N-(tert-But­oxy­carbon­yl)-L-valyl-L-valine methyl ester: a twisted parallel β-sheet in the crystal structure of a protected dipeptide

The title compound, C₁₆H₃₀N₂O₅, crystallizes with three mol­ecules in the asymmetric unit, each adopting a β-strand/polyproline II backbone conformation. The main-chain functional groups are hydrogen bonded into tapes having the characteristics of parallel β-sheets. Each tape has a left-handed twist and thus forms a helix, with six peptide mol­ecules needed to complete a full 360° rotation. A comparison of hydrogen-bond lengths and twisting modes is made with other related structures of protected dipeptides and with a hexa­peptide derived from amyloid-β containing the Val–Val segment. Additionally, a comparison of the backbone conformation is made with that of the Val141–Val142 segment of the water channel aqua­porin-4 (AQP4).

S1. Comment

The water channel aquaporin-4 (AQP4) is a tetrameric integral membrane protein selectively transporting water across the cell membrane, and constitutes an important clinical target for the treatment of brain oedema (Amiry-Moghaddam & Ottersen, 2003). In addition to its primary function as a passive water transporter, it has also been postulated that AQP4 may play a role in cell–cell adhesion (Hiroaki et al., 2006). The structure of the M23 isoform of rat AQP4 (rAQP4) was recently determined to 3.2 Å resolution by electron diffraction (ED) on two-dimensional crystals [Protein Data Bank (PDB) code 2D57; Hiroaki et al., 2006]. This has subsequently been improved to 2.8 Å resolution for an ED structure of an S180D AQP4M23 mutant of rAQP4 (PDB code 2ZZ9; Tani et al., 2009) and 1.8 Å for an X-ray structure of truncated human AQP4 (PDB code 3GD8; Ho et al., 2009). The ED structures revealed that adhesive interactions between rAQP4 tetramers in contiguous membranes are mediated by Pro139 and Val142 in the extracellular 3₁₀-helical loop C (Pro138–Pro139–Ser140–Val141–Val142–Gly143–Gly144). We believe that compounds mimicking loop C may be of value as starting points for the development of selective AQP4 ligands and eventually AQP4 inhibitors. As part of our ongoing synthetic and structural studies of loop C mimics (Jacobsen et al., 2009) the title compound, (I), corresponding to the Val141–Val142 segment of AQP4 loop C, was synthesized and its X-ray crystal structure determined.

(I) crystallizes in the orthorhombic space group P2₁2₁2₁ with three molecules in the asymmetric unit (Fig. 1). The molecular conformations are roughly similar, and in particular the r.m.s. value for the best overlay between molecules A and C is only 0.30 Å. Molecule B has a different orientation for the side chain of the C-terminal valine residue, Val2, as defined by the N2—C11—C12—C13 and N2—C11—C12—C14 torsion angles in Table 1, which together with a slightly larger main-chain C5—N1—C6—C10 torsion angle contribute to the slightly higher r.m.s. values of 0.79 and 0.69 Å for the best overlays with molecule A and molecule C, respectively. The average values for the torsion angles C5—N1—C6—C10 and N1—C6—C10—N2 (ϕ, ψ) of Val1 are -94 and 130°, respectively, which are quite close to the ideal values for a parallel β-sheet (Loughlin et al., 2010). The Val2 residues adopt polyproline II conformations, with the average dihedral angles being -59 and 145°, respectively. Polyproline II is one of the dominating conformations in unfolded peptides and proteins (Shi et al., 2006). The overall backbone conformation seen for all molecules in Fig. 1 is dominating [dominant?] among 29 peptide molecules in 18 other structures of acyclic L, L-dipeptides in the Cambridge Structural Database (CSD, Version 5.32 of November 2010; Allen, 2002) that are N-terminally protected as a carbamate and C-terminally protected as an ester (see Supplementary material). In particular, ten out of 12 molecules devoid of aromatic residues in the protecting groups and the side chains take on roughly the same folding as observed for (I). In contrast to the dipeptide (I), the dihedral angles of Val141 and Val142 in loop C of rAQP4 are (-63, -26°) and (-26, -39°), respectively, placing the Val141–Val142 segment in the 3₁₀- or mixed 3₁₀-/α-helical region of the Ramachandran plot. However, the difference in backbone structure between (I) and the Val141–Val142 segment of rAQP4 loop C could be explained by the fact that (I) is too short to form the stabilizing intramolecular i → i+3 hydrogen bonds (to a peptide cabonyl acceptor three residues down the chain) which are characteristic of 3₁₀-helices (the subscript 10 referring to the size of the hydrogen-bonded ring being formed).

The molecular packing of (I) is shown in Fig. 2. The molecules are hydrogen bonded along the c axis in a manner similar to the parallel β-sheet, thereby forming ribbons with a left-handed twist. A structural analogy in proteins is provided by the β-sheet of a Rossmann fold (Rao & Rossmann, 1973), which is frequently found in nucleotide-binding proteins, e.g. in the NADP(H)-binding proton pump transhydrogenase (Jeeves et al., 2000). The Rossmann fold is a supersecondary structural motif which consists of a β-sheet comprising three or more parallel β-strands that are connected by α-helices, β-strands or unfolded loops. The topological structure of the Rossmann fold is β–α–β–α–β. The structures of NAD(P)-dependent dehydrogenases feature two Rossmann folds with left-handed twisting of the β-sheets in their cofactor-binding domains (Kutzenko et al., 1998).

Extracellular deposition of insoluble, fibrous β-sheet protein aggregates (amyloid fibrils) is diagnostic of several debilitating and/or fatal diseases, e.g. Alzheimer's disease (AD). According to the amyloid hypothesis, formation of amyloid fibrils from amyloid-β (Aβ), a 39–42-residues long polypeptide formed by proteolytic cleavage of amyloid precursor protein (APP), also plays an important part in the pathogenesis of AD (Selkoe, 1991; Hardy & Allsop, 1991). Recent evidence, however, strongly suggests that the actual synaptotoxic species are soluble Aβ dimers and oligomers (Jin et al., 2011).

The hexapeptide Gly–Gly–Val–Val–Ile–Ala, (II), which constitutes a short segment of Aβ, forms both fibrils and microcrystals in vitro. The structures of the fibrillar and microcrystalline forms of (II) are believed to be closely related. X-ray crystallographic studies of microcrystals of (II) have revealed a cross-β spine structure, a quaternary structural feature characteristic of amyloid fibrils, consisting of two parallel β-sheets (PDB code 2ONV, Sawaya et al., 2007). In a cross-β spine, side chains on the two β-sheets interdigitate to form a tight, dry steric-zipper interface (Nelson et al., 2005; Sawaya et al., 2007). Importantly, residues 1 and 2 of (I) are identical with residues 3 and 4 of (II), suggesting that (I) could potentially serve as a minimal model compound for studies of the formation and properties of β-sheet structures associated with AD. Recent Monte Carlo simulations using a coarse-grained united-atom model of (II) have shown that (II) spontaneously forms three types of aggregation structures, including, like (I), a single-layer, left-handed, twisted β-sheet, and a fibril-like cross-β spine structure comprising left-handed, twisted parallel β-sheets with an average twisting angle of 12 ± 2° (Mu & Gao, 2009). For comparison, the observed average twisting angles between each β-strand in the crystal structures of (I) and (II) are 60 and 0°, respectively, the latter value corresponding to a flat sheet (Sawaya et al., 2007).

To get an overview of small-molecule structures containing parallel β-sheets, the CSD was searched for peptides (not just dipeptides) containing the search fragment depicted in Fig. 3. The query returned a total of 92 CSD entries, and subsequent manual scrutiny revealed infinite tapes in 69 peptide structures including 48 regular dipeptides, two structures where two dipeptides are linked by a disulfide bridge, 11 tripeptides, six tetrapeptides, one pentapeptide and one folded decapeptide (see Supplementary material). Most tapes are planar and straight (67 observations in 49 structures), as seen in Fig. 4(a), but some structures have tapes that are twisted into helices, as seen for (I) in Fig. 2.

