The peptide Z-Aib-Aib-Aib-L-Ala-OtBu

The title peptide, N-benzyl­oxycarbonyl-α-aminoisobutyryl-α-amino­isobutyryl-α-amino­isobutyryl-L-alanine tert-butyl ester or Z-Aib-Aib-Aib-L-Ala-OtBu (Aib is α-amino­isobutyric acid, Z is benzyl­oxycarbonyl and OtBu indicates the tert-butyl ester), C₂₇H₄₂N₄O₇, is a left-handed helix with a right-handed conformation in the fourth residue, which is the only chiral residue. There are two 4→1 intra­molecular hydrogen bonds in the structure. In the lattice, mol­ecules are hydrogen bonded to form columns along the c axis.

S1. Introduction

The sequence Aib-Aib-Aib-Ala represents a segment of the naturally occurring peptaibol anti­biotics, which are peptides containing α-amino­isobutyric acid (Aib) and a C-terminal β-amino alcohol (Brückner & Graf, 1983; Benedetti et al., 1982) such as trichotoxin (Brückner et al., 1985). We present here the crystal structure of Z-Aib-Aib-Aib-L-Ala-OtBu, (II), containing this tetra­peptide.

S2. Experimental

S2.1. Synthesis and crystallization

For the synthesis of Z-Aib-Aib-Aib-Ala-OtBu, the protected tripeptide acid Z-Aib-Aib-Aib-OH was reacted with acetic anhydride to provide the oxazolone Z-Aib-Aib-AibOx, (I) (AibOx is the oxazolone of C-terminal Aib; Leplawy et al. 1960; Brückner & Jung, 1982; Toniolo et al., 1983). To a solution of (I) (6.51 mmol) in propio­nitrile (30 ml), L-Ala-OtBu.HCl (7.81 mmol, 1.20 equivalents) and N-methyl­morpholine (0.87 ml, 1.20 equivalents) were added and the mixture was heated for 17 h at 373 K. This was followed by evaporation to dryness in vacuo using a rotary evaporator. To the remaining residue, n-butanol–ethyl acetate (1:1 v/v, 750 ml) was added, and the organic phase was washed successively with 5% aqueous KHSO₄, 5% aqueous NaHCO₃ and water. On evaporation of the organic phase, the protected tetra­peptide Z-Aib₃-L-Ala-OtBu, (II), started to crystallize. Crystallization was completed by addition of ethyl acetate and petroleum ether (b.p. 313–333 K; [Ratio or volumes?]), providing white needles (yield 2.01 g, 57.8%), uniform in thin-layer chromatography. A further qu­antity of (II) could be obtained from the mother liquor. Crystals suitable for X-ray crystallography were obtained from cooling a hot methanol–water mixture (70:30 v/v). Block-shaped crystals of (II) were observed after a few days at room temperature.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. In view of the crystal size, a spherical absorption correction was applied in addition to the correction based on symmetry-related measurements (Bruker, 2008). The four N-bound H atoms were located in a difference Fourier synthesis. Their positional parameters were refined with distance restraints and their isotropic displacement parameters were refined freely, except that of the N2—H02 group which was fixed at 1.2U_eq(N). C-bound H atoms were calculated with C—H = 0.93 (aryl), 0.96 (methyl), 0.97 (methyl­ene) and 0.98 Å (methine H atoms), and refined as riding, with U_iso(H) = 1.5U_eq(C) for methyl H atoms and 1.2U_eq(C) otherwise.

S3. Results and discussion

The backbone of the tetra­peptide of (II) adopts a quite unusual conformation, namely an incipient left-handed 3₁₀-helix with a reversal of the helical sense in the Ala residue (Fig. 1 and Table 2). The helix is stabilized by two 4→1 hydrogen bonds (Table 3). All residues, including the N-terminal protecting group, are involved in intra­molecular hydrogen bonding.

The peptide adopts the expected trans-planar conformation with significant deviations from planarity (ω = 180°; Table 2). The valence geometry around the C^α atom is asymmetric for the Aib residues (Table 4). If one designates as C_L and C_R the atoms which occupy the same position as C^β and the α-hydrogen in the L-amino acids, respectively, the bond angles N—C^α—C_L and C—C^α—C_L are significantly greater than N—C^α—C_R and C—C^α—C_R. This observation is in excellent agreement with theoretical calculations and with the bond angles of other left-handed 3₁₀-helical Aib peptides (Gessmann et al., 1997).

