L-Phenyl­alanyl-L-isoleucine 0.88-hydrate

The asymmetric unit in the crystal structure of the title compound, C₁₅H₂₂N₂O₃·0.88H₂O, contains two peptide mol­ecules with completely different conformations. The structure is divided into hydro­phobic and hydro­philic layers, with channels of water mol­ecules at the layer interface.

S1. Comment

A systematic survey has revealed that dipeptides constructed from two amino acid residues with large hydrophobic side chains may give porous structures with hydrophilic inner surfaces. This structural family has been referred to as the FF-class, after L-phenylalanyl-L-phenylalanine (FF; Görbitz, 2001), and includes L-leucyl-L-leucine (LL), L-leucyl-L-phenylalanine (LF), L-phenylalanyl-L-leucine (FL; Görbitz, 2001) and L-isoleucyl-L-leucine (IL; Görbitz, 2004b), as well as L-tryptophylglycine (WG; Emge et al., 2000; Birkedal et al., 2002). Channel size ranges from a rectangular 2.5 × 6.0 Å for LL, LF and IL, to circular with diameter 10 Å for FF. All peptide molecules which form this type of nanotube occur in unusual folded conformations that bring both side chains onto the same side of the plane defined by the peptide bond. The associated absolute values for the torsion angle θ (C₁^β-C₁^α···C₂^α-C₂^β) are thus close to 0°. Conformations with low θ values are also observed for L-Ile-L-Phe (IF; Görbitz, 2004a), L-valyl-L-phenylalanine (VF, orthorhombic modification; Görbitz, 2002), and L-alanyl-L-trpyptophane (AW; Emge et al., 2000), but these three structures are divided into hydrophobic and hydrophilic layers, the latter including one (AW) or two (IF and VF) water molecules per peptide molecule. Against this background, the crystal structure of L-phenylalanyl-L-isoleucine, FI, is presented. \sch

The crystal structure of FI is depicted in Fig. 1 and Table 1. Just as for LL, LF, FL and IL, there are two peptide molecules in the asymmetric unit, but unlike the other four peptide structures the two molecules appear completely different. Molecule B has the typical `nanotube conformation', with θ (C2B—C1B···C10B—C11B) −0.65 (19)° and C9B—N2B—C10B—C15B 52.3 (2)°, while molecule A has a more elongated conformation, with θ (C2A—C1A···C10A—C11A) −95.83 (17)° and C9A—N2A—C10A—C15A −83.2 (2)°, which is stabilized by a weak intramolecular C4A—H41A···O2A hydrogen bond between the phenyl ring and the carboxylate group (Table 2). The resulting structure (Fig. 2) is divided into wave-shaped hydrophobic and hydrophilic layers, but nevertheless incorporates obvious water-filled channels, although these are significantly reduced in size (to 1.8 × 4.0 Å) compared with the FF-class. The channels have partly hydrophilic and partly hydrophobic inner surfaces.

The L-Phe side chain in FI is in a gauche+ orientation for molecule A and a trans orientation for molecule B. Both Ile side chains have the common gauche-/trans,gauche- conformation (for N2—C10—C11—C13/C12 and C10—C11—C13—C14), but twisted about 30° away from the ideal staggered orientation at C10—C11 for molecule B, to relieve what would have been a very close contact with the neighbouring molecule B along the b axis, to which it is related by the twofold screw (Fig. 2). The resulting intermolecular C14B—H20B···C8B(1 − x, y − 1/2, −z) interaction has a normal 2.97 Å H···C distance. The twist also leads to additional intra- and intermolecular contacts (H···C ≥ 3.01 Å) involving the peptide B molecules.

Hydrogen bonds with O acceptors are listed in Table 2, including three with C(π)-H donors (one intramolecular, see above). There are several similarities with the set of interactions found in the structures of the FF-class, and in particular with LL, LF (Görbitz, 2001) and IL (Görbitz, 2004b), including the presence of a hydrogen bond between the two water molecules in the asymmetric unit, with atom O2W as the donor. The only major difference concerns the second H atom of O2W, which is donated to a carboxylate group in the three FF-class structures. In the FI structure, access to the corresponding carboxylate group (of molecule B) is blocked by the amino group of molecule A (2 in Fig. 2), and the pertinent H22W atom (3 in Fig. 2) is instead pointing in the opposite direction, where it is accepted by the aromatic ring of the molecule A L-Phe side chain.

An L-leucine residue in a dipeptide can often be interchanged with an L-phenylalanine residue without major modifications to the crystal structure. An equivalent observation has been made for L-valine and L-isoleucine residues (Görbitz, 2004c). The FI structure, however, is not related to either L-leucyl-L-isoleucine (Görbitz, 2004c) or L-phenylalanyl-L-valine (Görbitz, 2000).

