The antifolate trimetrexate: ­observation of the enzyme-binding conformation

The crystal structure of the title compound contains four 2,4-di­amino-5-methyl-6-[(3,4,5-tri­methoxy­anilino)­methyl]­quin­az­oline mol­ecules, two di­methyl sulfoxide mol­ecules and three water mol­ecules in the asymmetric unit, i.e. 4C₁₉H₂₃N₅O₃·2C₂H₆OS·3H₂O. All four quinazoline mol­ecules adopt trans,gauche conformations. An extensive hydrogen-bond network involving N...N base-pairing interactions, as well as the di­methyl sulfoxide and water mol­ecules, stabilizes the crystal structure.

S1. Comment

Trimetrexate (TMQ), a lipophilic antifolate, is a well known dihydrofolate reductase (DHFR) inhibitor and is widely used in cancer therapy and for the treatment of a variety of non-malignant disorders. We elucidated the present particular crystal structure of TMQ as a continuation of our studies into the effects of increased lipophilicity on the conformational properties and stereochemical parameters in antifolates, which may indicate a direction in development of new agents with better pharmacological profiles.

The asymmetric unit of the present crystal structure, (I), consists of four independent TMQ molecules, all adopting trans,gauche conformations [molecule A: τ₁ = 176.9 (3)° and τ₂ = 92.0 (4)°; molecule B: 178.8 (3)° and 80.9 (4)°; molecule C: 174.2 (3)° and 85.5 (4)°; molecule D: 164.9 (3)° and 92.8 (4)°; the τ₁ and τ₂ torsion angles are defined by C1—C2—C14—N15 and C2—C14–N15—-C16, respectively], two dimethyl sulfoxide molecules and three water molecules. All four TMQ molecules show partially folded conformations, with the planes of the trimethoxyanilino rings twisted from those of the quinazoline rings by 84.3 (1), 86.7 (1), 89.8 (1) and 85.8 (1)° for molecules A, B, C and D, respectively. In previously reported crystal forms of trimetrexate (Sutton & Cody, 1987; Hempel et al., 1988), the molecules exhibited gauche,trans conformations. There is substantial evidence, however, that the trans,gauche conformations observed for the first time in the present crystal structure is the one responsible for enzyme inhibition. The crystal structure of DHFR with methotrexate (MTX) (Bolin et al., 1982) showed MTX to have a similar trans,gauche conformation when bound to the enzyme. Simulated annealing calculations performed for the solution structure of the complex of Lactobacillus casei DHFR with MTX (Gargaro et al., 1998) showed that the stereochemistry of the binary complex in solution is very similar to that reported for the crystal structure. Similar calculations based on an analysis of the multidimensional NMR spectra of the complex of Lactobacillus casei DHFR with TMQ in solution have produced a family of 22 conformations of TMQ, all exclusively in the trans,gauche form, implying that this conformation of TMQ (molecules A or B in this report) is also that which is present in the active site of dihydrofolate reductase (Polshakov et al., 1999).

A conformational analysis of TMQ using empirical force-field and AM1 quantum mechanical methods, concluded that TMQ prefers a gauche,trans rather than a trans,gauche conformation, in contrast with MTX which prefers an approximate trans,gauche conformatio (Hoffman & Welsh, 1995). While this conclusion is in agreement with the conformations observed in the crystal structures of trimetrexate reported previously, it is not true for the crystal structure presented in this study, where TMQ molecules adopt the opposite trans,gauche form. A comparison of the stereochemistry of molecule A of TMQ with that of MTX bound to DHFR in the crystal structure complex is shown in Fig. 2. The two structures are conformationally very closely related, indicating possible replacement of MTX by TMQ with little change in the stereochemistry of the enzyme–inhibitor binding.

The four independent TMQ molecules are hydrogen bonded among themselves through N···N base-pairing interactions involving the N7···N13 and N5···N12 systems (Table 1 and Fig. 3). In other antifolate structures, only partial base-pairing interactions have been reported, i.e. N7···N13 for TMQ monoacetate monohydrate and free base (Hempel et al., 1988), N7···N12 for quinespar (Mastropaolo et al., 1986) and no base-pairing in TMQ dimethyl sulfoxide hydrate (Sutton & Cody, 1987). Interestingly, no direct N···O hydrogen bonds exist between TMQ molecules in the crystal packing. The N···O bond occurs exclusively between TMQ and solvent (water and dimethyl sulfoxide) molecules. The water molecules connect TMQ molecules through hydrogen bonds to methoxy O atoms and the N12 and N13 atoms of the quinazoline. Curiously, the two potential hydrogen-bond donors (N15B—H15B and N15C—H15C), being surrounded by N13 and N7 atom pairs from different molecules, do not participate in classical hydrogen bonding due to longer than usual D···A distances.

S2. Experimental

Trimetrexate (NSC 249008-T) was obtained from the NCI Drug Synthesis and Chemistry Branch (NCI National Service Center). Crystals were obtained as pale yellow prisms by slow solvent evaporation from a water–dimethyl sulfoxide mixture.

S3. Refinement

The H atoms bound to N atoms and those in the water molecules were found from the difference electron-density calculations and were refined independently [range of distances 0.72 (3)–0.98 (5) Å]. The remaining H atoms were calculated geometrically and were treated as riding atoms (range of distances 0.93–0.98 Å).

Computing details

Data collection: Nonius KappaCCD Server Software (Nonius, 1997); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. ORTEP-3 (Farrugia, 1997) view of the pairs of molecules (A/B and C/D) of similar conformation, showing 50% probability displacement elipsoids. For clarity, only H atoms taking part in hydrogen bonding are drawn as small circles of arbitrary radii.
	Fig. 2. Superposition of the TMQ (molecile A, solid lines) with that of MTX in the complex with DHFR (hollow lines).
	Fig. 3. The crystal packing and hydrogen-bond geometry (dashed lines) in the title compound.

2,4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline

Crystal data

4C19H23N5O3·2C2H6OS·3H2O	Z = 2
Mr = 1688.02	F(000) = 1796
Triclinic, P1	Dx = 1.330 Mg m^−3
a = 16.124 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 16.371 (2) Å	Cell parameters from all reflections reflections
c = 17.766 (1) Å	µ = 0.14 mm^−1
α = 81.676 (3)°	T = 100 K
β = 66.289 (2)°	Prism, pale yellow
γ = 80.050 (3)°	0.50 × 0.40 × 0.37 mm
V = 4214.4 (8) Å^3

Data collection

Nonius KappaCCD diffractometer	6946 reflections with I > 2σ(I)
Radiation source: rotating-anode	Rint = 0.000
Graphite monochromator	θmax = 26.4°, θmin = 4.1°
ω rotation scans	h = 0→20
16962 measured reflections	k = −19→20
16962 independent reflections	l = −20→22