In the crystal structure, one molecule of (II) is hydrogen-bonded in a head-to-tail manner to a symmetry-related molecule via two hydrogen bonds (Table 3 and Fig. 2), thus building infinite columns in the [001] direction. These columns pack parallel to the same columns translated in the [100] direction along the small a axis in the next unit cell, and these hydrogen-bonded columns pack in an anti­parallel manner to the space group symmetry-related columns in the [010] direction. The only polar group not involved in hydrogen bonding is the C═O group of Aib2, with a closest apolar contact of 3.44 Å to a C atom of the benzyl­oxycarbonyl protecting group.

The structure of the related peptide Z-Aib-Aib-Aib-L-Val-OtBu has been solved previously (Gessmann et al., 1997). The overall folding of the two molecules in the asymmetric unit is essentially the same as for the structure described herein, with an incipient left-handed 3₁₀-helix with reversal of the helical sense in the last residue. The r.m.s. deviation of the backbone and the common side-chain atoms in residues 1 to 4 of molecule A of the Val-substituted tetra­peptide and (II) is 0.69 Å, while the corresponding value for molecule B and (II) is 0.42 Å.

Related literature

For related literature, see: Benedetti et al. (1982); Brückner & Graf (1983); Brückner & Jung (1982); Brückner et al. (1985); Gessmann et al. (1997); Leplawy et al. (1960); Toniolo et al. (1983).

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: SHELXL97 (Sheldrick, 2008); molecular graphics: XTALVIEW (McRee 1999) and SwissPDBViewer (Guex & Peitsch, 1997); software used to prepare material for publication: CHEMDRAW (Mills, 2006) and ORTEP-3 for Windows (Farrugia, 2012).

Figures

	Fig. 1. The molecular structure of Z-Aib-Aib-Aib-Ala-OtBu, (II), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. The two intramolecular hydrogen bonds are shown as green dashed lines. [Can a revised figure be supplied with smaller labels and labels not overlapping atoms as far as possible?]
	Fig. 2. The crystal packing of Z-Aib-Aib-Aib-Ala-OtBu, (II), viewed approximately along the a axis. The four molecules in the unit cell and, by translation along unit-cell axes, symmetry-related molecules are shown when they possess atoms inside the unit cell. Hydrogen bonds are indicated as dashed lines and H atoms not involved in hydrogen bonding have been omitted for clarity.

N-benzyloxycarbonyl-α-aminoisobutyryl-α-aminoisobutyryl-α-aminoisobutyryl-L-alanine tert-butyl ester

Crystal data

C27H42N4O7	Z = 4
Mr = 534.65	F(000) = 1152
Orthorhombic, P212121	Dx = 1.169 Mg m^−3
Hall symbol: P 2ac 2ab	Cu Kα radiation, λ = 1.54184 Å
a = 9.3730 (19) Å	µ = 0.69 mm^−1
b = 17.032 (3) Å	T = 293 K
c = 19.032 (4) Å	Block, colourless
V = 3038.3 (11) Å^3	1.4 × 1.1 × 0.9 mm

Data collection

Bruker D8 Venture diffractometer	5541 independent reflections
Radiation source: microfocus tube IµS	5018 reflections with I > 2σ(I)
Multilayer optics monochromator	Rint = 0.034
ω and ψ scans	θmax = 72.4°, θmin = 3.5°
Absorption correction: multi-scan (SADABS; Bruker, 2008)	h = −11→11
Tmin = 0.423, Tmax = 0.754	k = −20→21
5835 measured reflections	l = −22→22

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.044	w = 1/[σ^2(Fo^2) + (0.1P)^2] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.142	(Δ/σ)max = 0.001
S = 1.16	Δρmax = 0.18 e Å^−3
5541 reflections	Δρmin = −0.23 e Å^−3
358 parameters	Absolute structure: Flack (1983), with how many Friedel pairs?
4 restraints	Absolute structure parameter: 0.05 (18)
Primary atom site location: structure-invariant direct methods