S2. Experimental

The title compound was obtained from Bachem. Crystals were grown by fast evaporation of an aqueous solution at elevated temperature (333 K), the same technique used for crystallizing compounds in the FF-class (Görbitz, 2001, 2004b).

S3. Refinement

Heavy atoms other than the low-occupancy water atoms O3W and O4W were refined anisotropically. Positional parameters were refined for H atoms involved in short hydrogen bonds (H···O < 2.50 Å), with water-molecule geometries being constrained by DFIX 0.85 0.01 commands for the O—H distances and DFIX 1.35 0.01 commands for the H···H distances (giving H—O—H angles close to 105°). H atoms bonded to O3W and O4W were introduced in positions giving the best possible hydrogen-bonding geometry (with O—H = 0.85 Å) and refined as riding. The remaining H atoms were positioned geometrically and refined with constraints to keep all C—H distances and C—C—H angles on one C atom the same. U_iso(H) values were 1.2U_eq of the carrier atom, or 1.5U_eq for amino and methyl groups and water molecules. In the absence of significant anomalous scattering effects, 1585 Friedel pairs were merged. The absolute configuration was known for the purchased material.

Computing details

Data collection: SMART (Bruker, 1998); cell refinement: SAINT-Plus (Bruker, 2001); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXTL (Bruker, 2000); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures

Fig. 1. The molecular structure of FI, showing the atom-numbering scheme. Displacement ellipsoids are shown at the 50% probability level and H atoms are shown as small spheres of arbitrary size. The drawing styles used for the water molecules reflect their occupancies: 0.709 (4) for W1 and W2, 0.291 (4) for W3, and 0.054 (4) for W4.

Fig. 2. The molecular packing and unit cell of FI, viewed along the a axis. Water molecules with low occupancy have been omitted. Peptide molecule B is shown in a darker tone. Hydrogen bonds (Table 2) are shown as black dashed lines. C—H···C contacts with H···C distances of less than 3.2 Å and C—H···C angles greater than 120° are indicated by grey dashed lines. The line drawing shows the Ile side-chain in a forced perfectly staggered orientation. Two of the very short C—H···C contacts (2.39 and 2.48 Å) are shown as black dotted lines. For a description of 1 (H20B), 2 and 3, see text.

L-Phenyl-L-isoleucine

Crystal data

C15H22N2O3·0.88H2O	F(000) = 635
Mr = 294.24	Dx = 1.243 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 5.5634 (3) Å	Cell parameters from 6894 reflections
b = 17.0558 (9) Å	θ = 1.7–27.1°
c = 16.6859 (9) Å	µ = 0.09 mm^−1
β = 96.744 (1)°	T = 105 K
V = 1572.34 (15) Å^3	Needle, colourless
Z = 4	0.75 × 0.15 × 0.12 mm

Data collection

Siemens SMART CCD area-detector diffractometer	3570 independent reflections
Radiation source: fine-focus sealed tube	3378 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.025
Detector resolution: 8.3 pixels mm^-1	θmax = 27.1°, θmin = 1.7°
Sets of exposures each taken over 0.3° ω rotation scans	h = −7→7
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	k = −13→21
Tmin = 0.899, Tmax = 0.989	l = −21→20
10060 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)] = 0.029	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.077	H atoms treated by a mixture of independent and constrained refinement
S = 1.00	w = 1/[σ^2(Fo^2) + (0.0431P)^2 + 0.3167P] where P = (Fo^2 + 2Fc^2)/3
3570 reflections	(Δ/σ)max < 0.001
434 parameters	Δρmax = 0.27 e Å^−3
8 restraints	Δρmin = −0.17 e Å^−3

