Cyclo-linopeptide K butanol disolvate monohydrate.

The title compound, C(56)H(83)N(9)O(11)S·2C(4)H(10)O·H(2)O, is a butanol-water solvate of the cyclo-linopeptide cyclo(Metsulfone(1)-Leu(2)-Ile(3)-Pro(4)-Pro(5)-Phe(6)-Phe(7)-Val(8)-Ile(9)) (henceforth referred to as CLP-K) which was isolated from flax oil. All the amino acid residues are in an l configuration based on the CORN rule. The cyclic nona-peptide exhibits eight trans peptide bonds and one cis peptide bond observed between the two proline residues. The conformation is stabilized by an α- and a β-turn, each containing an N-H⋯O hydrogen bond between the carbonyl group O atom of the first residue and the amide group H atom of the fourth (α-turn) and the third residue (β-turn), repectively. In the crystal, the components of the structure are linked by inter-molecular N-H⋯O and O-H⋯O hydrogen bonds into a two-dimensional network parallel to (001). The -C(H(2))OH group of one of the butanol solvent mol-ecules is disordered over two sets of sites with refined occupancies of 0.863 (4) and 0.137 (4).

Related literature

For isolation of cyclo­linopeptides A to B, B to E, F to I and characterization by multi-dimensional NMR spectroscopy, see: Matsumoto et al. (2002 ▶); Morita et al. (1999 ▶); Matsumoto et al. (2001 ▶) respectively. For the isolation of the related cyclo­linopeptide A and its structure determination by single crystal X-ray diffraction in the presence of different solvates, see: Di Blasio et al. (1987 ▶, 1989 ▶); Matsumoto et al. (2002 ▶); Quail et al. (2009 ▶). For the synthesis of cyclo­peptides, see: Rovero et al. (1991 ▶); Ghadiri et al. (1993 ▶). For immuno-suppressive activity of CLP-A, see: Wieczorek et al. (1991 ▶). For the cytoproctective ability of CLP-A, see: Gaymes et al. (1997 ▶). For the biomolecular inter­action with human albumin of CLP-A, see: Rempel et al. (2010 ▶). For details of the absolute configuration, see: Cahn et al. (1966 ▶); Flack & Bernardinelli (2000 ▶); Hooft et al. (2008 ▶); PLATON (Spek, 2009 ▶).

Experimental

Crystal data

C56H83N9O11S·2C4H10O·H2O

M = 1256.63

Orthorhombic,

a = 11.402 (9) Å

b = 23.521 (9) Å

c = 25.440 (7) Å

V = 6823 (6) Å3

Z = 4

Synchrotron radiation

λ = 0.68878 Å

μ = 0.12 mm−1

T = 100 K

0.15 × 0.12 × 0.10 mm

Data collection

300mm 16K Rayonix MX300 HE CCD detector with an ACCEL MD2 microdiffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T min = 0.983, T max = 0.989

549120 measured reflections

15641 independent reflections

14786 reflections with I > 2σ(I)

R int = 0.068

Refinement

R[F 2 > 2σ(F 2)] = 0.039

wR(F 2) = 0.098

S = 1.07

15641 reflections

888 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.68 e Å−3

Δρmin = −0.27 e Å−3

Absolute structure: Flack (1983 ▶), 7070 Friedel pairs

Flack parameter: 0.13 (5)

Data collection: MXDC (Canadian Light Source, 2007 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SIR2004 (Burla et al., 2005 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: CAMERON (Watkin et al., 1993 ▶) and SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811032363/lh5292sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811032363/lh5292Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C56H83N9O11S·2C4H10O·H2O	F(000) = 2720
Mr = 1256.63	Dx = 1.223 Mg m−3
Orthorhombic, P212121	Synchrotron radiation, λ = 0.68878 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9870 reflections
a = 11.402 (9) Å	θ = 2.4–26.5°
b = 23.521 (9) Å	µ = 0.12 mm−1
c = 25.440 (7) Å	T = 100 K
V = 6823 (6) Å3	Rod, colourless
Z = 4	0.15 × 0.12 × 0.10 mm

300mm 16K Rayonix MX300 HE CCD detector with an ACCEL MD2 microdiffractometer	15641 independent reflections
Radiation source: Beamline 081B-1 at the CLS	14786 reflections with I > 2σ(I)
double crystal Si(111)	Rint = 0.068
Detector resolution: 13.8 pixels mm-1	θmax = 26.6°, θmin = 1.1°
CCD rotation images, ω scans	h = −14→14
Absorption correction: multi-scan (SADABS; Bruker, 2008)	k = −30→30
Tmin = 0.983, Tmax = 0.989	l = −33→33
549120 measured reflections

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.039	w = 1/[σ2(Fo2) + (0.0428P)2 + 3.32078P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.098	(Δ/σ)max = 0.001
S = 1.07	Δρmax = 0.68 e Å−3
15641 reflections	Δρmin = −0.27 e Å−3
888 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
0 restraints	Extinction coefficient: 0.0066 (3)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 7070 Friedel pairs
Secondary atom site location: difference Fourier map	Flack parameter: 0.13 (5)

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.