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. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
C10	0.5062 (4)	0.31972 (14)	0.92733 (13)	0.0807 (8)
C20	0.4369 (4)	0.37358 (17)	0.96801 (16)	0.0857 (8)
H20	0.4895	0.4042	0.9991	0.103*
C30	0.2917 (5)	0.3838 (2)	0.9643 (2)	0.1199 (13)
H30	0.2469	0.4203	0.9933	0.144*
C40	0.2136 (6)	0.3407 (3)	0.9183 (4)	0.166 (3)
H40	0.1154	0.3475	0.9151	0.199*
C50	0.2831 (9)	0.2862 (4)	0.8760 (4)	0.198 (4)
H50	0.2300	0.2561	0.8447	0.237*
C60	0.4284 (6)	0.2756 (2)	0.8794 (2)	0.1279 (17)
H60	0.4737	0.2397	0.8501	0.153*
C70	0.6653 (5)	0.30493 (15)	0.93185 (17)	0.0986 (10)
H7A0	0.6816	0.2568	0.9579	0.118*
H7B0	0.7027	0.2975	0.8848	0.118*
O00	0.7426 (2)	0.36826 (10)	0.96550 (9)	0.0749 (5)
C80	0.7712 (2)	0.43054 (12)	0.92446 (10)	0.0541 (4)
O80	0.73385 (19)	0.43571 (8)	0.86297 (7)	0.0628 (4)
N1	0.84362 (18)	0.48500 (10)	0.95943 (8)	0.0531 (4)
H01	0.869 (3)	0.4784 (17)	1.0040 (10)	0.096 (9)*
CA1	0.8991 (2)	0.55453 (12)	0.92371 (9)	0.0502 (4)
CL1	1.0180 (2)	0.53321 (15)	0.87215 (12)	0.0658 (6)
HL11	0.9815	0.4977	0.8374	0.099*
HL21	1.0949	0.5086	0.8971	0.099*
HL31	1.0521	0.5800	0.8496	0.099*
CR1	0.9568 (3)	0.61072 (15)	0.98015 (12)	0.0701 (6)
HR11	1.0319	0.5853	1.0058	0.105*
HR21	0.8812	0.6247	1.0118	0.105*
HR31	0.9933	0.6572	0.9581	0.105*
C1	0.77989 (19)	0.59811 (10)	0.88472 (9)	0.0428 (4)
O1	0.80434 (14)	0.63206 (8)	0.82935 (7)	0.0517 (3)
N2	0.65117 (16)	0.59936 (9)	0.91577 (7)	0.0444 (3)
H02	0.643 (3)	0.5779 (12)	0.9571 (8)	0.053*
CA2	0.5316 (2)	0.64628 (11)	0.88785 (10)	0.0471 (4)
CL2	0.5637 (3)	0.73332 (13)	0.89584 (13)	0.0681 (6)
HL12	0.6483	0.7461	0.8698	0.102*
HL22	0.5782	0.7454	0.9446	0.102*
HL32	0.4849	0.7634	0.8782	0.102*
CR2	0.3978 (2)	0.62341 (14)	0.92878 (11)	0.0626 (5)
HR12	0.3803	0.5682	0.9232	0.094*
HR22	0.3176	0.6525	0.9112	0.094*
HR32	0.4113	0.6351	0.9777	0.094*
C2	0.50370 (19)	0.62624 (11)	0.80957 (9)	0.0481 (4)
O2	0.4652 (2)	0.67669 (10)	0.76925 (8)	0.0721 (5)
N3	0.51572 (15)	0.54954 (9)	0.79299 (8)	0.0443 (3)
H03	0.557 (2)	0.5194 (11)	0.8230 (10)	0.050 (5)*
CA3	0.47843 (19)	0.51504 (12)	0.72466 (9)	0.0498 (4)