Special details

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. Data were collected by measuring three sets of exposures with the detector set at 2θ = 29°, crystal-to-detector distance 5.00 cm. 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	0.1472 (2)	0.67637 (11)	0.48728 (8)	0.0344 (4)
O2A	0.1077 (2)	0.49230 (8)	0.34428 (8)	0.0237 (3)
O3A	−0.2329 (2)	0.56164 (9)	0.32458 (8)	0.0263 (3)
N1A	0.5293 (3)	0.70646 (11)	0.59045 (10)	0.0229 (3)
H1A	0.519 (5)	0.7546 (18)	0.5770 (16)	0.034*
H2A	0.385 (5)	0.6950 (16)	0.6051 (16)	0.034*
H3A	0.645 (5)	0.7002 (16)	0.6336 (16)	0.034*
N2A	0.3542 (3)	0.63444 (9)	0.38674 (9)	0.0193 (3)
H4A	0.495 (4)	0.6188 (14)	0.3709 (13)	0.023*
C1A	0.5770 (3)	0.65925 (12)	0.51901 (11)	0.0225 (4)
H11A	0.708 (4)	0.6867 (15)	0.4915 (14)	0.027*
C2A	0.6744 (4)	0.57726 (13)	0.54422 (12)	0.0268 (4)
H21A	0.6999	0.5473	0.4951	0.032*
H22A	0.8336	0.5831	0.5770	0.032*
C3A	0.5093 (4)	0.53088 (12)	0.59195 (12)	0.0245 (4)
C4A	0.3186 (4)	0.48692 (15)	0.55405 (14)	0.0381 (5)
H41A	0.2934	0.4846	0.4968	0.046*
C5A	0.1642 (5)	0.44627 (17)	0.59918 (17)	0.0482 (6)
H51A	0.0358	0.4159	0.5725	0.058*
C6A	0.1958 (5)	0.44969 (15)	0.68200 (16)	0.0426 (6)
H61A	0.0900	0.4217	0.7125	0.051*
C7A	0.3818 (5)	0.49398 (14)	0.72061 (13)	0.0399 (5)
H71A	0.4022	0.4974	0.7778	0.048*
C8A	0.5394 (4)	0.53355 (13)	0.67624 (12)	0.0329 (5)
H81A	0.6694	0.5628	0.7035	0.040*
C9A	0.3382 (3)	0.65728 (12)	0.46259 (11)	0.0213 (4)
C10A	0.1391 (3)	0.63225 (11)	0.32760 (10)	0.0189 (3)
H10A	0.0327	0.6772	0.3388	0.023*
C11A	0.2158 (3)	0.64347 (11)	0.24208 (10)	0.0217 (4)
H12A	0.3307	0.6001	0.2333	0.026*
C12A	−0.0005 (4)	0.63564 (15)	0.17682 (12)	0.0325 (5)
H13A	0.0538	0.6433	0.1236	0.049*
H14A	−0.1221	0.6753	0.1855	0.049*
H15A	−0.0714	0.5833	0.1796	0.049*
C13A	0.3534 (4)	0.72115 (12)	0.23516 (12)	0.0290 (4)
H16A	0.5106	0.7176	0.2695	0.035*
H17A	0.3881	0.7273	0.1787	0.035*
C14A	0.2213 (5)	0.79449 (14)	0.25922 (16)	0.0400 (5)
H18A	0.3106	0.8413	0.2457	0.060*
H19A	0.2106	0.7935	0.3174	0.060*
H20A	0.0579	0.7957	0.2300	0.060*
C15A	−0.0061 (3)	0.55595 (11)	0.33324 (10)	0.0191 (3)
O1B	0.8668 (2)	0.36151 (8)	0.19460 (8)	0.0229 (3)
O2B	0.8959 (2)	0.22315 (9)	0.33220 (8)	0.0267 (3)
O3B	1.1946 (2)	0.19973 (8)	0.25828 (8)	0.0233 (3)
N1B	0.4997 (3)	0.42731 (10)	0.29077 (10)	0.0215 (3)
H1B	0.552 (5)	0.3933 (17)	0.3265 (16)	0.032*
H2B	0.617 (5)	0.4630 (17)	0.2965 (15)	0.032*
H3B	0.366 (5)	0.4522 (16)	0.3031 (15)	0.032*
N2B	0.6018 (3)	0.25980 (9)	0.19158 (9)	0.0191 (3)
H4B	0.464 (4)	0.2467 (14)	0.2049 (13)	0.023*
C1B	0.4502 (3)	0.39037 (11)	0.20891 (11)	0.0191 (3)
