The achiral tetra­peptide Z-Aib-Aib-Aib-Gly-OtBu

The title achiral peptide N-benzyloxycarbonyl-α-aminoisobutyryl-α-aminoisobutyryl-α-aminoisobutyrylglycine tert-butyl ester or Z-Aib-Aib-Aib-Gly-OtBu (Aib is α-aminoisobutyric acid, Z is benzyloxycarbonyl, Gly is glycine and OtBu indicates the tert-butyl ester), C₂₆H₄₀N₄O₇, is partly hydrated (0.075H₂O) and has two different conformations which together constitute the asymmetric unit. Both mol­ecules form incipient 3₁₀-helices. They differ in the relative orientation of the N-terminal protection group and at the C-terminus. There are two 4→1 intra­molecular hydrogen bonds.

S1. Introduction

The sequence Aib-Aib-Aib-Gly represents a segment of the naturally occurring peptaibol anti­biotic peptides containing α-amino­isobutyric acid (Aib) and a C-terminal β-amino alcohol (Brückner & Graf, 1983; Benedetti et al., 1982). This sequence is found in several of the microheterogenous anti­amoebins and cephaibols, and also in sequences of alamethicin (Stoppacher et al., 2013; see also, for example, Bunkóczi et al., 2003). We present here the crystal structure of Z-Aib-Aib-Aib-Gly-OtBu.0.075H₂O, (I), containing this tetra­peptide, which was only recently crystallized.

S2. Experimental

S2.1. Synthesis and crystallization

For the synthesis of Z-Aib-Aib-Aib-Gly-OtBu, Z-Aib-Aib-Aib-OH was reacted with H-Gly-OtBu (Bachem, Bubendorf, Switzerland). Z-Aib-Aib-Aib-OH was synthesized from Z-Aib-Aib-Aib-OtBu by removal of the tert-butyl group by tri­fluoro­acetic acid in di­chloro­methane. Z-Aib-Aib-Aib-OtBu was synthesized via the oxazolone route as described previously (Gessmann et al., 2014). To Z-Aib-Aib-Aib-OH (1.25 g, 3.07 mmol) in N,N-di­methyl­formamide (30 ml), 1-hy­droxy­benzotriazole hydrate (0.83 g) and WSC.xHCl (WSC is water-soluble carbodi­imide; 0.59 g, 3.08 mmol) were added at room temperature. After 30 min, H-Gly-OtBu.xHCl (0.52 g, 3.10 mmol) and N-methyl­morpholine (0.35 ml, 3.18 mmol) were added and the mixture was kept at room temperature for 16 h. The solvent was removed in vacuo and ethyl acetate (300 ml) was added to the oily residue. The organic phase was washed successively with 5% KHCO₃, 5% KHSO₄ and water (300 ml each) until neutral. The organic phase was dried overnight over anhydrous Na₂SO₄ and the organic phase removed in vacuo. The remaining residue was dissolved in a small amount of methanol and the peptide precipitated by addition of di­ethyl ether and n-hexane [Qu­anti­ties/Ratio?]. The yield after drying was 1.24 g (77.60%) and the melting point was 479 K. ESI–MS: m/z 559 [M + K]⁺, 543 [M + Na]⁺. Single spot by analysis using thin-layer chromatography: R_F = 0.75; solvent system = chloro­form/methanol/acetic acid/water (65:25:3:4 v/v/v/v). The tetra­peptide was crystallized from 50% aqueous methanol.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms could be detected in a difference Fourier map and each of their four parameters was freely refined. A prominent sharp density peak remained, close to the carbonyl O atom of residue Aib13. This could be inter­preted as an H atom, bonded at a distance of 1.02 Å and a C—O—H angle of 97°. This density remained unexplained in the last cycles of refinement. In the void between the molecules at and close to one of the eight symmetry centres of the unit cell, three water molecules with small occupancy factors [Numerical values? Was SQUEEZE used?] were refined isotropically. These water molecules cannot co-exist in the same unit cell.

S3. Results and discussion

The achiral peptide (I) crystallizes with two molecules in the asymmetric unit. Both molecules form incipient 3₁₀-helices. They differ in the relative orientation of the N-terminal protection group and at the C-terminus, where one conformation reverses the sense of the helix in the last residue (molecule B), while the other conformation (molecule A) is semi-extended (Fig. 1 and Table 2). The conformations forming incipient right-handed 3₁₀-helices were chosen as the asymmetric unit for molecules A and B.

Both molecules are stabilized by two 4→ 1 hydrogen bonds (Table 3). All residues, including the N-terminal protecting groups, are involved in the intra­molecular hydrogen-bonding pattern of the peptide. The peptide adopts the usual trans planar conformation with significant deviations from planarity (ω = 180°; Table 2). The r.m.s. deviation (Kabsch, 1976) between the two molecules from the C═O group of the Z-protection group to the O atom of OtBu is 0.77 Å, and the superposition is shown in Fig. 2.

The valence geometry around the C^α atom is asymmetric for the Aib residues (Table 4). If one designates as CL and CR the atoms which occupy the same positions as C^β and the α-hydrogen in L-amino acids, respectively, the bond angles N—C^α—CL and C—C^α—CL are significantly smaller than N—C^α—CR and C—C^α—CR. This observation is in excellent agreement with theoretical calculations and with the bond angles of other right-handed 3₁₀-helical Aib-peptides (Gessmann et al., 2003). The opposite asymmetry is found for the last residue in molecule B and for the left-handed helices. In the crystal structure, right-handed molecules A are hydrogen-bonded at the N-terminus (NH of Aib1 and Aib2) to left-handed molecules B at their C-terminus (C═O of Aib2 and Aib3), building infinitely long helical columns of alternating handedness in the [111] direction. The opposite-handed molecules, viz. left-handed molecules A and right-handed molecules B, build infinitely long helical colums of alternating handedness along the [111] direction (Fig. 3). Looking down the helical axes, the rings of the Z-protection group of both hydrogen-bonded molecules are on the same side of the helices (orange/blue and red/light blue in Fig. 4), and the two C-terminal OtBu groups protrude in different directions due to the different C-terminal conformations of molecules A and B. The only polar group not involved in hydrogen bonding is the carboxyl group of Gly 4.

The structures of the related peptides Z-Aib-Aib-Aib-L-Val-OtBu, with two molecules in the asymmetric unit, and Z-Aib-Aib-Aib-L-Ala-OtBu were solved previously (Gessmann et al., 1997, 2014). Like the two left-handed helices of the title compound, these three other molecules also fold in incipient 3₁₀-helices and, as in molecules A and B of (I), one molecule of Z-(Aib)_3-L-Val-OtBu also adopts a semi-extended conformation in the fourth residue and the other reverses the sense of the helix. The molecule of Z-(Aib)_3-L-Ala-OtBu adopts only the latter conformation. The superpositions of all five molecules are shown in Fig. 2, and the variation in conformation is seen even in the overall folding, i.e. two times semi-extended or three times reversal of the helical sense in the last residue.

Related literature

For related literature, see: Benedetti et al. (1982); Brückner & Graf (1983); Bunkóczi et al. (2003); Gessmann et al. (1997, 2003, 2014); Kabsch (1976); Stoppacher et al. (2013).

Computing details

Data collection: PROTEUM2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS86 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2008); molecular graphics: XTALVIEW (McRee, 1999) and SwissPDBViewer (Guex & Peitsch, 1997); software used to prepare material for publication: CHEMDRAW (Mills, 2006), ORTEPIII (Burnett & Johnson, 1996), ORTEP-3 for Windows (Farrugia, 2012) and POVRAY (Cason, 2004).