CL3	0.3308 (2)	0.54203 (18)	0.69914 (12)	0.0726 (7)
HL13	0.2609	0.5309	0.7346	0.109*
HL23	0.3066	0.5146	0.6567	0.109*
HL33	0.3328	0.5975	0.6902	0.109*
CR3	0.4804 (3)	0.42615 (14)	0.73379 (13)	0.0677 (6)
HR13	0.5731	0.4099	0.7495	0.102*
HR23	0.4592	0.4014	0.6897	0.102*
HR33	0.4101	0.4111	0.7679	0.102*
C3	0.59109 (19)	0.53298 (11)	0.66821 (9)	0.0489 (4)
O3	0.56553 (18)	0.51739 (14)	0.60668 (8)	0.0823 (6)
N4	0.71787 (15)	0.55887 (9)	0.68888 (7)	0.0441 (3)
H04	0.741 (3)	0.5730 (14)	0.7301 (9)	0.059 (6)*
CA4	0.83797 (19)	0.55982 (11)	0.64070 (9)	0.0451 (4)
HA4	0.8076	0.5855	0.5971	0.054*
CL4	0.9623 (2)	0.60637 (13)	0.67140 (12)	0.0568 (5)
HL14	0.9309	0.6585	0.6829	0.085*
HL24	1.0380	0.6092	0.6375	0.085*
HL34	0.9962	0.5807	0.7131	0.085*
C4	0.88906 (19)	0.47719 (11)	0.62274 (9)	0.0470 (4)
O4	0.93292 (19)	0.45995 (10)	0.56531 (8)	0.0723 (4)
O5	0.88386 (18)	0.43023 (8)	0.67759 (7)	0.0631 (4)
C15	0.9361 (2)	0.34770 (12)	0.67624 (12)	0.0609 (5)
C25	1.0925 (3)	0.34759 (19)	0.6623 (3)	0.1191 (14)
H2A5	1.1101	0.3666	0.6156	0.179*
H2B5	1.1287	0.2951	0.6667	0.179*
H2C5	1.1396	0.3810	0.6956	0.179*
C35	0.8974 (6)	0.3175 (2)	0.74756 (17)	0.1367 (19)
H3A5	0.7957	0.3189	0.7532	0.205*
H3B5	0.9412	0.3498	0.7828	0.205*
H3C5	0.9305	0.2645	0.7525	0.205*
C45	0.8569 (4)	0.30347 (18)	0.6201 (2)	0.1093 (11)
H4A5	0.8820	0.3241	0.5748	0.164*
H4B5	0.7560	0.3092	0.6273	0.164*
H4C5	0.8819	0.2489	0.6223	0.164*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C10	0.136 (2)	0.0469 (12)	0.0593 (13)	−0.0278 (15)	−0.0160 (14)	0.0080 (10)
C20	0.109 (2)	0.0717 (16)	0.0765 (16)	−0.0142 (15)	−0.0238 (15)	0.0014 (13)
C30	0.123 (3)	0.099 (2)	0.137 (3)	−0.014 (2)	−0.024 (3)	0.038 (2)
C40	0.142 (4)	0.117 (4)	0.239 (7)	−0.058 (4)	−0.082 (5)	0.082 (4)
C50	0.236 (8)	0.122 (4)	0.234 (7)	−0.112 (5)	−0.138 (6)	0.057 (4)
C60	0.217 (5)	0.0707 (19)	0.095 (2)	−0.055 (3)	−0.035 (3)	0.0001 (17)
C70	0.165 (3)	0.0422 (12)	0.0889 (19)	−0.0050 (15)	0.008 (2)	−0.0008 (12)
O00	0.1035 (12)	0.0553 (8)	0.0660 (9)	0.0009 (8)	−0.0050 (8)	0.0133 (7)
C80	0.0628 (11)	0.0519 (10)	0.0475 (10)	0.0096 (9)	−0.0007 (9)	0.0028 (8)
