Plasticity in zwitterionic drugs: the bending properties of Pregabalin and Gabapentin and their hydrates

The investigation of mechanical properties in molecular crystals is emerging as a novel area of interest in crystal engineering. Indeed, good mechanical properties are required to manufacture pharmaceutical and technologically relevant substances into usable products. In such endeavour, bendable single crystals help to correlate microscopic structure to macroscopic properties for potential design. The hydrate forms of two anticonvulsant zwitterionic drugs, Pregabalin and Gabapentin, are two examples of crystalline materials that show macroscopic plasticity. The direct comparison of these structures with those of their anhydrous counterparts, which are brittle, suggests that the presence of water is critical for plasticity. In contrast, structural features such as molecular packing and anisotropic distribution of strong and weak interactions seem less important.

1. Introduction

In recent times, the classic idea of crystals as a brittle objects has been progressively abandoned (Dunitz, 1984). Observation of phenomena such as shearing (Reddy et al., 2005a) or bending (Reddy et al., 2005b) as well as martensitic (Zamir et al., 1994; Steiner et al., 1993; Ding et al., 1991; Etter & Siedle, 1983), super-elastic (Takamizawa & Miyamoto, 2014) and super-plastic (Takamizawa et al., 2018) transformations clearly show that organic crystals share many similarities with metallic and covalent inorganic analogues. Mechanical properties of molecular crystals are investigated and discussed with increasing frequency and those studies have attracted considerable attention (Reddy et al., 2010; Naumov et al., 2015). Aside from the understandable academic curiosity, mechanical properties are important for the manufacturing of crystalline solids into products. For example, in the pharmaceutical industry, good plasticity guarantees that microcrystalline drug substances can be readily manufactured into tablets without the addition of excipients (Thoorens et al., 2015; Chang & Sun, 2017).

A characteristic of molecular crystals is that they are held together by supramolecular interactions. It follows that crystal synthesis occurs in relatively mild conditions, whilst a supramolecular approach enables a certain degree of structure design (Desiraju, 1989; Etter, 1990; Moulton & Zaworotko, 2001). In this view, understanding how molecular features determine a crystal structure and, in turn, material properties would enable crystal engineering and properties design.

The rapid scientific advances of the past decades allow the confident prediction of how a given set of molecules will pack in a crystal structure (Reilly et al., 2016). On the other hand, a general theory is still missing to infer bulk chemical and mechanical properties from structures. Therefore, material development proceeds through the application of a series of practical rules, which often apply to specific types of materials (Lusi, 2018; Corpinot & Bučar, 2019).

The first attempts to rationalize the relationship between structure and mechanical properties in molecular crystals involved small aromatic molecules (Reddy et al., 2006b,a). In such materials, aromatic stacking and halogen or hydrogen interactions coexist in the same structure and extend along different crystallographic axes. Manipulation of face-indexed single crystals showed that bending occurred only perpendicular to the planes of the weaker interactions, whereas the stronger supramolecular bonds helped to preserve structural integrity in the other directions (Saha et al., 2018). Then, chemical anisotropy appeared as a requirement for plasticity and such features were thought to guarantee the realization of bendable single- and multi-component crystals (Krishna et al., 2016; Rao Khandavilli et al., 2017; Saha & Desiraju, 2017; Alimi et al., 2018; Nath et al., 2018). However, the discovery of plastic bending in the (quasi)-isotropic structures of di­methyl sulfone proves that alternative mechanisms might exist (Thomas et al., 2017).

Due to their relevance in manufacturing and processing, many studies of mechanical properties involve APIs (active pharmaceutical ingredients), which suggest that hydrate forms might have higher plasticity than their corresponding anhydrates (Sun & Grant, 2004; Liu et al., 2018; Fucke et al., 2012; Chang & Sun, 2017). In these cases, the mechanical properties were only observed at the microscopic level on polycrystalline powders, making the correlation between structure and properties elusive. In p-hy­droxy­benzoic acid (Sun & Grant, 2004) and uric acid (Liu et al., 2018), despite creating a rigid 3D hydrogen-bonded network, the inclusion of water enables the separation of zigzag chains that are interdigitated in the anhydrous forms (see Figs. S10 and S11 of the supporting information). Hence, increased plasticity was explained by the removal of a mechanical (or steric) obstacle to molecular movement, which was deemed necessary for plastic bending. Anhydrous theophylline shows a different story: hydrogen bonds, π stacking and weak C=O⋯H bonds support the structure along the orthogonal crystallographic directions, and there is no mechanical interlock to prevent molecular movement (Fucke et al., 2012; Chang & Sun, 2017). In that view, crystals of theophylline should be highly plastic. Instead, plasticity is lower than in the hydrate form, which is characterized by 2D hydrogen-bonded networks that pack in an interdigitated zigzag fashion (see Fig. S12 of the supporting information). In the theophylline system, increased plasticity was attributed to the `lubricant' action of water molecules that allows easier slippage of the 2D sheets. Ultimately, also in the case of hydrate forms, multiple mechanisms explain plastic bending and the observation of such a phenomenon on single crystals could give new insights into the role of water. This work reports on the mechanical properties in the anhydrous and hydrate forms of Pregabalin and Gabapentin (Fig. 1). Despite the similar crystal packing, the hydrate forms show superior plasticity, which results in macroscopic bending of single crystals whereas the anhydrous forms are brittle.

Figure 1 Molecular structure of Pregabalin (left) and Gabapentin (right).

2. Experimental

Pregabalin (SPG) and Gabapentin (GP) were purchased from Flourochem. Methanol was purchased from Sigma–Aldrich and Milli-Q water was used for the experiments.

Crystallization of SPG: SPG crystals were obtained from commercially available SPG dissolved in methanol to saturation and left at room temperature for 2 days.

Crystallization of SPGH I: SPG was dissolved in pure water and crystallized at 280 K for 3–5 days to obtain good-quality crystals.

Crystallization of GP and GPH: GP and its hydrate crystals are reproduced by following the same procedure mentioned in the literature (Wang et al., 2017; Reece & Levendis, 2008).

Optical microscopy: single crystals of SPGH I and GPH were selected and bent with tweezers and a needle, the images were captured using an Olympus IX53 microscope under 4× magnification.

IR spectroscopy: IR spectra for SPG and SPGH I were collected on a PerkinElmer Spectrum 100 F T-IR Spectrometer equipped with a PerkinElmer Universal ATR Sampling Accessory.

Raman spectroscopy: Raman spectra for SPG and SPGH I were collected on a Horiba Jobin Yvon LabRam Aramis spectrometer with a 532 nm laser source. The spectrometer was coupled with an Olympus BX40 confocal microscope with a CCD camera cooled by a thermoelectric Peltier device. Raman maps were processed using the LabSPEC 5 software package.

Powder X-ray diffraction: Powder X-ray diffraction data were collected on an Empyrean diffractometer (PANalytical, Philips) using Cu Kα_1,2 radiation (λ = 0.1541 nm) at room temperature operated at 40 kV and 40 mA. The samples were scanned over the range 4–40° 2θ using a step size of 0.02° 2θ and a scan speed of 0.02° 2θ s⁻¹.

Differential scanning calorimetry: calorimetric measurements of SPG and SPGH I were performed on a DSC 214 Polyma, NETZSCH instrument. Typically, 3–5 mg of sample was accurately weighed into a hermetically sealed aluminium pan and heated to 250 °C at a 10 °C min⁻¹ heating rate under a nitro­gen gas flow of 40 ml min⁻¹.

Thermogravimetric analysis: Thermograms of SPG and SPGH I were measured with a Perkin-Elmer TGA 4000 instrument at a heating rate of 10 °C min⁻¹ under a nitro­gen stream of 20 ml min⁻¹.

X-ray crystallography: single-crystal data for SPGH I were collected at ambient temperature using a three-circle Bruker D8 Quest diffractometer with a sealed tube Mo anode, Kα radiation = 0.71073 Å and a Photon 100 detector. Single-crystal data for SPGH II were collected at 150 K under a nitro­gen-flow (Oxford Cryosystem) using a three-circle Bruker D8 Quest with microfocus Cu anode, Kα radiation = 1.5418 Å and a Photon 100 detector.

The data were integrated and corrected for absorption with the Bruker Apex Suite. The structure solution was obtained by direct methods and refined against all F² with the SHELX software interfaced though X-SEED (Barbour, 2001). Non-hydrogen atoms were refined anisotropically and hydrogen atoms were placed in calculated positions, refined using idealized geometries (riding model) and assigned fixed isotropic displacement parameters.

3. Results and discussion

Amino ­acids are an important class of biologically active molecules that exist as zwitterionic tautomers under neutral conditions. Among them, (S)-3-iso­butyl-γ-amino­butyric acid, or Pregabalin (SPG), is an anticonvulsant blockbuster drug. In the anhydrous P2₁2₁2₁ crystal, which has the refcode CIDDEZ (Venu et al., 2007) in the CSD (Groom et al., 2016), the zwitterion dipoles pack along the b axis generating a double layer that is coplanar to the (110) plane. The structure is supported by a 2D network of charge-assisted hydrogen bonds between the ammonium and carboxyl­ate groups [Fig. 2(a)]. As multiple layers stack on top of each other, the iso­butyl groups interdigitate along the [001] direction. The crystals are brittle, as expected for mechanically interlocked structures.

Figure 2 Schematic representation of the crystal packing of (a) SPG, (b) SPGH form I and (c) SPGH form II. Hydrogen bonding interactions are in green, selected hydrogen atoms have been omitted for clarity.

Recrystallization of SPG in water at 280 K results in the monohydrate form SPGH I. Single-crystal analysis reveals a monoclinic C2 polar structure (Table 1). The zwitterions are arranged along the [010] axis and are intercalated by water molecules so that the double molecular layers separate into parallel planes. At the same time, the molecules in each layer come closer together preventing interdigitation [Fig. 2(b)].

Table 1
Crystallographic data for SPGH I and SPGH II

Crystal form	SPGH I	SPGH II
Formula	C8H17NO2, H2O	C8H17NO2, H2O
CCDC code	1879470	1879471
Temperature (K)	298	150
Space group	C2	P21
a (Å)	9.566 (7)	9.6559 (2)
b (Å)	7.440 (6)	29.8416 (6)
c (Å)	15.911 (12)	30.1248 (7)
β (°)	101.54 (3)	98.540 (1)
V (Å^3)	1109.5 (15)	8584.1 (3)
Z, Z′	4, 1	32, 16
ρ (g cm^−3)	1.061	1.097
μ (mm^−1)	0.080	0.677
R[F^2 > 2σ(F^2)] (No. of reflections)	0.0586 (1721)	0.0482 (28820)

SPGH I is unstable at room temperature, reverting to the anhydrous SPG phase in air (Fig. S6). As expected from the different crystal packing, the dehydration is associated with a loss of macroscopic crystallinity. SPGH I undergoes a polymorphic transition upon cooling below 150 K. The phase transition is reversible (enantiotropic) and occurs in a single-crystal-to-single-crystal fashion, as demonstrated by variable-temperature single-crystal diffraction experiments. The packing of the low-temperature SPGH II phase is virtually identical to the high-temperature phase. The differences are limited to a reduced symmetry (Z′ = 16) and a different arrangement of the hydrogen-bonded bridges with water [Fig. 2(c)].

In molecular materials, the single-crystal-to-single-crystal reduction of symmetry on cooling is known. Often, such transformations assume the aspect of an order–disorder transition, whereby a certain thermal energy is required for a molecule to rotate or vibrate between symmetry-related crystallographic positions (Lusi & Barbour, 2013; Braga et al., 2018). Here, the change occurs between two fully ordered structures instead. In that view, the preserved crystallinity is evidence of the high plasticity of these phases, and suggests that the supramolecular bonds with water can be easily broken and reformed without affecting the rest of the structure.

Indeed, crystals of SPGH I exhibit plastic bending on the application of a moment perpendicular to the c axis (Fig. 3). Hence, the bending mechanism involves the sliding of successive layers along the crystallographic b direction (Fig. 2). In order for this to happens, either the hydrogen bond between water and zwitterions or the dispersion forces between the non-polar-layer intermolecular bonds need to quickly break and reform; crystallographic studies cannot determine which are responsible for the bending.

Figure 3 Single crystals of SPGH I and GPH II before and after the mechanical deformation. The larger crystal faces are indexed.

GP is a molecular and pharmaceutical analogue of SPG. In GP, cyclo­pentane substitutes the iso­butyl group but the supramolecular feature of the two molecules are essentially equivalent. Due to extensive polymorph screening, multiple anhydrous and hydrate forms of GP are reported (Braga et al., 2008; Reece & Levendis, 2008; Wang et al., 2017).

Like SPG, the structure of GP form α (CCDC refcode QIMKIG) is dominated by 2D networks of charge-assisted hydrogen bonds. In the latter, the bulkier cyclo­pentane group prevents interdigitation of successive layers (Fig. 4). GPβ (CCDC refcode QIMKIG02) forms 1D chains (Reece & Levendis, 2008; Wang et al., 2017; Ibers, 2001; Vasudev et al., 2009), whereas the packing in the anhydrous γ form (CCDC refcode QIMKIG03) resembles those of the hydrate forms, GPH I and II (CCDC refcodes QIMKOM and QIMKOM02), and SPGH I and II, the zwitterionic groups being separated into two planes. Remarkably, despite structural similarities, only the hydrates undergo plastic bending, whereas all the anhydrous forms are brittle. This observation suggests that the intercalated water molecules, rather than the weak dispersion forces, are responsible for the observed plastic bending.

Figure 4 Schematic representation of the crystal packing of the (a) GP form α, (b) GP form β, (c) GP form γ, (d) GPH form I and (e) GPH form II. Hydrogen-bonding interactions are in green, selected hydrogen atoms have been omitted for clarity.

4. Conclusions

High plasticity is a desirable property that guarantees processability in crystalline drug materials. To date, different sets of factors have been identified as responsible for plastic crystals, but a universal supramolecular strategy to improve such a property is not recognized yet. For example, it was suggested that bending requires the anisotropic hierarchical distribution of strong and weak supramolecular interactions along perpendicular directions. On the other hand, interdigitation and cross-linked hydrogen bonds (mechanical and chemical interlocks, respectively) have been seen as detrimental for macroscopic plastic bending. At the same time, an increasing number of studies report that, at the microscopic level, hydrated forms exhibit higher plasticity than the anhydrous equivalents. In such phases, increased plasticity does not seem to correlate to a particular structural feature. This is also true for the two zwitterionic drugs SPG and GP. Here, plasticity occurs also at a macroscopic level, on large single crystals, allowing a rationalization for such a phenomenon.

Limited to the investigated systems, the alternation of 2D hydrogen-bonded networks and weak dispersive forces does not guarantee plastic deformation in the anhydrous crystals. In contrast, plasticity occurs in the hydrate forms even when mechanical and chemical interlocks are present. Therefore, in these instances the presence of water appears crucial. Many studies highlight the structural diversity possible for water molecules (Mascal et al., 2006; Infantes & Motherwell, 2002; Bajpai et al., 2016). We speculate that such promiscuity, together with the high mobility of these molecules, enables the quick rearrangement of the supramolecular interactions that are broken by mechanical stress.

Finally we note that SPG and GP are two examples of a wide class of amino acids with biological activity. As sustained by strong and directional charge-assisted hydrogen bonds, the molecular packing of SPG and GP is common to other zwitterionic β-amino­propionic and γ-amino­butyric acids. Therefore, it would be of little surprise if those systems showed the same properties, and the reported observations could be valid for a wide class of drug substances.

Supporting information

Computing details

For both structures, program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2014).