This second group of 20 peptides may be subdivided into smaller groups depending on the number of molecules required to complete a full turn of the helix. The only example with eight peptide molecules for a full turn is shown in Fig. 4(b). There is also just a single example of a structure with a repeating unit of seven molecules (with Z' = 7). The structure of (I) (Fig. 4c) adds to a larger group of 11 other structures with a repeating unit of six peptide molecules. Eight of these belong to the hexagonal space group P6₅ with Z' = 1, one, with a rare 2-methylvalyl residue, belongs to P6₁, one to the trigonal space group P3₂ with Z' = 2, while the last structure, like (I), is orthorhombic, P2₁2₁2₁, with Z' = 3. The last group, with a repeating unit of four peptide molecules (Fig. 4d) comprises seven structures, of which five are tetragonal and two are monoclinic. It is interesting to find that when only C^α monosubstituted L-amino acids are involved (18 out of 20 structures), the twist is always left-handed. This is in accordance with the preferred sense of twist observed for β-sheets in proteins (Chothia, 1973; Chou et al., 1983, note that our definition of handedness is the sense of rotation when going from one chain in the sheet to the next, while Chothia defines twisting as the observed rotation when viewing along a single polypeptide chain, which gives opposite results with respect to handedness). Another important observation is that the hydrogen bonds appear to get shorter when the twist increases. Thus, the average of the two hydrogen-bond lengths HB1 and HB2 in Fig. 3 is 2.140 Å for the flat tapes (or 2.095 Å when four clear outlier structures are removed from the statistics), but 2.087 and 2.057 Å for twisted tapes with a repeating unit of six and four molecules, respectively. Hydrogen-bond data for (I) are given in Table 2. After normalization of N—H bonds to 0.88 Å, the average length of the six N—H···O hydrogen bonds in the structure of (I) is 2.023 Å, which is short for this type of pattern.

Related literature

For related literature, see: Allen (2002); Amiry-Moghaddam & Ottersen (2003); Chothia (1973); Chou et al. (1983); Hardy & Allsop (1991); Hiroaki et al. (2006); Ho et al. (2009); Jacobsen et al. (2009); Jeeves et al. (2000); Jin et al. (2011); Kutzenko et al. (1998); Loughlin et al. (2010); Mu & Gao (2009); Nelson et al. (2005); Rao & Rossmann (1973); Sawaya et al. (2007); Selkoe (1991); Shi et al. (2006); Tani et al. (2009).

S2. Experimental

(I) was synthesized by standard solution-phase peptide coupling of L-valine methyl ester, which was generated in situ from L-valine methyl ester hydrochloride by deprotonation with N,N-diisopropylethylamine, with commercially available N-(tert-butoxycarbonyl)-L-valine. 3-[3-(Dimethylamino)propyl]-1-ethylcarbodiimide (EDC) was used as coupling reagent and 1-hydroxybenzotriazole (HOBt) as an additive to suppress epimerization (Jacobsen et al., 2009).

S3. Refinement

The L-Val side chain of residue 2 in molecule C is disordered over two positions, and atoms of the major orientation with occupancy 0.843 (7) were refined in a normal manner. The covalent geometry of the 0.157 (7) minor orientation was loosely tied to the geometry of the major component by a SHELX SAME restraint. C^α (C11D) and C^β (C12D) received the same set of thermal displacement parameters as their major counterparts (C11C and C12C), while a common isotropic displacement parameter was refined for C^γ1 (C13D) and C^γ2 (C14D). Positional parameters were refined for H atoms bonded to N, with a mild restraint on N—H distances imposed by a SHELX DFIX 0.88 0.02 command. Other H atoms were positioned with idealized geometry and fixed C–H distances at 0.98 and 1.00 Å for CH₃, and CH, respectively. Free rotation was permitted for methyl groups. U_iso values were set to 1.2U_eq of the carrier atom or 1.5U_eq for methyl groups. In the absence of significant anomalous scattering effects, 4636 Friedel pairs were merged.

Computing details

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT-Plus (Bruker, 2007); data reduction: SAINT-Plus (Bruker, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures

	Fig. 1. The structure of (I), showing the atom-numbering scheme for each molecule in the asymmetric unit (A, B and C). Displacement ellipsoids are shown at the 50% probability level and H atoms are shown as spheres of arbitrary size. The minor orientation of the second Val residue of molecule C [occupancy 0.157 (7)] is shown in wireframe representation.
	Fig. 2. The molecular packing of (I) viewed along the a axis. Dashed lines indicate hydrogen bonds. H atoms not involved in hydrogen bonding have been omitted. In the electronic version of the paper, C atoms of molecules A, B and C have been coloured in black, grey and white, respectively. A hydrogen-bonded helix has been highlighted by the twisted tape (yellow and red).
	Fig. 3. The search fragment used to find structures of acyclic peptides with parallel β-sheets in the CSD (Allen, 2002). The dashed C—N bonds have bond types `any', the central N—C bonds have been defined as acyclic, the number of H atoms on the central C^α atom can be 1 or 2 (V = variable), and the atom type for QA atoms is either C or O. The two hydrogen bonds HB1 and HB2 were defined as intermolecular contacts with H···O distances in the range 1.7–2.8 Å after normalization of the N—H bond lengths to 0.88 Å. The molecules connected by the N—H···O hydrogen bonds may additionally be connected by C—H···O hydrogen bonds, but these were not specified in the search.
	Fig. 4. (a) A straight parallel β-sheet (CSD refcode CEPQOE; Gerhardt & Weck, 2006) with a single strand is observed in the structure. Side chains are not shown. Hydrogen bonds with N—H and C—H donors are shown as dashed lines. (b) A twisted parallel β-sheet with eight peptide molecules for one complete turn (PIYSAS; Oku et al., 2008). (c) The twisted parallel β-sheet of (I) with six peptide molecules for one complete turn. (d) A twisted parallel β-sheet with four peptide molecules for one complete turn (FABLUP10; Varughese et al., 1986).

N-(tert-Butoxycarbonyl)-L-valyl-L-valine methyl ester

Crystal data

C16H30N2O5	F(000) = 2160
Mr = 330.42	Dx = 1.116 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 7630 reflections
a = 11.6937 (12) Å	θ = 1.9–25.0°
b = 18.6458 (19) Å	µ = 0.08 mm^−1
c = 27.047 (3) Å	T = 150 K
V = 5897.3 (10) Å^3	Needle, colourless
Z = 12	0.72 × 0.15 × 0.11 mm

Data collection

Bruker APEXII CCD diffractometer	5757 independent reflections
Radiation source: fine-focus sealed tube	4918 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.044
Detector resolution: 8.3 pixels mm^-1	θmax = 25.0°, θmin = 1.9°
Sets of exposures each taken over 0.5° ω rotation scans	h = −13→13
Absorption correction: multi-scan (SADABS; Bruker, 2007)	k = −22→22
Tmin = 0.900, Tmax = 0.980	l = −32→32
38750 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.036	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.089	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0439P)^2 + 1.1632P] where P = (Fo^2 + 2Fc^2)/3
5757 reflections	(Δ/σ)max < 0.001
651 parameters	Δρmax = 0.19 e Å^−3
12 restraints	Δρmin = −0.18 e Å^−3