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	−0.06845 (4)	0.127042 (18)	0.090277 (17)	0.02233 (9)
O1	−0.17707 (11)	0.11209 (5)	0.06398 (5)	0.0271 (3)
O2	−0.07595 (14)	0.16630 (6)	0.13357 (6)	0.0354 (3)
O3	−0.08897 (10)	0.29370 (5)	−0.04562 (5)	0.0195 (2)
O4	−0.13526 (13)	0.43495 (7)	−0.08748 (6)	0.0363 (3)
O5	−0.00833 (10)	0.52881 (5)	0.04376 (5)	0.0217 (2)
O6	−0.23894 (11)	0.60979 (5)	0.08609 (5)	0.0254 (3)
O7	0.14169 (11)	0.73331 (5)	0.00361 (5)	0.0235 (3)
O8	0.39874 (10)	0.61559 (5)	0.04670 (5)	0.0236 (3)
O9	0.46130 (11)	0.48642 (5)	−0.00112 (5)	0.0241 (3)
O10	0.49071 (11)	0.35178 (5)	0.09127 (5)	0.0249 (3)
O11	0.07474 (10)	0.33509 (5)	0.06117 (5)	0.0205 (2)
N1	0.17591 (13)	0.26283 (6)	0.02387 (6)	0.0181 (3)
H1D	0.236 (2)	0.2415 (11)	0.0257 (10)	0.039 (7)*
N2	0.08840 (13)	0.33307 (6)	−0.05879 (6)	0.0182 (3)
H2D	0.159 (2)	0.3328 (9)	−0.0533 (9)	0.027 (6)*
N3	−0.04192 (13)	0.41929 (6)	−0.01064 (6)	0.0191 (3)
H3D	0.013 (2)	0.3973 (11)	0.0051 (10)	0.040 (7)*
N4	−0.17491 (12)	0.54896 (6)	0.00023 (6)	0.0187 (3)
N5	−0.12916 (13)	0.68641 (6)	0.06591 (6)	0.0192 (3)
N6	0.10867 (13)	0.67134 (6)	0.07003 (6)	0.0198 (3)
H6D	0.058 (2)	0.6570 (10)	0.0901 (10)	0.035 (6)*
N7	0.22187 (13)	0.57544 (6)	0.03130 (6)	0.0187 (3)
H7D	0.149 (2)	0.5777 (9)	0.0358 (8)	0.020 (5)*
N8	0.35439 (13)	0.48453 (6)	0.07367 (6)	0.0194 (3)
H8D	0.289 (2)	0.4905 (9)	0.0850 (9)	0.023 (5)*
N9	0.29706 (13)	0.37135 (6)	0.09964 (6)	0.0184 (3)
H9D	0.2520 (19)	0.3925 (9)	0.1032 (8)	0.018 (5)*
C1	0.07734 (15)	0.24387 (7)	−0.00892 (6)	0.0181 (3)
H1	0.1088 (18)	0.2196 (9)	−0.0359 (8)	0.021 (5)*
C2	−0.01456 (15)	0.21152 (7)	0.02323 (7)	0.0193 (3)
H2A	−0.0383	0.2350	0.0537	0.023*
H2B	−0.0849	0.2051	0.0012	0.023*
C3	0.03106 (15)	0.15447 (7)	0.04287 (7)	0.0199 (3)
H3A	0.1095	0.1594	0.0589	0.024*
H3B	0.0383	0.1276	0.0131	0.024*
C4	0.00104 (19)	0.06480 (8)	0.11222 (7)	0.0286 (4)
H4A	0.0806	0.0739	0.1241	0.034*
H4B	0.0050	0.0373	0.0834	0.034*
H4C	−0.0437	0.0485	0.1414	0.034*
C5	0.01818 (14)	0.29271 (7)	−0.03886 (6)	0.0173 (3)
C6	0.04216 (15)	0.37934 (7)	−0.09113 (7)	0.0202 (3)
H6	0.1004 (17)	0.4084 (8)	−0.0936 (8)	0.016 (5)*
C7	0.00408 (17)	0.35989 (8)	−0.14566 (7)	0.0271 (4)
H7A	−0.0394	0.3913	−0.1628	0.033*
H7B	−0.0507	0.3275	−0.1417	0.033*
C8	0.10494 (19)	0.34175 (8)	−0.18180 (7)	0.0302 (4)
H8	0.1546	0.3132	−0.1630	0.036*