(I)

Crystal data

C8H19NO3	F(000) = 3136
Mr = 177.24	Dx = 1.097 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54178 Å
a = 9.6559 (2) Å	Cell parameters from 1234 reflections
b = 29.8416 (6) Å	θ = 4–40°
c = 30.1248 (7) Å	µ = 0.68 mm^−1
β = 98.540 (1)°	T = 150 K
V = 8584.1 (3) Å^3	Prism, colourless
Z = 32	0.33 × 0.21 × 0.10 mm

Data collection

Bruker D8 Quest diffractometer	Rint = 0.041
Absorption correction: multi-scan sadabs	θmax = 80.2°, θmin = 3.0°
Tmin = 0.648, Tmax = 0.754	h = −12→11
123474 measured reflections	k = −37→37
35695 independent reflections	l = −37→37
28820 reflections with I > 2σ(I)

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)] = 0.048	w = 1/[σ^2(Fo^2) + (0.0511P)^2 + 2.5076P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.134	(Δ/σ)max = 0.001
S = 1.01	Δρmax = 0.36 e Å^−3
35695 reflections	Δρmin = −0.21 e Å^−3
1834 parameters	Absolute structure: Flack x determined using 11798 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
1 restraint	Absolute structure parameter: 0.00 (4)

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
O83	0.90280 (18)	0.14068 (5)	0.08707 (7)	0.0311 (4)
O163	0.10703 (19)	1.01615 (5)	0.41722 (7)	0.0333 (4)
O143	0.40687 (18)	0.26416 (5)	0.10036 (7)	0.0320 (4)
O402	0.87056 (19)	0.85734 (6)	0.47760 (7)	0.0328 (4)
H40A	0.8804	0.8296	0.4699	0.049*
H40B	0.7918	0.8657	0.4620	0.049*
O411	0.12176 (19)	0.72935 (6)	0.01096 (7)	0.0318 (4)
H41A	0.121 (3)	0.7015 (12)	0.0187 (11)	0.048*
H41B	0.199 (4)	0.7373 (11)	0.0241 (11)	0.048*
O23	0.88745 (19)	0.88989 (5)	0.06970 (8)	0.0342 (4)
O416	0.65273 (19)	0.10625 (6)	0.04600 (7)	0.0329 (4)
H41C	0.7348	0.1150	0.0589	0.049*
H41D	0.6466	0.0786	0.0546	0.049*
O223	0.59712 (19)	0.14039 (5)	0.40558 (8)	0.0346 (4)
O404	0.87133 (19)	0.60385 (6)	0.48839 (7)	0.0328 (4)
H40C	0.8785	0.5764	0.4794	0.049*
H40D	0.7977	0.6143	0.4714	0.049*
O3	0.39496 (19)	1.01507 (5)	0.07857 (8)	0.0350 (4)
O409	0.1491 (2)	0.98066 (6)	0.03367 (7)	0.0350 (4)
H40E	0.2281	0.9897	0.0487	0.052*
H40F	0.1433	0.9526	0.0410	0.052*
O161	−0.11483 (19)	1.02014 (5)	0.42867 (8)	0.0352 (4)
O43	0.87614 (18)	0.64106 (5)	0.05333 (7)	0.0333 (4)
O412	0.6352 (2)	0.59758 (6)	0.01273 (7)	0.0388 (5)
H41E	0.6360	0.5709	0.0244	0.058*
H41F	0.7111	0.6102	0.0263	0.058*
O407	0.34917 (19)	0.22769 (7)	0.45056 (7)	0.0332 (4)
H40G	0.274 (4)	0.2376 (12)	0.4383 (12)	0.050*
H40H	0.351 (4)	0.2015 (12)	0.4388 (12)	0.050*
O63	0.8903 (2)	0.39108 (6)	0.06658 (8)	0.0385 (5)
O41	1.10099 (19)	0.64381 (6)	0.04495 (7)	0.0377 (5)
O103	0.36963 (18)	0.76601 (5)	0.04954 (7)	0.0342 (4)
O414	0.64205 (19)	0.34795 (6)	0.04492 (7)	0.0354 (4)
H41G	0.7235	0.3599	0.0540	0.053*
H41H	0.6462	0.3216	0.0575	0.053*
O203	0.11464 (19)	0.51708 (5)	0.44379 (7)	0.0354 (4)
O81	1.12504 (18)	0.14419 (5)	0.07645 (7)	0.0355 (4)
O243	0.62170 (19)	0.89233 (5)	0.43717 (8)	0.0367 (5)
O21	1.11104 (19)	0.89344 (6)	0.06010 (8)	0.0378 (5)
O183	0.11963 (18)	0.76676 (5)	0.44065 (7)	0.0327 (4)
O401	0.3541 (2)	0.98365 (6)	0.46785 (8)	0.0364 (4)
H40I	0.2780	0.9925	0.4510	0.055*
H40J	0.3664	0.9563	0.4592	0.055*
O141	0.63278 (19)	0.26914 (6)	0.09414 (8)	0.0408 (5)
O403	0.35933 (19)	0.72778 (6)	0.49061 (6)	0.0358 (4)
H40K	0.3631	0.7009	0.4795	0.054*
H40L	0.2874	0.7401	0.4744	0.054*
O263	0.62639 (19)	0.64146 (5)	0.44767 (8)	0.0368 (5)
O303	0.10017 (19)	0.26753 (5)	0.42080 (8)	0.0363 (5)
O101	0.59806 (19)	0.76938 (6)	0.04772 (8)	0.0370 (5)
O201	−0.11136 (19)	0.51968 (6)	0.45069 (8)	0.0387 (5)
O61	1.1166 (2)	0.39339 (6)	0.06067 (8)	0.0404 (5)
O413	0.1433 (2)	0.47623 (6)	0.02054 (8)	0.0401 (5)
H41I	0.1390	0.4481	0.0279	0.060*
H41J	0.2189	0.4862	0.0369	0.060*
O283	0.60146 (19)	0.39114 (5)	0.41217 (8)	0.0380 (5)
O410	0.6463 (2)	0.85508 (6)	0.01511 (7)	0.0367 (4)
H41K	0.6395	0.8268	0.0215	0.055*
H41L	0.7226	0.8639	0.0319	0.055*
O123	0.3808 (2)	0.51497 (6)	0.06806 (9)	0.0423 (5)
O405	0.3606 (2)	0.47266 (6)	0.47223 (8)	0.0407 (5)
H40M	0.3557	0.4463	0.4596	0.061*
H40N	0.2845	0.4862	0.4602	0.061*
O181	−0.10432 (19)	0.77026 (6)	0.44999 (8)	0.0372 (5)
O1	0.6229 (2)	1.01874 (6)	0.07509 (8)	0.0407 (5)
O408	0.8313 (2)	0.10479 (6)	0.45929 (7)	0.0415 (5)
H40O	0.7540	0.1139	0.4433	0.062*
H40P	0.8444	0.0781	0.4491	0.062*
O261	0.39879 (19)	0.64445 (6)	0.45113 (8)	0.0390 (5)
O241	0.3943 (2)	0.89595 (6)	0.44158 (9)	0.0407 (5)
O221	0.36927 (19)	0.14521 (6)	0.40882 (8)	0.0400 (5)
O301	−0.12473 (19)	0.27028 (6)	0.42844 (8)	0.0406 (5)
O415	0.1841 (2)	0.22690 (7)	0.04154 (8)	0.0486 (5)
H41M	0.2613	0.2355	0.0580	0.073*
H41N	0.1716	0.1996	0.0502	0.073*
O406	0.8273 (3)	0.35163 (7)	0.46816 (9)	0.0478 (6)
H40Q	0.760 (4)	0.3626 (14)	0.4534 (14)	0.072*
H40R	0.832 (4)	0.3253 (14)	0.4604 (14)	0.072*
N247	0.6340 (2)	0.73218 (6)	0.45447 (7)	0.0252 (4)
H24C	0.7231	0.7428	0.4568	0.038*
H24D	0.6356	0.7017	0.4540	0.038*
H24E	0.5945	0.7417	0.4784	0.038*
N187	0.1335 (2)	0.60769 (6)	0.44773 (8)	0.0270 (4)
H18A	0.2235	0.6176	0.4510	0.040*
H18B	0.1326	0.5772	0.4460	0.040*
H18C	0.0930	0.6166	0.4717	0.040*
O121	0.6048 (2)	0.51733 (6)	0.05950 (9)	0.0483 (6)
N27	0.8628 (2)	0.73175 (6)	0.05136 (7)	0.0276 (4)
H27A	0.7736	0.7425	0.0474	0.041*
H27B	0.8611	0.7013	0.0513	0.041*
H27C	0.9076	0.7417	0.0287	0.041*
N47	0.8682 (2)	0.48165 (6)	0.05963 (8)	0.0283 (5)
H47A	0.7773	0.4906	0.0574	0.042*
H47B	0.8733	0.4514	0.0632	0.042*
H47C	0.9029	0.4895	0.0342	0.042*
N167	0.1307 (2)	0.85776 (6)	0.43859 (8)	0.0287 (5)
H16A	0.2206	0.8680	0.4425	0.043*
H16B	0.1309	0.8273	0.4392	0.043*
H16C	0.0863	0.8684	0.4610	0.043*
N107	0.3653 (2)	0.60518 (6)	0.05002 (8)	0.0293 (5)
H10D	0.2756	0.6155	0.0463	0.044*
H10E	0.3653	0.5749	0.0535	0.044*
H10F	0.4054	0.6123	0.0254	0.044*
N147	0.3905 (2)	0.10702 (6)	0.08180 (8)	0.0276 (5)
H14A	0.3017	0.1178	0.0749	0.041*
H14B	0.3886	0.0765	0.0811	0.041*
H14C	0.4436	0.1173	0.0614	0.041*
N287	0.6102 (2)	0.23233 (6)	0.41468 (7)	0.0245 (4)
H28C	0.6992	0.2428	0.4221	0.037*
H28D	0.6120	0.2020	0.4120	0.037*
H28E	0.5587	0.2400	0.4365	0.037*
N7	0.3706 (2)	0.85681 (6)	0.04965 (8)	0.0279 (5)
H7A	0.2822	0.8681	0.0473	0.042*
H7B	0.3665	0.8264	0.0479	0.042*
H7C	0.4132	0.8677	0.0269	0.042*
O281	0.3775 (2)	0.39506 (6)	0.42092 (10)	0.0491 (6)
N267	0.6237 (2)	0.48117 (6)	0.43564 (9)	0.0311 (5)
H26C	0.7140	0.4908	0.4417	0.047*
H26D	0.6224	0.4512	0.4298	0.047*
H26E	0.5794	0.4866	0.4597	0.047*
N127	0.3811 (2)	0.35524 (6)	0.08044 (8)	0.0274 (5)
H12A	0.2915	0.3650	0.0727	0.041*
H12B	0.3807	0.3254	0.0864	0.041*
H12C	0.4302	0.3604	0.0574	0.041*
N307	0.1120 (2)	0.10784 (6)	0.41741 (8)	0.0263 (4)
H30D	0.2007	0.1176	0.4165	0.040*
H30E	0.1091	0.0775	0.4147	0.040*
H30F	0.0854	0.1159	0.4440	0.040*
N207	0.1191 (2)	0.35819 (6)	0.42857 (9)	0.0298 (5)
H20A	0.2091	0.3673	0.4287	0.045*
H20B	0.1133	0.3281	0.4238	0.045*
H20C	0.0920	0.3647	0.4555	0.045*
N67	0.8873 (2)	0.23192 (6)	0.08292 (7)	0.0280 (4)
H67A	0.7987	0.2421	0.0835	0.042*
H67B	0.8906	0.2019	0.0882	0.042*
H67C	0.9122	0.2376	0.0555	0.042*
N87	0.8844 (2)	−0.01877 (6)	0.07413 (8)	0.0289 (5)
H87A	0.7957	−0.0081	0.0728	0.043*
H87B	0.8830	−0.0492	0.0750	0.043*
H87C	0.9207	−0.0097	0.0494	0.043*
N227	0.6217 (2)	−0.01626 (6)	0.43296 (9)	0.0306 (5)
H22A	0.7090	−0.0041	0.4385	0.046*
H22B	0.6282	−0.0466	0.4348	0.046*
H22C	0.5694	−0.0060	0.4536	0.046*
C82	1.0158 (3)	0.12288 (7)	0.08007 (9)	0.0258 (5)
C42	0.9925 (3)	0.62289 (8)	0.05074 (9)	0.0280 (5)
C22	1.0021 (3)	0.87208 (8)	0.06443 (10)	0.0287 (5)
C142	0.5253 (3)	0.24724 (8)	0.09945 (9)	0.0283 (5)
C162	−0.0068 (3)	0.99853 (8)	0.42358 (9)	0.0274 (5)
C202	−0.0016 (3)	0.49869 (8)	0.44588 (10)	0.0294 (5)
C102	0.4873 (3)	0.74798 (8)	0.04836 (9)	0.0281 (5)
C146	0.4513 (3)	0.12226 (8)	0.12714 (9)	0.0297 (5)
H14D	0.5500	0.1123	0.1335	0.036*
H14E	0.3998	0.1080	0.1495	0.036*
C62	1.0063 (3)	0.37259 (8)	0.06471 (10)	0.0299 (5)
C86	0.9721 (3)	−0.00147 (8)	0.11495 (10)	0.0306 (6)
H86A	1.0699	−0.0115	0.1151	0.037*
H86B	0.9386	−0.0143	0.1417	0.037*
C262	0.5087 (3)	0.62332 (8)	0.44764 (10)	0.0308 (6)
C182	0.0045 (3)	0.74884 (8)	0.44493 (10)	0.0289 (5)
C165	0.0605 (3)	0.92450 (7)	0.38994 (10)	0.0293 (5)
H165	0.1606	0.9343	0.3946	0.035*
C302	−0.0149 (3)	0.24917 (8)	0.42504 (10)	0.0295 (6)
C149	0.3817 (3)	0.17298 (9)	0.21337 (9)	0.0383 (6)
H149	0.3722	0.1396	0.2123	0.046*
C45	0.9409 (3)	0.55473 (8)	0.09607 (9)	0.0299 (5)
H45	0.8398	0.5633	0.0929	0.036*
C145	0.4455 (3)	0.17350 (7)	0.13242 (9)	0.0278 (5)
H145	0.3473	0.1836	0.1220	0.033*
C222	0.4796 (3)	0.12315 (8)	0.40756 (10)	0.0313 (6)
C166	0.0569 (3)	0.87346 (8)	0.39482 (10)	0.0315 (6)
H16D	−0.0419	0.8634	0.3914	0.038*
H16E	0.1005	0.8596	0.3705	0.038*
C306	0.0155 (3)	0.12824 (8)	0.38005 (9)	0.0301 (5)
H30G	−0.0813	0.1184	0.3820	0.036*
H30H	0.0401	0.1173	0.3512	0.036*
C286	0.5465 (3)	0.25227 (8)	0.37134 (9)	0.0276 (5)
H28F	0.4471	0.2430	0.3648	0.033*
H28G	0.5951	0.2405	0.3471	0.033*
C282	0.4834 (3)	0.37379 (8)	0.41286 (11)	0.0340 (6)
C185	0.0608 (3)	0.67774 (8)	0.40482 (9)	0.0296 (5)
H185	0.1612	0.6870	0.4077	0.035*
C2	0.5102 (3)	0.99753 (8)	0.07349 (10)	0.0317 (6)
C25	0.9355 (3)	0.79892 (8)	0.09909 (9)	0.0290 (5)
H25	0.8355	0.8089	0.0946	0.035*
C226	0.5545 (3)	−0.00330 (8)	0.38745 (10)	0.0339 (6)
H22D	0.4559	−0.0136	0.3830	0.041*
H22E	0.6028	−0.0187	0.3650	0.041*
C105	0.4369 (3)	0.67738 (8)	0.08947 (9)	0.0301 (5)
H105	0.3364	0.6862	0.0879	0.036*
C265	0.5620 (3)	0.55648 (8)	0.40098 (10)	0.0328 (6)
H265	0.6632	0.5650	0.4047	0.039*
C46	0.9510 (3)	0.50357 (8)	0.09866 (10)	0.0320 (6)
H46A	1.0503	0.4945	0.1004	0.038*
H46B	0.9174	0.4932	0.1264	0.038*
C66	0.9857 (3)	0.25520 (8)	0.11811 (9)	0.0319 (6)
H66A	1.0826	0.2457	0.1158	0.038*
H66B	0.9649	0.2462	0.1481	0.038*
C85	0.9698 (3)	0.04983 (7)	0.11816 (9)	0.0277 (5)
H85	0.8712	0.0595	0.1191	0.033*
C26	0.9382 (3)	0.74784 (8)	0.09494 (10)	0.0312 (6)
H26A	1.0367	0.7376	0.0983	0.037*
H26B	0.8949	0.7344	0.1196	0.037*
C5	0.4493 (3)	0.92085 (8)	0.10172 (10)	0.0310 (6)
H5	0.3498	0.9304	0.1011	0.037*
C122	0.4983 (3)	0.49687 (8)	0.06744 (11)	0.0369 (7)
C106	0.4459 (3)	0.62607 (8)	0.09026 (10)	0.0331 (6)
H10G	0.5453	0.6170	0.0924	0.040*
H10H	0.4101	0.6148	0.1173	0.040*
C246	0.5512 (3)	0.74885 (8)	0.41266 (9)	0.0302 (5)
H24F	0.4525	0.7395	0.4119	0.036*
H24G	0.5864	0.7348	0.3868	0.036*
C245	0.5566 (3)	0.79976 (8)	0.40762 (9)	0.0286 (5)
H245	0.6560	0.8088	0.4070	0.034*
C225	0.5576 (3)	0.04729 (8)	0.37926 (10)	0.0320 (6)
H225	0.6567	0.0577	0.3868	0.038*
C186	0.0545 (3)	0.62653 (8)	0.40617 (9)	0.0314 (6)
H18D	−0.0446	0.6170	0.4037	0.038*
H18E	0.0930	0.6143	0.3800	0.038*
C206	0.0266 (3)	0.38159 (8)	0.39246 (10)	0.0325 (6)
H20D	−0.0715	0.3723	0.3931	0.039*
H20E	0.0519	0.3726	0.3631	0.039*
C305	0.0208 (3)	0.17966 (8)	0.38061 (9)	0.0286 (5)
H305	0.1187	0.1893	0.3784	0.034*
C65	0.9755 (3)	0.30632 (8)	0.11383 (10)	0.0311 (6)
H65	0.8767	0.3154	0.1155	0.037*
C205	0.0374 (3)	0.43262 (8)	0.39712 (10)	0.0311 (6)
H205	0.1373	0.4415	0.3973	0.037*
C242	0.5063 (3)	0.87459 (8)	0.44170 (10)	0.0313 (6)
C6	0.4515 (3)	0.87025 (8)	0.09327 (10)	0.0312 (6)
H6A	0.5498	0.8604	0.0943	0.037*
H6B	0.4127	0.8546	0.1177	0.037*
C285	0.5546 (3)	0.30367 (8)	0.37149 (10)	0.0288 (5)
H285	0.6544	0.3126	0.3811	0.035*
C44	1.0004 (3)	0.57210 (8)	0.05491 (10)	0.0348 (6)
H44A	1.0994	0.5626	0.0570	0.042*
H44B	0.9477	0.5585	0.0275	0.042*
C126	0.4476 (3)	0.37964 (8)	0.12084 (10)	0.0322 (6)
H12D	0.5476	0.3711	0.1273	0.039*
H12E	0.4023	0.3705	0.1468	0.039*
C204	−0.0085 (3)	0.44816 (8)	0.44114 (10)	0.0315 (6)
H20F	−0.1056	0.4380	0.4421	0.038*
H20G	0.0528	0.4343	0.4667	0.038*
C84	1.0198 (3)	0.07189 (8)	0.07730 (9)	0.0296 (5)
H84A	1.1167	0.0621	0.0755	0.036*
H84B	0.9594	0.0619	0.0496	0.036*
C125	0.4365 (3)	0.43076 (8)	0.11525 (10)	0.0336 (6)
H125	0.3352	0.4390	0.1082	0.040*
C104	0.4925 (3)	0.69685 (8)	0.04848 (10)	0.0329 (6)
H10I	0.5904	0.6869	0.0486	0.039*
H10J	0.4356	0.6853	0.0208	0.039*
C229	0.5931 (4)	0.03874 (10)	0.29563 (11)	0.0536 (9)
H229	0.5869	0.0053	0.2970	0.064*
C64	1.0125 (3)	0.32181 (8)	0.06867 (10)	0.0325 (6)
H64A	1.1079	0.3114	0.0656	0.039*
H64B	0.9461	0.3083	0.0441	0.039*