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)] = 0.065	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.168	H atoms treated by a mixture of independent and constrained refinement
S = 0.88	w = 1/[σ^2(Fo^2) + (0.0735P)^2] where P = (Fo^2 + 2Fc^2)/3
16962 reflections	(Δ/σ)max = 0.001
1174 parameters	Δρmax = 0.36 e Å^−3
0 restraints	Δρmin = −0.47 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. 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
C1A	0.3884 (2)	0.2290 (2)	0.5196 (2)	0.0306 (9)
C2A	0.3911 (2)	0.1537 (2)	0.56635 (19)	0.0315 (9)
C3A	0.4721 (2)	0.0975 (2)	0.5452 (2)	0.0341 (10)
H3A	0.4726	0.0468	0.5765	0.0264 (15)*
C4A	0.5501 (2)	0.1155 (2)	0.47994 (19)	0.0342 (10)
H4A	0.6029	0.0776	0.4683	0.0264 (15)*
N5A	0.63273 (18)	0.20490 (18)	0.36555 (15)	0.0288 (7)
C6A	0.6309 (2)	0.2746 (2)	0.31824 (19)	0.0290 (9)
N7A	0.5562 (2)	0.33161 (19)	0.32545 (16)	0.0302 (7)
C8A	0.4775 (2)	0.3201 (2)	0.38924 (19)	0.0285 (9)
C9A	0.4699 (2)	0.2479 (2)	0.44848 (19)	0.0280 (9)
C10A	0.5513 (2)	0.1909 (2)	0.43019 (19)	0.0291 (9)
C11A	0.3020 (2)	0.2895 (2)	0.5455 (2)	0.0385 (10)
H11A	0.2566	0.2659	0.5941	0.0478 (16)*
H11B	0.2799	0.3005	0.5019	0.0478 (16)*
H11C	0.3144	0.3405	0.5572	0.0478 (16)*
N12A	0.7108 (2)	0.2920 (2)	0.25637 (19)	0.0360 (9)
N13A	0.4065 (2)	0.3773 (2)	0.3897 (2)	0.0404 (9)
C14A	0.3066 (2)	0.1290 (2)	0.6414 (2)	0.0338 (10)
H14A	0.2892	0.1693	0.6818	0.0264 (15)*
H14B	0.2564	0.1318	0.6238	0.0264 (15)*
N15A	0.3196 (2)	0.0466 (2)	0.68071 (17)	0.0335 (8)
C16A	0.3481 (2)	0.0309 (2)	0.74604 (19)	0.0300 (9)
C17A	0.3826 (2)	0.0909 (2)	0.7694 (2)	0.0347 (10)
H17A	0.3894	0.1426	0.7396	0.0264 (15)*
C18A	0.4072 (2)	0.0734 (3)	0.8379 (2)	0.0338 (10)
C19A	0.3979 (2)	−0.0035 (3)	0.8827 (2)	0.0309 (9)
C20A	0.3652 (2)	−0.0643 (2)	0.85776 (19)	0.0293 (9)
C21A	0.3411 (2)	−0.0478 (2)	0.78995 (19)	0.0274 (9)
H21A	0.3203	−0.0889	0.7735	0.0264 (15)*
O22A	0.43835 (19)	0.13345 (19)	0.86320 (15)	0.0501 (8)
C23A	0.5237 (3)	0.1521 (3)	0.8135 (3)	0.0738 (16)
H23A	0.5665	0.1024	0.8071	0.0478 (16)*
H23B	0.5404	0.1919	0.8378	0.0478 (16)*
H23C	0.5242	0.1752	0.7604	0.0478 (16)*
O24A	0.41628 (16)	−0.02002 (16)	0.95432 (13)	0.0367 (7)
C25A	0.5040 (3)	−0.0685 (3)	0.9405 (2)	0.0397 (10)
H25A	0.5111	−0.1145	0.9096	0.0478 (16)*
H25B	0.5077	−0.0890	0.9926	0.0478 (16)*
H25C	0.5515	−0.0342	0.9101	0.0478 (16)*
O26A	0.35833 (16)	−0.13854 (16)	0.90676 (13)	0.0361 (7)
C27A	0.3344 (3)	−0.2051 (3)	0.8794 (2)	0.0428 (11)
H27A	0.2766	−0.1885	0.8745	0.0478 (16)*
H27B	0.3302	−0.2528	0.9185	0.0478 (16)*
H27C	0.3803	−0.2188	0.8266	0.0478 (16)*
C1B	0.5634 (2)	0.5593 (2)	0.02767 (19)	0.0268 (9)
C2B	0.5550 (2)	0.6213 (2)	−0.03224 (19)	0.0296 (9)
C3B	0.4889 (2)	0.6908 (2)	−0.0102 (2)	0.0322 (9)
H3B	0.4868	0.7330	−0.0508	0.0264 (15)*
C4B	0.4276 (2)	0.6987 (2)	0.06890 (19)	0.0283 (9)
H4B	0.3845	0.7457	0.0817	0.0264 (15)*
N5B	0.36028 (18)	0.64222 (19)	0.20859 (16)	0.0287 (7)
C6B	0.3613 (2)	0.5785 (2)	0.2640 (2)	0.0294 (9)
N7B	0.42905 (19)	0.5143 (2)	0.25532 (16)	0.0317 (8)
C8B	0.5009 (2)	0.5108 (2)	0.1822 (2)	0.0274 (9)
C9B	0.5008 (2)	0.5685 (2)	0.1119 (2)	0.0278 (9)
C10B	0.4297 (2)	0.6357 (2)	0.13101 (19)	0.0271 (9)
C11B	0.6336 (2)	0.4835 (2)	0.0015 (2)	0.0351 (10)
H11D	0.6502	0.4783	−0.0561	0.0478 (16)*
H11E	0.6083	0.4347	0.0332	0.0478 (16)*
H11F	0.6869	0.4897	0.0107	0.0478 (16)*
N12B	0.2867 (2)	0.5757 (2)	0.33609 (18)	0.0351 (9)
N13B	0.5685 (2)	0.4514 (2)	0.18107 (19)	0.0390 (10)
C14B	0.6171 (2)	0.6122 (2)	−0.12352 (19)	0.0335 (9)
H14C	0.6802	0.6080	−0.1297	0.0264 (15)*
H14D	0.6089	0.5607	−0.1391	0.0264 (15)*
N15B	0.6001 (2)	0.6798 (2)	−0.17920 (17)	0.0372 (9)
C16B	0.6344 (2)	0.7539 (2)	−0.1919 (2)	0.0324 (10)
C17B	0.6801 (2)	0.7709 (2)	−0.1452 (2)	0.0316 (9)
H17B	0.6855	0.7325	−0.1029	0.0264 (15)*
C18B	0.7177 (2)	0.8448 (2)	−0.1613 (2)	0.0323 (9)
C19B	0.7115 (3)	0.9035 (2)	−0.2263 (2)	0.0337 (9)
C20B	0.6624 (2)	0.8867 (3)	−0.2702 (2)	0.0342 (10)
C21B	0.6235 (2)	0.8142 (2)	−0.25381 (19)	0.0319 (9)
H21B	0.5902	0.8050	−0.2834	0.0264 (15)*
O22B	0.76314 (17)	0.86766 (17)	−0.11841 (14)	0.0405 (7)
C23B	0.7498 (3)	0.8248 (3)	−0.0391 (2)	0.0493 (12)
H23D	0.6857	0.8286	−0.0055	0.0478 (16)*
H23E	0.7802	0.8497	−0.0132	0.0478 (16)*
H23F	0.7746	0.7674	−0.0454	0.0478 (16)*
O24B	0.74881 (18)	0.97609 (17)	−0.24214 (14)	0.0419 (7)
C25B	0.8423 (3)	0.9684 (3)	−0.3003 (2)	0.0501 (12)
H25D	0.8788	0.9281	−0.2778	0.0478 (16)*
H25E	0.8648	1.0213	−0.3111	0.0478 (16)*
H25F	0.8456	0.9508	−0.3508	0.0478 (16)*
O26B	0.65810 (17)	0.94779 (17)	−0.33095 (14)	0.0416 (7)
C27B	0.6039 (3)	0.9377 (3)	−0.3747 (2)	0.0450 (11)
H27D	0.6267	0.8869	−0.4015	0.0478 (16)*
H27E	0.6067	0.9838	−0.4154	0.0478 (16)*
H27F	0.5417	0.9357	−0.3368	0.0478 (16)*
C1C	1.0667 (2)	0.0677 (2)	0.01269 (19)	0.0264 (9)
C2C	1.0541 (2)	0.1279 (2)	−0.04736 (19)	0.0282 (9)
C3C	0.9836 (2)	0.1942 (2)	−0.02490 (19)	0.0288 (9)
H3C	0.9781	0.2352	−0.0653	0.0264 (15)*
C4C	0.9224 (2)	0.2002 (2)	0.05537 (19)	0.0297 (9)
H4C	0.8763	0.2449	0.0685	0.0264 (15)*
N5C	0.86151 (18)	0.14490 (19)	0.19564 (15)	0.0286 (7)
C6C	0.8698 (2)	0.0860 (2)	0.25226 (19)	0.0278 (9)
N7C	0.94177 (19)	0.02541 (19)	0.24331 (15)	0.0274 (7)
C8C	1.0087 (2)	0.0196 (2)	0.16872 (19)	0.0259 (9)
C9C	1.0047 (2)	0.0739 (2)	0.09776 (19)	0.0266 (9)
C10C	0.9293 (2)	0.1393 (2)	0.1177 (2)	0.0280 (9)
C11C	1.1419 (2)	−0.0037 (2)	−0.0129 (2)	0.0344 (10)
H11G	1.1908	0.0043	0.0020	0.0478 (16)*
H11H	1.1187	−0.0549	0.0144	0.0478 (16)*
H11I	1.1643	−0.0062	−0.0716	0.0478 (16)*
N12C	0.7979 (2)	0.0818 (2)	0.32715 (18)	0.0317 (8)
N13C	1.0767 (2)	−0.0412 (2)	0.16541 (19)	0.0343 (9)
C14C	1.1147 (2)	0.1200 (2)	−0.13932 (19)	0.0335 (10)
H14E	1.1131	0.0653	−0.1531	0.0264 (15)*
H14F	1.1773	0.1240	−0.1477	0.0264 (15)*
N15C	1.0887 (2)	0.1818 (2)	−0.19516 (18)	0.0354 (9)
C16C	1.1155 (2)	0.2596 (2)	−0.2177 (2)	0.0326 (10)
C17C	1.1694 (2)	0.2881 (2)	−0.1843 (2)	0.0338 (10)
H17C	1.1858	0.2545	−0.1443	0.0264 (15)*
C18C	1.1983 (2)	0.3659 (3)	−0.2105 (2)	0.0357 (10)
C19C	1.1751 (2)	0.4178 (2)	−0.2711 (2)	0.0338 (10)
C20C	1.1201 (2)	0.3896 (3)	−0.3031 (2)	0.0343 (10)
C21C	1.0896 (2)	0.3125 (3)	−0.2767 (2)	0.0346 (10)
H21C	1.0519	0.2954	−0.2980	0.0264 (15)*
O22C	1.25143 (18)	0.39887 (17)	−0.18035 (14)	0.0437 (7)
C23C	1.2730 (3)	0.3496 (3)	−0.1156 (3)	0.0570 (13)
H23G	1.3029	0.2958	−0.1336	0.0478 (16)*
H23H	1.3129	0.3767	−0.1020	0.0478 (16)*
H23I	1.2179	0.3434	−0.0678	0.0478 (16)*
O24C	1.21111 (17)	0.49229 (17)	−0.30187 (14)	0.0410 (7)
C25C	1.1461 (3)	0.5658 (3)	−0.2762 (2)	0.0458 (11)
H25G	1.1203	0.5642	−0.2170	0.0478 (16)*
H25H	1.1766	0.6146	−0.2986	0.0478 (16)*
H25I	1.0984	0.5676	−0.2958	0.0478 (16)*
O26C	1.10361 (17)	0.44335 (16)	−0.36433 (14)	0.0385 (7)
C27C	1.0541 (3)	0.4155 (3)	−0.4050 (2)	0.0447 (11)