H11B	0.301 (4)	0.3593 (14)	0.2078 (13)	0.023*
C2B	0.4232 (4)	0.45568 (11)	0.14551 (11)	0.0229 (4)
H21B	0.2781	0.4873	0.1529	0.027*
H22B	0.5658	0.4907	0.1542	0.027*
C3B	0.4000 (3)	0.42496 (11)	0.05993 (11)	0.0213 (4)
C4B	0.2025 (3)	0.37977 (11)	0.02937 (11)	0.0239 (4)
H41B	0.0805	0.3676	0.0627	0.029*
C5B	0.1816 (4)	0.35209 (13)	−0.04984 (12)	0.0277 (4)
H51B	0.0459	0.3212	−0.0702	0.033*
C6B	0.3595 (4)	0.36977 (12)	−0.09887 (12)	0.0290 (4)
H61B	0.3458	0.3508	−0.1527	0.035*
C7B	0.5565 (4)	0.41501 (13)	−0.06920 (12)	0.0294 (4)
H71B	0.6773	0.4276	−0.1029	0.035*
C8B	0.5775 (4)	0.44214 (12)	0.00999 (12)	0.0257 (4)
H81B	0.7141	0.4727	0.0303	0.031*
C9B	0.6624 (3)	0.33557 (11)	0.19751 (10)	0.0177 (3)
C10B	0.7828 (3)	0.19743 (10)	0.19162 (11)	0.0187 (3)
H10B	0.6965	0.1473	0.2005	0.022*
C11B	0.8952 (3)	0.18705 (11)	0.11129 (11)	0.0224 (4)
H12B	1.0448	0.2200	0.1153	0.027*
C12B	0.9752 (4)	0.10118 (12)	0.10482 (13)	0.0298 (4)
H13B	1.0444	0.0936	0.0540	0.045*
H14B	0.8350	0.0666	0.1061	0.045*
H15B	1.0973	0.0887	0.1503	0.045*
C13B	0.7320 (4)	0.21370 (13)	0.03549 (11)	0.0281 (4)
H16B	0.6846	0.2689	0.0430	0.034*
H17B	0.8271	0.2120	−0.0110	0.034*
C14B	0.5037 (4)	0.16519 (16)	0.01515 (15)	0.0401 (5)
H18B	0.4052	0.1883	−0.0315	0.060*
H19B	0.4108	0.1646	0.0615	0.060*
H20B	0.5480	0.1114	0.0023	0.060*
C15B	0.9752 (3)	0.20827 (10)	0.26656 (10)	0.0184 (3)
O1W	0.0678 (6)	0.34683 (16)	0.42164 (15)	0.0502 (8)	0.709 (4)
H11W	0.013 (9)	0.3108 (18)	0.389 (2)	0.075*	0.709 (4)
H12W	0.060 (10)	0.3885 (15)	0.394 (2)	0.075*	0.709 (4)
O2W	0.6045 (5)	0.35782 (14)	0.45431 (13)	0.0390 (7)	0.709 (4)
H21W	0.757 (2)	0.364 (3)	0.457 (2)	0.058*	0.709 (4)
H22W	0.561 (6)	0.386 (2)	0.492 (2)	0.058*	0.709 (4)
O3W	−0.1496 (9)	0.3674 (3)	0.4048 (3)	0.0292 (14)*	0.291 (4)
H31W	−0.1526	0.3246	0.3787	0.044*	0.291 (4)
H32W	−0.0559	0.3970	0.3818	0.044*	0.291 (4)
O4W	0.563 (6)	0.328 (2)	0.516 (2)	0.044*	0.054 (4)
H41W	0.6547	0.3404	0.4806	0.044*	0.054 (4)
H42W	0.4949	0.3703	0.5300	0.044*	0.054 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1A	0.0169 (6)	0.0644 (11)	0.0215 (7)	0.0029 (7)	0.0004 (5)	−0.0096 (7)
O2A	0.0210 (6)	0.0230 (6)	0.0273 (7)	0.0010 (5)	0.0042 (5)	0.0007 (6)
O3A	0.0167 (6)	0.0319 (7)	0.0299 (7)	0.0007 (5)	0.0012 (5)	−0.0077 (6)
N1A	0.0180 (8)	0.0323 (9)	0.0177 (7)	−0.0016 (7)	−0.0013 (6)	−0.0011 (7)
N2A	0.0146 (7)	0.0246 (8)	0.0182 (7)	0.0016 (6)	0.0005 (6)	−0.0031 (6)
C1A	0.0168 (8)	0.0327 (10)	0.0178 (8)	−0.0013 (7)	0.0006 (7)	−0.0018 (7)
C2A	0.0173 (9)	0.0359 (11)	0.0260 (10)	0.0044 (8)	−0.0016 (7)	−0.0022 (8)