C68	1.0710 (3)	0.32782 (9)	0.15331 (10)	0.0393 (6)
H68A	1.1536	0.3082	0.1615	0.047*
H68B	1.1052	0.3568	0.1432	0.047*
C308	−0.0764 (3)	0.19801 (9)	0.33995 (10)	0.0378 (6)
H30I	−0.1565	0.1772	0.3327	0.045*
H30J	−0.1140	0.2272	0.3482	0.045*
C266	0.5510 (3)	0.50544 (8)	0.39603 (11)	0.0362 (6)
H26F	0.4509	0.4968	0.3913	0.043*
H26G	0.5916	0.4962	0.3691	0.043*
C264	0.5007 (3)	0.57252 (8)	0.44234 (11)	0.0371 (7)
H26H	0.4017	0.5629	0.4397	0.045*
H26I	0.5526	0.5583	0.4695	0.045*
C244	0.5044 (3)	0.82363 (8)	0.44709 (11)	0.0330 (6)
H24H	0.4077	0.8137	0.4491	0.040*
H24I	0.5646	0.8152	0.4754	0.040*
C151	0.2371 (3)	0.19307 (11)	0.19872 (10)	0.0468 (7)
H15A	0.1759	0.1856	0.2208	0.070*
H15B	0.1975	0.1808	0.1694	0.070*
H15C	0.2451	0.2257	0.1965	0.070*
C88	1.0601 (3)	0.06456 (9)	0.16194 (10)	0.0370 (6)
H88A	1.1408	0.0438	0.1682	0.044*
H88B	1.0979	0.0948	0.1574	0.044*
C304	−0.0198 (3)	0.19829 (8)	0.42444 (10)	0.0321 (6)
H30K	−0.1155	0.1881	0.4276	0.039*
H30L	0.0454	0.1865	0.4502	0.039*
C148	0.4850 (3)	0.18655 (9)	0.18186 (9)	0.0341 (6)
H14F	0.5770	0.1729	0.1932	0.041*
H14G	0.4969	0.2195	0.1835	0.041*
C289	0.6074 (3)	0.31187 (11)	0.28988 (11)	0.0457 (7)
H289	0.6237	0.2788	0.2899	0.055*
C184	−0.0021 (3)	0.69791 (8)	0.44406 (10)	0.0345 (6)
H18F	−0.1010	0.6884	0.4419	0.041*
H18G	0.0491	0.6861	0.4726	0.041*
C208	−0.0515 (4)	0.45458 (9)	0.35663 (11)	0.0439 (7)
H20H	−0.1424	0.4387	0.3508	0.053*
H20I	−0.0710	0.4859	0.3646	0.053*
C24	1.0086 (3)	0.82127 (8)	0.06340 (11)	0.0368 (7)
H24A	1.1080	0.8118	0.0678	0.044*
H24B	0.9648	0.8107	0.0334	0.044*
C144	0.5419 (3)	0.19643 (8)	0.10354 (10)	0.0340 (6)
H14H	0.5245	0.1833	0.0730	0.041*
H14I	0.6401	0.1896	0.1163	0.041*
C4	0.5115 (3)	0.94713 (8)	0.06552 (11)	0.0347 (6)
H4A	0.6091	0.9372	0.0651	0.042*
H4B	0.4570	0.9404	0.0358	0.042*
C150	0.4374 (4)	0.18620 (12)	0.26148 (11)	0.0543 (8)
H15D	0.4458	0.2189	0.2636	0.081*
H15E	0.5296	0.1725	0.2705	0.081*
H15F	0.3727	0.1757	0.2814	0.081*
C169	0.0771 (4)	0.92701 (11)	0.30449 (11)	0.0493 (8)
H169	0.0845	0.8937	0.3026	0.059*
C168	−0.0052 (3)	0.93813 (9)	0.34274 (11)	0.0397 (7)
H16F	−0.0211	0.9709	0.3426	0.048*
H16G	−0.0981	0.9236	0.3361	0.048*
C124	0.5112 (3)	0.44652 (9)	0.07637 (12)	0.0433 (7)
H12F	0.6116	0.4386	0.0832	0.052*
H12G	0.4714	0.4302	0.0488	0.052*
C9	0.4717 (4)	0.90998 (12)	0.18783 (11)	0.0591 (10)
H9	0.4802	0.8768	0.1849	0.071*
C164	−0.0136 (3)	0.94753 (8)	0.42518 (10)	0.0335 (6)
H16H	−0.1131	0.9382	0.4207	0.040*
H16I	0.0294	0.9373	0.4554	0.040*
C228	0.5070 (3)	0.05802 (9)	0.32984 (11)	0.0423 (7)
H22F	0.4097	0.0470	0.3222	0.051*
H22G	0.5044	0.0910	0.3264	0.051*
C268	0.4872 (4)	0.57845 (10)	0.35841 (12)	0.0495 (8)
H26J	0.4785	0.6109	0.3643	0.059*
H26K	0.3912	0.5660	0.3522	0.059*
C288	0.5083 (3)	0.32121 (9)	0.32390 (11)	0.0395 (7)
H28H	0.4160	0.3079	0.3124	0.047*
H28I	0.4950	0.3540	0.3256	0.047*
C108	0.5184 (4)	0.69600 (10)	0.13301 (10)	0.0463 (7)
H10K	0.6153	0.6844	0.1360	0.056*
H10L	0.5236	0.7290	0.1300	0.056*
C290	0.5426 (5)	0.32460 (14)	0.24279 (13)	0.0706 (11)
H29A	0.4585	0.3065	0.2337	0.106*
H29B	0.6101	0.3192	0.2221	0.106*
H29C	0.5171	0.3564	0.2420	0.106*
C284	0.4664 (3)	0.32351 (8)	0.40465 (12)	0.0393 (7)
H28J	0.3666	0.3173	0.3935	0.047*
H28K	0.4904	0.3078	0.4337	0.047*
C8	0.5294 (3)	0.93121 (9)	0.14813 (11)	0.0453 (7)
H8A	0.5311	0.9641	0.1523	0.054*
H8B	0.6274	0.9212	0.1489	0.054*
C310	0.0987 (4)	0.24273 (13)	0.30449 (13)	0.0617 (10)
H31D	0.0519	0.2706	0.3110	0.093*
H31E	0.1400	0.2464	0.2769	0.093*
H31F	0.1726	0.2357	0.3295	0.093*
C28	1.0026 (3)	0.81315 (10)	0.14593 (11)	0.0446 (8)
H28A	1.0143	0.8461	0.1459	0.054*
H28B	1.0975	0.7998	0.1518	0.054*
C29	0.9248 (4)	0.80066 (11)	0.18527 (12)	0.0585 (10)
H29	0.9207	0.7672	0.1870	0.070*
C188	−0.0146 (4)	0.69484 (10)	0.36019 (11)	0.0474 (8)
H18H	−0.0209	0.7279	0.3620	0.057*
H18I	−0.1114	0.6830	0.3561	0.057*
C248	0.4696 (4)	0.81352 (10)	0.36314 (11)	0.0452 (7)
H24J	0.3724	0.8030	0.3632	0.054*
H24K	0.4669	0.8467	0.3619	0.054*
C48	1.0164 (4)	0.57570 (10)	0.13925 (11)	0.0465 (8)
H48A	1.1144	0.5648	0.1439	0.056*
H48B	1.0194	0.6085	0.1349	0.056*
C311	−0.1197 (4)	0.21482 (14)	0.25775 (12)	0.0654 (10)
H31G	−0.1899	0.1909	0.2540	0.098*
H31H	−0.0750	0.2169	0.2307	0.098*
H31I	−0.1653	0.2434	0.2626	0.098*
C128	0.4977 (4)	0.45307 (10)	0.15944 (13)	0.0522 (9)
H12H	0.5901	0.4394	0.1700	0.063*
H12I	0.5138	0.4851	0.1535	0.063*
C70	1.1135 (5)	0.34920 (15)	0.23472 (13)	0.0717 (11)
H70A	1.1865	0.3262	0.2395	0.108*
H70B	1.0687	0.3519	0.2617	0.108*
H70C	1.1555	0.3780	0.2285	0.108*
C309	−0.0085 (4)	0.20442 (11)	0.29834 (11)	0.0478 (8)
H309	0.0408	0.1761	0.2923	0.057*
C224	0.4694 (3)	0.07228 (8)	0.40947 (12)	0.0420 (7)
H22H	0.3701	0.0635	0.4009	0.050*
H22I	0.4988	0.0625	0.4409	0.050*
C231	0.7464 (4)	0.05153 (16)	0.30619 (13)	0.0689 (11)
H23A	0.7966	0.0402	0.2825	0.103*
H23B	0.7868	0.0384	0.3350	0.103*
H23C	0.7549	0.0842	0.3079	0.103*
C71	0.8920 (5)	0.37318 (15)	0.18667 (14)	0.0743 (12)
H71A	0.9354	0.4010	0.1783	0.111*
H71B	0.8509	0.3781	0.2141	0.111*
H71C	0.8185	0.3640	0.1624	0.111*
C129	0.4098 (4)	0.45004 (13)	0.19705 (12)	0.0621 (10)
H129	0.3872	0.4177	0.2007	0.075*
C91	0.8795 (5)	0.10406 (15)	0.19919 (14)	0.0777 (13)
H91A	0.8385	0.1064	0.2270	0.117*
H91B	0.8054	0.0981	0.1740	0.117*
H91C	0.9266	0.1322	0.1940	0.117*
C291	0.7498 (4)	0.33411 (15)	0.30314 (13)	0.0676 (11)
H29D	0.8081	0.3288	0.2797	0.101*
H29E	0.7958	0.3214	0.3315	0.101*
H29F	0.7370	0.3664	0.3067	0.101*
C69	1.0041 (4)	0.33605 (12)	0.19494 (12)	0.0549 (9)
H69	0.9577	0.3077	0.2027	0.066*
C230	0.5327 (5)	0.05326 (13)	0.24834 (13)	0.0751 (13)
H23D	0.5353	0.0860	0.2463	0.113*
H23E	0.4355	0.0429	0.2414	0.113*
H23F	0.5882	0.0402	0.2269	0.113*
C89	0.9852 (4)	0.06601 (12)	0.20337 (11)	0.0492 (8)
H89	0.9344	0.0371	0.2054	0.059*
C249	0.5182 (5)	0.79663 (15)	0.32064 (13)	0.0750 (13)
H249	0.5158	0.7631	0.3214	0.090*
C171	−0.0008 (5)	0.94376 (14)	0.26009 (13)	0.0701 (11)
H17A	−0.0959	0.9314	0.2554	0.105*
H17B	0.0488	0.9341	0.2356	0.105*
H17C	−0.0055	0.9766	0.2606	0.105*
C269	0.5558 (5)	0.57305 (13)	0.31600 (13)	0.0677 (11)
H269	0.5640	0.5402	0.3104	0.081*
C10	0.5619 (6)	0.92358 (15)	0.23154 (14)	0.0925 (17)
H10A	0.5602	0.9562	0.2347	0.139*
H10B	0.6584	0.9136	0.2312	0.139*
H10C	0.5251	0.9097	0.2568	0.139*
C90	1.0905 (5)	0.07203 (15)	0.24589 (12)	0.0718 (12)
H90A	1.1420	0.1001	0.2440	0.108*
H90B	1.1564	0.0469	0.2490	0.108*
H90C	1.0409	0.0730	0.2720	0.108*
C31	0.7763 (5)	0.81818 (19)	0.17852 (16)	0.0915 (16)
H31A	0.7333	0.8120	0.2054	0.137*
H31B	0.7222	0.8033	0.1525	0.137*
H31C	0.7770	0.8506	0.1733	0.137*
C189	0.0505 (5)	0.68307 (13)	0.31820 (12)	0.0727 (13)
H189	0.0532	0.6497	0.3160	0.087*
C109	0.4607 (5)	0.68558 (15)	0.17638 (13)	0.0740 (12)
H109	0.4621	0.6523	0.1800	0.089*
C170	0.2253 (5)	0.94606 (19)	0.31354 (14)	0.0887 (16)
H17D	0.2208	0.9785	0.3182	0.133*
H17E	0.2737	0.9399	0.2878	0.133*
H17F	0.2766	0.9320	0.3405	0.133*
C49	0.9539 (5)	0.56665 (15)	0.18199 (12)	0.0692 (11)
H49	0.9543	0.5335	0.1867	0.083*
C11	0.3192 (6)	0.92032 (19)	0.18840 (16)	0.0937 (16)
H11A	0.2896	0.9073	0.2153	0.141*
H11B	0.2630	0.9075	0.1616	0.141*
H11C	0.3057	0.9529	0.1886	0.141*
C209	0.0117 (5)	0.45508 (16)	0.31403 (14)	0.0741 (12)
H209	0.0351	0.4235	0.3070	0.089*
C211	−0.0904 (6)	0.47253 (17)	0.27507 (15)	0.0944 (16)
H21A	−0.1167	0.5034	0.2813	0.142*
H21B	−0.1742	0.4536	0.2709	0.142*
H21C	−0.0465	0.4720	0.2478	0.142*
C131	0.2718 (6)	0.4748 (2)	0.18615 (16)	0.121 (2)
H13A	0.2198	0.4726	0.2116	0.181*
H13B	0.2165	0.4614	0.1595	0.181*
H13C	0.2899	0.5064	0.1802	0.181*
C130	0.4910 (6)	0.46589 (18)	0.24137 (17)	0.109 (2)
H13D	0.5786	0.4489	0.2479	0.164*
H13E	0.4346	0.4611	0.2654	0.164*
H13F	0.5122	0.4979	0.2393	0.164*
C271	0.7008 (6)	0.5924 (2)	0.32133 (17)	0.119 (2)
H27D	0.7370	0.5905	0.2927	0.179*
H27E	0.7621	0.5754	0.3442	0.179*
H27F	0.6979	0.6238	0.3306	0.179*
C30	1.0068 (7)	0.81765 (16)	0.22895 (15)	0.1010 (19)
H30A	1.0135	0.8504	0.2279	0.151*
H30B	1.1010	0.8047	0.2331	0.151*
H30C	0.9587	0.8089	0.2540	0.151*
C250	0.4151 (7)	0.81197 (19)	0.27977 (16)	0.108 (2)
H25A	0.4079	0.8447	0.2799	0.162*
H25B	0.3228	0.7988	0.2811	0.162*
H25C	0.4488	0.8022	0.2522	0.162*
C190	0.1982 (7)	0.6998 (2)	0.32109 (17)	0.117 (2)
H19A	0.2331	0.6936	0.2928	0.176*
H19B	0.2576	0.6845	0.3457	0.176*
H19C	0.2004	0.7321	0.3267	0.176*
C270	0.4608 (7)	0.59281 (18)	0.27582 (17)	0.108 (2)
H27G	0.4513	0.6252	0.2801	0.162*
H27H	0.3683	0.5787	0.2731	0.162*
H27I	0.5017	0.5873	0.2484	0.162*
C111	0.3126 (7)	0.7004 (3)	0.17543 (18)	0.130 (3)
H11D	0.2814	0.6927	0.2040	0.194*
H11E	0.2528	0.6852	0.1508	0.194*
H11F	0.3064	0.7329	0.1708	0.194*
C50	1.0458 (7)	0.58740 (17)	0.22215 (15)	0.1004 (19)
H50A	1.0481	0.6200	0.2184	0.151*
H50B	1.1411	0.5754	0.2242	0.151*
H50C	1.0075	0.5802	0.2496	0.151*
C51	0.8045 (7)	0.5823 (3)	0.17819 (18)	0.140 (3)
H51A	0.7690	0.5763	0.2064	0.210*
H51B	0.7472	0.5662	0.1537	0.210*
H51C	0.8001	0.6145	0.1720	0.210*
C251	0.6648 (7)	0.8104 (2)	0.31677 (17)	0.118 (2)
H25D	0.6736	0.8430	0.3201	0.178*
H25E	0.6870	0.8015	0.2873	0.178*
H25F	0.7299	0.7957	0.3404	0.178*
C110	0.5580 (7)	0.70490 (18)	0.21631 (15)	0.109 (2)
H11G	0.6526	0.6929	0.2166	0.163*
H11H	0.5237	0.6966	0.2442	0.163*
H11I	0.5602	0.7376	0.2138	0.163*
C191	−0.0443 (8)	0.70031 (17)	0.27693 (16)	0.122 (3)
H19D	−0.0579	0.7327	0.2798	0.184*
H19E	−0.1351	0.6851	0.2743	0.184*
H19F	−0.0010	0.6943	0.2501	0.184*
C210	0.1448 (8)	0.4818 (4)	0.3188 (2)	0.243 (7)
H21D	0.1385	0.5068	0.3395	0.364*
H21E	0.1588	0.4935	0.2894	0.364*
H21F	0.2239	0.4625	0.3307	0.364*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O83	0.0246 (9)	0.0151 (8)	0.0537 (12)	−0.0009 (7)	0.0066 (8)	0.0002 (7)
O163	0.0254 (9)	0.0146 (8)	0.0612 (13)	0.0013 (7)	0.0105 (8)	0.0031 (8)
O143	0.0263 (9)	0.0168 (8)	0.0533 (12)	−0.0006 (7)	0.0072 (8)	0.0018 (8)
O402	0.0263 (10)	0.0188 (8)	0.0524 (12)	0.0024 (7)	0.0033 (8)	−0.0039 (8)
O411	0.0264 (9)	0.0212 (8)	0.0462 (11)	−0.0022 (7)	−0.0001 (8)	0.0029 (8)
O23	0.0274 (10)	0.0159 (8)	0.0606 (13)	−0.0011 (7)	0.0104 (9)	−0.0044 (8)
O416	0.0264 (10)	0.0248 (9)	0.0464 (12)	−0.0026 (7)	0.0016 (8)	0.0029 (8)
O223	0.0253 (9)	0.0159 (8)	0.0632 (13)	0.0013 (7)	0.0081 (9)	0.0031 (8)
O404	0.0303 (10)	0.0211 (8)	0.0454 (11)	0.0050 (7)	0.0002 (8)	−0.0037 (8)
O3	0.0257 (9)	0.0169 (8)	0.0632 (13)	−0.0010 (7)	0.0088 (9)	−0.0056 (8)
O409	0.0329 (10)	0.0236 (9)	0.0469 (12)	−0.0046 (7)	0.0010 (8)	0.0027 (8)
O161	0.0241 (9)	0.0171 (8)	0.0640 (13)	0.0037 (7)	0.0060 (8)	−0.0027 (8)
O43	0.0268 (9)	0.0171 (8)	0.0562 (12)	−0.0012 (7)	0.0071 (8)	−0.0021 (8)
O412	0.0326 (11)	0.0297 (10)	0.0510 (12)	−0.0069 (8)	−0.0037 (9)	0.0069 (9)
O407	0.0249 (9)	0.0301 (9)	0.0437 (11)	0.0029 (8)	0.0020 (8)	−0.0051 (9)
O63	0.0265 (10)	0.0174 (8)	0.0713 (14)	−0.0007 (7)	0.0070 (9)	0.0059 (9)
O41	0.0277 (10)	0.0186 (8)	0.0667 (14)	−0.0026 (7)	0.0067 (9)	0.0065 (8)
O103	0.0252 (9)	0.0170 (8)	0.0601 (13)	−0.0010 (7)	0.0057 (8)	−0.0042 (8)
O414	0.0263 (10)	0.0301 (9)	0.0492 (12)	−0.0037 (7)	0.0033 (8)	0.0076 (8)
O203	0.0271 (10)	0.0154 (8)	0.0640 (13)	0.0001 (7)	0.0074 (9)	−0.0025 (8)
O81	0.0253 (9)	0.0178 (8)	0.0630 (13)	−0.0028 (7)	0.0053 (9)	0.0053 (8)
O243	0.0258 (10)	0.0147 (8)	0.0701 (14)	0.0001 (7)	0.0090 (9)	0.0030 (8)
O21	0.0262 (10)	0.0190 (8)	0.0691 (14)	−0.0036 (7)	0.0102 (9)	−0.0012 (8)
O183	0.0260 (9)	0.0144 (8)	0.0580 (12)	0.0018 (7)	0.0074 (8)	0.0025 (8)
O401	0.0266 (10)	0.0237 (9)	0.0572 (13)	0.0054 (7)	0.0003 (8)	−0.0055 (8)
O141	0.0283 (10)	0.0176 (8)	0.0782 (15)	−0.0034 (7)	0.0141 (10)	0.0070 (9)
O403	0.0322 (10)	0.0312 (9)	0.0418 (11)	0.0095 (8)	−0.0016 (8)	−0.0083 (9)
O263	0.0268 (10)	0.0157 (8)	0.0676 (14)	0.0016 (7)	0.0059 (9)	0.0013 (8)
O303	0.0251 (9)	0.0145 (8)	0.0691 (14)	0.0003 (7)	0.0065 (9)	−0.0031 (8)
O101	0.0264 (10)	0.0180 (8)	0.0664 (14)	−0.0030 (7)	0.0064 (9)	0.0007 (8)
O201	0.0269 (10)	0.0190 (8)	0.0696 (14)	0.0026 (7)	0.0057 (9)	−0.0103 (9)
O61	0.0275 (10)	0.0196 (8)	0.0736 (15)	−0.0024 (7)	0.0056 (9)	0.0111 (9)
O413	0.0401 (12)	0.0264 (9)	0.0517 (13)	−0.0059 (8)	−0.0001 (9)	0.0078 (9)