Figures

	Fig. 1. The molecular structure of Z-Aib-Aib-Aib-Gly-OtBu, with the residue-numbering scheme. Displacement ellipsoids are drawn at the 40% probability level. (a) Molecule A and (b) molecule B, both shown in approximately the same orientation. The two intramolecular hydrogen bonds are shown as green dashed lines.
	Fig. 2. A least-squares superposition of the two left-handed helices, with molecule A shown in red and molecule B shown in blue. Thin lines represent the superpositions on molecule A from the crystal structure of Z-(Aib)3-L-Ala-OtBu (grey) and the two molecules of Z-(Aib)3-L-Val-OtBu (light and dark green).
	Fig. 3. The crystal packing of Z-Aib-Aib-Aib-Gly-OtBu, viewed approximately perpendicular to the helical columns. Intramolecular hydrogen bonds are shown as green dashed lines and intermolecular hydrogen bonds are shown as blue dashed lines. H atoms have been omitted for clarity. Some positions of the disordered water molecules are shown in turquoise.
	Fig. 4. A stereoview of the crystal packing of Z-Aib-Aib-Aib-Gly-OtBu, viewed down the helical columns. Here, the right-handed molecules A are shown in orange and the left-handed molecules A in red, while right- and left-handed molecules B are shown in light blue and dark blue, respectively.

tert-Butyl N-benzyloxycarbonyl-α-aminoisobutyryl-α-aminoisobutyryl-α-aminoisobutyrylglycine 0.075-hydrate

Crystal data

C26H40N4O7·0.075H2O	V = 2849.5 (3) Å^3
Mr = 521.82	Z = 4
Triclinic, P1	F(000) = 1122
a = 12.7399 (8) Å	Dx = 1.216 Mg m^−3
b = 15.6208 (9) Å	Cu Kα radiation, λ = 1.54178 Å
c = 21.5890 (13) Å	µ = 0.73 mm^−1
α = 121.6297 (16)°	T = 100 K
β = 97.8306 (19)°	Rod, colourless
γ = 116.7275 (17)°	0.4 × 0.15 × 0.15 mm

Data collection

Bruker D8 Venture diffractometer	8961 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube IµS	Rint = 0.046
ω and ϕ scans	θmax = 65.7°, θmin = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −14→14
Tmin = 0.873, Tmax = 1.0	k = −18→18
42295 measured reflections	l = −24→25
9534 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.038	All H-atom parameters refined
wR(F^2) = 0.099	w = 1/[σ^2(Fo^2) + (0.0372P)^2 + 1.616P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
9534 reflections	Δρmax = 0.43 e Å^−3
996 parameters	Δρmin = −0.24 e Å^−3
0 restraints

