C1B—O5B—C5B—C4B	62.59 (16)
C3A—C4A—C5A—O5A	−54.54 (17)	O4B—C4B—C5B—O5B	−173.97 (12)
O4A—C4A—C5A—C6A	67.04 (17)	C3B—C4B—C5B—O5B	−53.46 (17)
C3A—C4A—C5A—C6A	−173.13 (15)	O4B—C4B—C5B—C6B	66.40 (17)
O5A—C5A—C6A—O6A	−64.46 (17)	C3B—C4B—C5B—C6B	−173.09 (14)
C4A—C5A—C6A—O6A	56.6 (2)	O5B—C5B—C6B—O6B	−63.23 (17)
C5B—O5B—C1B—O1B'	177.5 (4)	C4B—C5B—C6B—O6B	57.28 (18)
C5B—O5B—C1B—O1B	56.23 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1A—H1′···O2B^i	0.84	1.87	2.7089 (16)	174
O2A—H2′···O4B	0.84	1.87	2.6969 (17)	169
O4A—H4′···O6B^ii	0.84	1.88	2.7187 (16)	173
O6A—H6′···O4A^iii	0.84	1.96	2.7138 (17)	148
O1B—H1"···O5B^iv	0.84	1.94	2.7663 (17)	168
O1B′—H1B"···O6B^iv	0.84	1.89	2.642 (8)	148
O2B—H2"···O6A^v	0.84	1.84	2.6745 (16)	177
O4B—H4"···O1A^vi	0.84	1.94	2.7155 (16)	153
O4B—H4"···O2A^vi	0.84	2.58	3.1418 (18)	125
O6B—H6"···O2A^vi	0.84	1.90	2.7348 (16)	174

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