O283	0.0284 (10)	0.0154 (8)	0.0712 (14)	0.0011 (7)	0.0111 (9)	−0.0018 (8)
O410	0.0322 (10)	0.0297 (10)	0.0463 (12)	−0.0079 (8)	−0.0008 (8)	0.0060 (8)
O123	0.0273 (10)	0.0174 (8)	0.0825 (16)	−0.0010 (7)	0.0096 (10)	0.0016 (9)
O405	0.0280 (10)	0.0301 (10)	0.0626 (14)	0.0031 (8)	0.0019 (9)	−0.0082 (9)
O181	0.0258 (9)	0.0165 (8)	0.0694 (14)	0.0022 (7)	0.0081 (9)	−0.0039 (8)
O1	0.0265 (10)	0.0170 (8)	0.0787 (15)	−0.0024 (7)	0.0076 (9)	0.0001 (9)
O408	0.0443 (12)	0.0291 (10)	0.0470 (12)	0.0133 (9)	−0.0069 (9)	−0.0104 (9)
O261	0.0258 (10)	0.0184 (8)	0.0730 (15)	0.0016 (7)	0.0078 (9)	−0.0063 (9)
O241	0.0252 (10)	0.0163 (8)	0.0809 (15)	0.0021 (7)	0.0086 (9)	−0.0005 (9)
O221	0.0269 (10)	0.0162 (8)	0.0779 (15)	0.0053 (7)	0.0112 (9)	0.0000 (9)
O301	0.0249 (9)	0.0184 (8)	0.0773 (15)	0.0040 (7)	0.0036 (9)	−0.0098 (9)
O415	0.0524 (13)	0.0334 (11)	0.0536 (13)	−0.0145 (10)	−0.0129 (10)	0.0144 (10)
O406	0.0528 (14)	0.0315 (11)	0.0553 (14)	0.0132 (10)	−0.0048 (11)	−0.0117 (10)
N247	0.0252 (10)	0.0132 (8)	0.0376 (11)	0.0010 (8)	0.0056 (8)	0.0000 (8)
N187	0.0259 (11)	0.0133 (9)	0.0417 (12)	0.0017 (8)	0.0049 (9)	−0.0001 (8)
O121	0.0286 (10)	0.0214 (9)	0.0961 (18)	−0.0021 (8)	0.0129 (11)	0.0149 (10)
N27	0.0258 (10)	0.0135 (9)	0.0435 (12)	−0.0017 (8)	0.0054 (9)	−0.0024 (8)
N47	0.0277 (11)	0.0141 (9)	0.0429 (13)	−0.0029 (8)	0.0046 (9)	0.0033 (8)
N167	0.0243 (11)	0.0134 (9)	0.0488 (14)	0.0014 (8)	0.0071 (9)	0.0018 (9)
N107	0.0279 (11)	0.0135 (9)	0.0467 (13)	−0.0005 (8)	0.0059 (9)	0.0011 (9)
N147	0.0265 (11)	0.0149 (9)	0.0419 (13)	−0.0007 (8)	0.0064 (9)	−0.0013 (8)
N287	0.0222 (10)	0.0146 (8)	0.0367 (11)	0.0020 (8)	0.0048 (8)	−0.0008 (8)
N7	0.0265 (11)	0.0154 (9)	0.0421 (13)	−0.0025 (8)	0.0069 (9)	−0.0015 (8)
O281	0.0302 (11)	0.0194 (9)	0.1002 (18)	0.0023 (8)	0.0178 (11)	−0.0128 (10)
N267	0.0278 (11)	0.0136 (9)	0.0530 (14)	0.0010 (8)	0.0090 (10)	−0.0006 (9)
N127	0.0277 (11)	0.0140 (9)	0.0413 (13)	−0.0019 (8)	0.0074 (9)	0.0020 (8)
N307	0.0244 (11)	0.0129 (8)	0.0422 (12)	0.0007 (8)	0.0066 (9)	−0.0017 (8)
N207	0.0272 (11)	0.0123 (9)	0.0506 (14)	0.0014 (8)	0.0080 (9)	−0.0051 (9)
N67	0.0297 (11)	0.0127 (8)	0.0426 (12)	0.0003 (8)	0.0084 (9)	0.0037 (8)
N87	0.0272 (11)	0.0138 (9)	0.0462 (13)	−0.0003 (8)	0.0074 (9)	−0.0007 (8)
N227	0.0238 (11)	0.0142 (9)	0.0549 (14)	0.0017 (8)	0.0092 (10)	−0.0004 (9)
C82	0.0249 (12)	0.0148 (10)	0.0370 (14)	−0.0015 (9)	0.0022 (10)	0.0012 (9)
C42	0.0278 (13)	0.0147 (10)	0.0411 (15)	−0.0027 (9)	0.0037 (10)	0.0009 (10)
C22	0.0266 (13)	0.0145 (10)	0.0450 (15)	−0.0011 (9)	0.0048 (11)	−0.0010 (10)
C142	0.0282 (13)	0.0156 (10)	0.0412 (15)	−0.0009 (9)	0.0053 (11)	0.0018 (10)
C162	0.0256 (13)	0.0159 (10)	0.0403 (15)	0.0021 (9)	0.0039 (10)	0.0000 (10)
C202	0.0291 (13)	0.0158 (11)	0.0425 (15)	0.0021 (9)	0.0026 (11)	−0.0016 (10)
C102	0.0272 (13)	0.0154 (11)	0.0419 (15)	−0.0020 (9)	0.0054 (11)	−0.0009 (10)
C146	0.0315 (13)	0.0156 (11)	0.0410 (15)	−0.0026 (9)	0.0022 (11)	0.0020 (10)
C62	0.0282 (13)	0.0157 (11)	0.0446 (15)	−0.0015 (9)	0.0014 (11)	0.0038 (10)
C86	0.0332 (14)	0.0157 (11)	0.0428 (15)	0.0009 (10)	0.0052 (11)	0.0045 (10)
C262	0.0276 (13)	0.0150 (11)	0.0494 (16)	0.0020 (9)	0.0043 (11)	0.0005 (10)
C182	0.0265 (13)	0.0164 (11)	0.0437 (15)	0.0017 (9)	0.0044 (11)	0.0002 (10)
C165	0.0294 (13)	0.0138 (10)	0.0448 (15)	0.0007 (9)	0.0059 (11)	−0.0001 (10)
C302	0.0253 (13)	0.0155 (11)	0.0470 (16)	0.0016 (9)	0.0027 (11)	−0.0041 (10)
C149	0.0489 (17)	0.0291 (13)	0.0350 (15)	0.0025 (12)	0.0003 (12)	0.0018 (11)
C45	0.0322 (14)	0.0192 (11)	0.0372 (14)	0.0004 (10)	0.0014 (11)	0.0016 (10)
C145	0.0287 (13)	0.0136 (10)	0.0411 (15)	−0.0023 (9)	0.0048 (10)	0.0009 (9)
C222	0.0272 (13)	0.0146 (11)	0.0527 (17)	0.0029 (9)	0.0081 (12)	0.0034 (11)
C166	0.0338 (14)	0.0157 (11)	0.0446 (16)	0.0005 (10)	0.0046 (11)	−0.0008 (10)
C306	0.0317 (14)	0.0176 (11)	0.0399 (15)	−0.0008 (10)	0.0024 (11)	−0.0045 (10)
C286	0.0283 (13)	0.0173 (11)	0.0363 (14)	0.0017 (9)	0.0016 (10)	−0.0004 (10)
C282	0.0295 (14)	0.0169 (11)	0.0564 (18)	0.0016 (10)	0.0098 (12)	−0.0037 (11)
C185	0.0307 (13)	0.0152 (11)	0.0417 (15)	0.0003 (9)	0.0020 (11)	0.0005 (10)
C2	0.0284 (13)	0.0145 (11)	0.0524 (17)	−0.0021 (9)	0.0068 (12)	−0.0012 (10)
C25	0.0278 (13)	0.0144 (10)	0.0436 (15)	−0.0027 (9)	0.0018 (11)	−0.0022 (10)
C226	0.0285 (14)	0.0185 (12)	0.0529 (17)	−0.0004 (10)	−0.0001 (12)	−0.0009 (11)
C105	0.0310 (13)	0.0173 (11)	0.0408 (15)	−0.0017 (10)	0.0016 (11)	0.0017 (10)
C265	0.0314 (14)	0.0159 (11)	0.0494 (17)	−0.0010 (10)	0.0007 (12)	−0.0002 (11)
C46	0.0355 (14)	0.0200 (11)	0.0385 (15)	−0.0012 (10)	−0.0006 (11)	0.0030 (10)
C66	0.0326 (14)	0.0209 (12)	0.0412 (15)	0.0002 (10)	0.0021 (11)	0.0036 (10)
C85	0.0289 (13)	0.0149 (10)	0.0392 (14)	0.0001 (9)	0.0045 (11)	0.0008 (10)
C26	0.0309 (14)	0.0167 (11)	0.0437 (15)	−0.0042 (10)	−0.0019 (11)	−0.0004 (10)
C5	0.0302 (13)	0.0154 (11)	0.0467 (16)	−0.0006 (9)	0.0035 (11)	−0.0022 (10)
C122	0.0294 (14)	0.0146 (11)	0.067 (2)	−0.0015 (10)	0.0074 (13)	0.0039 (12)
C106	0.0340 (14)	0.0193 (11)	0.0438 (16)	−0.0034 (10)	−0.0014 (12)	0.0023 (11)
C246	0.0344 (14)	0.0164 (11)	0.0382 (14)	0.0006 (10)	0.0001 (11)	0.0002 (10)
C245	0.0297 (13)	0.0151 (11)	0.0398 (15)	0.0011 (9)	0.0015 (11)	0.0023 (10)
C225	0.0234 (13)	0.0158 (11)	0.0557 (17)	0.0001 (9)	0.0022 (11)	0.0004 (11)
C186	0.0346 (14)	0.0170 (11)	0.0407 (15)	−0.0004 (10)	−0.0009 (11)	−0.0019 (10)
C206	0.0338 (14)	0.0175 (11)	0.0457 (16)	0.0005 (10)	0.0040 (12)	−0.0030 (10)
C305	0.0289 (13)	0.0163 (11)	0.0394 (14)	0.0005 (9)	0.0017 (10)	0.0002 (10)
C65	0.0307 (14)	0.0175 (11)	0.0440 (16)	0.0017 (10)	0.0020 (11)	0.0004 (10)
C205	0.0333 (14)	0.0154 (11)	0.0450 (16)	−0.0007 (10)	0.0068 (11)	−0.0007 (10)
C242	0.0266 (13)	0.0162 (11)	0.0510 (17)	0.0025 (9)	0.0053 (11)	0.0021 (10)
C6	0.0322 (14)	0.0172 (11)	0.0429 (15)	−0.0015 (10)	0.0015 (11)	−0.0008 (10)
C285	0.0266 (13)	0.0173 (11)	0.0427 (15)	0.0003 (9)	0.0054 (11)	−0.0004 (10)
C44	0.0340 (15)	0.0174 (11)	0.0549 (18)	−0.0005 (10)	0.0133 (12)	−0.0003 (11)
C126	0.0319 (14)	0.0186 (11)	0.0449 (16)	−0.0018 (10)	0.0015 (11)	0.0012 (10)
C204	0.0308 (14)	0.0160 (11)	0.0487 (16)	0.0008 (10)	0.0089 (11)	−0.0014 (10)
C84	0.0305 (13)	0.0173 (11)	0.0421 (15)	−0.0013 (10)	0.0087 (11)	−0.0008 (10)
C125	0.0311 (14)	0.0171 (11)	0.0513 (17)	−0.0025 (10)	0.0016 (12)	−0.0003 (11)
C104	0.0321 (14)	0.0171 (11)	0.0505 (17)	−0.0015 (10)	0.0095 (12)	−0.0025 (11)
C229	0.082 (3)	0.0291 (14)	0.0441 (18)	0.0122 (15)	−0.0088 (17)	−0.0017 (13)
C64	0.0313 (14)	0.0179 (12)	0.0485 (17)	−0.0020 (10)	0.0067 (12)	0.0021 (11)
C68	0.0371 (16)	0.0281 (13)	0.0506 (18)	−0.0032 (11)	−0.0005 (13)	−0.0020 (12)
C308	0.0355 (15)	0.0310 (14)	0.0451 (16)	0.0044 (11)	0.0001 (12)	0.0022 (12)
C266	0.0340 (14)	0.0189 (12)	0.0537 (18)	−0.0003 (10)	0.0001 (12)	−0.0042 (11)
C264	0.0353 (15)	0.0153 (11)	0.0626 (19)	0.0009 (10)	0.0135 (13)	0.0007 (12)
C244	0.0300 (14)	0.0163 (11)	0.0542 (18)	0.0016 (10)	0.0108 (12)	0.0017 (11)
C151	0.0479 (18)	0.0524 (18)	0.0419 (17)	0.0035 (15)	0.0129 (13)	0.0022 (14)
C88	0.0421 (16)	0.0249 (13)	0.0429 (16)	−0.0003 (11)	0.0019 (12)	−0.0007 (11)
C304	0.0286 (13)	0.0161 (11)	0.0525 (17)	0.0008 (10)	0.0092 (11)	−0.0016 (11)
C148	0.0346 (14)	0.0214 (12)	0.0429 (16)	−0.0013 (10)	−0.0052 (11)	−0.0016 (11)
C289	0.0501 (19)	0.0432 (16)	0.0422 (17)	−0.0056 (14)	0.0018 (14)	0.0100 (13)
C184	0.0333 (14)	0.0159 (11)	0.0571 (18)	0.0003 (10)	0.0158 (12)	0.0006 (11)
C208	0.0564 (19)	0.0248 (13)	0.0485 (18)	0.0011 (13)	0.0008 (14)	0.0016 (12)
C24	0.0340 (15)	0.0179 (12)	0.0616 (19)	−0.0024 (10)	0.0173 (13)	−0.0046 (11)
C144	0.0314 (14)	0.0169 (11)	0.0556 (18)	−0.0010 (10)	0.0123 (12)	0.0007 (11)
C4	0.0295 (14)	0.0185 (11)	0.0586 (18)	−0.0021 (10)	0.0146 (12)	−0.0054 (11)
C150	0.071 (2)	0.0471 (18)	0.0411 (18)	−0.0006 (16)	−0.0044 (16)	−0.0021 (14)
C169	0.065 (2)	0.0404 (16)	0.0409 (17)	−0.0059 (15)	0.0019 (15)	−0.0065 (13)
C168	0.0441 (17)	0.0228 (13)	0.0500 (18)	0.0011 (11)	−0.0006 (13)	0.0014 (12)
C124	0.0366 (16)	0.0189 (12)	0.078 (2)	0.0003 (11)	0.0193 (15)	0.0076 (13)
C9	0.087 (3)	0.0449 (18)	0.0402 (18)	0.0042 (18)	−0.0086 (18)	−0.0070 (15)
C164	0.0322 (14)	0.0158 (11)	0.0547 (18)	0.0021 (10)	0.0141 (12)	0.0022 (11)
C228	0.0359 (15)	0.0242 (13)	0.061 (2)	0.0012 (11)	−0.0130 (13)	0.0028 (13)
C268	0.056 (2)	0.0253 (14)	0.061 (2)	0.0006 (13)	−0.0117 (16)	0.0036 (13)
C288	0.0373 (16)	0.0263 (13)	0.0522 (18)	0.0028 (11)	−0.0024 (13)	0.0076 (12)
C108	0.057 (2)	0.0315 (14)	0.0455 (17)	−0.0078 (14)	−0.0098 (14)	−0.0017 (13)
C290	0.084 (3)	0.071 (3)	0.051 (2)	0.001 (2)	−0.006 (2)	0.0191 (19)
C284	0.0352 (15)	0.0175 (12)	0.069 (2)	−0.0002 (10)	0.0216 (14)	−0.0041 (12)
C8	0.0515 (18)	0.0256 (13)	0.0528 (19)	0.0019 (12)	−0.0115 (14)	−0.0071 (12)
C310	0.067 (2)	0.065 (2)	0.057 (2)	−0.0055 (18)	0.0227 (18)	0.0160 (17)
C28	0.0494 (18)	0.0249 (13)	0.0531 (19)	−0.0013 (12)	−0.0138 (15)	−0.0068 (13)
C29	0.094 (3)	0.0349 (16)	0.0405 (19)	−0.0002 (17)	−0.0084 (18)	0.0002 (14)
C188	0.058 (2)	0.0246 (13)	0.0529 (19)	−0.0013 (13)	−0.0151 (15)	0.0052 (13)
C248	0.0525 (19)	0.0293 (14)	0.0489 (18)	0.0000 (13)	−0.0091 (14)	0.0095 (13)
C48	0.059 (2)	0.0262 (14)	0.0487 (18)	0.0021 (13)	−0.0112 (15)	−0.0028 (12)
C311	0.073 (3)	0.079 (3)	0.0419 (19)	0.017 (2)	0.0002 (17)	0.0067 (18)
C128	0.053 (2)	0.0255 (14)	0.072 (2)	0.0003 (13)	−0.0137 (17)	−0.0116 (14)
C70	0.087 (3)	0.074 (3)	0.051 (2)	−0.018 (2)	0.000 (2)	−0.012 (2)
C309	0.0523 (19)	0.0446 (17)	0.0469 (18)	0.0087 (14)	0.0083 (14)	0.0010 (14)
C224	0.0336 (15)	0.0172 (12)	0.080 (2)	0.0029 (11)	0.0237 (15)	0.0041 (13)
C231	0.067 (3)	0.093 (3)	0.048 (2)	0.034 (2)	0.0129 (18)	0.005 (2)
C71	0.074 (3)	0.086 (3)	0.067 (3)	0.012 (2)	0.025 (2)	−0.018 (2)
C129	0.077 (3)	0.053 (2)	0.049 (2)	0.0218 (19)	−0.0147 (18)	−0.0155 (16)
C91	0.102 (3)	0.079 (3)	0.057 (2)	0.031 (3)	0.029 (2)	−0.006 (2)
C291	0.059 (2)	0.088 (3)	0.058 (2)	−0.026 (2)	0.0155 (18)	0.003 (2)
C69	0.065 (2)	0.0472 (19)	0.052 (2)	−0.0167 (16)	0.0086 (17)	−0.0030 (15)
C230	0.114 (4)	0.048 (2)	0.053 (2)	0.008 (2)	−0.021 (2)	0.0025 (17)
C89	0.064 (2)	0.0444 (17)	0.0392 (17)	−0.0002 (15)	0.0064 (15)	0.0036 (14)
C249	0.115 (4)	0.065 (2)	0.040 (2)	0.014 (2)	−0.003 (2)	0.0085 (18)
C171	0.099 (3)	0.059 (2)	0.049 (2)	−0.002 (2)	−0.001 (2)	0.0037 (18)
C269	0.103 (3)	0.048 (2)	0.044 (2)	−0.007 (2)	−0.014 (2)	−0.0003 (16)
C10	0.156 (5)	0.060 (2)	0.049 (2)	−0.001 (3)	−0.026 (3)	−0.006 (2)
C90	0.096 (3)	0.073 (3)	0.044 (2)	−0.024 (2)	0.002 (2)	−0.0040 (18)
C31	0.100 (4)	0.124 (4)	0.057 (3)	0.023 (3)	0.032 (3)	0.006 (3)
C189	0.131 (4)	0.0424 (19)	0.0385 (19)	0.004 (2)	−0.008 (2)	0.0015 (15)
C109	0.115 (4)	0.061 (2)	0.041 (2)	−0.015 (2)	−0.004 (2)	0.0011 (18)
C170	0.072 (3)	0.146 (5)	0.053 (2)	−0.034 (3)	0.024 (2)	−0.018 (3)
C49	0.100 (3)	0.065 (2)	0.0390 (19)	0.010 (2)	−0.0034 (19)	−0.0077 (17)
C11	0.113 (4)	0.116 (4)	0.057 (3)	0.019 (3)	0.029 (3)	0.000 (3)
C209	0.090 (3)	0.085 (3)	0.047 (2)	0.001 (2)	0.009 (2)	0.006 (2)
C211	0.145 (5)	0.081 (3)	0.050 (2)	−0.003 (3)	−0.008 (3)	0.010 (2)
C131	0.126 (5)	0.177 (6)	0.058 (3)	0.100 (5)	0.008 (3)	0.002 (3)
C130	0.145 (5)	0.093 (4)	0.074 (3)	0.013 (4)	−0.036 (3)	−0.038 (3)
C271	0.120 (5)	0.184 (7)	0.059 (3)	−0.046 (5)	0.028 (3)	−0.004 (4)
C30	0.170 (6)	0.069 (3)	0.051 (3)	−0.020 (3)	−0.029 (3)	−0.005 (2)
C250	0.164 (6)	0.096 (4)	0.052 (3)	0.000 (4)	−0.029 (3)	0.021 (3)
C190	0.133 (5)	0.162 (6)	0.067 (3)	−0.018 (5)	0.048 (3)	0.008 (3)
C270	0.164 (6)	0.080 (3)	0.065 (3)	0.010 (3)	−0.031 (3)	0.015 (3)
C111	0.122 (5)	0.212 (8)	0.064 (3)	0.002 (5)	0.045 (3)	−0.020 (4)
C50	0.161 (5)	0.076 (3)	0.052 (3)	0.008 (3)	−0.023 (3)	−0.019 (2)
C51	0.123 (5)	0.247 (9)	0.057 (3)	0.056 (5)	0.033 (3)	−0.017 (4)
C251	0.123 (5)	0.179 (6)	0.063 (3)	0.023 (4)	0.043 (3)	0.032 (4)
C110	0.175 (6)	0.088 (3)	0.050 (3)	−0.026 (4)	−0.025 (3)	−0.006 (2)
C191	0.232 (7)	0.066 (3)	0.052 (3)	0.004 (4)	−0.037 (4)	0.011 (2)
C210	0.134 (6)	0.515 (18)	0.076 (4)	−0.166 (9)	0.004 (4)	0.092 (7)