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 in the range θ = 2.8–65.7°, 42297 reflections in total, 9535 unique. All non-hydrogen peptide atoms were detected by direct methods with the program SHELXS as the highest 74 peaks. Anisotropic refinement was performed without any constraints or restraints.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.37440 (16)	0.76075 (14)	0.73981 (9)	0.0243 (3)
C2	0.44957 (16)	0.71823 (16)	0.72089 (10)	0.0269 (3)
H2	0.4046 (18)	0.6284 (18)	0.6813 (11)	0.031 (5)*
C3	0.58856 (17)	0.80509 (16)	0.76088 (10)	0.0292 (3)
H3	0.6398 (19)	0.7742 (18)	0.7456 (11)	0.036 (5)*
C4	0.65397 (18)	0.93493 (17)	0.82003 (11)	0.0328 (4)
H4	0.749 (2)	0.9921 (18)	0.8485 (12)	0.036 (5)*
C5	0.57976 (17)	0.97804 (16)	0.84043 (10)	0.0313 (4)
H5	0.6220 (19)	1.066 (2)	0.8825 (12)	0.039 (5)*
C6	0.44133 (17)	0.89186 (15)	0.80112 (9)	0.0265 (3)
H6	0.3899 (18)	0.9220 (17)	0.8166 (11)	0.033 (5)*
C7	0.22303 (17)	0.67194 (15)	0.69494 (11)	0.0286 (3)
H71	0.1912 (17)	0.6953 (16)	0.7364 (11)	0.027 (4)*
H72	0.1827 (18)	0.6706 (17)	0.6510 (11)	0.031 (4)*
O1	0.16286 (11)	0.53800 (10)	0.64553 (6)	0.0259 (2)
C8	0.17335 (14)	0.50354 (14)	0.69068 (9)	0.0205 (3)
O8	0.22402 (10)	0.57709 (9)	0.76625 (6)	0.0236 (2)
N_1	0.12279 (12)	0.38045 (12)	0.64154 (8)	0.0196 (3)
H_1	0.0895 (16)	0.3354 (16)	0.5909 (11)	0.019 (4)*
CA_1	0.11577 (14)	0.32182 (13)	0.67779 (8)	0.0191 (3)
CL_1	0.07968 (16)	0.19133 (14)	0.61041 (9)	0.0224 (3)
HL1_1	−0.0047 (18)	0.1400 (16)	0.5628 (11)	0.025 (4)*
HL2_1	0.1469 (18)	0.2008 (17)	0.5923 (11)	0.030 (4)*
HL3_1	0.0681 (17)	0.1469 (17)	0.6321 (11)	0.029 (4)*
CR_1	0.00993 (15)	0.30591 (16)	0.70581 (10)	0.0248 (3)
HR1_1	0.0317 (17)	0.3847 (18)	0.7459 (11)	0.027 (4)*
HR2_1	−0.0767 (17)	0.2537 (15)	0.6567 (10)	0.021 (4)*
HR3_1	0.0041 (18)	0.2624 (17)	0.7262 (11)	0.032 (5)*
C_1	0.25562 (14)	0.40585 (13)	0.75257 (8)	0.0178 (3)
O_1	0.26810 (10)	0.43094 (9)	0.81875 (6)	0.0220 (2)
N_2	0.36080 (12)	0.44727 (11)	0.73928 (8)	0.0176 (2)
H_2	0.3464 (17)	0.4252 (16)	0.6941 (11)	0.021 (4)*
CA_2	0.49934 (14)	0.51281 (13)	0.79695 (8)	0.0186 (3)
CR_2	0.50572 (17)	0.42875 (15)	0.81149 (11)	0.0260 (3)
HR1_2	0.450 (2)	0.4100 (18)	0.8355 (12)	0.041 (5)*
HR2_2	0.4759 (19)	0.3524 (19)	0.7587 (13)	0.037 (5)*
HR3_2	0.601 (2)	0.4731 (17)	0.8476 (12)	0.034 (5)*
CL_2	0.58566 (15)	0.53897 (16)	0.75716 (10)	0.0241 (3)
HL1_2	0.5794 (17)	0.5885 (16)	0.7464 (10)	0.025 (4)*
HL2_2	0.6766 (19)	0.5836 (16)	0.7943 (11)	0.027 (4)*
HL3_2	0.5520 (17)	0.4573 (18)	0.7043 (12)	0.030 (4)*
C_2	0.55926 (14)	0.64290 (13)	0.88145 (8)	0.0181 (3)
O_2	0.66411 (10)	0.69646 (10)	0.94047 (6)	0.0250 (2)
N_3	0.49688 (13)	0.69438 (11)	0.88735 (8)	0.0182 (2)
H_3	0.4281 (18)	0.6560 (16)	0.8488 (11)	0.021 (4)*
CA_3	0.54063 (14)	0.81309 (13)	0.96688 (8)	0.0186 (3)
CL_3	0.43199 (16)	0.82923 (15)	0.95370 (10)	0.0227 (3)
HL1_3	0.4596 (16)	0.9032 (17)	1.0044 (11)	0.022 (4)*
HL2_3	0.4254 (17)	0.8373 (16)	0.9127 (11)	0.030 (4)*
HL3_3	0.3480 (19)	0.7579 (18)	0.9359 (11)	0.027 (4)*
CR_3	0.67550 (16)	0.92917 (15)	0.99680 (10)	0.0246 (3)
HR1_3	0.6997 (17)	1.0028 (17)	1.0486 (11)	0.027 (4)*
HR2_3	0.7473 (18)	0.9218 (16)	1.0052 (10)	0.027 (4)*
HR3_3	0.6661 (17)	0.9354 (17)	0.9535 (11)	0.031 (4)*
C_3	0.54618 (14)	0.79925 (13)	1.03243 (8)	0.0186 (3)
O_3	0.62732 (10)	0.89237 (9)	1.10723 (6)	0.0228 (2)
N_4	0.45147 (13)	0.68289 (12)	1.00445 (8)	0.0222 (3)
H_4	0.3969 (17)	0.6259 (17)	0.9565 (11)	0.019 (4)*
CA_4	0.43094 (16)	0.66387 (15)	1.06135 (10)	0.0236 (3)
H1_4	0.3973 (17)	0.5794 (18)	1.0368 (11)	0.029 (4)*
H2_4	0.5169 (19)	0.7228 (17)	1.1128 (11)	0.029 (4)*
C_4	0.33372 (15)	0.68549 (14)	1.08640 (9)	0.0231 (3)
O_4	0.27362 (11)	0.70980 (11)	1.05923 (7)	0.0300 (2)
O_5	0.32775 (11)	0.67294 (11)	1.14265 (7)	0.0281 (2)
C1_5	0.24326 (16)	0.69136 (17)	1.18123 (10)	0.0293 (3)
C2_5	0.09702 (17)	0.59615 (18)	1.11425 (11)	0.0333 (4)
H21_5	0.0801 (19)	0.6164 (18)	1.0798 (12)	0.041 (5)*
H22_5	0.0425 (19)	0.6015 (18)	1.1424 (12)	0.038 (5)*
H23_5	0.072 (2)	0.510 (2)	1.0790 (13)	0.044 (5)*
C3_5	0.2966 (2)	0.82888 (19)	1.23214 (12)	0.0404 (4)
H31_5	0.394 (2)	0.887 (2)	1.2731 (14)	0.051 (6)*
H32_5	0.261 (2)	0.852 (2)	1.2703 (13)	0.050 (6)*
H33_5	0.282 (2)	0.850 (2)	1.1951 (14)	0.054 (6)*
C4_5	0.2644 (2)	0.6616 (2)	1.23626 (13)	0.0405 (5)
H41_5	0.360 (2)	0.7231 (19)	1.2781 (13)	0.042 (5)*
H42_5	0.215 (2)	0.6685 (19)	1.2627 (13)	0.045 (5)*