H27G	0.9922	0.4122	−0.3671	0.0478 (16)*
H27H	1.0549	0.4541	−0.4513	0.0478 (16)*
H27I	1.0822	0.3616	−0.4237	0.0478 (16)*
C1D	−0.0953 (2)	0.7583 (2)	0.52608 (19)	0.0293 (9)
C2D	−0.0941 (2)	0.6861 (2)	0.57858 (19)	0.0308 (9)
C3D	−0.0104 (2)	0.6356 (2)	0.5665 (2)	0.0338 (10)
H3D	−0.0089	0.5903	0.6044	0.0264 (15)*
C4D	0.0690 (2)	0.6507 (2)	0.50095 (19)	0.0324 (9)
H4D	0.1231	0.6160	0.4950	0.0264 (15)*
N5D	0.14782 (19)	0.72581 (19)	0.37412 (15)	0.0309 (8)
C6D	0.1446 (2)	0.7865 (2)	0.3169 (2)	0.0291 (9)
N7D	0.07076 (19)	0.84447 (19)	0.32154 (16)	0.0300 (7)
C8D	−0.0052 (2)	0.8418 (2)	0.3911 (2)	0.0310 (9)
C9D	−0.0130 (2)	0.7747 (2)	0.45613 (19)	0.0290 (9)
C10D	0.0686 (2)	0.7187 (2)	0.44284 (19)	0.0296 (9)
C11D	−0.1844 (2)	0.8154 (2)	0.5425 (2)	0.0377 (10)
H11J	−0.2326	0.7908	0.5875	0.0478 (16)*
H11K	−0.1787	0.8682	0.5563	0.0478 (16)*
H11L	−0.1983	0.8234	0.4940	0.0478 (16)*
N12D	0.2214 (2)	0.7939 (2)	0.24910 (18)	0.0350 (9)
N13D	−0.0715 (2)	0.9046 (2)	0.3927 (2)	0.0438 (10)
C14D	−0.1817 (2)	0.6574 (2)	0.6469 (2)	0.0339 (10)
H14G	−0.2287	0.6638	0.6247	0.0264 (15)*
H14H	−0.2027	0.6935	0.6913	0.0264 (15)*
N15D	−0.1710 (2)	0.5721 (2)	0.68058 (17)	0.0343 (8)
C16D	−0.1497 (2)	0.5498 (3)	0.7501 (2)	0.0329 (10)
C17D	−0.1619 (2)	0.4695 (2)	0.78974 (19)	0.0295 (9)
H17D	−0.1829	0.4318	0.7693	0.0264 (15)*
C18D	−0.1422 (2)	0.4472 (2)	0.8598 (2)	0.0295 (9)
C19D	−0.1113 (2)	0.5041 (2)	0.89089 (19)	0.0297 (9)
C20D	−0.0984 (2)	0.5828 (2)	0.8513 (2)	0.0305 (9)
C21D	−0.1179 (2)	0.6064 (2)	0.78055 (19)	0.0323 (9)
H21D	−0.1095	0.6594	0.7540	0.0264 (15)*
O22D	−0.15137 (16)	0.37041 (16)	0.90407 (13)	0.0346 (6)
C23D	−0.1749 (3)	0.3081 (3)	0.8709 (2)	0.0421 (11)
H23J	−0.1279	0.2966	0.8180	0.0478 (16)*
H23K	−0.1811	0.2583	0.9075	0.0478 (16)*
H23L	−0.2317	0.3274	0.8646	0.0478 (16)*
O24D	−0.09359 (16)	0.47976 (16)	0.96293 (12)	0.0336 (6)
C25D	−0.0053 (3)	0.4303 (3)	0.9456 (2)	0.0389 (10)
H25J	0.0421	0.4642	0.9134	0.0478 (16)*
H25K	0.0013	0.4094	0.9965	0.0478 (16)*
H25L	−0.0007	0.3845	0.9154	0.0478 (16)*
O26D	−0.06626 (17)	0.63389 (16)	0.88488 (14)	0.0394 (7)
C27D	−0.0396 (3)	0.7114 (3)	0.8389 (2)	0.0489 (11)
H27J	−0.0913	0.7446	0.8312	0.0478 (16)*
H27K	−0.0175	0.7408	0.8686	0.0478 (16)*
H27L	0.0079	0.7006	0.7860	0.0478 (16)*
S1	0.52004 (8)	0.60969 (8)	0.42897 (6)	0.0550 (3)
O10	0.4202 (2)	0.6042 (2)	0.47965 (18)	0.0783 (11)
C10	0.5622 (3)	0.5290 (3)	0.3629 (2)	0.0539 (12)
H10A	0.5245	0.5311	0.3322	0.090 (5)*
H10B	0.6237	0.5355	0.3254	0.090 (5)*
H10C	0.5614	0.4764	0.3949	0.090 (5)*
C11	0.5236 (4)	0.6931 (3)	0.3520 (3)	0.0740 (15)
H11M	0.4963	0.7440	0.3778	0.090 (5)*
H11N	0.5859	0.6978	0.3159	0.090 (5)*
H11O	0.4905	0.6825	0.3208	0.090 (5)*
S2	0.81210 (8)	0.11711 (8)	0.52811 (6)	0.0506 (3)
O20	0.80403 (18)	0.04328 (17)	0.49061 (14)	0.0480 (8)
C20	0.7034 (3)	0.1397 (3)	0.6094 (2)	0.0562 (13)
H20A	0.6564	0.1471	0.588	0.090 (5)*
H20B	0.7021	0.1897	0.6323	0.090 (5)*
H20C	0.6932	0.0944	0.6516	0.090 (5)*
C21	0.8023 (3)	0.2082 (3)	0.4606 (3)	0.0655 (14)
H21E	0.8555	0.2066	0.4101	0.090 (5)*
H21F	0.7970	0.2571	0.4869	0.090 (5)*
H21G	0.7490	0.2094	0.4487	0.090 (5)*
O1	0.27720 (19)	0.92696 (19)	0.10636 (15)	0.0400 (8)
O2	0.77114 (19)	0.4361 (2)	0.11907 (16)	0.0414 (8)
O3	0.2827 (2)	0.5073 (2)	0.50438 (16)	0.0490 (8)
H12G	0.269 (2)	0.749 (2)	0.2418 (18)	0.0264 (15)*
H15D	−0.195 (2)	0.537 (2)	0.6678 (19)	0.0264 (15)*
H12A	0.755 (2)	0.255 (2)	0.2439 (19)	0.0264 (15)*
H12E	0.752 (2)	0.122 (2)	0.3346 (19)	0.0264 (15)*
H15A	0.293 (2)	0.006 (2)	0.6728 (19)	0.0264 (15)*
H12B	0.716 (2)	0.332 (2)	0.2244 (19)	0.0264 (15)*
H13C	0.613 (2)	0.450 (2)	0.146 (2)	0.0264 (15)*
H12C	0.293 (2)	0.548 (2)	0.3731 (19)	0.0264 (15)*
H13A	0.418 (2)	0.420 (2)	0.3487 (19)	0.0264 (15)*
H13E	1.076 (2)	−0.069 (2)	0.21 (2)	0.0264 (15)*
H12H	0.227 (2)	0.824 (2)	0.214 (2)	0.0264 (15)*
H13B	0.357 (2)	0.382 (2)	0.4318 (19)	0.0264 (15)*
H13G	−0.115 (2)	0.916 (2)	0.4384 (19)	0.0264 (15)*
H12F	0.811 (2)	0.055 (2)	0.363 (2)	0.0264 (15)*
H13F	1.124 (2)	−0.040 (2)	0.1296 (19)	0.0264 (15)*
H13D	0.565 (2)	0.421 (2)	0.228 (2)	0.0264 (15)*
H12D	0.251 (2)	0.624 (2)	0.3504 (19)	0.0264 (15)*
H15B	0.585 (2)	0.663 (2)	−0.21 (2)	0.0264 (15)*
H13H	−0.064 (2)	0.943 (2)	0.351 (19)	0.0264 (15)*
H15C	1.063 (2)	0.167 (2)	−0.216 (2)	0.0264 (15)*
H11	0.280 (3)	0.966 (3)	0.131 (2)	0.060 (6)*
H12	0.313 (3)	0.935 (3)	0.063 (2)	0.060 (6)*
H21	0.806 (3)	0.443 (3)	0.076 (2)	0.060 (6)*
H22	0.769 (3)	0.482 (3)	0.143 (2)	0.060 (6)*
H31	0.327 (3)	0.540 (3)	0.506 (2)	0.060 (6)*
H32	0.249 (3)	0.507 (3)	0.553 (2)	0.060 (6)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1A	0.031 (2)	0.030 (2)	0.0268 (19)	0.0006 (19)	−0.0094 (17)	0.0024 (17)
C2A	0.030 (2)	0.033 (3)	0.0232 (18)	−0.001 (2)	−0.0060 (16)	0.0059 (17)
C3A	0.038 (2)	0.028 (2)	0.0270 (19)	0.002 (2)	−0.0085 (18)	0.0077 (17)
C4A	0.030 (2)	0.032 (3)	0.028 (2)	0.0041 (19)	−0.0055 (17)	0.0058 (18)
N5A	0.0237 (17)	0.028 (2)	0.0240 (15)	0.0008 (15)	−0.0029 (13)	0.0069 (14)
C6A	0.028 (2)	0.029 (2)	0.0225 (19)	−0.004 (2)	−0.0036 (17)	0.0017 (18)
N7A	0.0303 (19)	0.026 (2)	0.0259 (16)	0.0041 (16)	−0.0065 (14)	0.0022 (14)
C8A	0.024 (2)	0.029 (2)	0.0235 (19)	0.0039 (19)	−0.0036 (16)	−0.0014 (17)
C9A	0.026 (2)	0.029 (2)	0.0216 (18)	0.0006 (18)	−0.0056 (16)	0.0022 (16)
C10A	0.030 (2)	0.030 (2)	0.0231 (18)	0.0030 (19)	−0.0096 (17)	0.0005 (17)
C11A	0.031 (2)	0.035 (3)	0.030 (2)	0.002 (2)	0.0006 (17)	0.0128 (18)
N12A	0.033 (2)	0.027 (2)	0.0322 (19)	0.0052 (17)	−0.0041 (17)	0.0108 (15)
N13A	0.027 (2)	0.040 (2)	0.0324 (19)	0.0020 (19)	0.0023 (15)	0.0159 (17)
C14A	0.028 (2)	0.038 (3)	0.0284 (19)	−0.0028 (19)	−0.0067 (17)	0.0030 (18)
N15A	0.037 (2)	0.030 (2)	0.0267 (16)	−0.0049 (16)	−0.0089 (15)	0.0069 (15)
C16A	0.023 (2)	0.040 (3)	0.0196 (18)	−0.0041 (19)	−0.0006 (16)	−0.0008 (18)
C17A	0.033 (2)	0.034 (3)	0.026 (2)	−0.008 (2)	0.0001 (17)	0.0047 (18)
C18A	0.028 (2)	0.038 (3)	0.026 (2)	−0.004 (2)	0.0011 (17)	−0.0070 (19)
C19A	0.024 (2)	0.040 (3)	0.0237 (19)	0.0019 (19)	−0.0065 (16)	−0.0047 (19)
C20A	0.019 (2)	0.035 (3)	0.0246 (19)	0.0001 (18)	−0.0018 (16)	0.0034 (18)
C21A	0.022 (2)	0.030 (2)	0.0252 (19)	−0.0046 (18)	−0.0049 (16)	0.0020 (17)
O22A	0.0468 (18)	0.061 (2)	0.0374 (15)	−0.0242 (16)	−0.0030 (13)	−0.0076 (15)
C23A	0.086 (4)	0.082 (4)	0.060 (3)	−0.038 (3)	−0.025 (3)	−0.004 (3)
O24A	0.0293 (15)	0.0478 (19)	0.0274 (13)	0.0013 (14)	−0.0071 (11)	−0.0043 (12)
C25A	0.040 (3)	0.045 (3)	0.033 (2)	0.004 (2)	−0.0155 (18)	−0.0056 (19)
O26A	0.0387 (16)	0.0379 (18)	0.0318 (13)	−0.0110 (14)	−0.0152 (12)	0.0089 (13)
C27A	0.042 (3)	0.042 (3)	0.045 (2)	−0.010 (2)	−0.022 (2)	0.014 (2)
C1B	0.0183 (19)	0.029 (2)	0.0275 (19)	−0.0031 (18)	−0.0040 (15)	0.0005 (17)