Geometric parameters (Å, º)

O83—C82	1.259 (3)	C6—H6B	0.9900
O163—C162	1.258 (3)	C285—C284	1.526 (4)
O143—C142	1.254 (3)	C285—C288	1.529 (4)
O402—H40A	0.8701	C285—H285	1.0000
O402—H40B	0.8699	C44—H44A	0.9900
O411—H41A	0.86 (4)	C44—H44B	0.9900
O411—H41B	0.83 (4)	C126—C125	1.537 (3)
O23—C22	1.259 (3)	C126—H12D	0.9900
O416—H41C	0.8701	C126—H12E	0.9900
O416—H41D	0.8695	C204—H20F	0.9900
O223—C222	1.256 (3)	C204—H20G	0.9900
O404—H40C	0.8699	C84—H84A	0.9900
O404—H40D	0.8700	C84—H84B	0.9900
O3—C2	1.259 (3)	C125—C128	1.527 (4)
O409—H40E	0.8702	C125—C124	1.537 (4)
O409—H40F	0.8699	C125—H125	1.0000
O161—C162	1.255 (3)	C104—H10I	0.9900
O43—C42	1.260 (3)	C104—H10J	0.9900
O412—H41E	0.8701	C229—C231	1.516 (5)
O412—H41F	0.8698	C229—C230	1.520 (5)
O407—H40G	0.82 (4)	C229—C228	1.529 (5)
O407—H40H	0.86 (4)	C229—H229	1.0000
O63—C62	1.258 (3)	C64—H64A	0.9900
O41—C42	1.254 (3)	C64—H64B	0.9900
O103—C102	1.263 (3)	C68—C69	1.514 (5)
O414—H41G	0.8699	C68—H68A	0.9900
O414—H41H	0.8701	C68—H68B	0.9900
O203—C202	1.259 (3)	C308—C309	1.510 (4)
O81—C82	1.251 (3)	C308—H30I	0.9900
O243—C242	1.259 (3)	C308—H30J	0.9900
O21—C22	1.253 (3)	C266—H26F	0.9900
O183—C182	1.257 (3)	C266—H26G	0.9900
O401—H40I	0.8699	C264—H26H	0.9900
O401—H40J	0.8698	C264—H26I	0.9900
O141—C142	1.256 (3)	C244—H24H	0.9900
O403—H40K	0.8701	C244—H24I	0.9900
O403—H40L	0.8699	C151—H15A	0.9800
O263—C262	1.259 (3)	C151—H15B	0.9800
O303—C302	1.262 (3)	C151—H15C	0.9800
O101—C102	1.248 (3)	C88—C89	1.533 (4)
O201—C202	1.258 (3)	C88—H88A	0.9900
O61—C62	1.254 (3)	C88—H88B	0.9900
O413—H41I	0.8700	C304—H30K	0.9900
O413—H41J	0.8701	C304—H30L	0.9900
O283—C282	1.255 (3)	C148—H14F	0.9900
O410—H41K	0.8697	C148—H14G	0.9900
O410—H41L	0.8699	C289—C290	1.512 (5)
O123—C122	1.259 (3)	C289—C291	1.526 (5)
O405—H40M	0.8702	C289—C288	1.528 (4)
O405—H40N	0.8701	C289—H289	1.0000
O181—C182	1.258 (3)	C184—H18F	0.9900
O1—C2	1.254 (3)	C184—H18G	0.9900
O408—H40O	0.8701	C208—C209	1.501 (5)
O408—H40P	0.8702	C208—H20H	0.9900
O261—C262	1.252 (3)	C208—H20I	0.9900
O241—C242	1.255 (3)	C24—H24A	0.9900
O221—C222	1.257 (3)	C24—H24B	0.9900
O301—C302	1.251 (3)	C144—H14H	0.9900
O415—H41M	0.8699	C144—H14I	0.9900
O415—H41N	0.8699	C4—H4A	0.9900
O406—H40Q	0.80 (4)	C4—H4B	0.9900
O406—H40R	0.82 (4)	C150—H15D	0.9800
N247—C246	1.475 (3)	C150—H15E	0.9800
N247—H24C	0.9100	C150—H15F	0.9800
N247—H24D	0.9100	C169—C171	1.519 (5)
N247—H24E	0.9100	C169—C170	1.526 (5)
N187—C186	1.477 (3)	C169—C168	1.530 (4)
N187—H18A	0.9100	C169—H169	1.0000
N187—H18B	0.9100	C168—H16F	0.9900
N187—H18C	0.9100	C168—H16G	0.9900
O121—C122	1.249 (3)	C124—H12F	0.9900
N27—C26	1.483 (3)	C124—H12G	0.9900
N27—H27A	0.9100	C9—C11	1.508 (6)
N27—H27B	0.9100	C9—C10	1.522 (5)
N27—H27C	0.9100	C9—C8	1.530 (5)
N47—C46	1.473 (3)	C9—H9	1.0000
N47—H47A	0.9100	C164—H16H	0.9900
N47—H47B	0.9100	C164—H16I	0.9900
N47—H47C	0.9100	C228—H22F	0.9900
N167—C166	1.479 (3)	C228—H22G	0.9900
N167—H16A	0.9100	C268—C269	1.532 (5)
N167—H16B	0.9100	C268—H26J	0.9900
N167—H16C	0.9100	C268—H26K	0.9900
N107—C106	1.478 (3)	C288—H28H	0.9900
N107—H10D	0.9100	C288—H28I	0.9900
N107—H10E	0.9100	C108—C109	1.527 (5)
N107—H10F	0.9100	C108—H10K	0.9900
N147—C146	1.476 (3)	C108—H10L	0.9900
N147—H14A	0.9100	C290—H29A	0.9800
N147—H14B	0.9100	C290—H29B	0.9800
N147—H14C	0.9100	C290—H29C	0.9800
N287—C286	1.483 (3)	C284—H28J	0.9900
N287—H28C	0.9100	C284—H28K	0.9900
N287—H28D	0.9100	C8—H8A	0.9900
N287—H28E	0.9100	C8—H8B	0.9900
N7—C6	1.481 (3)	C310—C309	1.535 (5)
N7—H7A	0.9100	C310—H31D	0.9800
N7—H7B	0.9100	C310—H31E	0.9800
N7—H7C	0.9100	C310—H31F	0.9800
O281—C282	1.257 (3)	C28—C29	1.540 (5)
N267—C266	1.481 (4)	C28—H28A	0.9900
N267—H26C	0.9100	C28—H28B	0.9900
N267—H26D	0.9100	C29—C31	1.512 (6)
N267—H26E	0.9100	C29—C30	1.519 (5)
N127—C126	1.480 (3)	C29—H29	1.0000
N127—H12A	0.9100	C188—C189	1.534 (5)
N127—H12B	0.9100	C188—H18H	0.9900
N127—H12C	0.9100	C188—H18I	0.9900
N307—C306	1.481 (3)	C248—C249	1.514 (5)
N307—H30D	0.9100	C248—H24J	0.9900
N307—H30E	0.9100	C248—H24K	0.9900
N307—H30F	0.9100	C48—C49	1.525 (5)
N207—C206	1.477 (3)	C48—H48A	0.9900
N207—H20A	0.9100	C48—H48B	0.9900
N207—H20B	0.9100	C311—C309	1.534 (5)
N207—H20C	0.9100	C311—H31G	0.9800
N67—C66	1.487 (3)	C311—H31H	0.9800
N67—H67A	0.9100	C311—H31I	0.9800
N67—H67B	0.9100	C128—C129	1.516 (6)
N67—H67C	0.9100	C128—H12H	0.9900
N87—C86	1.479 (3)	C128—H12I	0.9900
N87—H87A	0.9100	C70—C69	1.526 (5)
N87—H87B	0.9100	C70—H70A	0.9800
N87—H87C	0.9100	C70—H70B	0.9800
N227—C226	1.479 (4)	C70—H70C	0.9800
N227—H22A	0.9100	C309—H309	1.0000
N227—H22B	0.9100	C224—H22H	0.9900
N227—H22C	0.9100	C224—H22I	0.9900
C82—C84	1.525 (3)	C231—H23A	0.9800
C42—C44	1.522 (3)	C231—H23B	0.9800
C22—C24	1.518 (3)	C231—H23C	0.9800
C142—C144	1.528 (3)	C71—C69	1.543 (6)
C162—C164	1.525 (3)	C71—H71A	0.9800
C202—C204	1.515 (3)	C71—H71B	0.9800
C102—C104	1.527 (3)	C71—H71C	0.9800
C146—C145	1.539 (3)	C129—C131	1.517 (5)
C146—H14D	0.9900	C129—C130	1.520 (5)
C146—H14E	0.9900	C129—H129	1.0000
C62—C64	1.521 (3)	C91—C89	1.519 (5)
C86—C85	1.534 (3)	C91—H91A	0.9800
C86—H86A	0.9900	C91—H91B	0.9800
C86—H86B	0.9900	C91—H91C	0.9800
C262—C264	1.525 (3)	C291—H29D	0.9800
C182—C184	1.521 (3)	C291—H29E	0.9800
C165—C168	1.524 (4)	C291—H29F	0.9800
C165—C164	1.528 (4)	C69—H69	1.0000
C165—C166	1.531 (3)	C230—H23D	0.9800
C165—H165	1.0000	C230—H23E	0.9800
C302—C304	1.519 (3)	C230—H23F	0.9800
C149—C150	1.521 (4)	C89—C90	1.523 (5)
C149—C151	1.523 (4)	C89—H89	1.0000
C149—C148	1.530 (4)	C249—C251	1.494 (7)
C149—H149	1.0000	C249—C250	1.534 (6)
C45—C48	1.528 (4)	C249—H249	1.0000
C45—C46	1.531 (3)	C171—H17A	0.9800
C45—C44	1.532 (4)	C171—H17B	0.9800
C45—H45	1.0000	C171—H17C	0.9800
C145—C144	1.527 (3)	C269—C271	1.500 (7)
C145—C148	1.532 (4)	C269—C270	1.525 (6)
C145—H145	1.0000	C269—H269	1.0000
C222—C224	1.523 (3)	C10—H10A	0.9800
C166—H16D	0.9900	C10—H10B	0.9800
C166—H16E	0.9900	C10—H10C	0.9800
C306—C305	1.535 (3)	C90—H90A	0.9800
C306—H30G	0.9900	C90—H90B	0.9800
C306—H30H	0.9900	C90—H90C	0.9800
C286—C285	1.536 (3)	C31—H31A	0.9800
C286—H28F	0.9900	C31—H31B	0.9800
C286—H28G	0.9900	C31—H31C	0.9800
C282—C284	1.526 (3)	C189—C190	1.501 (7)
C185—C188	1.519 (4)	C189—C191	1.520 (6)
C185—C184	1.530 (4)	C189—H189	1.0000
C185—C186	1.530 (3)	C109—C111	1.492 (7)
C185—H185	1.0000	C109—C110	1.525 (6)
C2—C4	1.524 (3)	C109—H109	1.0000
C25—C28	1.523 (4)	C170—H17D	0.9800
C25—C24	1.525 (4)	C170—H17E	0.9800
C25—C26	1.530 (3)	C170—H17F	0.9800
C25—H25	1.0000	C49—C51	1.504 (7)
C226—C225	1.531 (3)	C49—C50	1.522 (6)
C226—H22D	0.9900	C49—H49	1.0000
C226—H22E	0.9900	C11—H11A	0.9800
C105—C108	1.530 (4)	C11—H11B	0.9800
C105—C104	1.532 (4)	C11—H11C	0.9800
C105—C106	1.534 (3)	C209—C210	1.501 (8)
C105—H105	1.0000	C209—C211	1.509 (6)
C265—C268	1.523 (4)	C209—H209	1.0000
C265—C266	1.533 (3)	C211—H21A	0.9800
C265—C264	1.533 (4)	C211—H21B	0.9800
C265—H265	1.0000	C211—H21C	0.9800
C46—H46A	0.9900	C131—H13A	0.9800
C46—H46B	0.9900	C131—H13B	0.9800
C66—C65	1.533 (3)	C131—H13C	0.9800
C66—H66A	0.9900	C130—H13D	0.9800
C66—H66B	0.9900	C130—H13E	0.9800
C85—C88	1.534 (4)	C130—H13F	0.9800
C85—C84	1.535 (3)	C271—H27D	0.9800
C85—H85	1.0000	C271—H27E	0.9800
C26—H26A	0.9900	C271—H27F	0.9800
C26—H26B	0.9900	C30—H30A	0.9800
C5—C8	1.525 (4)	C30—H30B	0.9800
C5—C6	1.532 (3)	C30—H30C	0.9800
C5—C4	1.536 (4)	C250—H25A	0.9800
C5—H5	1.0000	C250—H25B	0.9800
C122—C124	1.528 (3)	C250—H25C	0.9800
C106—H10G	0.9900	C190—H19A	0.9800
C106—H10H	0.9900	C190—H19B	0.9800
C246—C245	1.528 (3)	C190—H19C	0.9800
C246—H24F	0.9900	C270—H27G	0.9800
C246—H24G	0.9900	C270—H27H	0.9800
C245—C248	1.528 (4)	C270—H27I	0.9800
C245—C244	1.534 (4)	C111—H11D	0.9800
C245—H245	1.0000	C111—H11E	0.9800
C225—C224	1.530 (4)	C111—H11F	0.9800
C225—C228	1.530 (4)	C50—H50A	0.9800
C225—H225	1.0000	C50—H50B	0.9800
C186—H18D	0.9900	C50—H50C	0.9800
C186—H18E	0.9900	C51—H51A	0.9800
C206—C205	1.531 (3)	C51—H51B	0.9800
C206—H20D	0.9900	C51—H51C	0.9800
C206—H20E	0.9900	C251—H25D	0.9800
C305—C308	1.529 (4)	C251—H25E	0.9800
C305—C304	1.536 (4)	C251—H25F	0.9800
C305—H305	1.0000	C110—H11G	0.9800
C65—C64	1.528 (4)	C110—H11H	0.9800
C65—C68	1.533 (4)	C110—H11I	0.9800
C65—H65	1.0000	C191—H19D	0.9800
C205—C204	1.531 (4)	C191—H19E	0.9800
C205—C208	1.531 (4)	C191—H19F	0.9800
C205—H205	1.0000	C210—H21D	0.9800
C242—C244	1.530 (3)	C210—H21E	0.9800
C6—H6A	0.9900	C210—H21F	0.9800
H40A—O402—H40B	104.5	C245—C244—H24I	109.3
H41A—O411—H41B	101 (3)	H24H—C244—H24I	108.0
H41C—O416—H41D	104.5	C149—C151—H15A	109.5
H40C—O404—H40D	104.5	C149—C151—H15B	109.5
H40E—O409—H40F	104.5	H15A—C151—H15B	109.5
H41E—O412—H41F	104.5	C149—C151—H15C	109.5
H40G—O407—H40H	102 (3)	H15A—C151—H15C	109.5
H41G—O414—H41H	104.5	H15B—C151—H15C	109.5
H40I—O401—H40J	104.5	C89—C88—C85	115.5 (2)
H40K—O403—H40L	104.5	C89—C88—H88A	108.4
H41I—O413—H41J	104.5	C85—C88—H88A	108.4
H41K—O410—H41L	104.5	C89—C88—H88B	108.4
H40M—O405—H40N	104.5	C85—C88—H88B	108.4
H40O—O408—H40P	104.5	H88A—C88—H88B	107.5
H41M—O415—H41N	104.5	C302—C304—C305	111.1 (2)
H40Q—O406—H40R	108 (4)	C302—C304—H30K	109.4
C246—N247—H24C	109.5	C305—C304—H30K	109.4
C246—N247—H24D	109.5	C302—C304—H30L	109.4
H24C—N247—H24D	109.5	C305—C304—H30L	109.4
C246—N247—H24E	109.5	H30K—C304—H30L	108.0
H24C—N247—H24E	109.5	C149—C148—C145	116.4 (2)
H24D—N247—H24E	109.5	C149—C148—H14F	108.2
C186—N187—H18A	109.5	C145—C148—H14F	108.2
C186—N187—H18B	109.5	C149—C148—H14G	108.2
H18A—N187—H18B	109.5	C145—C148—H14G	108.2
C186—N187—H18C	109.5	H14F—C148—H14G	107.3
H18A—N187—H18C	109.5	C290—C289—C291	111.6 (3)
H18B—N187—H18C	109.5	C290—C289—C288	111.7 (3)
C26—N27—H27A	109.5	C291—C289—C288	112.0 (3)
C26—N27—H27B	109.5	C290—C289—H289	107.0
H27A—N27—H27B	109.5	C291—C289—H289	107.0
C26—N27—H27C	109.5	C288—C289—H289	107.0
H27A—N27—H27C	109.5	C182—C184—C185	112.7 (2)
H27B—N27—H27C	109.5	C182—C184—H18F	109.1
C46—N47—H47A	109.5	C185—C184—H18F	109.1
C46—N47—H47B	109.5	C182—C184—H18G	109.1
H47A—N47—H47B	109.5	C185—C184—H18G	109.1
C46—N47—H47C	109.5	H18F—C184—H18G	107.8
H47A—N47—H47C	109.5	C209—C208—C205	115.7 (3)
H47B—N47—H47C	109.5	C209—C208—H20H	108.3
C166—N167—H16A	109.5	C205—C208—H20H	108.3
C166—N167—H16B	109.5	C209—C208—H20I	108.3
H16A—N167—H16B	109.5	C205—C208—H20I	108.3
C166—N167—H16C	109.5	H20H—C208—H20I	107.4
H16A—N167—H16C	109.5	C22—C24—C25	113.4 (2)
H16B—N167—H16C	109.5	C22—C24—H24A	108.9