H34_5	0.228 (2)	0.569 (2)	1.2006 (13)	0.047 (6)*
C1_10	0.96080 (14)	0.78319 (14)	0.87412 (10)	0.0249 (3)
C2_10	1.02035 (17)	0.80128 (15)	0.94289 (10)	0.0303 (4)
H2_10	1.0253 (19)	0.8592 (19)	0.9940 (13)	0.041 (5)*
C3_10	1.07289 (17)	0.73807 (16)	0.93790 (12)	0.0353 (4)
H3_10	1.116 (2)	0.7518 (19)	0.9871 (13)	0.044 (5)*
C4_10	1.06337 (17)	0.65480 (16)	0.86377 (12)	0.0367 (4)
H4_10	1.104 (2)	0.611 (2)	0.8610 (13)	0.054 (6)*
C5_10	1.00280 (18)	0.63471 (17)	0.79481 (12)	0.0403 (4)
H5_10	0.991 (2)	0.571 (2)	0.7394 (14)	0.055 (6)*
C6_10	0.95229 (17)	0.69894 (17)	0.79960 (11)	0.0352 (4)
H6_10	0.9146 (18)	0.6923 (17)	0.7509 (11)	0.032 (5)*
C7_10	0.90485 (16)	0.85179 (15)	0.87957 (11)	0.0274 (3)
H71_10	0.8337 (18)	0.8049 (16)	0.8227 (11)	0.029 (4)*
H72_10	0.8699 (18)	0.8678 (17)	0.9210 (12)	0.036 (5)*
O1_10	1.01040 (10)	0.97876 (10)	0.91144 (6)	0.0254 (2)
C8_10	1.00323 (14)	0.99917 (13)	0.85800 (9)	0.0195 (3)
O8_10	0.91313 (10)	0.91947 (10)	0.78568 (6)	0.0253 (2)
N_11	1.10810 (12)	1.11906 (11)	0.89555 (8)	0.0195 (3)
H_11	1.1676 (18)	1.1671 (17)	0.9452 (12)	0.024 (4)*
CA_11	1.11041 (15)	1.17531 (14)	0.85830 (9)	0.0207 (3)
CR_11	0.99798 (18)	1.18768 (18)	0.85172 (11)	0.0289 (3)
HR1_11	0.9100 (19)	1.1048 (18)	0.8130 (11)	0.030 (5)*
HR2_11	1.0092 (18)	1.2328 (18)	0.8336 (11)	0.035 (5)*
HR3_11	1.0114 (18)	1.2423 (18)	0.9107 (12)	0.035 (5)*
CL_11	1.24773 (17)	1.30726 (14)	0.91446 (10)	0.0266 (3)
HL1_11	1.3179 (17)	1.3014 (15)	0.9217 (10)	0.021 (4)*
HL2_11	1.2527 (17)	1.3436 (17)	0.8907 (11)	0.031 (4)*
HL3_11	1.2538 (18)	1.3606 (18)	0.9695 (12)	0.037 (5)*
C_11	1.09578 (13)	1.09423 (13)	0.77109 (8)	0.0182 (3)
O_11	1.03308 (10)	1.08234 (9)	0.71474 (6)	0.0220 (2)
N_12	1.15663 (12)	1.04019 (11)	0.76125 (7)	0.0189 (2)
H_12	1.2028 (18)	1.0552 (17)	0.8031 (12)	0.030 (5)*
CA_12	1.15663 (14)	0.96437 (14)	0.68312 (9)	0.0205 (3)
CR_12	1.24237 (16)	1.04917 (16)	0.66732 (10)	0.0261 (3)
HR1_12	1.2403 (17)	1.0010 (16)	0.6165 (11)	0.026 (4)*
HR2_12	1.337 (2)	1.1139 (18)	0.7135 (12)	0.035 (5)*
HR3_12	1.2073 (19)	1.0915 (18)	0.6656 (11)	0.035 (5)*
CL_12	1.21467 (19)	0.90131 (17)	0.69105 (10)	0.0297 (4)
HL1_12	1.163 (2)	0.8491 (19)	0.7020 (12)	0.039 (5)*
HL2_12	1.2088 (17)	0.8463 (17)	0.6378 (11)	0.026 (4)*
HL3_12	1.308 (2)	0.967 (2)	0.7342 (13)	0.043 (5)*
C_12	1.01248 (15)	0.85484 (14)	0.60892 (9)	0.0212 (3)
O_12	0.99400 (11)	0.80684 (10)	0.53763 (6)	0.0277 (2)
N_13	0.91189 (12)	0.81112 (12)	0.62459 (8)	0.0224 (3)
H_13	0.9275 (18)	0.8493 (18)	0.6739 (13)	0.032 (5)*
CA_13	0.77062 (15)	0.70842 (14)	0.55788 (9)	0.0264 (3)
CR_13	0.68122 (17)	0.70197 (17)	0.59889 (10)	0.0306 (4)
HR1_13	0.6943 (19)	0.7822 (19)	0.6355 (12)	0.036 (5)*
HR2_13	0.6977 (18)	0.6740 (17)	0.6289 (12)	0.034 (5)*
HR3_13	0.584 (2)	0.6357 (18)	0.5554 (12)	0.034 (5)*
CL_13	0.74390 (19)	0.58062 (16)	0.50293 (11)	0.0336 (4)
HL1_13	0.648 (2)	0.512 (2)	0.4590 (13)	0.046 (5)*
HL2_13	0.802 (2)	0.5775 (19)	0.4759 (13)	0.047 (6)*
HL3_13	0.7719 (19)	0.5618 (18)	0.5361 (12)	0.040 (5)*
C_13	0.73352 (15)	0.74175 (15)	0.50704 (9)	0.0272 (3)
O_13	0.65293 (11)	0.65819 (11)	0.43164 (7)	0.0353 (3)
N_14	0.78349 (13)	0.86381 (13)	0.55089 (9)	0.0285 (3)
H_14	0.846 (2)	0.924 (2)	0.6056 (14)	0.042 (5)*
CA_14	0.73950 (17)	0.90270 (18)	0.51210 (11)	0.0328 (4)
H1_14	0.7545 (19)	0.8773 (18)	0.4645 (13)	0.041 (5)*
H2_14	0.792 (2)	1.003 (2)	0.5583 (14)	0.052 (6)*
C_14	0.59099 (16)	0.84216 (16)	0.47774 (10)	0.0309 (4)
O_14	0.52908 (12)	0.82023 (14)	0.41735 (8)	0.0449 (3)
O_15	0.54395 (11)	0.82381 (11)	0.52438 (7)	0.0310 (3)
C1_15	0.40082 (17)	0.76567 (17)	0.50243 (11)	0.0347 (4)
C2_15	0.3954 (2)	0.7634 (2)	0.57136 (13)	0.0405 (4)
H21_15	0.459 (2)	0.852 (2)	0.6247 (14)	0.045 (5)*
H22_15	0.301 (2)	0.722 (2)	0.5592 (13)	0.053 (6)*
H23_15	0.421 (2)	0.710 (2)	0.5720 (13)	0.049 (6)*
C3_15	0.3687 (2)	0.8497 (3)	0.50544 (16)	0.0510 (5)
H31_15	0.371 (2)	0.854 (2)	0.4623 (14)	0.050 (6)*
H32_15	0.437 (2)	0.941 (2)	0.5579 (15)	0.054 (6)*
H33_15	0.277 (3)	0.814 (2)	0.4980 (15)	0.067 (7)*
C4_15	0.3121 (2)	0.6309 (2)	0.41783 (13)	0.0470 (5)
H41_15	0.308 (2)	0.6298 (19)	0.3714 (14)	0.047 (6)*
H42_15	0.346 (2)	0.582 (2)	0.4179 (13)	0.054 (6)*
H43_15	0.218 (3)	0.597 (3)	0.4108 (16)	0.077 (8)*
O_20	0.0000	0.5000	0.5000	0.162 (19)*	0.1
O_21	0.040 (7)	0.471 (7)	0.458 (4)	0.14 (2)*	0.05
O_22	0.081 (9)	0.569 (9)	0.504 (5)	0.17 (3)*	0.05