Special details

Experimental. None

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.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1A	0.49640 (19)	−0.09751 (11)	0.69331 (7)	0.0478 (5)
O2A	0.57930 (19)	−0.06719 (11)	0.62027 (7)	0.0454 (5)
O3A	0.85040 (17)	0.00666 (11)	0.70577 (6)	0.0422 (5)
O4A	1.13948 (19)	0.00410 (13)	0.66892 (8)	0.0569 (6)
O5A	1.0444 (2)	0.10669 (12)	0.65924 (8)	0.0563 (6)
N1A	0.6074 (2)	−0.00280 (13)	0.68985 (8)	0.0346 (5)
H1A	0.592 (2)	0.0003 (16)	0.7206 (7)	0.041*
N2A	0.85771 (19)	0.02561 (12)	0.62425 (7)	0.0292 (5)
H2A	0.823 (2)	0.0421 (14)	0.5983 (8)	0.035*
C1A	0.4395 (3)	−0.16196 (17)	0.67449 (12)	0.0543 (9)
C2A	0.3782 (4)	−0.1883 (2)	0.72026 (14)	0.0926 (16)
H21A	0.4345	−0.2038	0.7449	0.139*
H22A	0.3286	−0.2288	0.7115	0.139*
H23A	0.3317	−0.1494	0.7340	0.139*
C3A	0.3541 (3)	−0.14190 (19)	0.63514 (13)	0.0665 (10)
H31A	0.3946	−0.1239	0.6060	0.100*
H32A	0.3030	−0.1045	0.6478	0.100*
H33A	0.3091	−0.1842	0.6260	0.100*
C4A	0.5260 (4)	−0.2142 (2)	0.6559 (2)	0.0980 (16)
H41A	0.5603	−0.1959	0.6254	0.147*
H42A	0.4887	−0.2603	0.6493	0.147*
H43A	0.5857	−0.2208	0.6809	0.147*
C5A	0.5634 (2)	−0.05687 (14)	0.66395 (9)	0.0333 (6)
C6A	0.6793 (2)	0.05132 (14)	0.66681 (9)	0.0301 (6)
H61A	0.6549	0.0569	0.6316	0.036*
C7A	0.6639 (2)	0.12366 (14)	0.69306 (9)	0.0324 (6)
H71A	0.6783	0.1166	0.7292	0.039*
C8A	0.5421 (3)	0.15018 (17)	0.68637 (12)	0.0503 (8)
H81A	0.4887	0.1146	0.6998	0.075*
H82A	0.5266	0.1573	0.6511	0.075*
H83A	0.5324	0.1958	0.7039	0.075*
C9A	0.7494 (3)	0.17798 (15)	0.67359 (10)	0.0436 (7)
H91A	0.8272	0.1605	0.6795	0.065*
H92A	0.7385	0.2238	0.6907	0.065*
H93A	0.7376	0.1847	0.6380	0.065*
C10A	0.8031 (2)	0.02623 (14)	0.66746 (9)	0.0301 (6)
C11A	0.9737 (2)	−0.00139 (15)	0.62067 (9)	0.0307 (6)
H10A	0.9748	−0.0512	0.6344	0.037*
C12A	1.0111 (2)	−0.00523 (16)	0.56612 (9)	0.0361 (6)
H11A	0.9509	−0.0329	0.5480	0.043*
C13A	1.1228 (3)	−0.0468 (2)	0.56067 (11)	0.0536 (9)
H12A	1.1156	−0.0934	0.5771	0.080*
H13A	1.1852	−0.0195	0.5759	0.080*
H14A	1.1394	−0.0540	0.5255	0.080*
C14A	1.0188 (3)	0.06776 (18)	0.54190 (11)	0.0506 (8)
H15A	1.0412	0.0621	0.5072	0.076*
H16A	1.0759	0.0969	0.5592	0.076*
H17A	0.9442	0.0916	0.5436	0.076*
C15A	1.0537 (3)	0.04445 (17)	0.65185 (10)	0.0384 (7)
C16A	1.2229 (3)	0.0428 (2)	0.69794 (16)	0.0899 (15)
H18A	1.2835	0.0098	0.7085	0.135*
H19A	1.1857	0.0634	0.7271	0.135*
H20A	1.2561	0.0813	0.6779	0.135*
O1B	0.78703 (19)	−0.14973 (9)	0.53897 (7)	0.0447 (5)
O2B	0.77226 (19)	−0.10896 (11)	0.46052 (7)	0.0477 (5)
O3B	0.72306 (16)	0.09860 (9)	0.55096 (6)	0.0303 (4)
O4B	0.76874 (16)	0.27789 (9)	0.53842 (6)	0.0353 (4)
O5B	0.60212 (16)	0.24088 (10)	0.50630 (7)	0.0364 (4)
N1B	0.69924 (19)	−0.04758 (11)	0.52536 (7)	0.0291 (5)
H1B	0.681 (2)	−0.0468 (14)	0.5560 (7)	0.035*
N2B	0.72894 (19)	0.12118 (11)	0.46954 (7)	0.0268 (5)
H2B	0.715 (2)	0.1070 (14)	0.4401 (7)	0.032*
C1B	0.8402 (3)	−0.21825 (14)	0.52547 (12)	0.0461 (8)
C2B	0.9501 (3)	−0.2066 (2)	0.4978 (2)	0.1004 (17)
H21B	1.0022	−0.1777	0.5180	0.151*
H22B	0.9342	−0.1814	0.4668	0.151*
H23B	0.9856	−0.2530	0.4906	0.151*
C3B	0.7592 (3)	−0.26276 (17)	0.49661 (16)	0.0694 (11)
H31B	0.6894	−0.2705	0.5159	0.104*
H32B	0.7946	−0.3091	0.4891	0.104*
H33B	0.7400	−0.2381	0.4657	0.104*
C4B	0.8639 (6)	−0.2512 (2)	0.57531 (16)	0.115 (2)
H41B	0.7915	−0.2588	0.5928	0.173*
H42B	0.9125	−0.2188	0.5946	0.173*
H43B	0.9029	−0.2972	0.5709	0.173*
C5B	0.7541 (2)	−0.10249 (13)	0.50405 (9)	0.0300 (6)
C6B	0.6445 (2)	0.00836 (12)	0.49649 (8)	0.0255 (5)
H61B	0.6556	−0.0026	0.4606	0.031*
C7B	0.5155 (2)	0.01176 (13)	0.50711 (9)	0.0303 (6)
H71B	0.5048	0.0237	0.5429	0.036*
C8B	0.4583 (3)	0.06980 (15)	0.47659 (11)	0.0404 (7)
H81B	0.4948	0.1160	0.4834	0.061*
H82B	0.3770	0.0725	0.4853	0.061*
H83B	0.4660	0.0584	0.4414	0.061*
C9B	0.4605 (3)	−0.06083 (15)	0.49744 (11)	0.0425 (7)
H91B	0.3784	−0.0580	0.5044	0.064*
H92B	0.4956	−0.0970	0.5189	0.064*
H93B	0.4722	−0.0743	0.4628	0.064*
C10B	0.7025 (2)	0.07975 (12)	0.50800 (8)	0.0242 (5)
C11B	0.7801 (2)	0.19143 (12)	0.47591 (8)	0.0261 (5)
H10B	0.8562	0.1857	0.4924	0.031*
C12B	0.7981 (2)	0.22597 (14)	0.42481 (9)	0.0324 (6)
H11B	0.7244	0.2231	0.4062	0.039*
C13B	0.8885 (3)	0.18444 (17)	0.39601 (10)	0.0438 (7)
H12B	0.8656	0.1340	0.3935	0.066*
H13B	0.9620	0.1878	0.4133	0.066*
H14B	0.8960	0.2049	0.3628	0.066*
C14B	0.8324 (3)	0.30448 (15)	0.42859 (11)	0.0471 (8)
H15B	0.7726	0.3312	0.4460	0.071*