C106—N107—H10D	109.5	C25—C24—H24A	108.9
C106—N107—H10E	109.5	C22—C24—H24B	108.9
H10D—N107—H10E	109.5	C25—C24—H24B	108.9
C106—N107—H10F	109.5	H24A—C24—H24B	107.7
H10D—N107—H10F	109.5	C145—C144—C142	115.1 (2)
H10E—N107—H10F	109.5	C145—C144—H14H	108.5
C146—N147—H14A	109.5	C142—C144—H14H	108.5
C146—N147—H14B	109.5	C145—C144—H14I	108.5
H14A—N147—H14B	109.5	C142—C144—H14I	108.5
C146—N147—H14C	109.5	H14H—C144—H14I	107.5
H14A—N147—H14C	109.5	C2—C4—C5	112.3 (2)
H14B—N147—H14C	109.5	C2—C4—H4A	109.1
C286—N287—H28C	109.5	C5—C4—H4A	109.1
C286—N287—H28D	109.5	C2—C4—H4B	109.1
H28C—N287—H28D	109.5	C5—C4—H4B	109.1
C286—N287—H28E	109.5	H4A—C4—H4B	107.9
H28C—N287—H28E	109.5	C149—C150—H15D	109.5
H28D—N287—H28E	109.5	C149—C150—H15E	109.5
C6—N7—H7A	109.5	H15D—C150—H15E	109.5
C6—N7—H7B	109.5	C149—C150—H15F	109.5
H7A—N7—H7B	109.5	H15D—C150—H15F	109.5
C6—N7—H7C	109.5	H15E—C150—H15F	109.5
H7A—N7—H7C	109.5	C171—C169—C170	111.3 (3)
H7B—N7—H7C	109.5	C171—C169—C168	110.3 (3)
C266—N267—H26C	109.5	C170—C169—C168	111.3 (3)
C266—N267—H26D	109.5	C171—C169—H169	107.9
H26C—N267—H26D	109.5	C170—C169—H169	107.9
C266—N267—H26E	109.5	C168—C169—H169	107.9
H26C—N267—H26E	109.5	C165—C168—C169	117.0 (2)
H26D—N267—H26E	109.5	C165—C168—H16F	108.0
C126—N127—H12A	109.5	C169—C168—H16F	108.0
C126—N127—H12B	109.5	C165—C168—H16G	108.0
H12A—N127—H12B	109.5	C169—C168—H16G	108.0
C126—N127—H12C	109.5	H16F—C168—H16G	107.3
H12A—N127—H12C	109.5	C122—C124—C125	113.6 (2)
H12B—N127—H12C	109.5	C122—C124—H12F	108.9
C306—N307—H30D	109.5	C125—C124—H12F	108.9
C306—N307—H30E	109.5	C122—C124—H12G	108.9
H30D—N307—H30E	109.5	C125—C124—H12G	108.9
C306—N307—H30F	109.5	H12F—C124—H12G	107.7
H30D—N307—H30F	109.5	C11—C9—C10	111.7 (4)
H30E—N307—H30F	109.5	C11—C9—C8	113.2 (3)
C206—N207—H20A	109.5	C10—C9—C8	109.8 (3)
C206—N207—H20B	109.5	C11—C9—H9	107.3
H20A—N207—H20B	109.5	C10—C9—H9	107.3
C206—N207—H20C	109.5	C8—C9—H9	107.3
H20A—N207—H20C	109.5	C162—C164—C165	113.6 (2)
H20B—N207—H20C	109.5	C162—C164—H16H	108.9
C66—N67—H67A	109.5	C165—C164—H16H	108.9
C66—N67—H67B	109.5	C162—C164—H16I	108.9
H67A—N67—H67B	109.5	C165—C164—H16I	108.9
C66—N67—H67C	109.5	H16H—C164—H16I	107.7
H67A—N67—H67C	109.5	C229—C228—C225	116.8 (2)
H67B—N67—H67C	109.5	C229—C228—H22F	108.1
C86—N87—H87A	109.5	C225—C228—H22F	108.1
C86—N87—H87B	109.5	C229—C228—H22G	108.1
H87A—N87—H87B	109.5	C225—C228—H22G	108.1
C86—N87—H87C	109.5	H22F—C228—H22G	107.3
H87A—N87—H87C	109.5	C265—C268—C269	116.6 (3)
H87B—N87—H87C	109.5	C265—C268—H26J	108.2
C226—N227—H22A	109.5	C269—C268—H26J	108.2
C226—N227—H22B	109.5	C265—C268—H26K	108.2
H22A—N227—H22B	109.5	C269—C268—H26K	108.2
C226—N227—H22C	109.5	H26J—C268—H26K	107.3
H22A—N227—H22C	109.5	C289—C288—C285	116.2 (2)
H22B—N227—H22C	109.5	C289—C288—H28H	108.2
O81—C82—O83	124.3 (2)	C285—C288—H28H	108.2
O81—C82—C84	118.3 (2)	C289—C288—H28I	108.2
O83—C82—C84	117.4 (2)	C285—C288—H28I	108.2
O41—C42—O43	124.4 (2)	H28H—C288—H28I	107.4
O41—C42—C44	118.3 (2)	C109—C108—C105	117.0 (3)
O43—C42—C44	117.3 (2)	C109—C108—H10K	108.1
O21—C22—O23	124.4 (2)	C105—C108—H10K	108.1
O21—C22—C24	117.9 (2)	C109—C108—H10L	108.1
O23—C22—C24	117.6 (2)	C105—C108—H10L	108.1
O143—C142—O141	124.5 (2)	H10K—C108—H10L	107.3
O143—C142—C144	118.9 (2)	C289—C290—H29A	109.5
O141—C142—C144	116.6 (2)	C289—C290—H29B	109.5
O161—C162—O163	124.4 (2)	H29A—C290—H29B	109.5
O161—C162—C164	117.9 (2)	C289—C290—H29C	109.5
O163—C162—C164	117.7 (2)	H29A—C290—H29C	109.5
O201—C202—O203	124.1 (2)	H29B—C290—H29C	109.5
O201—C202—C204	118.7 (2)	C282—C284—C285	115.5 (2)
O203—C202—C204	117.1 (2)	C282—C284—H28J	108.4
O101—C102—O103	124.0 (2)	C285—C284—H28J	108.4
O101—C102—C104	118.9 (2)	C282—C284—H28K	108.4
O103—C102—C104	117.1 (2)	C285—C284—H28K	108.4
N147—C146—C145	112.7 (2)	H28J—C284—H28K	107.5
N147—C146—H14D	109.0	C5—C8—C9	116.0 (3)
C145—C146—H14D	109.0	C5—C8—H8A	108.3
N147—C146—H14E	109.0	C9—C8—H8A	108.3
C145—C146—H14E	109.0	C5—C8—H8B	108.3
H14D—C146—H14E	107.8	C9—C8—H8B	108.3
O61—C62—O63	124.2 (2)	H8A—C8—H8B	107.4
O61—C62—C64	118.5 (2)	C309—C310—H31D	109.5
O63—C62—C64	117.3 (2)	C309—C310—H31E	109.5
N87—C86—C85	112.9 (2)	H31D—C310—H31E	109.5
N87—C86—H86A	109.0	C309—C310—H31F	109.5
C85—C86—H86A	109.0	H31D—C310—H31F	109.5
N87—C86—H86B	109.0	H31E—C310—H31F	109.5
C85—C86—H86B	109.0	C25—C28—C29	117.1 (3)
H86A—C86—H86B	107.8	C25—C28—H28A	108.0
O261—C262—O263	124.0 (2)	C29—C28—H28A	108.0
O261—C262—C264	118.6 (2)	C25—C28—H28B	108.0
O263—C262—C264	117.3 (2)	C29—C28—H28B	108.0
O183—C182—O181	124.3 (2)	H28A—C28—H28B	107.3
O183—C182—C184	117.3 (2)	C31—C29—C30	111.3 (4)
O181—C182—C184	118.4 (2)	C31—C29—C28	112.0 (3)
C168—C165—C164	110.8 (2)	C30—C29—C28	109.6 (4)
C168—C165—C166	110.1 (2)	C31—C29—H29	108.0
C164—C165—C166	111.2 (2)	C30—C29—H29	108.0
C168—C165—H165	108.2	C28—C29—H29	108.0
C164—C165—H165	108.2	C185—C188—C189	116.8 (3)
C166—C165—H165	108.2	C185—C188—H18H	108.1
O301—C302—O303	124.0 (2)	C189—C188—H18H	108.1
O301—C302—C304	118.6 (2)	C185—C188—H18I	108.1
O303—C302—C304	117.3 (2)	C189—C188—H18I	108.1
C150—C149—C151	110.7 (3)	H18H—C188—H18I	107.3
C150—C149—C148	110.6 (3)	C249—C248—C245	117.0 (3)
C151—C149—C148	111.7 (2)	C249—C248—H24J	108.1
C150—C149—H149	107.9	C245—C248—H24J	108.1
C151—C149—H149	107.9	C249—C248—H24K	108.1
C148—C149—H149	107.9	C245—C248—H24K	108.1
C48—C45—C46	110.3 (2)	H24J—C248—H24K	107.3
C48—C45—C44	111.2 (2)	C49—C48—C45	116.6 (3)
C46—C45—C44	110.5 (2)	C49—C48—H48A	108.1
C48—C45—H45	108.3	C45—C48—H48A	108.1
C46—C45—H45	108.3	C49—C48—H48B	108.1
C44—C45—H45	108.3	C45—C48—H48B	108.1
C144—C145—C148	110.8 (2)	H48A—C48—H48B	107.3
C144—C145—C146	110.6 (2)	C309—C311—H31G	109.5
C148—C145—C146	110.2 (2)	C309—C311—H31H	109.5
C144—C145—H145	108.4	H31G—C311—H31H	109.5
C148—C145—H145	108.4	C309—C311—H31I	109.5
C146—C145—H145	108.4	H31G—C311—H31I	109.5
O223—C222—O221	124.2 (2)	H31H—C311—H31I	109.5
O223—C222—C224	118.3 (2)	C129—C128—C125	116.0 (3)
O221—C222—C224	117.5 (2)	C129—C128—H12H	108.3
N167—C166—C165	112.7 (2)	C125—C128—H12H	108.3
N167—C166—H16D	109.1	C129—C128—H12I	108.3
C165—C166—H16D	109.1	C125—C128—H12I	108.3
N167—C166—H16E	109.1	H12H—C128—H12I	107.4
C165—C166—H16E	109.1	C69—C70—H70A	109.5
H16D—C166—H16E	107.8	C69—C70—H70B	109.5
N307—C306—C305	112.7 (2)	H70A—C70—H70B	109.5
N307—C306—H30G	109.0	C69—C70—H70C	109.5
C305—C306—H30G	109.0	H70A—C70—H70C	109.5
N307—C306—H30H	109.0	H70B—C70—H70C	109.5
C305—C306—H30H	109.0	C308—C309—C311	110.4 (3)
H30G—C306—H30H	107.8	C308—C309—C310	111.2 (3)
N287—C286—C285	112.6 (2)	C311—C309—C310	109.0 (3)
N287—C286—H28F	109.1	C308—C309—H309	108.7
C285—C286—H28F	109.1	C311—C309—H309	108.7
N287—C286—H28G	109.1	C310—C309—H309	108.7
C285—C286—H28G	109.1	C222—C224—C225	114.8 (2)
H28F—C286—H28G	107.8	C222—C224—H22H	108.6
O283—C282—O281	124.2 (2)	C225—C224—H22H	108.6
O283—C282—C284	118.6 (2)	C222—C224—H22I	108.6
O281—C282—C284	117.2 (2)	C225—C224—H22I	108.6
C188—C185—C184	111.0 (2)	H22H—C224—H22I	107.6
C188—C185—C186	110.1 (2)	C229—C231—H23A	109.5
C184—C185—C186	110.5 (2)	C229—C231—H23B	109.5
C188—C185—H185	108.4	H23A—C231—H23B	109.5
C184—C185—H185	108.4	C229—C231—H23C	109.5
C186—C185—H185	108.4	H23A—C231—H23C	109.5
O1—C2—O3	124.3 (2)	H23B—C231—H23C	109.5
O1—C2—C4	118.5 (2)	C69—C71—H71A	109.5
O3—C2—C4	117.2 (2)	C69—C71—H71B	109.5
C28—C25—C24	110.7 (2)	H71A—C71—H71B	109.5
C28—C25—C26	110.1 (2)	C69—C71—H71C	109.5
C24—C25—C26	111.3 (2)	H71A—C71—H71C	109.5
C28—C25—H25	108.2	H71B—C71—H71C	109.5
C24—C25—H25	108.2	C128—C129—C131	112.4 (3)
C26—C25—H25	108.2	C128—C129—C130	111.4 (4)
N227—C226—C225	113.0 (2)	C131—C129—C130	111.1 (4)
N227—C226—H22D	109.0	C128—C129—H129	107.2
C225—C226—H22D	109.0	C131—C129—H129	107.2
N227—C226—H22E	109.0	C130—C129—H129	107.2
C225—C226—H22E	109.0	C89—C91—H91A	109.5
H22D—C226—H22E	107.8	C89—C91—H91B	109.5
C108—C105—C104	110.9 (2)	H91A—C91—H91B	109.5
C108—C105—C106	109.2 (2)	C89—C91—H91C	109.5
C104—C105—C106	111.4 (2)	H91A—C91—H91C	109.5
C108—C105—H105	108.4	H91B—C91—H91C	109.5
C104—C105—H105	108.4	C289—C291—H29D	109.5
C106—C105—H105	108.4	C289—C291—H29E	109.5
C268—C265—C266	109.2 (2)	H29D—C291—H29E	109.5
C268—C265—C264	111.0 (2)	C289—C291—H29F	109.5
C266—C265—C264	111.1 (2)	H29D—C291—H29F	109.5
C268—C265—H265	108.5	H29E—C291—H29F	109.5
C266—C265—H265	108.5	C68—C69—C70	111.2 (3)
C264—C265—H265	108.5	C68—C69—C71	111.0 (3)
N47—C46—C45	112.3 (2)	C70—C69—C71	109.2 (3)
N47—C46—H46A	109.1	C68—C69—H69	108.5
C45—C46—H46A	109.1	C70—C69—H69	108.5
N47—C46—H46B	109.1	C71—C69—H69	108.5
C45—C46—H46B	109.1	C229—C230—H23D	109.5
H46A—C46—H46B	107.9	C229—C230—H23E	109.5
N67—C66—C65	112.3 (2)	H23D—C230—H23E	109.5
N67—C66—H66A	109.2	C229—C230—H23F	109.5
C65—C66—H66A	109.2	H23D—C230—H23F	109.5
N67—C66—H66B	109.2	H23E—C230—H23F	109.5
C65—C66—H66B	109.2	C91—C89—C90	109.7 (3)
H66A—C66—H66B	107.9	C91—C89—C88	110.2 (3)
C88—C85—C86	109.2 (2)	C90—C89—C88	110.5 (3)
C88—C85—C84	111.1 (2)	C91—C89—H89	108.8
C86—C85—C84	111.6 (2)	C90—C89—H89	108.8
C88—C85—H85	108.3	C88—C89—H89	108.8
C86—C85—H85	108.3	C251—C249—C248	113.0 (4)
C84—C85—H85	108.3	C251—C249—C250	111.4 (4)
N27—C26—C25	112.5 (2)	C248—C249—C250	109.5 (4)
N27—C26—H26A	109.1	C251—C249—H249	107.6
C25—C26—H26A	109.1	C248—C249—H249	107.6
N27—C26—H26B	109.1	C250—C249—H249	107.6
C25—C26—H26B	109.1	C169—C171—H17A	109.5
H26A—C26—H26B	107.8	C169—C171—H17B	109.5
C8—C5—C6	109.5 (2)	H17A—C171—H17B	109.5
C8—C5—C4	110.4 (2)	C169—C171—H17C	109.5
C6—C5—C4	111.7 (2)	H17A—C171—H17C	109.5
C8—C5—H5	108.4	H17B—C171—H17C	109.5
C6—C5—H5	108.4	C271—C269—C270	112.2 (4)
C4—C5—H5	108.4	C271—C269—C268	112.5 (3)
O121—C122—O123	124.2 (2)	C270—C269—C268	109.7 (4)
O121—C122—C124	117.8 (2)	C271—C269—H269	107.4
O123—C122—C124	118.0 (2)	C270—C269—H269	107.4
N107—C106—C105	112.8 (2)	C268—C269—H269	107.4
N107—C106—H10G	109.0	C9—C10—H10A	109.5
C105—C106—H10G	109.0	C9—C10—H10B	109.5
N107—C106—H10H	109.0	H10A—C10—H10B	109.5
C105—C106—H10H	109.0	C9—C10—H10C	109.5
H10G—C106—H10H	107.8	H10A—C10—H10C	109.5
N247—C246—C245	113.5 (2)	H10B—C10—H10C	109.5
N247—C246—H24F	108.9	C89—C90—H90A	109.5
C245—C246—H24F	108.9	C89—C90—H90B	109.5
N247—C246—H24G	108.9	H90A—C90—H90B	109.5
C245—C246—H24G	108.9	C89—C90—H90C	109.5
H24F—C246—H24G	107.7	H90A—C90—H90C	109.5
C248—C245—C246	109.4 (2)	H90B—C90—H90C	109.5
C248—C245—C244	110.7 (2)	C29—C31—H31A	109.5