C2B	0.023 (2)	0.033 (3)	0.0265 (19)	−0.0027 (19)	−0.0057 (16)	0.0020 (18)
C3B	0.034 (2)	0.026 (2)	0.031 (2)	−0.003 (2)	−0.0123 (18)	0.0110 (17)
C4B	0.023 (2)	0.026 (2)	0.030 (2)	−0.0006 (17)	−0.0066 (16)	0.0040 (17)
N5B	0.0212 (16)	0.035 (2)	0.0232 (15)	0.0021 (15)	−0.0055 (13)	0.0039 (14)
C6B	0.026 (2)	0.033 (3)	0.0241 (19)	−0.003 (2)	−0.0083 (17)	0.0062 (18)
N7B	0.0248 (18)	0.034 (2)	0.0272 (16)	0.0022 (16)	−0.0061 (14)	0.0073 (14)
C8B	0.025 (2)	0.025 (2)	0.029 (2)	0.0004 (19)	−0.0109 (17)	0.0033 (17)
C9B	0.022 (2)	0.026 (2)	0.031 (2)	0.0000 (18)	−0.0094 (16)	0.0041 (17)
C10B	0.024 (2)	0.029 (2)	0.0236 (18)	−0.0024 (18)	−0.0050 (16)	−0.0001 (17)
C11B	0.030 (2)	0.037 (3)	0.0282 (19)	0.001 (2)	−0.0063 (17)	0.0043 (18)
N12B	0.034 (2)	0.034 (2)	0.0229 (18)	0.0083 (17)	−0.0039 (16)	0.0058 (16)
N13B	0.030 (2)	0.043 (2)	0.0245 (18)	0.005 (2)	0.0004 (15)	0.0110 (17)
C14B	0.031 (2)	0.035 (3)	0.0277 (19)	−0.0077 (19)	−0.0055 (17)	0.0039 (18)
N15B	0.043 (2)	0.044 (3)	0.0233 (18)	−0.0103 (18)	−0.0115 (15)	0.0021 (16)
C16B	0.024 (2)	0.036 (3)	0.029 (2)	−0.005 (2)	−0.0005 (17)	−0.0054 (19)
C17B	0.026 (2)	0.034 (3)	0.0271 (19)	−0.0018 (19)	−0.0040 (17)	0.0032 (17)
C18B	0.030 (2)	0.034 (3)	0.0248 (19)	−0.001 (2)	−0.0034 (17)	−0.0030 (18)
C19B	0.037 (2)	0.028 (3)	0.029 (2)	−0.007 (2)	−0.0054 (18)	0.0035 (18)
C20B	0.032 (2)	0.036 (3)	0.0230 (19)	0.005 (2)	−0.0042 (17)	0.0055 (18)
C21B	0.030 (2)	0.041 (3)	0.0209 (18)	−0.006 (2)	−0.0074 (16)	0.0050 (18)
O22B	0.0439 (16)	0.0418 (19)	0.0342 (14)	−0.0126 (14)	−0.0146 (13)	0.0091 (13)
C23B	0.060 (3)	0.058 (3)	0.030 (2)	−0.019 (3)	−0.019 (2)	0.011 (2)
O24B	0.0460 (18)	0.0376 (19)	0.0357 (14)	−0.0083 (15)	−0.0111 (13)	0.0060 (13)
C25B	0.053 (3)	0.053 (3)	0.040 (2)	−0.023 (2)	−0.012 (2)	0.010 (2)
O26B	0.0429 (17)	0.0454 (19)	0.0310 (14)	−0.0022 (14)	−0.0145 (13)	0.0100 (13)
C27B	0.039 (2)	0.049 (3)	0.037 (2)	0.000 (2)	−0.013 (2)	0.014 (2)
C1C	0.020 (2)	0.028 (2)	0.0270 (19)	−0.0041 (18)	−0.0066 (16)	0.0029 (17)
C2C	0.026 (2)	0.029 (2)	0.0237 (18)	−0.0040 (19)	−0.0044 (16)	0.0024 (17)
C3C	0.032 (2)	0.026 (2)	0.0272 (19)	−0.0055 (19)	−0.0116 (17)	0.0070 (17)
C4C	0.023 (2)	0.026 (2)	0.033 (2)	0.0004 (18)	−0.0066 (17)	0.0022 (17)
N5C	0.0256 (17)	0.031 (2)	0.0208 (15)	0.0001 (15)	−0.0031 (13)	0.0029 (14)
C6C	0.026 (2)	0.030 (2)	0.0225 (19)	−0.0027 (19)	−0.0053 (17)	−0.0014 (17)
N7C	0.0230 (17)	0.030 (2)	0.0224 (15)	0.0015 (15)	−0.0060 (13)	0.0039 (13)
C8C	0.019 (2)	0.028 (2)	0.0277 (19)	−0.0034 (18)	−0.0079 (16)	0.0037 (17)
C9C	0.028 (2)	0.023 (2)	0.0262 (19)	−0.0069 (18)	−0.0084 (16)	0.0040 (16)
C10C	0.024 (2)	0.030 (2)	0.029 (2)	−0.0039 (18)	−0.0105 (17)	0.0044 (17)
C11C	0.032 (2)	0.042 (3)	0.0243 (19)	−0.002 (2)	−0.0075 (16)	−0.0012 (18)
N12C	0.0244 (19)	0.034 (2)	0.0248 (17)	0.0066 (16)	−0.0042 (15)	0.0066 (15)
N13C	0.027 (2)	0.040 (2)	0.0224 (18)	0.0013 (19)	−0.0011 (14)	0.0078 (16)
C14C	0.038 (2)	0.030 (2)	0.0275 (19)	−0.007 (2)	−0.0087 (17)	0.0046 (18)
N15C	0.040 (2)	0.039 (2)	0.0255 (17)	−0.0110 (18)	−0.0112 (15)	0.0037 (16)
C16C	0.028 (2)	0.034 (3)	0.0230 (19)	−0.005 (2)	0.0023 (17)	0.0002 (18)
C17C	0.033 (2)	0.036 (3)	0.0254 (19)	−0.003 (2)	−0.0067 (17)	0.0032 (18)
C18C	0.034 (2)	0.042 (3)	0.027 (2)	−0.010 (2)	−0.0061 (18)	−0.0027 (19)
C19C	0.033 (2)	0.031 (3)	0.029 (2)	−0.006 (2)	−0.0050 (18)	0.0067 (18)
C20C	0.030 (2)	0.037 (3)	0.0249 (19)	0.001 (2)	−0.0024 (17)	0.0024 (19)
C21C	0.034 (2)	0.041 (3)	0.0249 (19)	−0.004 (2)	−0.0079 (17)	−0.0012 (19)
O22C	0.0495 (17)	0.0422 (19)	0.0423 (15)	−0.0098 (15)	−0.0237 (14)	0.0096 (14)
C23C	0.073 (3)	0.044 (3)	0.074 (3)	−0.014 (3)	−0.052 (3)	0.010 (2)
O24C	0.0407 (17)	0.0322 (18)	0.0429 (15)	−0.0041 (15)	−0.0130 (13)	0.0092 (13)
C25C	0.048 (3)	0.039 (3)	0.049 (2)	−0.002 (2)	−0.021 (2)	0.004 (2)
O26C	0.0460 (17)	0.0311 (17)	0.0347 (14)	0.0002 (14)	−0.0167 (13)	0.0057 (13)
C27C	0.061 (3)	0.037 (3)	0.037 (2)	0.001 (2)	−0.024 (2)	−0.002 (2)
C1D	0.024 (2)	0.032 (2)	0.0268 (19)	−0.0009 (18)	−0.0068 (16)	−0.0002 (17)
C2D	0.032 (2)	0.030 (2)	0.0230 (18)	−0.004 (2)	−0.0050 (16)	0.0046 (17)
C3D	0.038 (2)	0.031 (2)	0.027 (2)	−0.001 (2)	−0.0128 (18)	0.0098 (17)
C4D	0.023 (2)	0.036 (3)	0.0280 (19)	0.0046 (18)	−0.0055 (17)	0.0035 (18)
N5D	0.0267 (18)	0.035 (2)	0.0204 (15)	−0.0013 (15)	−0.0010 (13)	0.0039 (14)
C6D	0.027 (2)	0.028 (2)	0.025 (2)	−0.0024 (19)	−0.0035 (17)	−0.0002 (18)
N7D	0.0273 (18)	0.026 (2)	0.0276 (16)	0.0015 (16)	−0.0058 (14)	0.0045 (14)
C8D	0.029 (2)	0.031 (3)	0.026 (2)	0.001 (2)	−0.0071 (17)	0.0045 (17)
C9D	0.030 (2)	0.026 (2)	0.0269 (19)	−0.0008 (19)	−0.0096 (17)	0.0034 (17)
C10D	0.033 (2)	0.026 (2)	0.0248 (19)	0.0002 (19)	−0.0094 (17)	0.0037 (17)
C11D	0.031 (2)	0.039 (3)	0.030 (2)	−0.001 (2)	−0.0034 (17)	0.0091 (18)
N12D	0.033 (2)	0.027 (2)	0.0269 (18)	0.0055 (17)	−0.0003 (17)	0.0103 (15)
N13D	0.033 (2)	0.045 (3)	0.0256 (18)	0.0112 (19)	0.0040 (15)	0.0144 (17)
C14D	0.027 (2)	0.039 (3)	0.030 (2)	−0.0007 (19)	−0.0091 (17)	0.0061 (18)
N15D	0.037 (2)	0.037 (2)	0.0261 (17)	−0.0061 (17)	−0.0118 (14)	0.0094 (16)
C16D	0.021 (2)	0.042 (3)	0.0247 (19)	0.0021 (19)	−0.0032 (16)	0.0050 (19)
C17D	0.025 (2)	0.034 (3)	0.0251 (19)	−0.0026 (18)	−0.0073 (16)	0.0022 (17)
C18D	0.022 (2)	0.032 (3)	0.0242 (19)	−0.0035 (18)	−0.0013 (16)	0.0063 (18)
C19D	0.022 (2)	0.038 (3)	0.0232 (19)	0.0019 (19)	−0.0082 (16)	0.0047 (18)
C20D	0.027 (2)	0.032 (3)	0.029 (2)	−0.0040 (19)	−0.0088 (17)	0.0047 (18)
C21D	0.028 (2)	0.034 (3)	0.027 (2)	−0.0026 (19)	−0.0062 (17)	0.0078 (18)
O22D	0.0391 (16)	0.0317 (17)	0.0328 (14)	−0.0068 (13)	−0.0158 (12)	0.0066 (13)
C23D	0.039 (2)	0.040 (3)	0.044 (2)	−0.006 (2)	−0.0167 (19)	0.012 (2)
O24D	0.0318 (15)	0.0383 (17)	0.0263 (13)	0.0024 (13)	−0.0111 (11)	0.0026 (12)
C25D	0.042 (3)	0.038 (3)	0.035 (2)	0.005 (2)	−0.0182 (19)	0.0002 (19)
O26D	0.0492 (17)	0.0326 (18)	0.0400 (15)	−0.0098 (14)	−0.0222 (13)	0.0063 (13)
C27D	0.056 (3)	0.040 (3)	0.058 (3)	−0.013 (2)	−0.030 (2)	0.003 (2)
S1	0.0592 (8)	0.0563 (9)	0.0477 (6)	−0.0058 (7)	−0.0212 (6)	0.0004 (6)
O10	0.046 (2)	0.098 (3)	0.069 (2)	−0.013 (2)	0.0031 (17)	−0.011 (2)
C10	0.057 (3)	0.049 (3)	0.054 (3)	−0.010 (2)	−0.021 (2)	0.002 (2)
C11	0.092 (4)	0.061 (4)	0.066 (3)	−0.008 (3)	−0.033 (3)	0.010 (3)
S2	0.0513 (7)	0.0598 (9)	0.0377 (6)	−0.0044 (6)	−0.0177 (5)	0.0040 (6)
O20	0.0603 (19)	0.0409 (19)	0.0337 (14)	0.0074 (15)	−0.0158 (13)	0.0010 (13)
C20	0.051 (3)	0.063 (4)	0.052 (3)	−0.002 (3)	−0.018 (2)	−0.008 (2)
C21	0.087 (4)	0.058 (4)	0.060 (3)	−0.022 (3)	−0.038 (3)	0.012 (3)
O1	0.0336 (17)	0.046 (2)	0.0297 (15)	−0.0043 (15)	−0.0044 (12)	0.0056 (14)
O2	0.0370 (17)	0.046 (2)	0.0326 (16)	−0.0083 (16)	−0.0072 (13)	0.0075 (14)
O3	0.047 (2)	0.052 (2)	0.0333 (15)	0.0020 (16)	−0.0062 (14)	0.0064 (15)