H16B	0.8424	0.3243	0.3953	0.071*
H17B	0.9045	0.3084	0.4469	0.071*
C15B	0.7045 (2)	0.23771 (13)	0.50815 (9)	0.0294 (6)
C16B	0.7076 (3)	0.32764 (15)	0.56933 (10)	0.0423 (7)
H18B	0.7621	0.3546	0.5897	0.063*
H19B	0.6549	0.3012	0.5908	0.063*
H20B	0.6642	0.3610	0.5486	0.063*
O1C	1.00074 (15)	−0.05171 (11)	0.37052 (6)	0.0386 (5)
O2C	0.92916 (16)	−0.02679 (11)	0.29466 (6)	0.0416 (5)
O3C	0.68130 (17)	0.05731 (10)	0.37772 (6)	0.0377 (5)
O4C	0.55551 (17)	0.21872 (10)	0.35588 (7)	0.0377 (5)
O5C	0.45338 (18)	0.12008 (11)	0.33855 (8)	0.0470 (5)
N1C	0.81564 (19)	−0.06512 (13)	0.35680 (8)	0.0317 (5)
H1C	0.815 (2)	−0.0730 (14)	0.3883 (7)	0.038*
N2C	0.6565 (2)	0.06497 (12)	0.29594 (7)	0.0315 (5)
H2C	0.657 (3)	0.0430 (14)	0.2681 (7)	0.038*
C1C	1.1198 (2)	−0.03693 (17)	0.35642 (10)	0.0374 (7)
C2C	1.1324 (3)	0.03910 (18)	0.33766 (13)	0.0583 (9)
H21C	1.1073	0.0727	0.3633	0.087*
H22C	1.0854	0.0455	0.3080	0.087*
H23C	1.2128	0.0483	0.3296	0.087*
C3C	1.1592 (3)	−0.09207 (18)	0.31974 (12)	0.0512 (8)
H31C	1.1479	−0.1401	0.3335	0.077*
H32C	1.2406	−0.0848	0.3126	0.077*
H33C	1.1150	−0.0873	0.2891	0.077*
C4C	1.1820 (3)	−0.0453 (2)	0.40566 (11)	0.0598 (10)
H41C	1.1742	−0.0949	0.4173	0.090*
H42C	1.1486	−0.0126	0.4301	0.090*
H43C	1.2632	−0.0339	0.4012	0.090*
C5C	0.9166 (2)	−0.04594 (15)	0.33699 (9)	0.0307 (6)
C6C	0.7096 (2)	−0.05041 (13)	0.33120 (9)	0.0288 (6)
H61C	0.7199	−0.0615	0.2953	0.035*
C7C	0.6139 (2)	−0.09752 (15)	0.35164 (10)	0.0352 (6)
H71C	0.6069	−0.0878	0.3879	0.042*
C8C	0.6426 (3)	−0.17666 (15)	0.34486 (13)	0.0532 (8)
H81C	0.5817	−0.2060	0.3593	0.080*
H82C	0.7152	−0.1874	0.3614	0.080*
H83C	0.6493	−0.1874	0.3095	0.080*
C9C	0.5006 (3)	−0.07905 (17)	0.32738 (13)	0.0500 (8)
H91C	0.4408	−0.1109	0.3401	0.075*
H92C	0.5072	−0.0851	0.2915	0.075*
H93C	0.4807	−0.0292	0.3349	0.075*
C10C	0.6813 (2)	0.02898 (14)	0.33670 (9)	0.0279 (6)
C11C	0.6353 (3)	0.14138 (14)	0.29801 (9)	0.0351 (6)	0.843 (7)
H10C	0.7051	0.1648	0.3119	0.042*	0.843 (7)
C12C	0.6148 (6)	0.1728 (4)	0.24571 (18)	0.0514 (12)	0.843 (7)
H11C	0.6724	0.1499	0.2234	0.062*	0.843 (7)
C13C	0.6382 (6)	0.2518 (2)	0.24456 (17)	0.0801 (19)	0.843 (7)
H12C	0.6347	0.2690	0.2104	0.120*	0.843 (7)
H13C	0.7145	0.2612	0.2581	0.120*	0.843 (7)
H14C	0.5808	0.2770	0.2645	0.120*	0.843 (7)
C14C	0.4977 (4)	0.1525 (2)	0.22559 (13)	0.0637 (15)	0.843 (7)
H15C	0.4919	0.1002	0.2233	0.096*	0.843 (7)
H16C	0.4877	0.1735	0.1927	0.096*	0.843 (7)
H17C	0.4382	0.1707	0.2478	0.096*	0.843 (7)
C11D	0.6353 (3)	0.14138 (14)	0.29801 (9)	0.0351 (6)	0.157 (7)
H10D	0.7055	0.1669	0.3096	0.042*	0.157 (7)
C12D	0.605 (3)	0.166 (2)	0.2450 (8)	0.0514 (12)	0.157 (7)
H11D	0.5547	0.1296	0.2286	0.062*	0.157 (7)
C13D	0.545 (3)	0.2383 (15)	0.2466 (11)	0.091 (8)*	0.157 (7)
H12D	0.5403	0.2583	0.2132	0.136*	0.157 (7)
H13D	0.5873	0.2711	0.2680	0.136*	0.157 (7)
H14D	0.4670	0.2320	0.2597	0.136*	0.157 (7)
C14D	0.714 (2)	0.1737 (16)	0.2170 (9)	0.091 (8)*	0.157 (7)
H15D	0.7554	0.1279	0.2173	0.136*	0.157 (7)
H16D	0.7616	0.2107	0.2327	0.136*	0.157 (7)
H17D	0.6978	0.1876	0.1828	0.136*	0.157 (7)
C15C	0.5361 (3)	0.15686 (14)	0.33294 (9)	0.0335 (6)
C16C	0.4715 (3)	0.24052 (16)	0.39171 (11)	0.0459 (8)
H18C	0.4955	0.2856	0.4072	0.069*
H19C	0.4640	0.2033	0.4171	0.069*
H20C	0.3976	0.2475	0.3753	0.069*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1A	0.0619 (14)	0.0496 (12)	0.0319 (10)	−0.0241 (11)	0.0005 (10)	0.0069 (9)
O2A	0.0624 (14)	0.0459 (11)	0.0280 (10)	−0.0115 (11)	0.0071 (10)	−0.0051 (9)
O3A	0.0489 (12)	0.0589 (13)	0.0188 (9)	0.0096 (11)	−0.0026 (9)	0.0105 (9)
O4A	0.0482 (13)	0.0712 (15)	0.0514 (13)	0.0159 (12)	−0.0251 (11)	−0.0163 (12)
O5A	0.0577 (15)	0.0483 (14)	0.0629 (14)	−0.0026 (12)	−0.0213 (12)	−0.0098 (11)
N1A	0.0448 (14)	0.0412 (13)	0.0177 (10)	−0.0118 (12)	0.0061 (10)	0.0001 (10)
N2A	0.0302 (12)	0.0407 (12)	0.0167 (10)	−0.0001 (10)	−0.0019 (9)	0.0055 (9)
C1A	0.069 (2)	0.0401 (17)	0.0534 (19)	−0.0208 (17)	−0.0127 (17)	0.0088 (15)
C2A	0.126 (4)	0.089 (3)	0.063 (2)	−0.067 (3)	−0.015 (2)	0.024 (2)
C3A	0.077 (3)	0.063 (2)	0.059 (2)	−0.024 (2)	−0.015 (2)	0.0046 (17)
C4A	0.102 (4)	0.043 (2)	0.150 (4)	0.001 (2)	−0.026 (3)	−0.007 (3)
C5A	0.0410 (16)	0.0341 (14)	0.0249 (14)	−0.0009 (13)	0.0026 (12)	0.0033 (12)
C6A	0.0373 (15)	0.0357 (15)	0.0174 (11)	−0.0019 (12)	0.0026 (11)	0.0031 (11)
C7A	0.0375 (16)	0.0361 (14)	0.0237 (13)	0.0001 (12)	−0.0018 (12)	0.0013 (11)