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0332 (8)	0.0257 (8)	0.0223 (8)	0.0195 (7)	0.0140 (7)	0.0186 (7)
C2	0.0346 (9)	0.0256 (8)	0.0207 (8)	0.0193 (7)	0.0135 (7)	0.0149 (7)
C3	0.0348 (9)	0.0391 (9)	0.0267 (8)	0.0254 (8)	0.0200 (7)	0.0247 (8)
C4	0.0303 (9)	0.0336 (9)	0.0318 (9)	0.0142 (8)	0.0156 (8)	0.0247 (8)
C5	0.0393 (9)	0.0227 (8)	0.0268 (8)	0.0153 (8)	0.0141 (7)	0.0176 (7)
C6	0.0382 (9)	0.0261 (8)	0.0241 (8)	0.0224 (8)	0.0159 (7)	0.0186 (7)
C7	0.0345 (9)	0.0247 (8)	0.0312 (9)	0.0207 (7)	0.0145 (7)	0.0191 (7)
O1	0.0316 (6)	0.0228 (5)	0.0226 (5)	0.0170 (5)	0.0094 (5)	0.0154 (5)
C8	0.0184 (7)	0.0236 (7)	0.0213 (8)	0.0133 (6)	0.0096 (6)	0.0155 (7)
O8	0.0258 (5)	0.0235 (5)	0.0191 (5)	0.0166 (5)	0.0107 (4)	0.0120 (5)
N_1	0.0222 (6)	0.0192 (6)	0.0136 (6)	0.0117 (5)	0.0073 (5)	0.0102 (6)
CA_1	0.0195 (7)	0.0199 (7)	0.0172 (7)	0.0112 (6)	0.0086 (6)	0.0128 (6)
CL_1	0.0231 (8)	0.0188 (7)	0.0202 (8)	0.0109 (7)	0.0084 (7)	0.0126 (7)
CR_1	0.0211 (8)	0.0272 (8)	0.0236 (8)	0.0134 (7)	0.0125 (7)	0.0165 (8)
C_1	0.0207 (7)	0.0152 (7)	0.0162 (7)	0.0110 (6)	0.0085 (6)	0.0100 (6)
O_1	0.0243 (5)	0.0236 (5)	0.0172 (5)	0.0133 (5)	0.0105 (4)	0.0142 (4)
N_2	0.0184 (6)	0.0190 (6)	0.0125 (6)	0.0108 (5)	0.0071 (5)	0.0098 (5)
CA_2	0.0175 (7)	0.0185 (7)	0.0162 (7)	0.0108 (6)	0.0069 (6)	0.0103 (6)
CR_2	0.0259 (8)	0.0234 (8)	0.0278 (9)	0.0162 (7)	0.0101 (7)	0.0164 (8)
CL_2	0.0194 (8)	0.0259 (8)	0.0197 (8)	0.0124 (7)	0.0098 (7)	0.0130 (7)
C_2	0.0189 (7)	0.0194 (7)	0.0161 (7)	0.0112 (6)	0.0090 (6)	0.0123 (6)
O_2	0.0249 (5)	0.0254 (5)	0.0167 (5)	0.0161 (5)	0.0054 (4)	0.0108 (5)
N_3	0.0186 (6)	0.0183 (6)	0.0130 (6)	0.0108 (5)	0.0057 (5)	0.0091 (5)
CA_3	0.0213 (7)	0.0160 (7)	0.0149 (7)	0.0110 (6)	0.0075 (6)	0.0092 (6)
CL_3	0.0279 (8)	0.0202 (8)	0.0174 (8)	0.0160 (7)	0.0086 (6)	0.0108 (7)
CR_3	0.0267 (8)	0.0198 (8)	0.0219 (8)	0.0119 (7)	0.0105 (7)	0.0136 (7)
C_3	0.0216 (7)	0.0190 (7)	0.0176 (7)	0.0147 (6)	0.0101 (6)	0.0114 (6)
O_3	0.0281 (5)	0.0211 (5)	0.0148 (5)	0.0156 (5)	0.0071 (4)	0.0101 (5)
N_4	0.0264 (7)	0.0193 (6)	0.0156 (7)	0.0116 (6)	0.0100 (6)	0.0111 (6)
CA_4	0.0319 (8)	0.0233 (8)	0.0236 (8)	0.0181 (7)	0.0168 (7)	0.0177 (7)
C_4	0.0270 (8)	0.0198 (7)	0.0207 (7)	0.0130 (7)	0.0116 (6)	0.0138 (6)
O_4	0.0369 (6)	0.0363 (6)	0.0328 (6)	0.0258 (6)	0.0199 (5)	0.0273 (6)
O_5	0.0353 (6)	0.0430 (6)	0.0301 (6)	0.0298 (6)	0.0234 (5)	0.0293 (5)
C1_5	0.0333 (9)	0.0442 (10)	0.0285 (8)	0.0293 (8)	0.0217 (7)	0.0269 (8)
C2_5	0.0337 (9)	0.0427 (10)	0.0345 (9)	0.0252 (8)	0.0198 (8)	0.0288 (9)
C3_5	0.0425 (11)	0.0421 (11)	0.0325 (10)	0.0286 (10)	0.0215 (9)	0.0201 (9)
C4_5	0.0455 (11)	0.0745 (15)	0.0423 (11)	0.0461 (12)	0.0334 (10)	0.0479 (12)
C1_10	0.0189 (7)	0.0192 (7)	0.0282 (8)	0.0081 (6)	0.0118 (6)	0.0148 (7)
C2_10	0.0332 (9)	0.0259 (8)	0.0275 (9)	0.0175 (7)	0.0146 (7)	0.0163 (7)
C3_10	0.0317 (9)	0.0293 (9)	0.0379 (10)	0.0174 (8)	0.0126 (8)	0.0212 (8)
C4_10	0.0249 (8)	0.0263 (9)	0.0464 (11)	0.0153 (7)	0.0159 (8)	0.0188 (8)
C5_10	0.0342 (9)	0.0337 (10)	0.0395 (10)	0.0212 (8)	0.0223 (8)	0.0168 (9)
C6_10	0.0322 (9)	0.0345 (9)	0.0303 (9)	0.0179 (8)	0.0168 (8)	0.0194 (8)
C7_10	0.0238 (8)	0.0247 (8)	0.0306 (9)	0.0116 (7)	0.0122 (7)	0.0199 (7)
O1_10	0.0260 (5)	0.0231 (5)	0.0236 (5)	0.0114 (5)	0.0101 (4)	0.0175 (5)
C8_10	0.0216 (7)	0.0220 (7)	0.0178 (7)	0.0145 (6)	0.0109 (6)	0.0133 (7)
O8_10	0.0224 (5)	0.0239 (5)	0.0182 (5)	0.0104 (5)	0.0076 (5)	0.0122 (5)
N_11	0.0212 (6)	0.0184 (6)	0.0145 (6)	0.0107 (5)	0.0061 (5)	0.0106 (5)
CA_11	0.0254 (7)	0.0211 (7)	0.0203 (7)	0.0154 (6)	0.0114 (6)	0.0151 (6)
CR_11	0.0366 (10)	0.0374 (10)	0.0314 (9)	0.0291 (9)	0.0210 (8)	0.0256 (8)
CL_11	0.0330 (9)	0.0197 (8)	0.0214 (8)	0.0134 (7)	0.0111 (7)	0.0138 (7)
C_11	0.0172 (7)	0.0166 (7)	0.0183 (7)	0.0088 (6)	0.0071 (6)	0.0119 (6)
O_11	0.0247 (5)	0.0241 (5)	0.0194 (5)	0.0156 (5)	0.0088 (4)	0.0155 (5)
N_12	0.0217 (6)	0.0206 (6)	0.0140 (6)	0.0139 (5)	0.0067 (5)	0.0109 (5)
CA_12	0.0239 (7)	0.0219 (7)	0.0156 (7)	0.0154 (6)	0.0088 (6)	0.0116 (6)
CR_12	0.0255 (8)	0.0283 (8)	0.0241 (8)	0.0165 (7)	0.0139 (7)	0.0167 (7)
CL_12	0.0404 (10)	0.0342 (9)	0.0226 (8)	0.0295 (9)	0.0151 (8)	0.0174 (8)
C_12	0.0266 (8)	0.0202 (7)	0.0165 (7)	0.0149 (6)	0.0093 (6)	0.0119 (6)
O_12	0.0296 (6)	0.0283 (6)	0.0157 (5)	0.0144 (5)	0.0100 (4)	0.0131 (5)
N_13	0.0246 (7)	0.0201 (6)	0.0131 (6)	0.0109 (5)	0.0074 (5)	0.0094 (5)
CA_13	0.0242 (8)	0.0223 (8)	0.0167 (7)	0.0088 (7)	0.0079 (6)	0.0105 (7)
CR_13	0.0254 (9)	0.0285 (9)	0.0219 (8)	0.0102 (8)	0.0102 (7)	0.0147 (8)
CL_13	0.0359 (10)	0.0226 (8)	0.0232 (8)	0.0117 (8)	0.0134 (8)	0.0117 (7)
C_13	0.0177 (7)	0.0330 (9)	0.0177 (8)	0.0105 (7)	0.0077 (6)	0.0150 (7)
O_13	0.0262 (6)	0.0368 (6)	0.0188 (6)	0.0104 (5)	0.0066 (5)	0.0154 (5)
N_14	0.0238 (7)	0.0312 (7)	0.0226 (7)	0.0142 (6)	0.0068 (6)	0.0174 (7)
CA_14	0.0298 (9)	0.0425 (10)	0.0326 (9)	0.0219 (8)	0.0152 (8)	0.0283 (9)
C_14	0.0308 (9)	0.0348 (9)	0.0253 (8)	0.0192 (8)	0.0121 (7)	0.0202 (8)
O_14	0.0347 (7)	0.0666 (9)	0.0394 (7)	0.0288 (7)	0.0160 (6)	0.0404 (7)
O_15	0.0276 (6)	0.0376 (6)	0.0278 (6)	0.0191 (5)	0.0142 (5)	0.0224 (5)
C1_15	0.0269 (8)	0.0405 (10)	0.0339 (9)	0.0200 (8)	0.0163 (7)	0.0236 (8)
C2_15	0.0406 (11)	0.0483 (12)	0.0393 (11)	0.0283 (10)	0.0268 (9)	0.0297 (10)
C3_15	0.0473 (12)	0.0693 (16)	0.0607 (14)	0.0432 (12)	0.0332 (12)	0.0472 (14)
C4_15	0.0332 (10)	0.0468 (12)	0.0360 (11)	0.0159 (9)	0.0153 (9)	0.0232 (10)