Geometric parameters (Å, º)

C1A—C2A	1.389 (5)	C6C—N12C	1.371 (4)
C1A—C9A	1.452 (4)	N7C—C8C	1.334 (4)
C1A—C11A	1.508 (5)	C8C—N13C	1.336 (5)
C2A—C3A	1.408 (5)	C8C—C9C	1.451 (5)
C2A—C14A	1.540 (4)	C9C—C10C	1.437 (5)
C3A—C4A	1.367 (5)	C11C—H11G	0.9600
C3A—H3A	0.9300	C11C—H11H	0.9600
C4A—C10A	1.407 (5)	C11C—H11I	0.9600
C4A—H4A	0.9300	N12C—H12E	0.88 (4)
N5A—C6A	1.319 (4)	N12C—H12F	0.80 (3)
N5A—C10A	1.382 (4)	N13C—H13E	0.85 (3)
C6A—N12A	1.359 (4)	N13C—H13F	0.78 (3)
C6A—N7A	1.364 (4)	C14C—N15C	1.442 (5)
N7A—C8A	1.340 (4)	C14C—H14E	0.9700
C8A—N13A	1.346 (5)	C14C—H14F	0.9700
C8A—C9A	1.451 (5)	N15C—C16C	1.370 (5)
C9A—C10A	1.423 (5)	N15C—H15C	0.75 (3)
C11A—H11A	0.9600	C16C—C17C	1.399 (5)
C11A—H11B	0.9600	C16C—C21C	1.409 (5)
C11A—H11C	0.9600	C17C—C18C	1.384 (5)
N12A—H12A	0.83 (3)	C17C—H17C	0.9300
N12A—H12B	0.80 (3)	C18C—O22C	1.387 (4)
N13A—H13A	0.92 (3)	C18C—C19C	1.403 (5)
N13A—H13B	0.84 (3)	C19C—O24C	1.385 (4)
C14A—N15A	1.449 (5)	C19C—C20C	1.396 (5)
C14A—H14A	0.9700	C20C—O26C	1.379 (4)
C14A—H14B	0.9700	C20C—C21C	1.383 (5)
N15A—C16A	1.387 (4)	C21C—H21C	0.9300
N15A—H15A	0.90 (3)	O22C—C23C	1.432 (4)
C16A—C17A	1.393 (5)	C23C—H23G	0.9600
C16A—C21A	1.404 (5)	C23C—H23H	0.9600
C17A—C18A	1.403 (5)	C23C—H23I	0.9600
C17A—H17A	0.9300	O24C—C25C	1.447 (4)
C18A—O22A	1.378 (4)	C25C—H25G	0.9600
C18A—C19A	1.386 (5)	C25C—H25H	0.9600
C19A—O24A	1.399 (4)	C25C—H25I	0.9600
C19A—C20A	1.401 (5)	O26C—C27C	1.432 (4)
C20A—O26A	1.382 (4)	C27C—H27G	0.9600
C20A—C21A	1.386 (4)	C27C—H27H	0.9600
C21A—H21A	0.9300	C27C—H27I	0.9600
O22A—C23A	1.362 (5)	C1D—C2D	1.399 (5)
C23A—H23A	0.9600	C1D—C9D	1.441 (4)
C23A—H23B	0.9600	C1D—C11D	1.517 (5)
C23A—H23C	0.9600	C2D—C3D	1.409 (5)
O24A—C25A	1.442 (4)	C2D—C14D	1.540 (5)
C25A—H25A	0.9600	C3D—C4D	1.373 (4)
C25A—H25B	0.9600	C3D—H3D	0.9300
C25A—H25C	0.9600	C4D—C10D	1.406 (5)
O26A—C27A	1.421 (4)	C4D—H4D	0.9300
C27A—H27A	0.9600	N5D—C6D	1.325 (4)
C27A—H27B	0.9600	N5D—C10D	1.375 (4)
C27A—H27C	0.9600	C6D—N12D	1.345 (4)
C1B—C2B	1.392 (5)	C6D—N7D	1.371 (4)
C1B—C9B	1.442 (4)	N7D—C8D	1.348 (4)
C1B—C11B	1.514 (5)	C8D—N13D	1.343 (5)
C2B—C3B	1.399 (5)	C8D—C9D	1.456 (5)
C2B—C14B	1.539 (4)	C9D—C10D	1.423 (5)
C3B—C4B	1.364 (4)	C11D—H11J	0.9600
C3B—H3B	0.9300	C11D—H11K	0.9600
C4B—C10B	1.405 (5)	C11D—H11L	0.9600
C4B—H4B	0.9300	N12D—H12G	0.95 (3)
N5B—C6B	1.330 (4)	N12D—H12H	0.72 (3)
N5B—C10B	1.387 (4)	N13D—H13G	0.85 (3)
C6B—N7B	1.355 (4)	N13D—H13H	0.89 (3)
C6B—N12B	1.361 (4)	C14D—N15D	1.447 (5)
N7B—C8B	1.349 (4)	C14D—H14G	0.9700
C8B—N13B	1.325 (5)	C14D—H14H	0.9700
C8B—C9B	1.453 (5)	N15D—C16D	1.395 (4)
C9B—C10B	1.413 (5)	N15D—H15D	0.85 (3)
C11B—H11D	0.9600	C16D—C21D	1.395 (5)
C11B—H11E	0.9600	C16D—C17D	1.404 (5)
C11B—H11F	0.9600	C17D—C18D	1.389 (5)
N12B—H12C	0.78 (3)	C17D—H17D	0.9300
N12B—H12D	0.89 (3)	C18D—O22D	1.380 (4)
N13B—H13C	0.74 (3)	C18D—C19D	1.397 (5)
N13B—H13D	0.89 (3)	C19D—C20D	1.382 (5)
C14B—N15B	1.441 (5)	C19D—O24D	1.409 (4)
C14B—H14C	0.9700	C20D—O26D	1.366 (4)
C14B—H14D	0.9700	C20D—C21D	1.401 (5)
N15B—C16B	1.371 (5)	C21D—H21D	0.9300
N15B—H15B	0.78 (3)	O22D—C23D	1.422 (4)
C16B—C17B	1.393 (5)	C23D—H23J	0.9600
C16B—C21B	1.413 (5)	C23D—H23K	0.9600
C17B—C18B	1.388 (5)	C23D—H23L	0.9600
C17B—H17B	0.9300	O24D—C25D	1.449 (4)
C18B—O22B	1.372 (4)	C25D—H25J	0.9600
C18B—C19B	1.416 (5)	C25D—H25K	0.9600
C19B—O24B	1.367 (4)	C25D—H25L	0.9600
C19B—C20B	1.394 (5)	O26D—C27D	1.439 (4)
C20B—O26B	1.377 (4)	C27D—H27J	0.9600
C20B—C21B	1.378 (5)	C27D—H27K	0.9600
C21B—H21B	0.9300	C27D—H27L	0.9600
O22B—C23B	1.430 (4)	S1—O10	1.507 (3)
C23B—H23D	0.9600	S1—C10	1.756 (4)
C23B—H23E	0.9600	S1—C11	1.778 (4)
C23B—H23F	0.9600	C10—H10A	0.9600
O24B—C25B	1.440 (4)	C10—H10B	0.9600
C25B—H25D	0.9600	C10—H10C	0.9600
C25B—H25E	0.9600	C11—H11M	0.9600
C25B—H25F	0.9600	C11—H11N	0.9600
O26B—C27B	1.425 (4)	C11—H11O	0.9600
C27B—H27D	0.9600	S2—O20	1.510 (3)
C27B—H27E	0.9600	S2—C20	1.786 (4)
C27B—H27F	0.9600	S2—C21	1.800 (4)
C1C—C2C	1.397 (5)	C20—H20A	0.9600
C1C—C9C	1.445 (4)	C20—H20B	0.9600
C1C—C11C	1.506 (5)	C20—H20C	0.9600
C2C—C3C	1.402 (5)	C21—H21E	0.9600
C2C—C14C	1.541 (4)	C21—H21F	0.9600
C3C—C4C	1.376 (4)	C21—H21G	0.9600
C3C—H3C	0.9300	O1—H11	0.85 (4)
C4C—C10C	1.405 (5)	O1—H12	0.76 (4)
C4C—H4C	0.9300	O2—H21	0.75 (4)
N5C—C6C	1.320 (4)	O2—H22	0.90 (4)
N5C—C10C	1.380 (4)	O3—H31	0.98 (4)
C6C—N7C	1.362 (4)	O3—H32	0.82 (4)
C2A—C1A—C9A	118.8 (3)	N7C—C8C—N13C	114.3 (3)
C2A—C1A—C11A	119.0 (3)	N7C—C8C—C9C	121.7 (3)
C9A—C1A—C11A	122.2 (3)	N13C—C8C—C9C	123.9 (3)
C1A—C2A—C3A	120.1 (3)	C10C—C9C—C1C	119.2 (3)
C1A—C2A—C14A	121.5 (3)	C10C—C9C—C8C	113.8 (3)
C3A—C2A—C14A	118.5 (3)	C1C—C9C—C8C	127.0 (3)
C4A—C3A—C2A	121.7 (3)	N5C—C10C—C4C	117.7 (3)
C4A—C3A—H3A	119.1	N5C—C10C—C9C	123.1 (3)
C2A—C3A—H3A	119.1	C4C—C10C—C9C	119.2 (3)
C3A—C4A—C10A	120.7 (4)	C1C—C11C—H11G	109.5
C3A—C4A—H4A	119.7	C1C—C11C—H11H	109.5
C10A—C4A—H4A	119.7	H11G—C11C—H11H	109.5
C6A—N5A—C10A	116.0 (3)	C1C—C11C—H11I	109.5
N5A—C6A—N12A	117.4 (3)	H11G—C11C—H11I	109.5
N5A—C6A—N7A	126.2 (3)	H11H—C11C—H11I	109.5
N12A—C6A—N7A	116.3 (3)	C6C—N12C—H12E	116 (2)
C8A—N7A—C6A	118.3 (3)	C6C—N12C—H12F	114 (2)
N7A—C8A—N13A	114.4 (3)	H12E—N12C—H12F	125 (3)
N7A—C8A—C9A	121.6 (3)	C8C—N13C—H13E	118 (2)
N13A—C8A—C9A	123.8 (3)	C8C—N13C—H13F	121 (3)