C8A	0.0438 (19)	0.0482 (18)	0.059 (2)	0.0069 (15)	−0.0021 (16)	−0.0039 (16)
C9A	0.055 (2)	0.0376 (16)	0.0385 (16)	−0.0027 (15)	0.0051 (14)	0.0033 (13)
C10A	0.0386 (16)	0.0317 (14)	0.0201 (13)	−0.0028 (12)	−0.0001 (12)	0.0043 (10)
C11A	0.0306 (15)	0.0391 (15)	0.0223 (12)	0.0024 (12)	−0.0023 (11)	0.0041 (11)
C12A	0.0293 (15)	0.0511 (17)	0.0280 (14)	−0.0016 (13)	−0.0008 (11)	−0.0069 (12)
C13A	0.0420 (19)	0.079 (2)	0.0402 (17)	0.0103 (18)	0.0009 (14)	−0.0137 (16)
C14A	0.0467 (19)	0.069 (2)	0.0359 (16)	−0.0063 (17)	0.0084 (14)	0.0126 (15)
C15A	0.0366 (17)	0.0485 (19)	0.0301 (15)	0.0008 (14)	−0.0065 (12)	−0.0037 (13)
C16A	0.065 (3)	0.114 (4)	0.091 (3)	0.017 (3)	−0.052 (2)	−0.035 (3)
O1B	0.0644 (14)	0.0313 (10)	0.0384 (11)	0.0196 (10)	−0.0086 (10)	0.0038 (8)
O2B	0.0648 (15)	0.0457 (12)	0.0326 (11)	0.0205 (11)	0.0169 (10)	0.0067 (9)
O3B	0.0437 (11)	0.0315 (9)	0.0158 (8)	−0.0008 (9)	−0.0034 (8)	−0.0001 (7)
O4B	0.0338 (11)	0.0351 (10)	0.0369 (10)	−0.0048 (9)	0.0019 (8)	−0.0133 (8)
O5B	0.0307 (12)	0.0406 (11)	0.0379 (11)	0.0000 (9)	−0.0012 (9)	−0.0020 (8)
N1B	0.0404 (13)	0.0266 (11)	0.0204 (10)	0.0058 (10)	−0.0006 (10)	0.0009 (9)
N2B	0.0359 (12)	0.0289 (11)	0.0155 (10)	−0.0038 (10)	−0.0020 (9)	−0.0019 (9)
C1B	0.0456 (19)	0.0273 (14)	0.065 (2)	0.0118 (14)	−0.0142 (16)	−0.0027 (14)
C2B	0.040 (2)	0.054 (2)	0.207 (5)	0.0153 (19)	0.009 (3)	−0.012 (3)
C3B	0.061 (2)	0.0375 (18)	0.109 (3)	0.0073 (17)	−0.025 (2)	−0.0124 (19)
C4B	0.200 (6)	0.060 (2)	0.086 (3)	0.065 (3)	−0.050 (4)	0.002 (2)
C5B	0.0282 (14)	0.0289 (13)	0.0329 (15)	0.0011 (12)	−0.0015 (12)	0.0032 (12)
C6B	0.0316 (14)	0.0263 (12)	0.0185 (11)	0.0038 (11)	−0.0010 (11)	0.0003 (10)
C7B	0.0347 (15)	0.0302 (14)	0.0259 (13)	0.0020 (12)	−0.0011 (11)	−0.0025 (11)
C8B	0.0372 (16)	0.0372 (15)	0.0468 (17)	0.0065 (13)	−0.0037 (14)	−0.0004 (13)
C9B	0.0393 (17)	0.0352 (15)	0.0531 (18)	−0.0033 (14)	−0.0029 (14)	0.0002 (14)
C10B	0.0255 (13)	0.0301 (13)	0.0170 (12)	0.0050 (11)	−0.0009 (10)	−0.0006 (10)
C11B	0.0268 (14)	0.0289 (12)	0.0227 (12)	−0.0015 (11)	−0.0042 (11)	−0.0001 (10)
C12B	0.0315 (15)	0.0397 (15)	0.0260 (13)	−0.0047 (13)	0.0001 (11)	0.0048 (11)
C13B	0.0399 (18)	0.0560 (19)	0.0354 (16)	−0.0057 (15)	0.0092 (13)	−0.0033 (14)
C14B	0.054 (2)	0.0401 (17)	0.0476 (17)	−0.0068 (15)	0.0058 (15)	0.0103 (14)
C15B	0.0354 (17)	0.0266 (13)	0.0262 (13)	−0.0037 (12)	−0.0022 (12)	0.0035 (10)
C16B	0.0470 (18)	0.0359 (15)	0.0439 (16)	0.0031 (14)	0.0057 (14)	−0.0142 (13)
O1C	0.0261 (10)	0.0674 (13)	0.0224 (9)	0.0006 (10)	−0.0015 (8)	0.0049 (9)
O2C	0.0383 (12)	0.0673 (13)	0.0190 (9)	−0.0094 (10)	−0.0025 (8)	0.0047 (9)
O3C	0.0543 (13)	0.0391 (10)	0.0198 (9)	−0.0008 (10)	−0.0045 (8)	−0.0075 (8)
O4C	0.0421 (12)	0.0361 (10)	0.0349 (10)	0.0076 (9)	−0.0008 (9)	−0.0089 (8)
O5C	0.0386 (12)	0.0453 (12)	0.0570 (13)	−0.0026 (10)	0.0021 (10)	−0.0084 (10)
N1C	0.0268 (12)	0.0482 (13)	0.0201 (10)	0.0034 (11)	0.0025 (9)	0.0042 (10)
N2C	0.0418 (13)	0.0349 (12)	0.0179 (10)	0.0048 (11)	−0.0021 (10)	−0.0045 (9)
C1C	0.0250 (15)	0.0574 (18)	0.0299 (14)	−0.0018 (13)	−0.0036 (11)	−0.0052 (13)
C2C	0.054 (2)	0.057 (2)	0.064 (2)	−0.0202 (18)	−0.0143 (18)	−0.0003 (17)
C3C	0.0354 (17)	0.068 (2)	0.0505 (19)	−0.0003 (16)	0.0093 (15)	−0.0118 (16)
C4C	0.0362 (18)	0.100 (3)	0.0432 (18)	0.0047 (19)	−0.0112 (15)	−0.0032 (18)
C5C	0.0303 (15)	0.0405 (15)	0.0211 (13)	0.0016 (12)	−0.0028 (11)	−0.0037 (11)
C6C	0.0276 (14)	0.0360 (14)	0.0229 (12)	0.0021 (12)	−0.0005 (11)	−0.0052 (11)
C7C	0.0301 (15)	0.0373 (15)	0.0381 (15)	0.0000 (13)	0.0029 (12)	−0.0046 (12)
C8C	0.049 (2)	0.0360 (16)	0.074 (2)	−0.0033 (15)	0.0020 (17)	−0.0019 (16)
C9C	0.0318 (17)	0.0495 (18)	0.069 (2)	−0.0042 (14)	−0.0043 (15)	−0.0050 (16)
C10C	0.0256 (14)	0.0378 (14)	0.0203 (12)	−0.0024 (11)	−0.0007 (11)	−0.0028 (11)
C11C	0.0458 (18)	0.0347 (15)	0.0247 (13)	0.0016 (13)	−0.0009 (12)	−0.0015 (11)
C12C	0.084 (3)	0.040 (2)	0.0304 (15)	0.010 (2)	0.0034 (17)	0.0041 (14)
C13C	0.134 (5)	0.050 (3)	0.056 (3)	0.003 (3)	0.014 (3)	0.015 (2)
C14C	0.096 (4)	0.063 (3)	0.032 (2)	0.033 (3)	−0.026 (2)	−0.0031 (18)
C11D	0.0458 (18)	0.0347 (15)	0.0247 (13)	0.0016 (13)	−0.0009 (12)	−0.0015 (11)
C12D	0.084 (3)	0.040 (2)	0.0304 (15)	0.010 (2)	0.0034 (17)	0.0041 (14)
C15C	0.0421 (17)	0.0342 (15)	0.0242 (13)	0.0093 (14)	−0.0092 (12)	−0.0021 (12)
C16C	0.056 (2)	0.0432 (17)	0.0384 (16)	0.0183 (16)	0.0050 (15)	−0.0041 (13)