O80	0.0881 (10)	0.0515 (8)	0.0487 (7)	−0.0016 (7)	−0.0046 (7)	−0.0041 (6)
N1	0.0583 (9)	0.0590 (9)	0.0418 (8)	0.0058 (7)	−0.0078 (7)	0.0050 (7)
CA1	0.0468 (9)	0.0610 (11)	0.0429 (9)	−0.0013 (8)	−0.0020 (7)	0.0001 (8)
CL1	0.0484 (10)	0.0894 (16)	0.0596 (12)	0.0119 (11)	0.0025 (9)	0.0035 (11)
CR1	0.0752 (14)	0.0852 (15)	0.0498 (11)	−0.0208 (12)	−0.0142 (10)	−0.0013 (10)
C1	0.0478 (9)	0.0419 (9)	0.0386 (8)	−0.0022 (7)	−0.0011 (7)	−0.0053 (7)
O1	0.0546 (7)	0.0562 (7)	0.0443 (6)	−0.0024 (6)	0.0027 (5)	0.0044 (6)
N2	0.0472 (7)	0.0488 (8)	0.0371 (7)	0.0032 (6)	0.0030 (6)	−0.0001 (6)
CA2	0.0499 (9)	0.0462 (9)	0.0451 (9)	0.0077 (7)	0.0046 (7)	0.0010 (7)
CL2	0.0834 (15)	0.0475 (11)	0.0733 (14)	0.0123 (10)	0.0044 (12)	−0.0111 (10)
CR2	0.0522 (10)	0.0807 (14)	0.0548 (11)	0.0133 (11)	0.0095 (9)	0.0110 (10)
C2	0.0495 (9)	0.0513 (10)	0.0435 (9)	0.0044 (8)	0.0033 (7)	0.0032 (7)
O2	0.0969 (12)	0.0620 (9)	0.0573 (9)	0.0175 (8)	−0.0084 (8)	0.0147 (7)
N3	0.0448 (7)	0.0502 (8)	0.0379 (7)	0.0033 (6)	−0.0026 (6)	0.0000 (6)
CA3	0.0421 (9)	0.0649 (11)	0.0425 (9)	−0.0024 (8)	−0.0018 (7)	−0.0061 (8)
CL3	0.0454 (10)	0.109 (2)	0.0632 (12)	0.0041 (11)	−0.0092 (9)	−0.0072 (13)
CR3	0.0762 (14)	0.0627 (13)	0.0642 (12)	−0.0178 (11)	−0.0037 (11)	−0.0073 (10)
C3	0.0494 (9)	0.0602 (10)	0.0371 (8)	0.0002 (8)	−0.0018 (7)	−0.0039 (7)
O3	0.0675 (9)	0.1385 (17)	0.0408 (7)	−0.0235 (10)	0.0002 (7)	−0.0187 (9)
N4	0.0421 (7)	0.0550 (9)	0.0353 (7)	0.0037 (6)	−0.0016 (6)	−0.0029 (6)
CA4	0.0432 (8)	0.0524 (10)	0.0397 (8)	0.0058 (7)	0.0010 (7)	0.0012 (7)
CL4	0.0499 (9)	0.0596 (11)	0.0609 (11)	−0.0012 (8)	0.0025 (9)	−0.0020 (9)
C4	0.0451 (8)	0.0534 (10)	0.0426 (9)	0.0017 (8)	0.0016 (7)	−0.0031 (7)
O4	0.0936 (11)	0.0714 (10)	0.0519 (8)	0.0141 (8)	0.0192 (8)	−0.0052 (7)
O5	0.0907 (10)	0.0507 (7)	0.0479 (7)	0.0204 (7)	0.0081 (7)	0.0014 (6)
C15	0.0717 (13)	0.0451 (10)	0.0659 (12)	0.0141 (9)	0.0015 (11)	−0.0056 (9)
C25	0.0610 (15)	0.0785 (18)	0.218 (4)	0.0135 (14)	−0.015 (2)	0.014 (2)
C35	0.240 (5)	0.0813 (19)	0.089 (2)	0.078 (3)	0.040 (3)	0.0299 (17)
C45	0.125 (3)	0.0600 (15)	0.143 (3)	−0.0191 (16)	−0.033 (2)	−0.0080 (17)