C10A—C9A—C1A	119.7 (3)	H13E—N13C—H13F	116 (4)
C10A—C9A—C8A	113.9 (3)	N15C—C14C—C2C	114.6 (3)
C1A—C9A—C8A	126.4 (3)	N15C—C14C—H14E	108.6
N5A—C10A—C4A	117.4 (3)	C2C—C14C—H14E	108.6
N5A—C10A—C9A	123.6 (3)	N15C—C14C—H14F	108.6
C4A—C10A—C9A	119.0 (3)	C2C—C14C—H14F	108.6
C1A—C11A—H11A	109.5	H14E—C14C—H14F	107.6
C1A—C11A—H11B	109.5	C16C—N15C—C14C	125.3 (3)
H11A—C11A—H11B	109.5	C16C—N15C—H15C	120 (3)
C1A—C11A—H11C	109.5	C14C—N15C—H15C	115 (3)
H11A—C11A—H11C	109.5	N15C—C16C—C17C	121.5 (3)
H11B—C11A—H11C	109.5	N15C—C16C—C21C	119.7 (4)
C6A—N12A—H12A	119 (2)	C17C—C16C—C21C	118.7 (4)
C6A—N12A—H12B	125 (3)	C18C—C17C—C16C	120.3 (4)
H12A—N12A—H12B	115 (3)	C18C—C17C—H17C	119.8
C8A—N13A—H13A	117 (2)	C16C—C17C—H17C	119.8
C8A—N13A—H13B	122 (2)	C17C—C18C—O22C	123.9 (3)
H13A—N13A—H13B	119 (3)	C17C—C18C—C19C	121.2 (4)
N15A—C14A—C2A	114.4 (3)	O22C—C18C—C19C	114.8 (3)
N15A—C14A—H14A	108.7	O24C—C19C—C20C	121.2 (3)
C2A—C14A—H14A	108.7	O24C—C19C—C18C	120.6 (3)
N15A—C14A—H14B	108.7	C20C—C19C—C18C	118.1 (4)
C2A—C14A—H14B	108.7	O26C—C20C—C21C	124.6 (4)
H14A—C14A—H14B	107.6	O26C—C20C—C19C	114.0 (3)
C16A—N15A—C14A	123.6 (3)	C21C—C20C—C19C	121.3 (4)
C16A—N15A—H15A	116 (2)	C20C—C21C—C16C	120.3 (4)
C14A—N15A—H15A	118 (2)	C20C—C21C—H21C	119.9
N15A—C16A—C17A	122.1 (3)	C16C—C21C—H21C	119.9
N15A—C16A—C21A	118.6 (3)	C18C—O22C—C23C	116.7 (3)
C17A—C16A—C21A	119.3 (3)	O22C—C23C—H23G	109.5
C16A—C17A—C18A	120.1 (4)	O22C—C23C—H23H	109.5
C16A—C17A—H17A	120.0	H23G—C23C—H23H	109.5
C18A—C17A—H17A	120.0	O22C—C23C—H23I	109.5
O22A—C18A—C19A	119.0 (3)	H23G—C23C—H23I	109.5
O22A—C18A—C17A	120.4 (4)	H23H—C23C—H23I	109.5
C19A—C18A—C17A	120.6 (4)	C19C—O24C—C25C	114.6 (3)
C18A—C19A—O24A	121.3 (3)	O24C—C25C—H25G	109.5
C18A—C19A—C20A	119.1 (3)	O24C—C25C—H25H	109.5
O24A—C19A—C20A	119.5 (3)	H25G—C25C—H25H	109.5
O26A—C20A—C21A	124.8 (3)	O24C—C25C—H25I	109.5
O26A—C20A—C19A	114.4 (3)	H25G—C25C—H25I	109.5
C21A—C20A—C19A	120.7 (3)	H25H—C25C—H25I	109.5
C20A—C21A—C16A	120.1 (3)	C20C—O26C—C27C	117.2 (3)
C20A—C21A—H21A	119.9	O26C—C27C—H27G	109.5
C16A—C21A—H21A	119.9	O26C—C27C—H27H	109.5
C23A—O22A—C18A	115.9 (3)	H27G—C27C—H27H	109.5
O22A—C23A—H23A	109.5	O26C—C27C—H27I	109.5
O22A—C23A—H23B	109.5	H27G—C27C—H27I	109.5
H23A—C23A—H23B	109.5	H27H—C27C—H27I	109.5
O22A—C23A—H23C	109.5	C2D—C1D—C9D	119.3 (3)
H23A—C23A—H23C	109.5	C2D—C1D—C11D	118.8 (3)
H23B—C23A—H23C	109.5	C9D—C1D—C11D	121.8 (3)
C19A—O24A—C25A	112.5 (2)	C1D—C2D—C3D	118.9 (3)
O24A—C25A—H25A	109.5	C1D—C2D—C14D	122.5 (3)
O24A—C25A—H25B	109.5	C3D—C2D—C14D	118.5 (3)
H25A—C25A—H25B	109.5	C4D—C3D—C2D	122.5 (3)
O24A—C25A—H25C	109.5	C4D—C3D—H3D	118.8
H25A—C25A—H25C	109.5	C2D—C3D—H3D	118.8
H25B—C25A—H25C	109.5	C3D—C4D—C10D	119.9 (3)
C20A—O26A—C27A	116.6 (3)	C3D—C4D—H4D	120.1
O26A—C27A—H27A	109.5	C10D—C4D—H4D	120.1
O26A—C27A—H27B	109.5	C6D—N5D—C10D	116.7 (3)
H27A—C27A—H27B	109.5	N5D—C6D—N12D	117.4 (3)
O26A—C27A—H27C	109.5	N5D—C6D—N7D	125.9 (3)
H27A—C27A—H27C	109.5	N12D—C6D—N7D	116.6 (3)
H27B—C27A—H27C	109.5	C8D—N7D—C6D	117.9 (3)
C2B—C1B—C9B	117.8 (3)	N13D—C8D—N7D	113.7 (3)
C2B—C1B—C11B	119.1 (3)	N13D—C8D—C9D	124.7 (3)
C9B—C1B—C11B	123.0 (3)	N7D—C8D—C9D	121.6 (3)
C1B—C2B—C3B	120.4 (3)	C10D—C9D—C1D	119.7 (3)
C1B—C2B—C14B	119.7 (3)	C10D—C9D—C8D	114.1 (3)
C3B—C2B—C14B	119.8 (3)	C1D—C9D—C8D	126.0 (3)
C4B—C3B—C2B	122.1 (3)	N5D—C10D—C4D	117.3 (3)
C4B—C3B—H3B	118.9	N5D—C10D—C9D	123.4 (3)
C2B—C3B—H3B	118.9	C4D—C10D—C9D	119.3 (3)
C3B—C4B—C10B	119.8 (3)	C1D—C11D—H11J	109.5
C3B—C4B—H4B	120.1	C1D—C11D—H11K	109.5
C10B—C4B—H4B	120.1	H11J—C11D—H11K	109.5
C6B—N5B—C10B	115.8 (3)	C1D—C11D—H11L	109.5
N5B—C6B—N7B	126.4 (3)	H11J—C11D—H11L	109.5
N5B—C6B—N12B	117.5 (3)	H11K—C11D—H11L	109.5
N7B—C6B—N12B	116.1 (3)	C6D—N12D—H12G	116.5 (19)
C8B—N7B—C6B	118.1 (3)	C6D—N12D—H12H	127 (3)
N13B—C8B—N7B	114.6 (3)	H12G—N12D—H12H	116 (4)
N13B—C8B—C9B	124.5 (3)	C8D—N13D—H13G	120 (2)
N7B—C8B—C9B	120.9 (3)	C8D—N13D—H13H	121 (2)
C10B—C9B—C1B	120.3 (3)	H13G—N13D—H13H	117 (3)
C10B—C9B—C8B	114.5 (3)	N15D—C14D—C2D	114.5 (3)
C1B—C9B—C8B	125.1 (3)	N15D—C14D—H14G	108.6
N5B—C10B—C4B	117.7 (3)	C2D—C14D—H14G	108.6
N5B—C10B—C9B	123.1 (3)	N15D—C14D—H14H	108.6
C4B—C10B—C9B	119.2 (3)	C2D—C14D—H14H	108.6
C1B—C11B—H11D	109.5	H14G—C14D—H14H	107.6
C1B—C11B—H11E	109.5	C16D—N15D—C14D	123.0 (3)
H11D—C11B—H11E	109.5	C16D—N15D—H15D	116 (2)
C1B—C11B—H11F	109.5	C14D—N15D—H15D	118 (2)
H11D—C11B—H11F	109.5	N15D—C16D—C21D	120.8 (3)
H11E—C11B—H11F	109.5	N15D—C16D—C17D	118.8 (3)
C6B—N12B—H12C	117 (3)	C21D—C16D—C17D	120.4 (3)
C6B—N12B—H12D	117 (2)	C18D—C17D—C16D	119.2 (3)
H12C—N12B—H12D	113 (3)	C18D—C17D—H17D	120.4
C8B—N13B—H13C	120 (3)	C16D—C17D—H17D	120.4
C8B—N13B—H13D	119 (2)	O22D—C18D—C17D	124.7 (3)
H13C—N13B—H13D	119 (4)	O22D—C18D—C19D	114.9 (3)
N15B—C14B—C2B	114.1 (3)	C17D—C18D—C19D	120.4 (3)
N15B—C14B—H14C	108.7	C20D—C19D—C18D	120.3 (3)
C2B—C14B—H14C	108.7	C20D—C19D—O24D	120.9 (3)
N15B—C14B—H14D	108.7	C18D—C19D—O24D	118.9 (3)
C2B—C14B—H14D	108.7	O26D—C20D—C19D	116.4 (3)
H14C—C14B—H14D	107.6	O26D—C20D—C21D	123.5 (3)
C16B—N15B—C14B	122.4 (3)	C19D—C20D—C21D	120.1 (3)
C16B—N15B—H15B	125 (3)	C16D—C21D—C20D	119.6 (4)
C14B—N15B—H15B	109 (3)	C16D—C21D—H21D	120.2
N15B—C16B—C17B	121.4 (4)	C20D—C21D—H21D	120.2