Geometric parameters (Å, º)

O1A—C5A	1.349 (3)	C8B—H81B	0.9800
O1A—C1A	1.465 (4)	C8B—H82B	0.9800
O2A—C5A	1.211 (3)	C8B—H83B	0.9800
O3A—C10A	1.230 (3)	C9B—H91B	0.9800
O4A—C15A	1.336 (4)	C9B—H92B	0.9800
O4A—C16A	1.445 (4)	C9B—H93B	0.9800
O5A—C15A	1.183 (3)	C11B—C15B	1.512 (4)
N1A—C5A	1.331 (3)	C11B—C12B	1.539 (3)
N1A—C6A	1.454 (3)	C11B—H10B	1.0000
N1A—H1A	0.851 (17)	C12B—C14B	1.522 (4)
N2A—C10A	1.332 (3)	C12B—C13B	1.525 (4)
N2A—C11A	1.451 (3)	C12B—H11B	1.0000
N2A—H2A	0.865 (17)	C13B—H12B	0.9800
C1A—C4A	1.491 (6)	C13B—H13B	0.9800
C1A—C3A	1.507 (5)	C13B—H14B	0.9800
C1A—C2A	1.512 (5)	C14B—H15B	0.9800
C2A—H21A	0.9800	C14B—H16B	0.9800
C2A—H22A	0.9800	C14B—H17B	0.9800
C2A—H23A	0.9800	C16B—H18B	0.9800
C3A—H31A	0.9800	C16B—H19B	0.9800
C3A—H32A	0.9800	C16B—H20B	0.9800
C3A—H33A	0.9800	O1C—C5C	1.343 (3)
C4A—H41A	0.9800	O1C—C1C	1.469 (3)
C4A—H42A	0.9800	O2C—C5C	1.208 (3)
C4A—H43A	0.9800	O3C—C10C	1.229 (3)
C6A—C10A	1.521 (4)	O4C—C15C	1.329 (3)
C6A—C7A	1.535 (4)	O4C—C16C	1.439 (3)
C6A—H61A	1.0000	O5C—C15C	1.196 (3)
C7A—C9A	1.517 (4)	N1C—C5C	1.345 (3)
C7A—C8A	1.519 (4)	N1C—C6C	1.447 (3)
C7A—H71A	1.0000	N1C—H1C	0.865 (17)
C8A—H81A	0.9800	N2C—C10C	1.323 (3)
C8A—H82A	0.9800	N2C—C11C	1.447 (3)
C8A—H83A	0.9800	N2C—H2C	0.859 (17)
C9A—H91A	0.9800	C1C—C3C	1.501 (4)
C9A—H92A	0.9800	C1C—C2C	1.513 (4)
C9A—H93A	0.9800	C1C—C4C	1.526 (4)
C11A—C15A	1.522 (4)	C2C—H21C	0.9800
C11A—C12A	1.540 (3)	C2C—H22C	0.9800
C11A—H10A	1.0000	C2C—H23C	0.9800
C12A—C14A	1.513 (4)	C3C—H31C	0.9800
C12A—C13A	1.526 (4)	C3C—H32C	0.9800
C12A—H11A	1.0000	C3C—H33C	0.9800
C13A—H12A	0.9800	C4C—H41C	0.9800
C13A—H13A	0.9800	C4C—H42C	0.9800
C13A—H14A	0.9800	C4C—H43C	0.9800
C14A—H15A	0.9800	C6C—C10C	1.524 (4)
C14A—H16A	0.9800	C6C—C7C	1.526 (4)
C14A—H17A	0.9800	C6C—H61C	1.0000
C16A—H18A	0.9800	C7C—C9C	1.518 (4)
C16A—H19A	0.9800	C7C—C8C	1.524 (4)
C16A—H20A	0.9800	C7C—H71C	1.0000
O1B—C5B	1.348 (3)	C8C—H81C	0.9800
O1B—C1B	1.467 (3)	C8C—H82C	0.9800
O2B—C5B	1.202 (3)	C8C—H83C	0.9800
O3B—C10B	1.237 (3)	C9C—H91C	0.9800
O4B—C15B	1.340 (3)	C9C—H92C	0.9800
O4B—C16B	1.439 (3)	C9C—H93C	0.9800
O5B—C15B	1.200 (3)	C11C—C15C	1.523 (4)
N1B—C5B	1.338 (3)	C11C—C12C	1.550 (5)
N1B—C6B	1.452 (3)	C11C—H10C	1.0000
N1B—H1B	0.854 (17)	C12C—C13C	1.498 (8)
N2B—C10B	1.332 (3)	C12C—C14C	1.521 (8)
N2B—C11B	1.450 (3)	C12C—H11C	1.0000
N2B—H2B	0.855 (17)	C13C—H12C	0.9800
C1B—C3B	1.481 (4)	C13C—H13C	0.9800
C1B—C2B	1.503 (5)	C13C—H14C	0.9800
C1B—C4B	1.507 (5)	C14C—H15C	0.9800
C2B—H21B	0.9800	C14C—H16C	0.9800
C2B—H22B	0.9800	C14C—H17C	0.9800
C2B—H23B	0.9800	C12D—C14D	1.49 (2)
C3B—H31B	0.9800	C12D—C13D	1.52 (2)
C3B—H32B	0.9800	C12D—H11D	1.0000
C3B—H33B	0.9800	C13D—H12D	0.9800
C4B—H41B	0.9800	C13D—H13D	0.9800
C4B—H42B	0.9800	C13D—H14D	0.9800
C4B—H43B	0.9800	C14D—H15D	0.9800
C6B—C10B	1.526 (3)	C14D—H16D	0.9800
C6B—C7B	1.537 (4)	C14D—H17D	0.9800
C6B—H61B	1.0000	C16C—H18C	0.9800
C7B—C8B	1.516 (4)	C16C—H19C	0.9800
C7B—C9B	1.521 (4)	C16C—H20C	0.9800
C7B—H71B	1.0000
C5A—O1A—C1A	121.3 (2)	H91B—C9B—H92B	109.5
C15A—O4A—C16A	114.4 (3)	C7B—C9B—H93B	109.5
C5A—N1A—C6A	121.6 (2)	H91B—C9B—H93B	109.5
C5A—N1A—H1A	119 (2)	H92B—C9B—H93B	109.5
C6A—N1A—H1A	119 (2)	O3B—C10B—N2B	121.6 (2)
C10A—N2A—C11A	120.7 (2)	O3B—C10B—C6B	121.7 (2)
C10A—N2A—H2A	119.1 (19)	N2B—C10B—C6B	116.72 (19)
C11A—N2A—H2A	120.3 (19)	N2B—C11B—C15B	110.0 (2)
O1A—C1A—C4A	110.2 (3)	N2B—C11B—C12B	109.11 (19)
O1A—C1A—C3A	110.1 (3)	C15B—C11B—C12B	111.0 (2)
C4A—C1A—C3A	112.0 (3)	N2B—C11B—H10B	108.9
O1A—C1A—C2A	101.4 (3)	C15B—C11B—H10B	108.9
C4A—C1A—C2A	112.6 (3)	C12B—C11B—H10B	108.9
C3A—C1A—C2A	110.2 (3)	C14B—C12B—C13B	109.9 (2)
C1A—C2A—H21A	109.5	C14B—C12B—C11B	112.2 (2)
C1A—C2A—H22A	109.5	C13B—C12B—C11B	109.9 (2)
H21A—C2A—H22A	109.5	C14B—C12B—H11B	108.2
C1A—C2A—H23A	109.5	C13B—C12B—H11B	108.2
H21A—C2A—H23A	109.5	C11B—C12B—H11B	108.2
H22A—C2A—H23A	109.5	C12B—C13B—H12B	109.5
C1A—C3A—H31A	109.5	C12B—C13B—H13B	109.5
C1A—C3A—H32A	109.5	H12B—C13B—H13B	109.5
H31A—C3A—H32A	109.5	C12B—C13B—H14B	109.5
C1A—C3A—H33A	109.5	H12B—C13B—H14B	109.5
H31A—C3A—H33A	109.5	H13B—C13B—H14B	109.5
H32A—C3A—H33A	109.5	C12B—C14B—H15B	109.5
C1A—C4A—H41A	109.5	C12B—C14B—H16B	109.5
C1A—C4A—H42A	109.5	H15B—C14B—H16B	109.5