Geometric parameters (Å, º)

C1—C2	1.385 (2)	C1_10—C2_10	1.386 (2)
C1—C6	1.397 (2)	C1_10—C6_10	1.391 (2)
C1—C7	1.502 (2)	C1_10—C7_10	1.499 (2)
C2—C3	1.384 (2)	C2_10—C3_10	1.392 (2)
C2—H2	0.956 (19)	C2_10—H2_10	0.96 (2)
C3—C4	1.383 (2)	C3_10—C4_10	1.375 (3)
C3—H3	0.97 (2)	C3_10—H3_10	0.98 (2)
C4—C5	1.384 (3)	C4_10—C5_10	1.375 (3)
C4—H4	0.94 (2)	C4_10—H4_10	1.00 (2)
C5—C6	1.379 (2)	C5_10—C6_10	1.386 (3)
C5—H5	0.95 (2)	C5_10—H5_10	1.01 (2)
C6—H6	0.967 (19)	C6_10—H6_10	1.025 (19)
C7—O1	1.4480 (18)	C7_10—O1_10	1.4604 (18)
C7—H71	0.993 (18)	C7_10—H71_10	1.011 (18)
C7—H72	0.999 (19)	C7_10—H72_10	1.017 (19)
O1—C8	1.3554 (17)	O1_10—C8_10	1.3508 (17)
C8—O8	1.2160 (17)	C8_10—O8_10	1.2217 (17)
C8—N_1	1.3408 (19)	C8_10—N_11	1.3458 (19)
N_1—CA_1	1.4686 (18)	N_11—CA_11	1.4644 (18)
N_1—H_1	0.817 (18)	N_11—H_11	0.842 (19)
CA_1—CR_1	1.525 (2)	CA_11—CR_11	1.527 (2)
CA_1—CL_1	1.532 (2)	CA_11—CL_11	1.529 (2)
CA_1—C_1	1.5471 (19)	CA_11—C_11	1.5410 (19)
CL_1—HL1_1	0.957 (18)	CR_11—HR1_11	0.97 (2)
CL_1—HL2_1	0.973 (19)	CR_11—HR2_11	0.94 (2)
CL_1—HL3_1	0.996 (18)	CR_11—HR3_11	1.024 (19)
CR_1—HR1_1	0.922 (19)	CL_11—HL1_11	0.940 (18)
CR_1—HR2_1	0.986 (17)	CL_11—HL2_11	0.934 (19)
CR_1—HR3_1	0.969 (19)	CL_11—HL3_11	1.00 (2)
C_1—O_1	1.2307 (17)	C_11—O_11	1.2317 (17)
C_1—N_2	1.3477 (18)	C_11—N_12	1.3431 (18)
N_2—CA_2	1.4670 (18)	N_12—CA_12	1.4673 (18)
N_2—H_2	0.804 (18)	N_12—H_12	0.852 (19)
CA_2—CL_2	1.528 (2)	CA_12—CR_12	1.529 (2)
CA_2—CR_2	1.533 (2)	CA_12—CL_12	1.531 (2)
CA_2—C_2	1.5418 (19)	CA_12—C_12	1.537 (2)
CR_2—HR1_2	0.96 (2)	CR_12—HR1_12	0.937 (18)
CR_2—HR2_2	0.96 (2)	CR_12—HR2_12	0.99 (2)
CR_2—HR3_2	0.99 (2)	CR_12—HR3_12	0.96 (2)
CL_2—HL1_2	0.948 (18)	CL_12—HL1_12	0.95 (2)
CL_2—HL2_2	0.952 (18)	CL_12—HL2_12	0.974 (18)
CL_2—HL3_2	0.981 (19)	CL_12—HL3_12	0.97 (2)
C_2—O_2	1.2333 (17)	C_12—O_12	1.2322 (17)
C_2—N_3	1.3377 (18)	C_12—N_13	1.340 (2)
N_3—CA_3	1.4722 (18)	N_13—CA_13	1.470 (2)
N_3—H_3	0.791 (19)	N_13—H_13	0.84 (2)
CA_3—CR_3	1.524 (2)	CA_13—CL_13	1.518 (2)
CA_3—CL_3	1.530 (2)	CA_13—CR_13	1.535 (2)
CA_3—C_3	1.5368 (19)	CA_13—C_13	1.542 (2)
CL_3—HL1_3	0.928 (18)	CR_13—HR1_13	0.98 (2)
CL_3—HL2_3	0.955 (19)	CR_13—HR2_13	0.998 (19)
CL_3—HL3_3	0.949 (19)	CR_13—HR3_13	0.998 (19)
CR_3—HR1_3	0.952 (19)	CL_13—HL1_13	0.99 (2)
CR_3—HR2_3	0.978 (18)	CL_13—HL2_13	1.01 (2)
CR_3—HR3_3	0.988 (19)	CL_13—HL3_13	0.99 (2)
C_3—O_3	1.2332 (17)	C_13—O_13	1.2322 (18)
C_3—N_4	1.3423 (19)	C_13—N_14	1.337 (2)
N_4—CA_4	1.4374 (19)	N_14—CA_14	1.448 (2)
N_4—H_4	0.792 (19)	N_14—H_14	0.90 (2)
CA_4—C_4	1.519 (2)	CA_14—C_14	1.515 (2)
CA_4—H1_4	0.949 (19)	CA_14—H1_14	0.97 (2)
CA_4—H2_4	0.985 (19)	CA_14—H2_14	1.06 (2)
C_4—O_4	1.2030 (18)	C_14—O_14	1.203 (2)
C_4—O_5	1.3343 (18)	C_14—O_15	1.3295 (19)
O_5—C1_5	1.4854 (18)	O_15—C1_15	1.4825 (19)
C1_5—C3_5	1.514 (3)	C1_15—C3_15	1.515 (3)
C1_5—C2_5	1.514 (2)	C1_15—C2_15	1.517 (2)
C1_5—C4_5	1.519 (2)	C1_15—C4_15	1.520 (3)
C2_5—H21_5	0.98 (2)	C2_15—H21_15	0.98 (2)
C2_5—H22_5	0.99 (2)	C2_15—H22_15	0.99 (2)
C2_5—H23_5	0.99 (2)	C2_15—H23_15	1.02 (2)
C3_5—H31_5	1.00 (2)	C3_15—H31_15	0.97 (2)
C3_5—H32_5	0.98 (2)	C3_15—H32_15	1.00 (2)
C3_5—H33_5	1.03 (2)	C3_15—H33_15	0.99 (3)
C4_5—H41_5	0.98 (2)	C4_15—H41_15	0.99 (2)
C4_5—H42_5	0.91 (2)	C4_15—H42_15	1.04 (2)
C4_5—H34_5	1.01 (2)	C4_15—H43_15	1.01 (3)
C2—C1—C6	118.96 (15)	C3_10—C4_10—H4_10	119.5 (12)
C2—C1—C7	122.68 (14)	C4_10—C5_10—C6_10	120.46 (17)
C6—C1—C7	118.33 (14)	C4_10—C5_10—H5_10	120.9 (13)
C3—C2—C1	120.17 (15)	C6_10—C5_10—H5_10	118.6 (13)
C3—C2—H2	120.5 (11)	C5_10—C6_10—C1_10	120.21 (17)
C1—C2—H2	119.3 (11)	C5_10—C6_10—H6_10	122.2 (10)
C4—C3—C2	120.57 (16)	C1_10—C6_10—H6_10	117.4 (10)
C4—C3—H3	120.1 (12)	O1_10—C7_10—C1_10	110.64 (12)
C2—C3—H3	119.3 (12)	O1_10—C7_10—H71_10	106.3 (10)
C3—C4—C5	119.60 (16)	C1_10—C7_10—H71_10	111.3 (10)
C3—C4—H4	119.1 (11)	O1_10—C7_10—H72_10	104.9 (11)
C5—C4—H4	121.1 (12)	C1_10—C7_10—H72_10	111.6 (10)
C6—C5—C4	120.05 (16)	H71_10—C7_10—H72_10	111.8 (14)
C6—C5—H5	118.4 (12)	C8_10—O1_10—C7_10	117.45 (12)