C9	0.0533 (3)	0.31392 (14)	−0.23131 (10)	0.0657 (9)
H9A	0.0068	0.3420	−0.2507	0.079*
H9B	0.0031	0.2820	−0.2211	0.079*
H9C	0.1172	0.3001	−0.2537	0.079*
C10	0.18107 (19)	0.39122 (9)	−0.19816 (8)	0.0329 (4)
H10A	0.1328	0.4197	−0.2161	0.039*
H10B	0.2425	0.3778	−0.2221	0.039*
H10C	0.2172	0.4082	−0.1670	0.039*
C11	−0.05535 (16)	0.41260 (7)	−0.06280 (7)	0.0222 (3)
C12	−0.13120 (15)	0.44886 (7)	0.02026 (7)	0.0196 (3)
H12	−0.2079 (16)	0.4453 (8)	0.0012 (7)	0.011 (4)*
C13	−0.14060 (15)	0.42277 (7)	0.07553 (7)	0.0214 (3)
H13	−0.0595	0.4167	0.0894	0.026*
C14	−0.20542 (18)	0.46237 (8)	0.11314 (8)	0.0291 (4)
H14A	−0.1622	0.4982	0.1163	0.035*
H14B	−0.2114	0.4444	0.1478	0.035*
H14C	−0.2843	0.4699	0.0995	0.035*
C15	−0.20159 (16)	0.36443 (7)	0.07129 (7)	0.0241 (4)
H15A	−0.2856	0.3705	0.0631	0.029*
H15B	−0.1665	0.3430	0.0417	0.029*
C16	−0.1920 (2)	0.32872 (9)	0.12116 (8)	0.0334 (4)
H16A	−0.1092	0.3240	0.1305	0.040*
H16B	−0.2273	0.2913	0.1151	0.040*
H16C	−0.2333	0.3479	0.1499	0.040*
C17	−0.10061 (14)	0.51252 (7)	0.02211 (6)	0.0185 (3)
C18	−0.28831 (15)	0.53559 (7)	−0.02517 (8)	0.0242 (4)
H18A	−0.3384	0.5124	−0.0017	0.029*
H18B	−0.2763	0.5149	−0.0586	0.029*
C19	−0.34284 (15)	0.59379 (7)	−0.03497 (8)	0.0255 (4)
H19A	−0.3925	0.6055	−0.0049	0.031*
H19B	−0.3911	0.5936	−0.0673	0.031*
C20	−0.23707 (15)	0.63339 (7)	−0.04102 (7)	0.0232 (3)
H20A	−0.2586	0.6733	−0.0334	0.028*
H20B	−0.2038	0.6311	−0.0769	0.028*
C21	−0.15010 (14)	0.61022 (7)	0.00013 (7)	0.0183 (3)
H21	−0.0659 (18)	0.6162 (8)	−0.0107 (8)	0.020 (5)*
C22	−0.17600 (14)	0.63503 (7)	0.05464 (7)	0.0191 (3)
C23	−0.16410 (17)	0.71832 (8)	0.11377 (7)	0.0248 (4)
H23A	−0.1416	0.6974	0.1460	0.030*
H23B	−0.2497	0.7252	0.1143	0.030*
C24	−0.09648 (17)	0.77413 (7)	0.10923 (7)	0.0261 (4)
H24A	−0.0194	0.7714	0.1269	0.031*
H24B	−0.1414	0.8060	0.1248	0.031*
C25	−0.08167 (16)	0.78212 (7)	0.04989 (7)	0.0231 (3)
H25A	−0.0147	0.8075	0.0419	0.028*
H25B	−0.1537	0.7980	0.0339	0.028*
C26	−0.05830 (15)	0.72114 (7)	0.03017 (7)	0.0200 (3)
H26	−0.0833 (18)	0.7144 (8)	−0.0064 (8)	0.021 (5)*
C27	0.07336 (15)	0.70872 (7)	0.03343 (7)	0.0195 (3)
C28	0.23268 (14)	0.66436 (7)	0.08197 (7)	0.0194 (3)
H28	0.2752 (17)	0.6983 (8)	0.0714 (7)	0.013 (4)*
C29	0.25020 (17)	0.65554 (7)	0.14107 (7)	0.0241 (4)
H29A	0.2097	0.6202	0.1520	0.029*
H29B	0.3349	0.6508	0.1484	0.029*