C3A	0.0246 (9)	0.0253 (9)	0.0230 (9)	0.0042 (7)	0.0004 (7)	−0.0021 (7)
C4A	0.0385 (12)	0.0438 (13)	0.0306 (11)	−0.0096 (10)	−0.0020 (9)	−0.0049 (10)
C5A	0.0427 (14)	0.0465 (15)	0.0530 (16)	−0.0165 (12)	−0.0039 (12)	0.0038 (12)
C6A	0.0433 (13)	0.0354 (12)	0.0506 (14)	−0.0002 (10)	0.0115 (11)	0.0157 (11)
C7A	0.0660 (16)	0.0274 (10)	0.0273 (10)	0.0012 (11)	0.0099 (10)	0.0054 (9)
C8A	0.0477 (13)	0.0263 (10)	0.0228 (10)	−0.0050 (9)	−0.0040 (9)	−0.0005 (8)
C9A	0.0165 (8)	0.0281 (10)	0.0188 (8)	−0.0008 (7)	0.0003 (6)	−0.0009 (7)
C10A	0.0168 (8)	0.0215 (9)	0.0178 (8)	0.0034 (7)	−0.0009 (6)	−0.0024 (7)
C11A	0.0250 (9)	0.0225 (9)	0.0174 (8)	0.0019 (7)	0.0015 (7)	−0.0004 (7)
C12A	0.0342 (11)	0.0439 (13)	0.0181 (9)	−0.0005 (9)	−0.0024 (8)	0.0014 (8)
C13A	0.0333 (11)	0.0265 (10)	0.0278 (10)	0.0002 (8)	0.0067 (8)	0.0030 (8)
C14A	0.0520 (15)	0.0237 (11)	0.0455 (13)	0.0027 (10)	0.0101 (11)	0.0021 (9)
C15A	0.0191 (8)	0.0252 (9)	0.0130 (8)	−0.0004 (7)	0.0026 (6)	−0.0033 (7)
O1B	0.0160 (6)	0.0219 (6)	0.0309 (7)	−0.0006 (5)	0.0029 (5)	−0.0012 (5)
O2B	0.0273 (7)	0.0338 (8)	0.0195 (6)	−0.0044 (6)	0.0042 (5)	−0.0021 (6)
O3B	0.0159 (6)	0.0297 (7)	0.0236 (6)	0.0018 (5)	−0.0004 (5)	0.0033 (5)
N1B	0.0196 (8)	0.0246 (8)	0.0199 (8)	0.0030 (7)	0.0004 (6)	−0.0032 (6)
N2B	0.0137 (7)	0.0198 (7)	0.0233 (7)	0.0015 (6)	0.0006 (6)	0.0003 (6)
C1B	0.0157 (8)	0.0203 (8)	0.0212 (8)	0.0009 (6)	0.0010 (6)	−0.0036 (7)
C2B	0.0239 (9)	0.0195 (9)	0.0241 (9)	0.0035 (7)	−0.0021 (7)	−0.0011 (7)
C3B	0.0218 (9)	0.0187 (8)	0.0223 (9)	0.0051 (7)	−0.0023 (7)	0.0011 (7)
C4B	0.0217 (9)	0.0256 (10)	0.0244 (9)	0.0008 (7)	0.0020 (7)	0.0014 (7)
C5B	0.0270 (10)	0.0284 (10)	0.0260 (9)	−0.0008 (8)	−0.0036 (7)	−0.0009 (8)
C6B	0.0351 (11)	0.0312 (11)	0.0202 (8)	0.0058 (9)	0.0013 (8)	0.0004 (8)
C7B	0.0254 (10)	0.0361 (11)	0.0276 (10)	0.0041 (8)	0.0063 (8)	0.0073 (8)
C8B	0.0221 (9)	0.0246 (10)	0.0293 (10)	−0.0001 (7)	−0.0016 (8)	0.0046 (8)
C9B	0.0154 (8)	0.0204 (8)	0.0166 (8)	0.0026 (6)	−0.0016 (6)	−0.0009 (6)
C10B	0.0154 (8)	0.0169 (8)	0.0231 (9)	0.0014 (6)	−0.0001 (6)	0.0005 (6)
C11B	0.0244 (9)	0.0218 (9)	0.0202 (9)	0.0015 (7)	0.0001 (7)	−0.0035 (7)
C12B	0.0305 (11)	0.0256 (10)	0.0333 (11)	0.0055 (8)	0.0039 (8)	−0.0062 (8)
C13B	0.0327 (10)	0.0300 (10)	0.0211 (9)	0.0017 (8)	0.0010 (8)	−0.0016 (8)
C14B	0.0375 (12)	0.0395 (13)	0.0402 (13)	−0.0025 (10)	−0.0084 (10)	−0.0061 (10)
C15B	0.0197 (8)	0.0156 (8)	0.0195 (8)	−0.0013 (6)	−0.0003 (6)	0.0040 (6)
O1W	0.079 (2)	0.0310 (13)	0.0356 (13)	−0.0189 (13)	−0.0143 (12)	0.0026 (10)
O2W	0.0631 (16)	0.0278 (12)	0.0256 (11)	0.0059 (11)	0.0032 (10)	−0.0036 (9)