C4—C5—H5	121.5 (12)	O8_10—C8_10—N_11	124.97 (13)
C5—C6—C1	120.61 (15)	O8_10—C8_10—O1_10	124.33 (13)
C5—C6—H6	119.9 (11)	N_11—C8_10—O1_10	110.70 (12)
C1—C6—H6	119.4 (11)	C8_10—N_11—CA_11	121.83 (12)
O1—C7—C1	114.46 (12)	C8_10—N_11—H_11	118.9 (12)
O1—C7—H71	107.9 (10)	CA_11—N_11—H_11	118.5 (12)
C1—C7—H71	109.2 (10)	N_11—CA_11—CR_11	110.86 (12)
O1—C7—H72	100.6 (10)	N_11—CA_11—CL_11	107.32 (12)
C1—C7—H72	112.8 (10)	CR_11—CA_11—CL_11	110.12 (13)
H71—C7—H72	111.6 (14)	N_11—CA_11—C_11	110.95 (11)
C8—O1—C7	114.50 (11)	CA_11—CR_11—HR1_11	111.5 (11)
O8—C8—N_1	125.37 (13)	CA_11—CR_11—HR2_11	108.1 (11)
O8—C8—O1	123.23 (13)	HR1_11—CR_11—HR2_11	109.8 (16)
N_1—C8—O1	111.39 (12)	CA_11—CR_11—HR3_11	107.1 (10)
C8—N_1—CA_1	119.89 (12)	HR1_11—CR_11—HR3_11	112.5 (15)
C8—N_1—H_1	121.0 (12)	HR2_11—CR_11—HR3_11	107.8 (15)
CA_1—N_1—H_1	118.9 (12)	CA_11—CL_11—HL1_11	110.9 (10)
N_1—CA_1—CL_1	107.25 (11)	CA_11—CL_11—HL2_11	108.7 (11)
N_1—CA_1—CR_1	110.93 (12)	HL1_11—CL_11—HL2_11	110.9 (15)
N_1—CA_1—CL_1	107.25 (11)	CA_11—CL_11—HL3_11	107.5 (11)
CR_1—CA_1—CL_1	110.38 (12)	HL1_11—CL_11—HL3_11	109.4 (15)
N_1—CA_1—C_1	109.41 (11)	HL2_11—CL_11—HL3_11	109.4 (15)
CR_1—CA_1—C_1	110.17 (11)	O_11—C_11—N_12	122.81 (13)
CL_1—CA_1—C_1	108.63 (11)	O_11—C_11—CA_11	120.97 (12)
CA_1—CL_1—HL1_1	109.3 (10)	N_12—C_11—CA_11	116.21 (12)
CA_1—CL_1—HL2_1	110.8 (10)	C_11—N_12—CA_12	122.90 (12)
HL1_1—CL_1—HL2_1	107.4 (14)	C_11—N_12—H_12	119.0 (12)
CA_1—CL_1—HL3_1	108.9 (10)	CA_12—N_12—H_12	117.9 (12)
HL1_1—CL_1—HL3_1	107.4 (14)	N_12—CA_12—CR_12	110.87 (12)
HL2_1—CL_1—HL3_1	112.8 (14)	N_12—CA_12—CL_12	107.53 (11)
CA_1—CR_1—HR1_1	109.9 (11)	CR_12—CA_12—CL_12	109.94 (13)
CA_1—CR_1—HR2_1	107.3 (9)	N_12—CA_12—C_12	111.31 (11)
HR1_1—CR_1—HR2_1	108.6 (14)	CR_12—CA_12—C_12	110.72 (12)
CA_1—CR_1—HR3_1	108.8 (11)	CL_12—CA_12—C_12	106.32 (12)
HR1_1—CR_1—HR3_1	112.0 (15)	CA_12—CR_12—HR1_12	111.4 (11)
HR2_1—CR_1—HR3_1	110.1 (15)	CA_12—CR_12—HR2_12	109.1 (11)
O_1—C_1—N_2	123.11 (13)	HR1_12—CR_12—HR2_12	109.4 (15)
O_1—C_1—CA_1	121.65 (12)	CA_12—CR_12—HR3_12	108.7 (11)
N_2—C_1—CA_1	115.23 (12)	HR1_12—CR_12—HR3_12	108.7 (15)
C_1—N_2—CA_2	124.26 (12)	HR2_12—CR_12—HR3_12	109.5 (16)
C_1—N_2—H_2	118.9 (12)	CA_12—CL_12—HL1_12	111.2 (12)
CA_2—N_2—H_2	116.1 (12)	CA_12—CL_12—HL2_12	107.5 (10)
N_2—CA_2—CL_2	107.48 (11)	HL1_12—CL_12—HL2_12	107.9 (16)
N_2—CA_2—CR_2	110.68 (12)	CA_12—CL_12—HL3_12	108.9 (12)
CL_2—CA_2—CR_2	109.41 (12)	HL1_12—CL_12—HL3_12	111.8 (17)
N_2—CA_2—C_2	112.35 (11)	HL2_12—CL_12—HL3_12	109.4 (16)
CL_2—CA_2—C_2	107.33 (12)	O_12—C_12—N_13	122.50 (14)
CR_2—CA_2—C_2	109.48 (12)	O_12—C_12—CA_12	119.50 (13)
CA_2—CR_2—HR1_2	110.4 (12)	N_13—C_12—CA_12	117.91 (12)
CA_2—CR_2—HR2_2	107.4 (11)	C_12—N_13—CA_13	121.80 (12)
HR1_2—CR_2—HR2_2	111.3 (17)	C_12—N_13—H_13	119.7 (13)
CA_2—CR_2—HR3_2	108.7 (11)	CA_13—N_13—H_13	118.0 (13)
HR1_2—CR_2—HR3_2	111.8 (16)	N_13—CA_13—CL_13	110.99 (14)
HR2_2—CR_2—HR3_2	107.1 (15)	N_13—CA_13—CR_13	107.96 (12)
CA_2—CL_2—HL1_2	109.5 (10)	CL_13—CA_13—CR_13	109.52 (13)
CA_2—CL_2—HL2_2	108.9 (10)	N_13—CA_13—C_13	110.24 (12)
HL1_2—CL_2—HL2_2	110.3 (15)	CL_13—CA_13—C_13	111.91 (13)
CA_2—CL_2—HL3_2	109.0 (11)	CR_13—CA_13—C_13	106.03 (13)
HL1_2—CL_2—HL3_2	109.0 (14)	CA_13—CR_13—HR1_13	113.3 (11)
HL2_2—CL_2—HL3_2	110.1 (14)	CA_13—CR_13—HR2_13	108.1 (11)
O_2—C_2—N_3	122.61 (13)	HR1_13—CR_13—HR2_13	112.1 (15)
O_2—C_2—CA_2	118.71 (12)	CA_13—CR_13—HR3_13	110.3 (11)
N_3—C_2—CA_2	118.66 (12)	HR1_13—CR_13—HR3_13	106.0 (15)
C_2—N_3—CA_3	122.44 (12)	HR2_13—CR_13—HR3_13	106.8 (15)
C_2—N_3—H_3	119.9 (13)	CA_13—CL_13—HL1_13	110.2 (12)
CA_3—N_3—H_3	117.1 (12)	CA_13—CL_13—HL2_13	115.1 (12)
N_3—CA_3—CR_3	111.70 (12)	HL1_13—CL_13—HL2_13	109.0 (17)
N_3—CA_3—CL_3	107.93 (12)	CA_13—CL_13—HL3_13	111.5 (11)
CR_3—CA_3—CL_3	109.98 (12)	HL1_13—CL_13—HL3_13	112.0 (17)
N_3—CA_3—C_3	109.58 (11)	HL2_13—CL_13—HL3_13	98.7 (16)
CR_3—CA_3—C_3	111.46 (12)	O_13—C_13—N_14	122.27 (15)
CL_3—CA_3—C_3	105.98 (11)	O_13—C_13—CA_13	121.40 (15)
CA_3—CL_3—HL1_3	107.2 (10)	N_14—C_13—CA_13	116.01 (13)