Geometric parameters (Å, º)

C10—C60	1.389 (4)	CR2—HR22	0.9600
C10—C20	1.365 (5)	CR2—HR32	0.9600
C10—C70	1.515 (5)	C2—O2	1.207 (2)
C20—C30	1.375 (5)	C2—N3	1.349 (3)
C20—H20	0.9300	N3—CA3	1.469 (2)
C30—C40	1.358 (7)	N3—H03	0.861 (16)
C30—H30	0.9300	CA3—CL3	1.537 (3)
C40—C50	1.390 (11)	CA3—CR3	1.524 (3)
C40—H40	0.9300	CA3—C3	1.537 (3)
C50—C60	1.376 (9)	CL3—HL13	0.9600
C50—H50	0.9300	CL3—HL23	0.9600
C60—H60	0.9300	CL3—HL33	0.9600
C70—O00	1.449 (4)	CG3—HR13	0.9600
C70—H7A0	0.9700	CG3—HR23	0.9600
C70—H7B0	0.9700	CG3—HR33	0.9600
O00—C80	1.344 (3)	C3—O3	1.224 (2)
C80—O80	1.225 (2)	C3—N4	1.327 (2)
C80—N1	1.328 (3)	N4—CA4	1.452 (2)
N1—CA1	1.461 (3)	N4—H04	0.849 (16)
N1—H01	0.888 (18)	CA4—CL4	1.526 (3)
CA1—CL1	1.528 (3)	CA4—C4	1.525 (3)
CA1—CR1	1.537 (3)	CA4—HA4	0.9800
CA1—C1	1.533 (3)	CL4—HL14	0.9600
CL1—HL11	0.9600	CL4—HL24	0.9600
CL1—HL21	0.9600	CL4—HL34	0.9600
CL1—HL31	0.9600	C4—O4	1.204 (2)
CR1—HR11	0.9600	C4—O5	1.316 (2)
CR1—HR21	0.9600	O5—C15	1.489 (2)
CR1—HR31	0.9600	C15—C35	1.496 (4)
C1—O1	1.224 (2)	C15—C25	1.490 (4)
C1—N2	1.344 (2)	C15—C45	1.503 (4)
N2—CA2	1.475 (2)	C25—H2A5	0.9600
N2—H02	0.871 (15)	C25—H2B5	0.9600
CA2—CL2	1.521 (3)	C25—H2C5	0.9600
CA2—CR2	1.527 (3)	C35—H3A5	0.9600
CA2—C2	1.551 (3)	C35—H3B5	0.9600
CG2—HL12	0.9600	C35—H3C5	0.9600
CG2—HL22	0.9600	C45—H4A5	0.9600
CG2—HL32	0.9600	C45—H4B5	0.9600
CR2—HR12	0.9600	C45—H4C5	0.9600
C60—C10—C20	119.1 (4)	CA2—CL2—HL32	109.5
C60—C10—C70	117.7 (4)	HL12—CL2—HL32	109.5
C20—C10—C70	123.2 (3)	HL22—CL2—HL32	109.5
C30—C20—C10	121.9 (3)	O2—C2—N3	124.44 (18)
C30—C20—H20	119.1	O2—C2—CA2	120.30 (17)
C10—C20—H20	119.1	N3—C2—CA2	115.08 (15)
C20—C30—C40	119.9 (5)	C2—N3—CA3	125.08 (16)
C20—C30—H30	120.1	C2—N3—H03	117.5 (14)
C40—C30—H30	120.1	CA3—N3—H03	117.1 (14)
C30—C40—C50	118.8 (6)	N3—CA3—CL3	111.98 (17)
C30—C40—H40	120.6	N3—CA3—C3	112.07 (14)
C50—C40—H40	120.6	C3—CA3—CL3	109.77 (16)
C60—C50—C40	121.6 (5)	CL3—CA3—CR3	110.13 (19)
C60—C50—H50	119.2	CA3—CR3—HR13	109.5
C40—C50—H50	119.2	CA3—CR3—HR23	109.5
C50—C60—C10	118.7 (5)	HR13—CR3—HR23	109.5
C50—C60—H60	120.7	CA3—CR3—HR33	109.5
C10—C60—H60	120.7	HR13—CR3—HR33	109.5
O00—C70—C10	113.2 (2)	HR23—CR3—HR33	109.5
O00—C70—H7A0	108.9	CA3—CL3—HL13	109.5
C10—C70—H7A0	108.9	CA3—CL3—HL23	109.5
O00—C70—H7B0	108.9	HL13—CL3—HL23	109.5
C10—C70—H7B0	108.9	CA3—CL3—HL33	109.5