Geometric parameters (Å, º)

O1A—C9A	1.228 (2)	N1B—H2B	0.89 (3)
O2A—C15A	1.259 (2)	N1B—H3B	0.90 (3)
O3A—C15A	1.257 (2)	N2B—C9B	1.336 (2)
N1A—C1A	1.488 (2)	N2B—C10B	1.465 (2)
N1A—H1A	0.85 (3)	N2B—H4B	0.85 (2)
N1A—H2A	0.89 (3)	C1B—C2B	1.531 (3)
N1A—H3A	0.91 (3)	C1B—C9B	1.535 (2)
N2A—C9A	1.337 (2)	C1B—H11B	0.98 (2)
N2A—C10A	1.460 (2)	C2B—C3B	1.512 (3)
N2A—H4A	0.90 (2)	C2B—H21B	0.9900
C1A—C9A	1.536 (3)	C2B—H22B	0.9900
C1A—C2A	1.540 (3)	C3B—C4B	1.389 (3)
C1A—H11A	1.02 (2)	C3B—C8B	1.396 (3)
C2A—C3A	1.509 (3)	C4B—C5B	1.395 (3)
C2A—H21A	0.9900	C4B—H41B	0.9500
C2A—H22A	0.9900	C5B—C6B	1.389 (3)
C3A—C4A	1.389 (3)	C5B—H51B	0.9500
C3A—C8A	1.397 (3)	C6B—C7B	1.383 (3)
C4A—C5A	1.392 (4)	C6B—H61B	0.9500
C4A—H41A	0.9500	C7B—C8B	1.392 (3)
C5A—C6A	1.374 (4)	C7B—H71B	0.9500
C5A—H51A	0.9500	C8B—H81B	0.9500
C6A—C7A	1.379 (4)	C10B—C11B	1.554 (3)
C6A—H61A	0.9500	C10B—C15B	1.559 (2)
C7A—C8A	1.387 (3)	C10B—H10B	1.0000
C7A—H71A	0.9500	C11B—C13B	1.537 (3)
C8A—H81A	0.9500	C11B—C12B	1.538 (3)
C10A—C15A	1.540 (3)	C11B—H12B	1.0000
C10A—C11A	1.548 (2)	C12B—H13B	0.9800
C10A—H10A	1.0000	C12B—H14B	0.9800
C11A—C12A	1.531 (3)	C12B—H15B	0.9800
C11A—C13A	1.541 (3)	C13B—C14B	1.520 (3)
C11A—H12A	1.0000	C13B—H16B	0.9900
C12A—H13A	0.9800	C13B—H17B	0.9900
C12A—H14A	0.9800	C14B—H18B	0.9800
C12A—H15A	0.9800	C14B—H19B	0.9800
C13A—C14A	1.528 (3)	C14B—H20B	0.9800
C13A—H16A	0.9900	O1W—H11W	0.849 (10)
C13A—H17A	0.9900	O1W—H12W	0.848 (10)
C14A—H18A	0.9800	O2W—H21W	0.852 (10)
C14A—H19A	0.9800	O2W—H22W	0.847 (10)
C14A—H20A	0.9800	O2W—H41W	0.5746
O1B—C9B	1.227 (2)	O3W—H31W	0.8493
O2B—C15B	1.254 (2)	O3W—H32W	0.8489
O3B—C15B	1.253 (2)	O4W—H41W	0.8495
N1B—C1B	1.500 (2)	O4W—H42W	0.8624
N1B—H1B	0.86 (3)
C1A—N1A—H1A	108.9 (18)	H1B—N1B—H2B	102 (2)
C1A—N1A—H2A	110.7 (18)	C1B—N1B—H3B	109.7 (16)
H1A—N1A—H2A	104 (3)	H1B—N1B—H3B	112 (2)
C1A—N1A—H3A	113.0 (17)	H2B—N1B—H3B	106 (2)
H1A—N1A—H3A	110 (3)	C9B—N2B—C10B	122.33 (15)
H2A—N1A—H3A	109 (2)	C9B—N2B—H4B	117.5 (16)
C9A—N2A—C10A	120.45 (15)	C10B—N2B—H4B	116.6 (16)
C9A—N2A—H4A	121.6 (14)	N1B—C1B—C2B	108.43 (15)
C10A—N2A—H4A	117.9 (14)	N1B—C1B—C9B	107.86 (14)
N1A—C1A—C9A	106.27 (15)	C2B—C1B—C9B	111.82 (15)
N1A—C1A—C2A	111.26 (16)	N1B—C1B—H11B	108.0 (13)
C9A—C1A—C2A	113.50 (16)	C2B—C1B—H11B	111.5 (14)
N1A—C1A—H11A	108.4 (14)	C9B—C1B—H11B	109.2 (14)
C9A—C1A—H11A	110.4 (13)	C3B—C2B—C1B	113.01 (15)
C2A—C1A—H11A	107.0 (14)	C3B—C2B—H21B	109.0
C3A—C2A—C1A	113.81 (16)	C1B—C2B—H21B	109.0
C3A—C2A—H21A	108.8	C3B—C2B—H22B	109.0
C1A—C2A—H21A	108.8	C1B—C2B—H22B	109.0
C3A—C2A—H22A	108.8	H21B—C2B—H22B	107.8
C1A—C2A—H22A	108.8	C4B—C3B—C8B	118.81 (17)