C30	0.20363 (16)	0.70476 (8)	0.17311 (7)	0.0249 (4)
C31	0.24759 (19)	0.75914 (9)	0.16578 (8)	0.0320 (4)
H31	0.3056	0.7657	0.1397	0.038*
C32	0.2071 (2)	0.80423 (9)	0.19648 (10)	0.0423 (5)
H32	0.2362	0.8416	0.1907	0.051*
C33	0.1246 (2)	0.79445 (11)	0.23530 (9)	0.0452 (6)
H33	0.0982	0.8249	0.2567	0.054*
C34	0.0809 (2)	0.74078 (12)	0.24280 (9)	0.0473 (6)
H34	0.0248	0.7341	0.2697	0.057*
C35	0.11831 (19)	0.69604 (9)	0.21119 (8)	0.0353 (5)
H35	0.0853	0.6593	0.2157	0.042*
C36	0.29122 (15)	0.61622 (7)	0.05117 (7)	0.0202 (3)
C37	0.27005 (15)	0.53101 (7)	−0.00266 (7)	0.0196 (3)
H37	0.2069 (18)	0.5028 (8)	−0.0056 (8)	0.016 (5)*
C38	0.30238 (16)	0.55437 (8)	−0.05705 (7)	0.0240 (4)
H38A	0.3555	0.5873	−0.0527	0.029*
H38B	0.3453	0.5247	−0.0769	0.029*
C39	0.19690 (15)	0.57258 (7)	−0.08839 (7)	0.0221 (3)
C40	0.1399 (2)	0.53331 (8)	−0.11996 (8)	0.0338 (4)
H40	0.1677	0.4953	−0.1212	0.041*
C41	0.0432 (2)	0.54846 (10)	−0.14979 (10)	0.0432 (5)
H41	0.0048	0.5208	−0.1709	0.052*
C42	0.00256 (19)	0.60398 (9)	−0.14873 (8)	0.0356 (4)
H42	−0.0632	0.6147	−0.1694	0.043*
C43	0.05820 (18)	0.64371 (8)	−0.11743 (8)	0.0294 (4)
H43	0.0309	0.6819	−0.1166	0.035*
C44	0.15384 (16)	0.62784 (7)	−0.08726 (7)	0.0244 (3)
H44	0.1907	0.6552	−0.0654	0.029*
C45	0.37290 (15)	0.49933 (7)	0.02332 (7)	0.0192 (3)
C46	0.43758 (15)	0.44978 (7)	0.10252 (6)	0.0193 (3)
H46	0.5132 (19)	0.4548 (9)	0.0867 (8)	0.020 (5)*
C47	0.44064 (16)	0.46801 (8)	0.16082 (7)	0.0245 (4)
H47	0.3592	0.4651	0.1752	0.029*
C48	0.4794 (2)	0.53018 (9)	0.16478 (9)	0.0382 (5)
H48A	0.4822	0.5415	0.2018	0.046*
H48B	0.4234	0.5543	0.1459	0.046*
H48C	0.5574	0.5345	0.1491	0.046*
C49	0.52034 (17)	0.43021 (8)	0.19405 (7)	0.0276 (4)
H49A	0.6017	0.4347	0.1824	0.033*
H49B	0.4966	0.3904	0.1900	0.033*
H49C	0.5139	0.4412	0.2311	0.033*
C50	0.41129 (14)	0.38636 (7)	0.09661 (6)	0.0188 (3)
C51	0.26020 (15)	0.31211 (7)	0.10027 (6)	0.0175 (3)
H51	0.3301 (17)	0.2884 (8)	0.0892 (8)	0.015 (4)*
C52	0.21596 (15)	0.29313 (7)	0.15511 (6)	0.0202 (3)
H52	0.1436	0.3154	0.1636	0.024*
C53	0.18312 (18)	0.23028 (8)	0.15318 (7)	0.0266 (4)
H53A	0.2479	0.2085	0.1378	0.032*
H53B	0.1127	0.2254	0.1316	0.032*
H53C	0.1676	0.2166	0.1889	0.032*
C54	0.30799 (17)	0.30602 (8)	0.19729 (7)	0.0265 (4)
H54A	0.3815	0.2860	0.1881	0.032*
H54B	0.3247	0.3473	0.1969	0.032*
C55	0.2724 (2)	0.28895 (10)	0.25270 (8)	0.0367 (5)