C246—C245—C244	111.4 (2)	C29—C31—H31B	109.5
C248—C245—H245	108.4	H31A—C31—H31B	109.5
C246—C245—H245	108.4	C29—C31—H31C	109.5
C244—C245—H245	108.4	H31A—C31—H31C	109.5
C224—C225—C228	110.6 (2)	H31B—C31—H31C	109.5
C224—C225—C226	111.0 (2)	C190—C189—C191	112.7 (4)
C228—C225—C226	110.6 (2)	C190—C189—C188	112.2 (3)
C224—C225—H225	108.2	C191—C189—C188	109.0 (4)
C228—C225—H225	108.2	C190—C189—H189	107.5
C226—C225—H225	108.2	C191—C189—H189	107.5
N187—C186—C185	112.7 (2)	C188—C189—H189	107.5
N187—C186—H18D	109.1	C111—C109—C110	112.3 (4)
C185—C186—H18D	109.1	C111—C109—C108	113.2 (4)
N187—C186—H18E	109.1	C110—C109—C108	109.7 (4)
C185—C186—H18E	109.1	C111—C109—H109	107.1
H18D—C186—H18E	107.8	C110—C109—H109	107.1
N207—C206—C205	112.2 (2)	C108—C109—H109	107.1
N207—C206—H20D	109.2	C169—C170—H17D	109.5
C205—C206—H20D	109.2	C169—C170—H17E	109.5
N207—C206—H20E	109.2	H17D—C170—H17E	109.5
C205—C206—H20E	109.2	C169—C170—H17F	109.5
H20D—C206—H20E	107.9	H17D—C170—H17F	109.5
C308—C305—C306	109.5 (2)	H17E—C170—H17F	109.5
C308—C305—C304	110.7 (2)	C51—C49—C50	112.0 (4)
C306—C305—C304	111.0 (2)	C51—C49—C48	112.1 (4)
C308—C305—H305	108.5	C50—C49—C48	110.0 (4)
C306—C305—H305	108.5	C51—C49—H49	107.5
C304—C305—H305	108.5	C50—C49—H49	107.5
C64—C65—C66	110.8 (2)	C48—C49—H49	107.5
C64—C65—C68	111.8 (2)	C9—C11—H11A	109.5
C66—C65—C68	109.1 (2)	C9—C11—H11B	109.5
C64—C65—H65	108.4	H11A—C11—H11B	109.5
C66—C65—H65	108.4	C9—C11—H11C	109.5
C68—C65—H65	108.4	H11A—C11—H11C	109.5
C204—C205—C208	111.1 (2)	H11B—C11—H11C	109.5
C204—C205—C206	110.9 (2)	C208—C209—C210	111.9 (4)
C208—C205—C206	109.3 (2)	C208—C209—C211	111.5 (4)
C204—C205—H205	108.5	C210—C209—C211	110.0 (5)
C208—C205—H205	108.5	C208—C209—H209	107.7
C206—C205—H205	108.5	C210—C209—H209	107.7
O241—C242—O243	124.2 (2)	C211—C209—H209	107.7
O241—C242—C244	118.8 (2)	C209—C211—H21A	109.5
O243—C242—C244	117.0 (2)	C209—C211—H21B	109.5
N7—C6—C5	113.3 (2)	H21A—C211—H21B	109.5
N7—C6—H6A	108.9	C209—C211—H21C	109.5
C5—C6—H6A	108.9	H21A—C211—H21C	109.5
N7—C6—H6B	108.9	H21B—C211—H21C	109.5
C5—C6—H6B	108.9	C129—C131—H13A	109.5
H6A—C6—H6B	107.7	C129—C131—H13B	109.5
C284—C285—C288	111.5 (2)	H13A—C131—H13B	109.5
C284—C285—C286	110.9 (2)	C129—C131—H13C	109.5
C288—C285—C286	109.3 (2)	H13A—C131—H13C	109.5
C284—C285—H285	108.3	H13B—C131—H13C	109.5
C288—C285—H285	108.3	C129—C130—H13D	109.5
C286—C285—H285	108.3	C129—C130—H13E	109.5
C42—C44—C45	112.5 (2)	H13D—C130—H13E	109.5
C42—C44—H44A	109.1	C129—C130—H13F	109.5
C45—C44—H44A	109.1	H13D—C130—H13F	109.5
C42—C44—H44B	109.1	H13E—C130—H13F	109.5
C45—C44—H44B	109.1	C269—C271—H27D	109.5
H44A—C44—H44B	107.8	C269—C271—H27E	109.5
N127—C126—C125	112.6 (2)	H27D—C271—H27E	109.5
N127—C126—H12D	109.1	C269—C271—H27F	109.5
C125—C126—H12D	109.1	H27D—C271—H27F	109.5
N127—C126—H12E	109.1	H27E—C271—H27F	109.5
C125—C126—H12E	109.1	C29—C30—H30A	109.5
H12D—C126—H12E	107.8	C29—C30—H30B	109.5
C202—C204—C205	111.6 (2)	H30A—C30—H30B	109.5
C202—C204—H20F	109.3	C29—C30—H30C	109.5
C205—C204—H20F	109.3	H30A—C30—H30C	109.5
C202—C204—H20G	109.3	H30B—C30—H30C	109.5
C205—C204—H20G	109.3	C249—C250—H25A	109.5
H20F—C204—H20G	108.0	C249—C250—H25B	109.5
C82—C84—C85	111.7 (2)	H25A—C250—H25B	109.5
C82—C84—H84A	109.3	C249—C250—H25C	109.5
C85—C84—H84A	109.3	H25A—C250—H25C	109.5
C82—C84—H84B	109.3	H25B—C250—H25C	109.5
C85—C84—H84B	109.3	C189—C190—H19A	109.5
H84A—C84—H84B	107.9	C189—C190—H19B	109.5
C128—C125—C126	109.0 (2)	H19A—C190—H19B	109.5
C128—C125—C124	111.5 (2)	C189—C190—H19C	109.5
C126—C125—C124	110.8 (2)	H19A—C190—H19C	109.5
C128—C125—H125	108.5	H19B—C190—H19C	109.5
C126—C125—H125	108.5	C269—C270—H27G	109.5
C124—C125—H125	108.5	C269—C270—H27H	109.5
C102—C104—C105	111.4 (2)	H27G—C270—H27H	109.5
C102—C104—H10I	109.3	C269—C270—H27I	109.5
C105—C104—H10I	109.3	H27G—C270—H27I	109.5
C102—C104—H10J	109.3	H27H—C270—H27I	109.5
C105—C104—H10J	109.3	C109—C111—H11D	109.5
H10I—C104—H10J	108.0	C109—C111—H11E	109.5
C231—C229—C230	110.6 (3)	H11D—C111—H11E	109.5
C231—C229—C228	112.0 (3)	C109—C111—H11F	109.5
C230—C229—C228	110.7 (3)	H11D—C111—H11F	109.5
C231—C229—H229	107.8	H11E—C111—H11F	109.5
C230—C229—H229	107.8	C49—C50—H50A	109.5
C228—C229—H229	107.8	C49—C50—H50B	109.5
C62—C64—C65	111.1 (2)	H50A—C50—H50B	109.5
C62—C64—H64A	109.4	C49—C50—H50C	109.5
C65—C64—H64A	109.4	H50A—C50—H50C	109.5
C62—C64—H64B	109.4	H50B—C50—H50C	109.5
C65—C64—H64B	109.4	C49—C51—H51A	109.5
H64A—C64—H64B	108.0	C49—C51—H51B	109.5
C69—C68—C65	115.4 (3)	H51A—C51—H51B	109.5
C69—C68—H68A	108.4	C49—C51—H51C	109.5
C65—C68—H68A	108.4	H51A—C51—H51C	109.5
C69—C68—H68B	108.4	H51B—C51—H51C	109.5
C65—C68—H68B	108.4	C249—C251—H25D	109.5
H68A—C68—H68B	107.5	C249—C251—H25E	109.5
C309—C308—C305	114.8 (2)	H25D—C251—H25E	109.5
C309—C308—H30I	108.6	C249—C251—H25F	109.5
C305—C308—H30I	108.6	H25D—C251—H25F	109.5
C309—C308—H30J	108.6	H25E—C251—H25F	109.5
C305—C308—H30J	108.6	C109—C110—H11G	109.5
H30I—C308—H30J	107.5	C109—C110—H11H	109.5
N267—C266—C265	113.0 (2)	H11G—C110—H11H	109.5
N267—C266—H26F	109.0	C109—C110—H11I	109.5
C265—C266—H26F	109.0	H11G—C110—H11I	109.5
N267—C266—H26G	109.0	H11H—C110—H11I	109.5
C265—C266—H26G	109.0	C189—C191—H19D	109.5
H26F—C266—H26G	107.8	C189—C191—H19E	109.5
C262—C264—C265	112.1 (2)	H19D—C191—H19E	109.5
C262—C264—H26H	109.2	C189—C191—H19F	109.5
C265—C264—H26H	109.2	H19D—C191—H19F	109.5
C262—C264—H26I	109.2	H19E—C191—H19F	109.5
C265—C264—H26I	109.2	C209—C210—H21D	109.5
H26H—C264—H26I	107.9	C209—C210—H21E	109.5
C242—C244—C245	111.7 (2)	H21D—C210—H21E	109.5
C242—C244—H24H	109.3	C209—C210—H21F	109.5
C245—C244—H24H	109.3	H21D—C210—H21F	109.5
C242—C244—H24I	109.3	H21E—C210—H21F	109.5
N147—C146—C145—C144	−67.4 (3)	O21—C22—C24—C25	137.1 (3)
N147—C146—C145—C148	169.8 (2)	O23—C22—C24—C25	−42.8 (4)
C168—C165—C166—N167	174.7 (2)	C28—C25—C24—C22	−60.3 (3)
C164—C165—C166—N167	−62.1 (3)	C26—C25—C24—C22	176.9 (2)
C48—C45—C46—N47	174.5 (2)	C148—C145—C144—C142	−68.0 (3)
C44—C45—C46—N47	−62.2 (3)	C146—C145—C144—C142	169.5 (2)
N87—C86—C85—C88	178.5 (2)	O143—C142—C144—C145	−32.0 (4)
N87—C86—C85—C84	−58.3 (3)	O141—C142—C144—C145	149.9 (3)
C28—C25—C26—N27	174.9 (2)	O1—C2—C4—C5	126.0 (3)
C24—C25—C26—N27	−62.0 (3)	O3—C2—C4—C5	−53.2 (4)
C108—C105—C106—N107	177.9 (2)	C8—C5—C4—C2	−57.8 (3)
C104—C105—C106—N107	−59.3 (3)	C6—C5—C4—C2	−180.0 (2)
N247—C246—C245—C248	179.2 (2)	C164—C165—C168—C169	166.0 (2)
N247—C246—C245—C244	−58.1 (3)	C166—C165—C168—C169	−70.6 (3)
N227—C226—C225—C224	−65.4 (3)	C171—C169—C168—C165	−178.6 (3)
N227—C226—C225—C228	171.5 (2)	C170—C169—C168—C165	−54.6 (4)
C188—C185—C186—N187	176.5 (2)	O121—C122—C124—C125	137.9 (3)
C184—C185—C186—N187	−60.5 (3)	O123—C122—C124—C125	−42.9 (4)
N307—C306—C305—C308	177.4 (2)	C128—C125—C124—C122	−61.2 (3)
N307—C306—C305—C304	−60.0 (3)	C126—C125—C124—C122	177.3 (2)
N67—C66—C65—C64	−61.1 (3)	O161—C162—C164—C165	139.0 (3)
N67—C66—C65—C68	175.5 (2)	O163—C162—C164—C165	−40.9 (4)
N207—C206—C205—C204	−61.9 (3)	C168—C165—C164—C162	−60.3 (3)
N207—C206—C205—C208	175.3 (2)	C166—C165—C164—C162	177.0 (2)
C8—C5—C6—N7	177.4 (2)	C231—C229—C228—C225	−54.5 (4)
C4—C5—C6—N7	−59.9 (3)	C230—C229—C228—C225	−178.4 (3)
N287—C286—C285—C284	−65.5 (3)	C224—C225—C228—C229	174.8 (2)
N287—C286—C285—C288	171.2 (2)	C226—C225—C228—C229	−61.8 (3)
O41—C42—C44—C45	129.8 (3)	C266—C265—C268—C269	−69.2 (3)
O43—C42—C44—C45	−50.2 (3)	C264—C265—C268—C269	168.1 (3)
C48—C45—C44—C42	−57.4 (3)	C290—C289—C288—C285	171.8 (3)
C46—C45—C44—C42	179.9 (2)	C291—C289—C288—C285	−62.1 (4)
O201—C202—C204—C205	121.9 (3)	C284—C285—C288—C289	167.3 (2)
O203—C202—C204—C205	−56.7 (3)	C286—C285—C288—C289	−69.7 (3)
C208—C205—C204—C202	−57.0 (3)	C104—C105—C108—C109	170.6 (3)
C206—C205—C204—C202	−178.7 (2)	C106—C105—C108—C109	−66.3 (4)
O81—C82—C84—C85	126.1 (3)	O283—C282—C284—C285	−34.3 (4)
O83—C82—C84—C85	−52.1 (3)	O281—C282—C284—C285	147.2 (3)
C88—C85—C84—C82	−58.7 (3)	C288—C285—C284—C282	−66.6 (3)
C86—C85—C84—C82	179.2 (2)	C286—C285—C284—C282	171.3 (2)
N127—C126—C125—C128	175.8 (2)	C6—C5—C8—C9	−61.1 (3)
N127—C126—C125—C124	−61.2 (3)	C4—C5—C8—C9	175.6 (3)
O101—C102—C104—C105	122.1 (3)	C11—C9—C8—C5	−54.1 (4)
O103—C102—C104—C105	−57.0 (3)	C10—C9—C8—C5	−179.7 (3)
C108—C105—C104—C102	−56.6 (3)	C24—C25—C28—C29	169.0 (2)
C106—C105—C104—C102	−178.4 (2)	C26—C25—C28—C29	−67.6 (3)
O61—C62—C64—C65	117.5 (3)	C25—C28—C29—C31	−55.8 (4)
O63—C62—C64—C65	−61.2 (3)	C25—C28—C29—C30	−179.8 (3)
C66—C65—C64—C62	−178.5 (2)	C184—C185—C188—C189	171.2 (3)
C68—C65—C64—C62	−56.6 (3)	C186—C185—C188—C189	−66.1 (3)
C64—C65—C68—C69	148.4 (3)	C246—C245—C248—C249	−63.3 (4)
C66—C65—C68—C69	−88.7 (3)	C244—C245—C248—C249	173.6 (3)
C306—C305—C308—C309	−89.7 (3)	C46—C45—C48—C49	−65.8 (4)
C304—C305—C308—C309	147.6 (2)	C44—C45—C48—C49	171.4 (3)
C268—C265—C266—N267	178.8 (2)	C126—C125—C128—C129	−73.2 (3)
C264—C265—C266—N267	−58.6 (3)	C124—C125—C128—C129	164.3 (3)
O261—C262—C264—C265	126.1 (3)	C305—C308—C309—C311	170.0 (3)
O263—C262—C264—C265	−53.0 (4)	C305—C308—C309—C310	−68.9 (3)
C268—C265—C264—C262	−57.6 (3)	O223—C222—C224—C225	−39.8 (4)
C266—C265—C264—C262	−179.2 (2)	O221—C222—C224—C225	141.3 (3)
O241—C242—C244—C245	122.5 (3)	C228—C225—C224—C222	−63.5 (3)
O243—C242—C244—C245	−56.8 (3)	C226—C225—C224—C222	173.3 (2)
C248—C245—C244—C242	−56.7 (3)	C125—C128—C129—C131	−64.6 (5)
C246—C245—C244—C242	−178.7 (2)	C125—C128—C129—C130	170.0 (3)
C86—C85—C88—C89	−86.7 (3)	C65—C68—C69—C70	169.4 (3)
C84—C85—C88—C89	149.8 (2)	C65—C68—C69—C71	−68.8 (4)
O301—C302—C304—C305	119.9 (3)	C85—C88—C89—C91	−69.6 (4)
O303—C302—C304—C305	−58.2 (3)	C85—C88—C89—C90	168.9 (3)
C308—C305—C304—C302	−58.0 (3)	C245—C248—C249—C251	−57.7 (5)
C306—C305—C304—C302	−179.9 (2)	C245—C248—C249—C250	177.5 (3)
C150—C149—C148—C145	177.5 (2)	C265—C268—C269—C271	−60.0 (5)
C151—C149—C148—C145	−58.7 (3)	C265—C268—C269—C270	174.4 (3)
C144—C145—C148—C149	169.3 (2)	C185—C188—C189—C190	−58.1 (5)
C146—C145—C148—C149	−68.0 (3)	C185—C188—C189—C191	176.3 (3)
O183—C182—C184—C185	−48.1 (4)	C105—C108—C109—C111	−56.1 (5)
O181—C182—C184—C185	132.1 (3)	C105—C108—C109—C110	177.5 (3)
C188—C185—C184—C182	−58.8 (3)	C45—C48—C49—C51	−58.2 (5)
C186—C185—C184—C182	178.7 (2)	C45—C48—C49—C50	176.6 (3)
C204—C205—C208—C209	159.7 (3)	C205—C208—C209—C210	−62.8 (6)
C206—C205—C208—C209	−77.7 (3)	C205—C208—C209—C211	173.5 (3)