H7A0—C70—H7B0	107.8	HL13—CL3—HL33	109.5
C80—O00—C70	115.51 (19)	HL23—CL3—HL33	109.5
O80—C80—N1	125.1 (2)	O3—C3—N4	122.05 (17)
O80—C80—O00	123.7 (2)	O3—C3—CA3	119.40 (17)
N1—C80—O00	111.22 (17)	N4—C3—CA3	118.30 (15)
C80—N1—CA1	120.98 (16)	C3—N4—CA4	120.71 (14)
C80—N1—H01	122 (2)	C3—N4—H04	126.8 (16)
CA1—N1—H01	117 (2)	CA4—N4—H04	112.4 (17)
N1—CA1—CR1	107.73 (16)	N4—CA4—CL4	110.86 (14)
N1—CA1—C1	110.98 (15)	N4—CA4—C4	112.00 (15)
C1—CA1—CR1	107.06 (17)	CL4—CA4—C4	108.99 (15)
N2—CA2—CR2	107.58 (14)	N4—CA4—HA4	108.3
C2—CA2—CR2	107.19 (16)	CL4—CA4—HA4	108.3
N3—CA3—CR3	107.07 (17)	C4—CA4—HA4	108.3
C3—CA3—CR3	105.60 (17)	CL4—CL4—HL14	109.5
N1—CA1—CL1	111.44 (18)	CL4—CL4—HL24	109.5
CR1—CA1—CL1	109.90 (18)	HL14—CL4—HL24	109.5
C1—CA1—CL1	109.61 (14)	CA4—CL4—HL34	109.5
CA1—CL1—HL11	109.5	HL14—CL4—HL34	109.5
CA1—CL1—HL21	109.5	HL24—CL4—HL34	109.5
HL11—CL1—HL21	109.5	O4—C4—O5	125.77 (17)
CA1—CL1—HL31	109.5	O4—C4—CA4	122.39 (17)
HL11—CL1—HL31	109.5	O5—C4—CA4	111.79 (14)
HL21—CL1—HL31	109.5	C4—O5—C15	123.23 (16)
CA1—CR1—HR11	109.5	O5—C15—C35	103.25 (18)
CA1—CR1—HR21	109.5	O5—C15—C25	109.1 (2)
HR11—CR1—HR21	109.5	C35—C15—C25	113.5 (3)
CA1—CR1—HR31	109.5	O5—C15—C45	108.9 (2)
HR11—CR1—HR31	109.5	C35—C15—C45	110.7 (3)
HR21—CR1—HR31	109.5	C25—C15—C45	111.0 (3)
O1—C1—N2	122.64 (17)	C15—C25—H2A5	109.5
O1—C1—CA1	120.60 (16)	C15—C25—H2B5	109.5
N2—C1—CA1	116.71 (14)	H2A5—C25—H2B5	109.5
C1—N2—CA2	122.16 (14)	C15—C25—H2C5	109.5
C1—N2—H02	118.2 (16)	H2A5—C25—H2C5	109.5
CA2—N2—H02	118.9 (16)	H2B5—C25—H2C5	109.5
N2—CA2—CL2	109.97 (17)	C15—C35—H3A5	109.5
CR2—CA2—CL2	111.13 (17)	C15—C35—H3B5	109.5
N2—CA2—C2	110.79 (14)	H3A5—C35—H3B5	109.5
C2—CA2—CL2	110.12 (17)	C15—C35—H3C5	109.5
CA2—CR2—HR12	109.5	H3A5—C35—H3C5	109.5
CA2—CR2—HR22	109.5	H3B5—C35—H3C5	109.5
HR12—CR2—HR22	109.5	C15—C45—H4A5	109.5
CA2—CR2—HR32	109.5	C15—C45—H4B5	109.5
HR12—CR2—HR32	109.5	H4A5—C45—H4B5	109.5
HR22—CR2—HR32	109.5	C15—C45—H4C5	109.5
CA2—CL2—HL12	109.5	H4A5—C45—H4C5	109.5
CA2—CL2—HL22	109.5	H4B5—C45—H4C5	109.5
HL12—CL2—HL22	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H03···O80	0.86 (2)	2.31 (2)	3.117 (2)	156 (2)
N4—H04···O1	0.85 (2)	2.22 (2)	3.059 (2)	169 (2)
N1—H01···O3^i	0.89 (2)	2.05 (2)	2.929 (2)	171 (3)
N2—H02···O4^i	0.87 (2)	2.27 (2)	3.121 (2)	165 (2)

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