CA_3—CL_3—HL2_3	108.1 (11)	C_13—N_14—CA_14	120.97 (14)
HL1_3—CL_3—HL2_3	110.6 (15)	C_13—N_14—H_14	120.3 (13)
CA_3—CL_3—HL3_3	110.5 (10)	CA_14—N_14—H_14	118.7 (13)
HL1_3—CL_3—HL3_3	110.0 (15)	N_14—CA_14—C_14	115.20 (14)
HL2_3—CL_3—HL3_3	110.4 (15)	N_14—CA_14—H1_14	109.0 (11)
CA_3—CR_3—HR1_3	108.3 (11)	C_14—CA_14—H1_14	105.3 (12)
CA_3—CR_3—HR2_3	112.3 (10)	N_14—CA_14—H2_14	107.8 (12)
HR1_3—CR_3—HR2_3	108.3 (15)	C_14—CA_14—H2_14	106.0 (12)
CA_3—CR_3—HR3_3	108.4 (11)	H1_14—CA_14—H2_14	113.6 (17)
HR1_3—CR_3—HR3_3	112.4 (15)	O_14—C_14—O_15	126.40 (15)
HR2_3—CR_3—HR3_3	107.1 (14)	O_14—C_14—CA_14	121.80 (15)
O_3—C_3—N_4	122.18 (13)	O_15—C_14—CA_14	111.73 (13)
O_3—C_3—CA_3	121.38 (12)	C_14—O_15—C1_15	121.02 (12)
N_4—C_3—CA_3	116.25 (12)	O_15—C1_15—C3_15	110.32 (15)
C_3—N_4—CA_4	121.07 (13)	O_15—C1_15—C2_15	101.81 (13)
C_3—N_4—H_4	120.2 (12)	C3_15—C1_15—C2_15	111.09 (16)
CA_4—N_4—H_4	117.8 (13)	O_15—C1_15—C4_15	108.92 (14)
N_4—CA_4—C_4	113.06 (12)	C3_15—C1_15—C4_15	113.07 (18)
N_4—CA_4—H1_4	109.7 (11)	C2_15—C1_15—C4_15	111.04 (17)
C_4—CA_4—H1_4	108.7 (11)	C1_15—C2_15—H21_15	107.6 (12)
N_4—CA_4—H2_4	110.5 (11)	C1_15—C2_15—H22_15	106.0 (13)
C_4—CA_4—H2_4	107.5 (10)	H21_15—C2_15—H22_15	113.5 (17)
H1_4—CA_4—H2_4	107.3 (15)	C1_15—C2_15—H23_15	112.4 (12)
O_4—C_4—O_5	126.94 (14)	H21_15—C2_15—H23_15	109.3 (17)
O_4—C_4—CA_4	124.72 (13)	H22_15—C2_15—H23_15	108.1 (17)
O_5—C_4—CA_4	108.35 (12)	C1_15—C3_15—H31_15	113.7 (13)
C_4—O_5—C1_5	121.67 (11)	C1_15—C3_15—H32_15	111.8 (13)
O_5—C1_5—C3_5	109.06 (14)	H31_15—C3_15—H32_15	103.0 (19)
O_5—C1_5—C2_5	109.79 (13)	C1_15—C3_15—H33_15	108.1 (14)
C3_5—C1_5—C2_5	113.03 (15)	H31_15—C3_15—H33_15	107.8 (19)
O_5—C1_5—C4_5	102.09 (12)	H32_15—C3_15—H33_15	112.4 (19)
C3_5—C1_5—C4_5	111.69 (16)	C1_15—C4_15—H41_15	112.6 (12)
C2_5—C1_5—C4_5	110.61 (15)	C1_15—C4_15—H42_15	109.2 (12)
C1_5—C2_5—H21_5	112.0 (12)	H41_15—C4_15—H42_15	111.2 (17)
C1_5—C2_5—H22_5	107.6 (11)	C1_15—C4_15—H43_15	103.1 (15)
H21_5—C2_5—H22_5	107.4 (16)	H41_15—C4_15—H43_15	104.2 (19)
C1_5—C2_5—H23_5	108.9 (12)	H42_15—C4_15—H43_15	116 (2)
H21_5—C2_5—H23_5	110.2 (16)	N_1—CA_1—CL_1	107.25 (11)
H22_5—C2_5—H23_5	110.7 (17)	C_1—CA_1—CL_1	108.63 (11)
C1_5—C3_5—H31_5	109.7 (12)	N_2—CA_2—CL_2	107.48 (11)
C1_5—C3_5—H32_5	112.0 (13)	C_2—CA_2—CL_2	107.33 (12)
H31_5—C3_5—H32_5	100.0 (17)	N_3—CA_3—CL_3	107.93 (12)
C1_5—C3_5—H33_5	112.1 (13)	C_3—CA_3—CL_3	105.98 (11)
H31_5—C3_5—H33_5	110.3 (18)	N_11—CA_11—CL_11	107.32 (12)
H32_5—C3_5—H33_5	112.2 (17)	C_11—CA_11—CL_11	108.05 (12)
C1_5—C4_5—H41_5	108.9 (12)	N_12—CA_12—CL_12	107.53 (11)
C1_5—C4_5—H42_5	109.6 (13)	C_12—CA_12—CL_12	106.32 (12)
H41_5—C4_5—H42_5	109.0 (17)	N_13—CA_13—CL_13	110.99 (14)
C1_5—C4_5—H34_5	110.0 (12)	C_13—CA_13—CL_13	111.91 (13)
H41_5—C4_5—H34_5	113.7 (17)	N_1—CA_1—CR_1	110.93 (12)
H42_5—C4_5—H34_5	105.5 (18)	C_1—CA_1—CR_1	110.17 (11)
C2_10—C1_10—C6_10	118.79 (15)	N_2—CA_2—CR_2	110.68 (12)
C2_10—C1_10—C7_10	120.62 (14)	C_2—CA_2—CR_2	109.48 (12)
C6_10—C1_10—C7_10	120.58 (15)	N_3—CA_3—CR_3	111.70 (12)
C1_10—C2_10—C3_10	120.59 (16)	C_3—CA_3—CR_3	111.46 (12)
C1_10—C2_10—H2_10	118.3 (12)	N_11—CA_11—CR_11	110.86 (12)
C3_10—C2_10—H2_10	121.1 (12)	C_11—CA_11—CR_11	109.48 (12)
C4_10—C3_10—C2_10	119.95 (17)	N_12—CA_12—CR_12	110.87 (12)
C4_10—C3_10—H3_10	119.8 (12)	C_12—CA_12—CR_12	110.72 (12)
C2_10—C3_10—H3_10	120.3 (12)	N_13—CA_13—CR_13	107.96 (12)
C5_10—C4_10—C3_10	119.98 (17)	C_13—CA_13—CR_13	106.03 (13)
C5_10—C4_10—H4_10	120.5 (12)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N_3—H_3···O8	0.79 (2)	2.24 (2)	3.008 (2)	165 (2)
N_4—H_4···O_1	0.79 (2)	2.34 (2)	3.106 (2)	162 (2)
N_13—H_13···O8_10	0.84 (2)	2.14 (2)	2.958 (2)	165 (2)
N_14—H_14···O_11	0.90 (2)	2.10 (2)	2.964 (2)	159 (2)
N_1—H_1···O_12^i	0.82 (2)	2.09 (2)	2.895 (2)	168 (2)
N_2—H_2···O_13^i	0.80 (2)	2.31 (2)	3.091 (2)	161 (2)
N_11—H_11···O_2^ii	0.84 (2)	2.04 (2)	2.870 (2)	168 (2)
N_12—H_12···O_3^ii	0.85 (2)	2.17 (2)	2.979 (2)	159 (2)

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