(SPGHI)

Crystal data

C8H19NO3	F(000) = 392
Mr = 177.24	Dx = 1.061 Mg m^−3
Monoclinic, C2	Mo Kα radiation, λ = 0.71073 Å
a = 9.566 (7) Å	Cell parameters from 465 reflections
b = 7.440 (6) Å	θ = 3–30°
c = 15.911 (12) Å	µ = 0.08 mm^−1
β = 101.54 (3)°	T = 298 K
V = 1109.5 (15) Å^3	Prism, colourless
Z = 4	0.20 × 0.05 × 0.05 mm

Data collection

Bruker D8 Quest diffractometer	Rint = 0.040
Absorption correction: multi-scan sadabs	θmax = 26.6°, θmin = 2.6°
Tmin = 0.641, Tmax = 0.745	h = −11→11
6482 measured reflections	k = −9→9
2286 independent reflections	l = −19→19
1721 reflections with I > 2σ(I)

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)] = 0.059	w = 1/[σ^2(Fo^2) + (0.0579P)^2 + 0.5616P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.141	(Δ/σ)max < 0.001
S = 1.06	Δρmax = 0.19 e Å^−3
2286 reflections	Δρmin = −0.13 e Å^−3
131 parameters	Absolute structure: Flack x determined using 588 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
1 restraint	Absolute structure parameter: 0.1 (8)

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
H12A	0.811 (6)	0.310 (8)	0.575 (3)	0.080 (16)*
H12B	0.887 (6)	0.449 (9)	0.566 (4)	0.09 (2)*
H1A	0.695 (4)	0.946 (7)	0.636 (3)	0.061 (13)*
H1B	0.634 (5)	0.800 (6)	0.584 (3)	0.052 (14)*
H1C	0.782 (5)	0.784 (6)	0.622 (3)	0.061 (13)*
O6	0.6844 (2)	0.1902 (3)	0.6378 (2)	0.0577 (9)
O12	0.8769 (3)	0.3435 (4)	0.5506 (2)	0.0624 (9)
O7	0.4526 (2)	0.1752 (3)	0.6269 (2)	0.0669 (10)
N1	0.6889 (3)	0.8253 (4)	0.6301 (3)	0.0422 (8)
C5	0.5647 (4)	0.2604 (4)	0.6324 (3)	0.0455 (10)
C3	0.6591 (4)	0.5455 (4)	0.7099 (3)	0.0450 (10)
H3	0.7564	0.5090	0.7070	0.054*
C2	0.6522 (4)	0.7499 (5)	0.7072 (3)	0.0511 (11)
H2A	0.5564	0.7878	0.7106	0.061*
H2B	0.7170	0.7975	0.7570	0.061*
C4	0.5585 (4)	0.4649 (4)	0.6341 (3)	0.0553 (12)
H4A	0.5819	0.5115	0.5816	0.066*
H4B	0.4618	0.5020	0.6356	0.066*
C8	0.6262 (7)	0.4767 (7)	0.7935 (4)	0.0811 (16)
H8A	0.5387	0.5332	0.8019	0.097*
H8B	0.6080	0.3486	0.7875	0.097*
C9	0.7372 (12)	0.5060 (13)	0.8725 (5)	0.140 (3)
H9	0.7516	0.6359	0.8796	0.169*
C10	0.6759 (17)	0.4364 (16)	0.9499 (5)	0.232 (7)
H10A	0.7346	0.4780	1.0024	0.348*
H10B	0.6746	0.3074	0.9495	0.348*
H10C	0.5805	0.4808	0.9457	0.348*
C11	0.8741 (15)	0.426 (3)	0.8677 (7)	0.300 (14)
H11A	0.8610	0.3014	0.8529	0.450*
H11B	0.9378	0.4373	0.9223	0.450*
H11C	0.9138	0.4872	0.8248	0.450*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O6	0.0425 (14)	0.0205 (11)	0.117 (3)	−0.0022 (11)	0.0314 (15)	0.0037 (14)
O12	0.0625 (18)	0.0464 (18)	0.089 (2)	−0.0165 (16)	0.0412 (17)	−0.0116 (18)
O7	0.0427 (14)	0.0233 (12)	0.142 (3)	−0.0071 (12)	0.0365 (16)	−0.0085 (17)
N1	0.0358 (15)	0.0183 (13)	0.074 (3)	−0.0036 (12)	0.0145 (17)	−0.0022 (15)
C5	0.040 (2)	0.0199 (15)	0.080 (3)	−0.0059 (14)	0.020 (2)	0.0009 (17)
C3	0.049 (2)	0.0212 (17)	0.070 (3)	0.0011 (15)	0.025 (2)	0.0021 (16)
C2	0.057 (2)	0.0258 (16)	0.077 (3)	−0.0025 (16)	0.029 (2)	−0.0067 (18)
C4	0.041 (2)	0.0216 (18)	0.104 (4)	−0.0008 (14)	0.016 (2)	0.0047 (19)
C8	0.124 (4)	0.045 (3)	0.090 (4)	0.002 (3)	0.059 (4)	0.004 (3)
C9	0.235 (10)	0.123 (6)	0.075 (4)	−0.001 (8)	0.061 (6)	0.011 (5)
C10	0.42 (2)	0.200 (15)	0.096 (6)	0.019 (11)	0.112 (10)	0.039 (6)
C11	0.215 (12)	0.56 (4)	0.107 (7)	0.196 (19)	−0.014 (8)	0.009 (11)

Geometric parameters (Å, º)

O6—C5	1.245 (4)	C4—H4A	0.9700
O12—H12A	0.84 (6)	C4—H4B	0.9700
O12—H12B	0.82 (6)	C8—C9	1.490 (11)
O7—C5	1.234 (4)	C8—H8A	0.9700
N1—C2	1.455 (5)	C8—H8B	0.9700
N1—H1A	0.90 (5)	C9—C11	1.453 (13)
N1—H1B	0.84 (5)	C9—C10	1.556 (11)
N1—H1C	0.97 (5)	C9—H9	0.9800
C5—C4	1.523 (5)	C10—H10A	0.9600
C3—C4	1.509 (6)	C10—H10B	0.9600
C3—C8	1.516 (6)	C10—H10C	0.9600
C3—C2	1.522 (5)	C11—H11A	0.9600
C3—H3	0.9800	C11—H11B	0.9600
C2—H2A	0.9700	C11—H11C	0.9600
C2—H2B	0.9700
H12A—O12—H12B	101 (5)	C5—C4—H4B	109.0
C2—N1—H1A	109 (3)	H4A—C4—H4B	107.8
C2—N1—H1B	116 (3)	C9—C8—C3	116.9 (5)
H1A—N1—H1B	109 (4)	C9—C8—H8A	108.1
C2—N1—H1C	112 (2)	C3—C8—H8A	108.1
H1A—N1—H1C	106 (4)	C9—C8—H8B	108.1
H1B—N1—H1C	104 (4)	C3—C8—H8B	108.1
O7—C5—O6	124.3 (3)	H8A—C8—H8B	107.3
O7—C5—C4	118.6 (3)	C11—C9—C8	113.2 (8)
O6—C5—C4	117.1 (3)	C11—C9—C10	113.1 (10)
C4—C3—C8	110.9 (4)	C8—C9—C10	107.5 (9)
C4—C3—C2	111.0 (3)	C11—C9—H9	107.6
C8—C3—C2	110.3 (3)	C8—C9—H9	107.6
C4—C3—H3	108.2	C10—C9—H9	107.6
C8—C3—H3	108.2	C9—C10—H10A	109.5
C2—C3—H3	108.2	C9—C10—H10B	109.5
N1—C2—C3	113.1 (3)	H10A—C10—H10B	109.5
N1—C2—H2A	109.0	C9—C10—H10C	109.5
C3—C2—H2A	109.0	H10A—C10—H10C	109.5
N1—C2—H2B	109.0	H10B—C10—H10C	109.5
C3—C2—H2B	109.0	C9—C11—H11A	109.5
H2A—C2—H2B	107.8	C9—C11—H11B	109.5
C3—C4—C5	113.0 (4)	H11A—C11—H11B	109.5
C3—C4—H4A	109.0	C9—C11—H11C	109.5
C5—C4—H4A	109.0	H11A—C11—H11C	109.5
C3—C4—H4B	109.0	H11B—C11—H11C	109.5
C4—C3—C2—N1	−59.3 (5)	O6—C5—C4—C3	−52.6 (6)
C8—C3—C2—N1	177.4 (4)	C4—C3—C8—C9	164.8 (5)
C8—C3—C4—C5	−58.8 (5)	C2—C3—C8—C9	−71.9 (7)
C2—C3—C4—C5	178.3 (3)	C3—C8—C9—C11	−58.1 (12)
O7—C5—C4—C3	126.5 (4)	C3—C8—C9—C10	176.3 (7)