H41A—C4A—H42A	109.5	C12B—C14B—H17B	109.5
C1A—C4A—H43A	109.5	H15B—C14B—H17B	109.5
H41A—C4A—H43A	109.5	H16B—C14B—H17B	109.5
H42A—C4A—H43A	109.5	O5B—C15B—O4B	123.9 (2)
O2A—C5A—N1A	125.1 (2)	O5B—C15B—C11B	126.0 (2)
O2A—C5A—O1A	125.0 (3)	O4B—C15B—C11B	110.1 (2)
N1A—C5A—O1A	109.9 (2)	O4B—C16B—H18B	109.5
N1A—C6A—C10A	109.4 (2)	O4B—C16B—H19B	109.5
N1A—C6A—C7A	110.1 (2)	H18B—C16B—H19B	109.5
C10A—C6A—C7A	112.1 (2)	O4B—C16B—H20B	109.5
N1A—C6A—H61A	108.4	H18B—C16B—H20B	109.5
C10A—C6A—H61A	108.4	H19B—C16B—H20B	109.5
C7A—C6A—H61A	108.4	C5C—O1C—C1C	120.28 (19)
C9A—C7A—C8A	111.0 (2)	C15C—O4C—C16C	116.3 (2)
C9A—C7A—C6A	110.4 (2)	C5C—N1C—C6C	120.8 (2)
C8A—C7A—C6A	109.9 (2)	C5C—N1C—H1C	116.7 (19)
C9A—C7A—H71A	108.5	C6C—N1C—H1C	119.5 (19)
C8A—C7A—H71A	108.5	C10C—N2C—C11C	120.3 (2)
C6A—C7A—H71A	108.5	C10C—N2C—H2C	119.2 (19)
C7A—C8A—H81A	109.5	C11C—N2C—H2C	120.4 (19)
C7A—C8A—H82A	109.5	O1C—C1C—C3C	109.5 (2)
H81A—C8A—H82A	109.5	O1C—C1C—C2C	110.8 (2)
C7A—C8A—H83A	109.5	C3C—C1C—C2C	113.0 (3)
H81A—C8A—H83A	109.5	O1C—C1C—C4C	101.9 (2)
H82A—C8A—H83A	109.5	C3C—C1C—C4C	111.1 (3)
C7A—C9A—H91A	109.5	C2C—C1C—C4C	110.0 (3)
C7A—C9A—H92A	109.5	C1C—C2C—H21C	109.5
H91A—C9A—H92A	109.5	C1C—C2C—H22C	109.5
C7A—C9A—H93A	109.5	H21C—C2C—H22C	109.5
H91A—C9A—H93A	109.5	C1C—C2C—H23C	109.5
H92A—C9A—H93A	109.5	H21C—C2C—H23C	109.5
O3A—C10A—N2A	121.4 (2)	H22C—C2C—H23C	109.5
O3A—C10A—C6A	121.9 (2)	C1C—C3C—H31C	109.5
N2A—C10A—C6A	116.7 (2)	C1C—C3C—H32C	109.5
N2A—C11A—C15A	110.1 (2)	H31C—C3C—H32C	109.5
N2A—C11A—C12A	110.2 (2)	C1C—C3C—H33C	109.5
C15A—C11A—C12A	112.5 (2)	H31C—C3C—H33C	109.5
N2A—C11A—H10A	108.0	H32C—C3C—H33C	109.5
C15A—C11A—H10A	108.0	C1C—C4C—H41C	109.5
C12A—C11A—H10A	108.0	C1C—C4C—H42C	109.5
C14A—C12A—C13A	111.3 (3)	H41C—C4C—H42C	109.5
C14A—C12A—C11A	112.9 (2)	C1C—C4C—H43C	109.5
C13A—C12A—C11A	111.0 (2)	H41C—C4C—H43C	109.5
C14A—C12A—H11A	107.1	H42C—C4C—H43C	109.5
C13A—C12A—H11A	107.1	O2C—C5C—O1C	125.1 (2)
C11A—C12A—H11A	107.1	O2C—C5C—N1C	124.3 (2)
C12A—C13A—H12A	109.5	O1C—C5C—N1C	110.7 (2)
C12A—C13A—H13A	109.5	N1C—C6C—C10C	108.9 (2)
H12A—C13A—H13A	109.5	N1C—C6C—C7C	110.2 (2)
C12A—C13A—H14A	109.5	C10C—C6C—C7C	111.4 (2)
H12A—C13A—H14A	109.5	N1C—C6C—H61C	108.8
H13A—C13A—H14A	109.5	C10C—C6C—H61C	108.8
C12A—C14A—H15A	109.5	C7C—C6C—H61C	108.8
C12A—C14A—H16A	109.5	C9C—C7C—C8C	111.1 (3)
H15A—C14A—H16A	109.5	C9C—C7C—C6C	110.6 (2)
C12A—C14A—H17A	109.5	C8C—C7C—C6C	110.6 (2)
H15A—C14A—H17A	109.5	C9C—C7C—H71C	108.1
H16A—C14A—H17A	109.5	C8C—C7C—H71C	108.1
O5A—C15A—O4A	124.3 (3)	C6C—C7C—H71C	108.1
O5A—C15A—C11A	126.0 (3)	C7C—C8C—H81C	109.5
O4A—C15A—C11A	109.7 (3)	C7C—C8C—H82C	109.5
O4A—C16A—H18A	109.5	H81C—C8C—H82C	109.5
O4A—C16A—H19A	109.5	C7C—C8C—H83C	109.5
H18A—C16A—H19A	109.5	H81C—C8C—H83C	109.5
O4A—C16A—H20A	109.5	H82C—C8C—H83C	109.5
H18A—C16A—H20A	109.5	C7C—C9C—H91C	109.5
H19A—C16A—H20A	109.5	C7C—C9C—H92C	109.5
C5B—O1B—C1B	121.1 (2)	H91C—C9C—H92C	109.5
C15B—O4B—C16B	115.9 (2)	C7C—C9C—H93C	109.5
C5B—N1B—C6B	121.9 (2)	H91C—C9C—H93C	109.5
C5B—N1B—H1B	123.2 (19)	H92C—C9C—H93C	109.5
C6B—N1B—H1B	113.6 (19)	O3C—C10C—N2C	122.3 (2)
C10B—N2B—C11B	121.8 (2)	O3C—C10C—C6C	120.4 (2)
C10B—N2B—H2B	120.1 (18)	N2C—C10C—C6C	117.3 (2)
C11B—N2B—H2B	118.1 (18)	N2C—C11C—C15C	109.9 (2)
O1B—C1B—C3B	110.4 (2)	N2C—C11C—C12C	111.3 (3)
O1B—C1B—C2B	111.1 (3)	C15C—C11C—C12C	112.1 (3)
C3B—C1B—C2B	111.4 (4)	N2C—C11C—H10C	107.7
O1B—C1B—C4B	102.1 (3)	C15C—C11C—H10C	107.7
C3B—C1B—C4B	111.2 (3)	C12C—C11C—H10C	107.7
C2B—C1B—C4B	110.3 (4)	C13C—C12C—C14C	113.7 (5)
C1B—C2B—H21B	109.5	C13C—C12C—C11C	111.3 (5)
C1B—C2B—H22B	109.5	C14C—C12C—C11C	111.8 (4)
H21B—C2B—H22B	109.5	C13C—C12C—H11C	106.5
C1B—C2B—H23B	109.5	C14C—C12C—H11C	106.5
H21B—C2B—H23B	109.5	C11C—C12C—H11C	106.5
H22B—C2B—H23B	109.5	H12C—C13C—H13C	109.5
C1B—C3B—H31B	109.5	H12C—C13C—H14C	109.5
C1B—C3B—H32B	109.5	H13C—C13C—H14C	109.5
H31B—C3B—H32B	109.5	C12C—C13C—H12C	109.5
C1B—C3B—H33B	109.5	C12C—C13C—H13C	109.5
H31B—C3B—H33B	109.5	C12C—C13C—H14C	109.5
H32B—C3B—H33B	109.5	C12C—C14C—H15C	109.5
C1B—C4B—H41B	109.5	C12C—C14C—H16C	109.5
C1B—C4B—H42B	109.5	C12C—C14C—H17C	109.5
H41B—C4B—H42B	109.5	H15C—C14C—H16C	109.5
C1B—C4B—H43B	109.5	H15C—C14C—H17C	109.5
H41B—C4B—H43B	109.5	H16C—C14C—H17C	109.5