H21A—C2A—H22A	107.7	C4B—C3B—C2B	120.98 (17)
C4A—C3A—C8A	118.1 (2)	C8B—C3B—C2B	120.22 (17)
C4A—C3A—C2A	121.49 (18)	C3B—C4B—C5B	120.65 (18)
C8A—C3A—C2A	120.38 (19)	C3B—C4B—H41B	119.7
C3A—C4A—C5A	120.6 (2)	C5B—C4B—H41B	119.7
C3A—C4A—H41A	119.7	C6B—C5B—C4B	119.90 (19)
C5A—C4A—H41A	119.7	C6B—C5B—H51B	120.1
C6A—C5A—C4A	120.6 (2)	C4B—C5B—H51B	120.1
C6A—C5A—H51A	119.7	C7B—C6B—C5B	119.97 (18)
C4A—C5A—H51A	119.7	C7B—C6B—H61B	120.0
C5A—C6A—C7A	119.6 (2)	C5B—C6B—H61B	120.0
C5A—C6A—H61A	120.2	C6B—C7B—C8B	119.99 (19)
C7A—C6A—H61A	120.2	C6B—C7B—H71B	120.0
C6A—C7A—C8A	120.3 (2)	C8B—C7B—H71B	120.0
C6A—C7A—H71A	119.9	C7B—C8B—C3B	120.69 (18)
C8A—C7A—H71A	119.9	C7B—C8B—H81B	119.7
C7A—C8A—C3A	120.8 (2)	C3B—C8B—H81B	119.7
C7A—C8A—H81A	119.6	O1B—C9B—N2B	124.96 (17)
C3A—C8A—H81A	119.6	O1B—C9B—C1B	121.03 (16)
O1A—C9A—N2A	123.46 (17)	N2B—C9B—C1B	114.00 (15)
O1A—C9A—C1A	120.59 (16)	N2B—C10B—C11B	115.37 (14)
N2A—C9A—C1A	115.94 (16)	N2B—C10B—C15B	108.76 (14)
N2A—C10A—C15A	112.00 (15)	C11B—C10B—C15B	113.42 (14)
N2A—C10A—C11A	109.09 (14)	N2B—C10B—H10B	106.2
C15A—C10A—C11A	111.34 (14)	C11B—C10B—H10B	106.2
N2A—C10A—H10A	108.1	C15B—C10B—H10B	106.2
C15A—C10A—H10A	108.1	C13B—C11B—C12B	111.83 (16)
C11A—C10A—H10A	108.1	C13B—C11B—C10B	114.67 (15)
C12A—C11A—C13A	112.17 (16)	C12B—C11B—C10B	108.54 (16)
C12A—C11A—C10A	111.48 (16)	C13B—C11B—H12B	107.1
C13A—C11A—C10A	111.62 (15)	C12B—C11B—H12B	107.1
C12A—C11A—H12A	107.1	C10B—C11B—H12B	107.1
C13A—C11A—H12A	107.1	C11B—C12B—H13B	109.5
C10A—C11A—H12A	107.1	C11B—C12B—H14B	109.5
C11A—C12A—H13A	109.5	H13B—C12B—H14B	109.5
C11A—C12A—H14A	109.5	C11B—C12B—H15B	109.5
H13A—C12A—H14A	109.5	H13B—C12B—H15B	109.5
C11A—C12A—H15A	109.5	H14B—C12B—H15B	109.5
H13A—C12A—H15A	109.5	C14B—C13B—C11B	114.84 (18)
H14A—C12A—H15A	109.5	C14B—C13B—H16B	108.6
C14A—C13A—C11A	115.19 (17)	C11B—C13B—H16B	108.6
C14A—C13A—H16A	108.5	C14B—C13B—H17B	108.6
C11A—C13A—H16A	108.5	C11B—C13B—H17B	108.6
C14A—C13A—H17A	108.5	H16B—C13B—H17B	107.5
C11A—C13A—H17A	108.5	C13B—C14B—H18B	109.5
H16A—C13A—H17A	107.5	C13B—C14B—H19B	109.5
C13A—C14A—H18A	109.5	H18B—C14B—H19B	109.5
C13A—C14A—H19A	109.5	C13B—C14B—H20B	109.5
H18A—C14A—H19A	109.5	H18B—C14B—H20B	109.5
C13A—C14A—H20A	109.5	H19B—C14B—H20B	109.5
H18A—C14A—H20A	109.5	O3B—C15B—O2B	124.55 (16)
H19A—C14A—H20A	109.5	O3B—C15B—C10B	118.94 (15)
O3A—C15A—O2A	124.33 (17)	O2B—C15B—C10B	116.49 (15)
O3A—C15A—C10A	117.02 (16)	H11W—O1W—H12W	105.6 (17)
O2A—C15A—C10A	118.63 (15)	H21W—O2W—H22W	105.6 (17)
C1B—N1B—H1B	111.1 (18)	H31W—O3W—H32W	104.9
C1B—N1B—H2B	116.1 (17)	H41W—O4W—H42W	107.3
N1A—C1A—C9A—N2A	164.38 (17)	N1B—C1B—C9B—N2B	114.94 (17)