N15B—C16B—C21B	119.4 (3)	C18D—O22D—C23D	116.9 (3)
C17B—C16B—C21B	119.2 (4)	O22D—C23D—H23J	109.5
C18B—C17B—C16B	120.5 (4)	O22D—C23D—H23K	109.5
C18B—C17B—H17B	119.7	H23J—C23D—H23K	109.5
C16B—C17B—H17B	119.7	O22D—C23D—H23L	109.5
O22B—C18B—C17B	124.9 (3)	H23J—C23D—H23L	109.5
O22B—C18B—C19B	114.5 (3)	H23K—C23D—H23L	109.5
C17B—C18B—C19B	120.5 (4)	C19D—O24D—C25D	111.9 (2)
O24B—C19B—C20B	121.5 (3)	O24D—C25D—H25J	109.5
O24B—C19B—C18B	120.4 (3)	O24D—C25D—H25K	109.5
C20B—C19B—C18B	118.0 (4)	H25J—C25D—H25K	109.5
O26B—C20B—C21B	124.0 (3)	O24D—C25D—H25L	109.5
O26B—C20B—C19B	114.1 (3)	H25J—C25D—H25L	109.5
C21B—C20B—C19B	121.9 (3)	H25K—C25D—H25L	109.5
C20B—C21B—C16B	119.7 (3)	C20D—O26D—C27D	117.8 (3)
C20B—C21B—H21B	120.2	O26D—C27D—H27J	109.5
C16B—C21B—H21B	120.2	O26D—C27D—H27K	109.5
C18B—O22B—C23B	117.3 (3)	H27J—C27D—H27K	109.5
O22B—C23B—H23D	109.5	O26D—C27D—H27L	109.5
O22B—C23B—H23E	109.5	H27J—C27D—H27L	109.5
H23D—C23B—H23E	109.5	H27K—C27D—H27L	109.5
O22B—C23B—H23F	109.5	O10—S1—C10	108.2 (2)
H23D—C23B—H23F	109.5	O10—S1—C11	105.7 (2)
H23E—C23B—H23F	109.5	C10—S1—C11	97.0 (2)
C19B—O24B—C25B	112.4 (3)	S1—C10—H10A	109.5
O24B—C25B—H25D	109.5	S1—C10—H10B	109.5
O24B—C25B—H25E	109.5	H10A—C10—H10B	109.5
H25D—C25B—H25E	109.5	S1—C10—H10C	109.5
O24B—C25B—H25F	109.5	H10A—C10—H10C	109.5
H25D—C25B—H25F	109.5	H10B—C10—H10C	109.5
H25E—C25B—H25F	109.5	S1—C11—H11M	109.5
C20B—O26B—C27B	117.3 (3)	S1—C11—H11N	109.5
O26B—C27B—H27D	109.5	H11M—C11—H11N	109.5
O26B—C27B—H27E	109.5	S1—C11—H11O	109.5
H27D—C27B—H27E	109.5	H11M—C11—H11O	109.5
O26B—C27B—H27F	109.5	H11N—C11—H11O	109.5
H27D—C27B—H27F	109.5	O20—S2—C20	105.42 (18)
H27E—C27B—H27F	109.5	O20—S2—C21	107.35 (18)
C2C—C1C—C9C	119.0 (3)	C20—S2—C21	96.5 (2)
C2C—C1C—C11C	119.4 (3)	S2—C20—H20A	109.5
C9C—C1C—C11C	121.6 (3)	S2—C20—H20B	109.5
C1C—C2C—C3C	120.3 (3)	H20A—C20—H20B	109.5
C1C—C2C—C14C	120.4 (3)	S2—C20—H20C	109.5
C3C—C2C—C14C	119.2 (3)	H20A—C20—H20C	109.5
C4C—C3C—C2C	121.7 (3)	H20B—C20—H20C	109.5
C4C—C3C—H3C	119.2	S2—C21—H21E	109.5
C2C—C3C—H3C	119.2	S2—C21—H21F	109.5
C3C—C4C—C10C	120.4 (4)	H21E—C21—H21F	109.5
C3C—C4C—H4C	119.8	S2—C21—H21G	109.5
C10C—C4C—H4C	119.8	H21E—C21—H21G	109.5
C6C—N5C—C10C	115.9 (3)	H21F—C21—H21G	109.5
N5C—C6C—N7C	126.7 (3)	H11—O1—H12	103 (4)
N5C—C6C—N12C	118.0 (3)	H21—O2—H22	103 (4)
N7C—C6C—N12C	115.3 (3)	H31—O3—H32	98 (4)
C8C—N7C—C6C	118.2 (3)
C9A—C1A—C2A—C3A	0.8 (5)	C9C—C1C—C2C—C3C	1.4 (5)
C11A—C1A—C2A—C3A	−177.6 (3)	C11C—C1C—C2C—C3C	179.1 (3)
C9A—C1A—C2A—C14A	−178.7 (3)	C9C—C1C—C2C—C14C	−175.9 (3)
C11A—C1A—C2A—C14A	3.0 (5)	C11C—C1C—C2C—C14C	1.8 (5)
C1A—C2A—C3A—C4A	1.2 (5)	C1C—C2C—C3C—C4C	−3.1 (5)
C14A—C2A—C3A—C4A	−179.4 (3)	C14C—C2C—C3C—C4C	174.2 (3)
C2A—C3A—C4A—C10A	−1.4 (5)	C2C—C3C—C4C—C10C	0.1 (5)
C10A—N5A—C6A—N12A	177.1 (3)	C10C—N5C—C6C—N7C	6.3 (5)
C10A—N5A—C6A—N7A	−2.6 (5)	C10C—N5C—C6C—N12C	−170.7 (3)
N5A—C6A—N7A—C8A	4.6 (5)	N5C—C6C—N7C—C8C	−5.5 (5)
N12A—C6A—N7A—C8A	−175.1 (3)	N12C—C6C—N7C—C8C	171.6 (3)
C6A—N7A—C8A—N13A	−177.4 (3)	C6C—N7C—C8C—N13C	179.8 (3)
C6A—N7A—C8A—C9A	−1.7 (5)	C6C—N7C—C8C—C9C	−2.0 (5)
C2A—C1A—C9A—C10A	−2.5 (5)	C2C—C1C—C9C—C10C	3.1 (5)
C11A—C1A—C9A—C10A	175.7 (3)	C11C—C1C—C9C—C10C	−174.5 (3)
C2A—C1A—C9A—C8A	174.9 (3)	C2C—C1C—C9C—C8C	−177.6 (3)
C11A—C1A—C9A—C8A	−6.8 (5)	C11C—C1C—C9C—C8C	4.8 (5)
N7A—C8A—C9A—C10A	−2.4 (5)	N7C—C8C—C9C—C10C	7.3 (5)
N13A—C8A—C9A—C10A	172.8 (3)	N13C—C8C—C9C—C10C	−174.8 (3)
N7A—C8A—C9A—C1A	−179.9 (3)	N7C—C8C—C9C—C1C	−172.0 (3)
N13A—C8A—C9A—C1A	−4.7 (6)	N13C—C8C—C9C—C1C	5.9 (6)
C6A—N5A—C10A—C4A	177.6 (3)	C6C—N5C—C10C—C4C	179.2 (3)
C6A—N5A—C10A—C9A	−2.2 (5)	C6C—N5C—C10C—C9C	0.2 (5)
C3A—C4A—C10A—N5A	179.7 (3)	C3C—C4C—C10C—N5C	−174.6 (3)
C3A—C4A—C10A—C9A	−0.5 (5)	C3C—C4C—C10C—C9C	4.5 (5)
C1A—C9A—C10A—N5A	−177.8 (3)	C1C—C9C—C10C—N5C	173.0 (3)
C8A—C9A—C10A—N5A	4.5 (5)	C8C—C9C—C10C—N5C	−6.4 (5)
C1A—C9A—C10A—C4A	2.4 (5)	C1C—C9C—C10C—C4C	−6.1 (5)
C8A—C9A—C10A—C4A	−175.3 (3)	C8C—C9C—C10C—C4C	174.6 (3)
C1A—C2A—C14A—N15A	176.9 (3)	C1C—C2C—C14C—N15C	174.2 (3)
C3A—C2A—C14A—N15A	−2.5 (5)	C3C—C2C—C14C—N15C	−3.1 (5)
C2A—C14A—N15A—C16A	92.0 (4)	C2C—C14C—N15C—C16C	85.5 (4)
C14A—N15A—C16A—C17A	−12.1 (5)	C14C—N15C—C16C—C17C	−2.9 (5)
C14A—N15A—C16A—C21A	167.5 (3)	C14C—N15C—C16C—C21C	176.3 (3)
N15A—C16A—C17A—C18A	177.5 (3)	N15C—C16C—C17C—C18C	177.6 (3)
C21A—C16A—C17A—C18A	−2.1 (5)	C21C—C16C—C17C—C18C	−1.6 (5)
C16A—C17A—C18A—O22A	−177.7 (3)	C16C—C17C—C18C—O22C	179.7 (3)
C16A—C17A—C18A—C19A	0.4 (5)	C16C—C17C—C18C—C19C	−0.4 (5)
O22A—C18A—C19A—O24A	2.4 (5)	C17C—C18C—C19C—O24C	−174.3 (3)
C17A—C18A—C19A—O24A	−175.7 (3)	O22C—C18C—C19C—O24C	5.6 (5)
O22A—C18A—C19A—C20A	179.3 (3)	C17C—C18C—C19C—C20C	1.5 (5)
C17A—C18A—C19A—C20A	1.2 (5)	O22C—C18C—C19C—C20C	−178.6 (3)
C18A—C19A—C20A—O26A	−179.8 (3)	O24C—C19C—C20C—O26C	−2.0 (5)
O24A—C19A—C20A—O26A	−2.9 (4)	C18C—C19C—C20C—O26C	−177.8 (3)
C18A—C19A—C20A—C21A	−0.9 (5)	O24C—C19C—C20C—C21C	175.2 (3)
O24A—C19A—C20A—C21A	176.0 (3)	C18C—C19C—C20C—C21C	−0.6 (5)
O26A—C20A—C21A—C16A	177.9 (3)	O26C—C20C—C21C—C16C	175.5 (3)
C19A—C20A—C21A—C16A	−0.9 (5)	C19C—C20C—C21C—C16C	−1.4 (5)
N15A—C16A—C21A—C20A	−177.2 (3)	N15C—C16C—C21C—C20C	−176.7 (3)
C17A—C16A—C21A—C20A	2.4 (5)	C17C—C16C—C21C—C20C	2.5 (5)