H42B—C4B—H43B	109.5	C14D—C12D—C13D	109 (2)
O2B—C5B—N1B	125.7 (2)	C14D—C12D—H11D	110.1
O2B—C5B—O1B	124.7 (2)	C13D—C12D—H11D	110.1
N1B—C5B—O1B	109.6 (2)	C12D—C13D—H12D	109.5
N1B—C6B—C10B	108.70 (19)	C12D—C13D—H13D	109.5
N1B—C6B—C7B	111.2 (2)	H12D—C13D—H13D	109.5
C10B—C6B—C7B	111.3 (2)	C12D—C13D—H14D	109.5
N1B—C6B—H61B	108.5	H12D—C13D—H14D	109.5
C10B—C6B—H61B	108.5	H13D—C13D—H14D	109.5
C7B—C6B—H61B	108.5	C12D—C14D—H15D	109.5
C8B—C7B—C9B	110.8 (2)	C12D—C14D—H16D	109.5
C8B—C7B—C6B	111.1 (2)	H15D—C14D—H16D	109.5
C9B—C7B—C6B	110.2 (2)	C12D—C14D—H17D	109.5
C8B—C7B—H71B	108.2	H15D—C14D—H17D	109.5
C9B—C7B—H71B	108.2	H16D—C14D—H17D	109.5
C6B—C7B—H71B	108.2	O5C—C15C—O4C	125.2 (3)
C7B—C8B—H81B	109.5	O5C—C15C—C11C	125.9 (2)
C7B—C8B—H82B	109.5	O4C—C15C—C11C	108.9 (2)
H81B—C8B—H82B	109.5	O4C—C16C—H18C	109.5
C7B—C8B—H83B	109.5	O4C—C16C—H19C	109.5
H81B—C8B—H83B	109.5	H18C—C16C—H19C	109.5
H82B—C8B—H83B	109.5	O4C—C16C—H20C	109.5
C7B—C9B—H91B	109.5	H18C—C16C—H20C	109.5
C7B—C9B—H92B	109.5	H19C—C16C—H20C	109.5
C1A—O1A—C5A—N1A	−178.4 (3)	C6B—N1B—C5B—O2B	6.3 (4)
O1A—C5A—N1A—C6A	−177.4 (2)	C5B—N1B—C6B—C7B	119.6 (3)
C5A—N1A—C6A—C10A	−87.6 (3)	C10B—C6B—C7B—C8B	59.1 (3)
N1A—C6A—C10A—N2A	126.2 (2)	C10B—C6B—C7B—C9B	−177.6 (2)
C6A—C10A—N2A—C11A	−176.4 (2)	C11B—N2B—C10B—O3B	−1.8 (4)
C10A—N2A—C11A—C15A	−62.6 (3)	N1B—C6B—C10B—O3B	−46.5 (3)
N2A—C11A—C15A—O4A	149.1 (2)	C7B—C6B—C10B—O3B	76.3 (3)
C11A—C15A—O4A—C16A	178.2 (3)	C7B—C6B—C10B—N2B	−102.9 (3)
N1A—C6A—C7A—C8A	−64.3 (3)	C10B—N2B—C11B—C12B	−179.0 (2)
N1A—C6A—C7A—C9A	172.9 (2)	C15B—C11B—C12B—C14B	48.8 (3)
N2A—C11A—C12A—C13A	−168.9 (2)	C15B—C11B—C12B—C13B	171.4 (2)
N2A—C11A—C12A—C14A	65.2 (3)	C16B—O4B—C15B—O5B	−0.9 (4)
C5A—O1A—C1A—C4A	59.7 (4)	N2B—C11B—C15B—O5B	−41.0 (3)
C5A—O1A—C1A—C3A	−64.2 (4)	C12B—C11B—C15B—O5B	79.9 (3)
C5A—O1A—C1A—C2A	179.2 (3)	C12B—C11B—C15B—O4B	−97.5 (2)
C1A—O1A—C5A—O2A	3.0 (4)	C1C—O1C—C5C—N1C	177.0 (2)
O2A—C5A—N1A—C6A	1.2 (4)	O1C—C5C—N1C—C6C	168.0 (2)
C5A—N1A—C6A—C7A	148.7 (3)	C5C—N1C—C6C—C10C	−76.2 (3)
C10A—C6A—C7A—C9A	50.8 (3)	N1C—C6C—C10C—N2C	129.5 (2)
C10A—C6A—C7A—C8A	173.7 (2)	C6C—C10C—N2C—C11C	−176.4 (2)
C11A—N2A—C10A—O3A	2.8 (4)	C10C—N2C—C11C—C15C	−58.3 (3)
N1A—C6A—C10A—O3A	−52.9 (3)	N2C—C11C—C15C—O4C	145.5 (2)
C7A—C6A—C10A—O3A	69.5 (3)	C11C—C15C—O4C—C16C	−178.0 (2)
C7A—C6A—C10A—N2A	−111.3 (3)	N1C—C6C—C7C—C8C	−60.2 (3)
C10A—N2A—C11A—C12A	172.7 (2)	N1C—C6C—C7C—C9C	176.3 (2)
C15A—C11A—C12A—C14A	−58.0 (3)	N2C—C11C—C12C—C13C	−157.8 (4)
C15A—C11A—C12A—C13A	67.9 (3)	N2C—C11C—C12C—C14C	73.9 (5)
C16A—O4A—C15A—O5A	0.0 (5)	C5C—O1C—C1C—C3C	−65.7 (3)
N2A—C11A—C15A—O5A	−32.7 (4)	C5C—O1C—C1C—C2C	59.5 (3)
C12A—C11A—C15A—O5A	90.6 (4)	C5C—O1C—C1C—C4C	176.6 (3)
C12A—C11A—C15A—O4A	−87.6 (3)	C1C—O1C—C5C—O2C	−2.4 (4)
C1B—O1B—C5B—N1B	174.5 (2)	C6C—N1C—C5C—O2C	−12.6 (4)
O1B—C5B—N1B—C6B	−174.1 (2)	C5C—N1C—C6C—C7C	161.4 (2)
C5B—N1B—C6B—C10B	−117.6 (2)	C10C—C6C—C7C—C9C	55.3 (3)
N1B—C6B—C10B—N2B	134.3 (2)	C10C—C6C—C7C—C8C	178.8 (2)
C6B—C10B—N2B—C11B	177.5 (2)	C11C—N2C—C10C—O3C	4.0 (4)
C10B—N2B—C11B—C15B	−57.0 (3)	N1C—C6C—C10C—O3C	−50.9 (3)
N2B—C11B—C15B—O4B	141.6 (2)	C7C—C6C—C10C—O3C	70.9 (3)
C11B—C15B—O4B—C16B	176.6 (2)	C7C—C6C—C10C—N2C	−108.8 (3)
N1B—C6B—C7B—C8B	−179.5 (2)	C10C—N2C—C11C—C12C	176.8 (3)
N1B—C6B—C7B—C9B	−56.3 (3)	C15C—C11C—C12C—C13C	78.6 (5)
N2B—C11B—C12B—C13B	−67.2 (3)	C15C—C11C—C12C—C14C	−49.8 (6)
N2B—C11B—C12B—C14B	170.2 (2)	C16C—O4C—C15C—O5C	2.8 (4)
C5B—O1B—C1B—C3B	−62.9 (4)	C16C—O4C—C15C—C11C	−178.0 (2)
C5B—O1B—C1B—C2B	61.2 (4)	N2C—C11C—C15C—O5C	−35.4 (4)
C5B—O1B—C1B—C4B	178.8 (3)	C12C—C11C—C15C—O5C	89.0 (4)
C1B—O1B—C5B—O2B	−5.9 (4)	C12C—C11C—C15C—O4C	−90.1 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1A—H1A···O2C^i	0.85 (2)	2.08 (2)	2.920 (3)	169 (3)
N2A—H2A···O3B	0.87 (2)	2.03 (2)	2.874 (3)	165 (3)
C6A—H61A···O3B	1.00	2.45	3.295 (3)	142
N1B—H1B···O2A	0.85 (2)	2.14 (2)	2.948 (3)	157 (3)
N2B—H2B···O3C	0.86 (2)	1.97 (2)	2.810 (3)	170 (3)
C6B—H61B···O3C	1.00	2.52	3.367 (3)	142
N1C—H1C···O2B	0.87 (2)	2.12 (2)	2.966 (3)	164 (3)
N2C—H2C···O3A^ii	0.86 (2)	1.92 (2)	2.782 (3)	177 (3)
C6C—H61C···O3A^ii	1.00	2.75	3.559 (3)	138

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