C1A—C9A—N2A—C10A	−178.54 (16)	C1B—C9B—N2B—C10B	−171.42 (15)
C9A—N2A—C10A—C15A	−83.2 (2)	C9B—N2B—C10B—C15B	52.3 (2)
N2A—C10A—C15A—O2A	−41.0 (2)	N2B—C10B—C15B—O2B	44.7 (2)
N1A—C1A—C2A—C3A	57.2 (2)	N1B—C1B—C2B—C3B	173.66 (15)
C1A—C2A—C3A—C4A	84.8 (2)	C1B—C2B—C3B—C4B	64.3 (2)
C1A—C2A—C3A—C8A	−92.7 (2)	C1B—C2B—C3B—C8B	−116.06 (19)
N2A—C10A—C11A—C12A	175.79 (16)	N2B—C10B—C11B—C12B	−152.49 (16)
N2A—C10A—C11A—C13A	−57.9 (2)	N2B—C10B—C11B—C13B	−26.6 (2)
C10A—C11A—C13A—C14A	−54.3 (2)	C10B—C11B—C13B—C14B	−66.3 (2)
C9A—C1A—C2A—C3A	−62.7 (2)	C9B—C1B—C2B—C3B	54.9 (2)
C8A—C3A—C4A—C5A	−0.6 (4)	C8B—C3B—C4B—C5B	−0.1 (3)
C2A—C3A—C4A—C5A	−178.2 (2)	C2B—C3B—C4B—C5B	179.56 (18)
C3A—C4A—C5A—C6A	0.8 (4)	C3B—C4B—C5B—C6B	0.0 (3)
C4A—C5A—C6A—C7A	0.2 (4)	C4B—C5B—C6B—C7B	−0.2 (3)
C5A—C6A—C7A—C8A	−1.3 (4)	C5B—C6B—C7B—C8B	0.6 (3)
C6A—C7A—C8A—C3A	1.6 (4)	C6B—C7B—C8B—C3B	−0.7 (3)
C4A—C3A—C8A—C7A	−0.6 (3)	C4B—C3B—C8B—C7B	0.5 (3)
C2A—C3A—C8A—C7A	177.0 (2)	C2B—C3B—C8B—C7B	−179.18 (18)
C10A—N2A—C9A—O1A	1.0 (3)	C10B—N2B—C9B—O1B	8.4 (3)
N1A—C1A—C9A—O1A	−15.2 (3)	N1B—C1B—C9B—O1B	−64.9 (2)
C2A—C1A—C9A—O1A	107.4 (2)	C2B—C1B—C9B—O1B	54.2 (2)
C2A—C1A—C9A—N2A	−73.0 (2)	C2B—C1B—C9B—N2B	−125.93 (17)
C9A—N2A—C10A—C11A	153.13 (16)	C9B—N2B—C10B—C11B	−76.5 (2)
C15A—C10A—C11A—C12A	51.7 (2)	C15B—C10B—C11B—C13B	−153.03 (16)
C15A—C10A—C11A—C13A	177.99 (15)	C15B—C10B—C11B—C12B	81.12 (19)
C12A—C11A—C13A—C14A	71.6 (2)	C12B—C11B—C13B—C14B	57.8 (2)
N2A—C10A—C15A—O3A	140.58 (16)	N2B—C10B—C15B—O3B	−137.13 (16)
C11A—C10A—C15A—O3A	−96.97 (18)	C11B—C10B—C15B—O3B	−7.3 (2)
C11A—C10A—C15A—O2A	81.47 (19)	C11B—C10B—C15B—O2B	174.52 (16)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1A—H1A···O2W^i	0.85 (3)	1.94 (3)	2.765 (3)	163 (3)
N1A—H2A···O2B^i	0.89 (2)	2.04 (3)	2.839 (2)	150 (2)
N1A—H3A···O3B^ii	0.91 (3)	1.92 (3)	2.799 (2)	162 (2)
N2A—H4A···O3A^iii	0.90 (2)	2.03 (3)	2.908 (2)	167 (2)
C1A—H11A···O1A^iii	1.02 (2)	2.46 (2)	3.290 (2)	138.3 (18)
C4A—H41A···O2A	0.95	2.64	3.560 (3)	165
C8A—H81A···O3B^ii	0.95	2.51	3.322 (3)	143
N1B—H1B···O2W	0.86 (3)	2.20 (3)	2.969 (3)	149 (2)
N1B—H2B···O3A^iii	0.89 (2)	1.91 (3)	2.754 (2)	157 (2)
N1B—H3B···O2A	0.90 (3)	1.80 (3)	2.691 (2)	170 (2)
N2B—H4B···O3B^iv	0.85 (2)	2.00 (3)	2.831 (2)	165 (2)
C1B—H11B···O1B^iv	0.98 (2)	2.40 (2)	3.263 (2)	146.2 (19)
C4B—H41B···O1B^iv	0.95	2.62	3.521 (2)	158
O1W—H11W···O2B^iv	0.85 (3)	1.85 (3)	2.694 (3)	172 (4)
O1W—H12W···O2A	0.85 (3)	1.98 (3)	2.818 (3)	167 (5)
O2W—H21W···O1W^iii	0.85 (3)	1.91 (3)	2.703 (4)	154 (3)
O2W—H22W···C4A	0.85 (3)	2.49 (3)	3.282 (4)	156 (4)

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