C19A—C18A—O22A—C23A	110.2 (4)	C17C—C18C—O22C—C23C	−3.0 (5)
C17A—C18A—O22A—C23A	−71.7 (5)	C19C—C18C—O22C—C23C	177.1 (3)
C18A—C19A—O24A—C25A	−102.0 (4)	C20C—C19C—O24C—C25C	75.4 (4)
C20A—C19A—O24A—C25A	81.1 (4)	C18C—C19C—O24C—C25C	−108.9 (4)
C21A—C20A—O26A—C27A	7.4 (5)	C21C—C20C—O26C—C27C	−2.3 (5)
C19A—C20A—O26A—C27A	−173.8 (3)	C19C—C20C—O26C—C27C	174.9 (3)
C9B—C1B—C2B—C3B	1.4 (5)	C9D—C1D—C2D—C3D	6.4 (5)
C11B—C1B—C2B—C3B	178.1 (3)	C11D—C1D—C2D—C3D	−176.2 (3)
C9B—C1B—C2B—C14B	−177.0 (3)	C9D—C1D—C2D—C14D	−170.8 (3)
C11B—C1B—C2B—C14B	−0.3 (5)	C11D—C1D—C2D—C14D	6.6 (5)
C1B—C2B—C3B—C4B	−3.6 (5)	C1D—C2D—C3D—C4D	−5.6 (5)
C14B—C2B—C3B—C4B	174.8 (3)	C14D—C2D—C3D—C4D	171.7 (3)
C2B—C3B—C4B—C10B	−0.1 (5)	C2D—C3D—C4D—C10D	0.0 (6)
C10B—N5B—C6B—N7B	9.1 (5)	C10D—N5D—C6D—N12D	−179.6 (3)
C10B—N5B—C6B—N12B	−169.2 (3)	C10D—N5D—C6D—N7D	2.7 (5)
N5B—C6B—N7B—C8B	−3.9 (5)	N5D—C6D—N7D—C8D	2.0 (5)
N12B—C6B—N7B—C8B	174.5 (3)	N12D—C6D—N7D—C8D	−175.8 (3)
C6B—N7B—C8B—N13B	173.3 (3)	C6D—N7D—C8D—N13D	175.3 (3)
C6B—N7B—C8B—C9B	−7.0 (5)	C6D—N7D—C8D—C9D	−6.4 (5)
C2B—C1B—C9B—C10B	4.2 (5)	C2D—C1D—C9D—C10D	−1.9 (5)
C11B—C1B—C9B—C10B	−172.3 (3)	C11D—C1D—C9D—C10D	−179.2 (3)
C2B—C1B—C9B—C8B	−178.8 (3)	C2D—C1D—C9D—C8D	173.0 (3)
C11B—C1B—C9B—C8B	4.6 (5)	C11D—C1D—C9D—C8D	−4.2 (6)
N13B—C8B—C9B—C10B	−169.0 (4)	N13D—C8D—C9D—C10D	−175.9 (4)
N7B—C8B—C9B—C10B	11.4 (5)	N7D—C8D—C9D—C10D	6.0 (5)
N13B—C8B—C9B—C1B	13.9 (6)	N13D—C8D—C9D—C1D	8.9 (6)
N7B—C8B—C9B—C1B	−165.8 (3)	N7D—C8D—C9D—C1D	−169.2 (3)
C6B—N5B—C10B—C4B	175.6 (3)	C6D—N5D—C10D—C4D	175.1 (3)
C6B—N5B—C10B—C9B	−3.5 (5)	C6D—N5D—C10D—C9D	−2.9 (5)
C3B—C4B—C10B—N5B	−173.4 (3)	C3D—C4D—C10D—N5D	−173.5 (3)
C3B—C4B—C10B—C9B	5.7 (5)	C3D—C4D—C10D—C9D	4.6 (5)
C1B—C9B—C10B—N5B	171.3 (3)	C1D—C9D—C10D—N5D	174.3 (3)
C8B—C9B—C10B—N5B	−6.0 (5)	C8D—C9D—C10D—N5D	−1.2 (5)
C1B—C9B—C10B—C4B	−7.8 (5)	C1D—C9D—C10D—C4D	−3.6 (5)
C8B—C9B—C10B—C4B	174.9 (3)	C8D—C9D—C10D—C4D	−179.2 (3)
C1B—C2B—C14B—N15B	178.8 (3)	C1D—C2D—C14D—N15D	164.9 (3)
C3B—C2B—C14B—N15B	0.4 (5)	C3D—C2D—C14D—N15D	−12.3 (5)
C2B—C14B—N15B—C16B	80.9 (4)	C2D—C14D—N15D—C16D	92.8 (4)
C14B—N15B—C16B—C17B	−6.6 (5)	C14D—N15D—C16D—C21D	−14.2 (5)
C14B—N15B—C16B—C21B	173.2 (3)	C14D—N15D—C16D—C17D	165.1 (3)
N15B—C16B—C17B—C18B	177.3 (3)	N15D—C16D—C17D—C18D	−179.0 (3)
C21B—C16B—C17B—C18B	−2.5 (5)	C21D—C16D—C17D—C18D	0.3 (5)
C16B—C17B—C18B—O22B	179.3 (3)	C16D—C17D—C18D—O22D	180.0 (3)
C16B—C17B—C18B—C19B	−1.0 (5)	C16D—C17D—C18D—C19D	0.4 (5)
O22B—C18B—C19B—O24B	−0.1 (5)	O22D—C18D—C19D—C20D	179.3 (3)
C17B—C18B—C19B—O24B	−179.8 (3)	C17D—C18D—C19D—C20D	−1.1 (5)
O22B—C18B—C19B—C20B	−176.8 (3)	O22D—C18D—C19D—O24D	−0.7 (4)
C17B—C18B—C19B—C20B	3.5 (5)	C17D—C18D—C19D—O24D	178.9 (3)
O24B—C19B—C20B—O26B	2.0 (5)	C18D—C19D—C20D—O26D	−178.7 (3)
C18B—C19B—C20B—O26B	178.6 (3)	O24D—C19D—C20D—O26D	1.3 (5)
O24B—C19B—C20B—C21B	−179.1 (3)	C18D—C19D—C20D—C21D	1.1 (5)
C18B—C19B—C20B—C21B	−2.4 (5)	O24D—C19D—C20D—C21D	−178.9 (3)
O26B—C20B—C21B—C16B	177.8 (3)	N15D—C16D—C21D—C20D	178.9 (3)
C19B—C20B—C21B—C16B	−1.1 (5)	C17D—C16D—C21D—C20D	−0.4 (5)
N15B—C16B—C21B—C20B	−176.2 (3)	O26D—C20D—C21D—C16D	179.4 (3)
C17B—C16B—C21B—C20B	3.6 (5)	C19D—C20D—C21D—C16D	−0.3 (5)
C17B—C18B—O22B—C23B	−17.9 (5)	C17D—C18D—O22D—C23D	5.8 (5)
C19B—C18B—O22B—C23B	162.4 (3)	C19D—C18D—O22D—C23D	−174.7 (3)
C20B—C19B—O24B—C25B	−93.5 (4)	C20D—C19D—O24D—C25D	−99.5 (4)
C18B—C19B—O24B—C25B	90.0 (4)	C18D—C19D—O24D—C25D	80.5 (4)
C21B—C20B—O26B—C27B	5.2 (5)	C19D—C20D—O26D—C27D	171.1 (3)
C19B—C20B—O26B—C27B	−175.9 (3)	C21D—C20D—O26D—C27D	−8.6 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N12A—H12A···N5C	0.83 (3)	2.26 (3)	3.081 (4)	168 (3)
N12A—H12B···O2	0.79 (3)	2.34 (3)	3.111 (4)	165 (3)
N12B—H12C···O3	0.77 (3)	2.28 (3)	3.016 (4)	160 (3)
N12B—H12D···N5D	0.90 (3)	2.10 (3)	2.979 (5)	167 (3)
N12C—H12E···N5A	0.88 (3)	2.08 (3)	2.950 (5)	172 (3)
N12C—H12F···O20	0.80 (3)	2.21 (3)	2.919 (4)	149 (3)
N12D—H12G···N5B	0.95 (3)	2.07 (3)	3.000 (5)	167 (3)
N12D—H12H···O1	0.72 (3)	2.33 (3)	3.038 (4)	165 (4)
N13A—H13A···N7B	0.92 (3)	2.07 (3)	2.983 (4)	173 (3)
N13A—H13B···O3	0.85 (3)	2.45 (3)	3.030 (4)	127 (3)
N13B—H13C···O2	0.74 (3)	2.37 (4)	2.976 (5)	140 (3)
N13B—H13D···N7A	0.89 (3)	2.07 (3)	2.955 (4)	169 (3)
N13C—H13E···N7D^i	0.85 (3)	2.24 (3)	3.091 (4)	173 (3)
N13C—H13F···O1^i	0.77 (3)	2.31 (4)	2.945 (5)	140 (3)
N13D—H13G···O20^ii	0.85 (3)	2.36 (3)	2.995 (4)	132 (3)
N13D—H13H···N7C^ii	0.88 (3)	2.15 (3)	3.028 (4)	171 (3)
N15A—H15A···N12C^iii	0.91 (3)	2.22 (3)	3.115 (5)	168 (3)
N15D—H15D···N12B^iv	0.85 (3)	2.58 (3)	3.411 (5)	167 (3)
O1—H11···O24B^v	0.84 (5)	2.16 (4)	2.929 (4)	152 (4)
O1—H12···O24A^vi	0.76 (4)	2.11 (4)	2.864 (4)	167 (5)
O2—H21···O24D^vii	0.75 (4)	2.10 (4)	2.839 (4)	170 (5)
O2—H22···O22C^viii	0.90 (5)	2.08 (5)	2.968 (4)	167 (4)
O3—H31···O10	0.98 (5)	1.85 (5)	2.803 (5)	165 (3)
O3—H32···O24C^ix	0.81 (3)	2.38 (3)	3.146 (3)	156 (5)
O3—H32···O26C^ix	0.81 (3)	2.52 (5)	3.130 (4)	132 (4)
C10—H10A···N7B	0.96	2.50	3.454 (6)	172
C25B—H25E···N7D^v	0.96	2.54	3.495 (6)	172

Symmetry codes: (i) x+1, y−1, z; (ii) x−1, y+1, z; (iii) −x+1, −y, −z+1; (iv) −x, −y+1, −z+1; (v) −x+1, −y+2, −z; (vi) x, y+1, z−1; (vii) x+1, y, z−1; (viii) −x+2, −y+1, −z; (ix) x−1, y, z+1.