H55A	0.1925	0.3022	0.2597	0.044*
H55B	0.3265	0.3062	0.2781	0.044*
H55C	0.2754	0.2475	0.2560	0.044*
C56	0.16265 (14)	0.30451 (7)	0.05998 (6)	0.0168 (3)
O60	0.12773 (12)	0.47775 (6)	0.12012 (5)	0.0297 (3)
H60	0.079 (3)	0.4921 (13)	0.0981 (12)	0.057 (8)*
C61	0.1074 (2)	0.49805 (9)	0.17215 (8)	0.0353 (4)
H61A	0.0341	0.5206	0.1728	0.042*
H61B	0.1727	0.5233	0.1828	0.042*
C62	0.09782 (19)	0.44943 (9)	0.21069 (8)	0.0328 (4)
H62A	0.1664	0.4241	0.2063	0.039*
H62B	0.0265	0.4271	0.2026	0.039*
C63	0.0921 (2)	0.46934 (10)	0.26723 (9)	0.0410 (5)
H63A	0.1635	0.4917	0.2751	0.049*
H63B	0.0238	0.4950	0.2713	0.049*
C64	0.0819 (3)	0.42177 (10)	0.30675 (9)	0.0476 (6)
H64A	0.0121	0.3990	0.2990	0.057*
H64B	0.0753	0.4378	0.3422	0.057*
H64C	0.1518	0.3976	0.3048	0.057*
O70A	0.1247 (2)	0.09480 (8)	0.31769 (7)	0.0434 (6)	0.863 (4)
H70A	0.1276	0.1154	0.3446	0.052*	0.863 (4)
C71A	0.1982 (3)	0.11838 (12)	0.27765 (10)	0.0463 (8)	0.863 (4)
H71A	0.2799	0.1210	0.2907	0.056*	0.863 (4)
H71B	0.1712	0.1572	0.2688	0.056*	0.863 (4)
O70B	0.2098 (14)	0.0817 (5)	0.3176 (4)	0.0434 (6)	0.137 (4)
H70B	0.2402	0.0965	0.3444	0.052*	0.137 (4)
C71B	0.266 (2)	0.1064 (8)	0.2685 (7)	0.0463 (8)	0.137 (4)
H71C	0.2609	0.1484	0.2679	0.056*	0.137 (4)
H71D	0.3491	0.0947	0.2652	0.056*	0.137 (4)
C72	0.1942 (2)	0.08097 (10)	0.22855 (9)	0.0414 (5)
H72A	0.1115	0.0774	0.2171	0.050*
H72B	0.2378	0.1003	0.2001	0.050*
C73	0.2445 (3)	0.02210 (11)	0.23559 (10)	0.0499 (6)
H73A	0.2037	0.0032	0.2652	0.060*
H73B	0.3284	0.0255	0.2451	0.060*
C74	0.2337 (2)	−0.01505 (10)	0.18712 (11)	0.0489 (6)
H74A	0.1507	−0.0199	0.1782	0.059*
H74B	0.2688	−0.0523	0.1942	0.059*
H74C	0.2747	0.0030	0.1577	0.059*
O80	0.48874 (14)	0.21728 (6)	0.41673 (6)	0.0350 (3)
H80A	0.439 (3)	0.2245 (14)	0.4479 (14)	0.075 (10)*
H80B	0.506 (3)	0.1789 (13)	0.4284 (12)	0.058 (8)*

	U11	U22	U33	U12	U13	U23
S1	0.0253 (2)	0.01835 (18)	0.0233 (2)	−0.00384 (16)	0.00250 (17)	−0.00053 (16)
O1	0.0224 (6)	0.0243 (6)	0.0345 (7)	−0.0015 (5)	−0.0004 (5)	0.0024 (5)
O2	0.0452 (8)	0.0292 (7)	0.0320 (7)	−0.0096 (7)	0.0143 (7)	−0.0108 (6)
O3	0.0193 (6)	0.0169 (5)	0.0223 (6)	−0.0013 (4)	−0.0007 (5)	−0.0008 (4)
O4	0.0384 (8)	0.0424 (8)	0.0281 (7)	0.0204 (7)	0.0000 (6)	0.0053 (6)
O5	0.0183 (6)	0.0194 (6)	0.0272 (6)	−0.0022 (5)	−0.0012 (5)	0.0026 (5)
O6	0.0271 (6)	0.0229 (6)	0.0261 (6)	−0.0041 (5)	0.0055 (5)	−0.0012 (5)
O7	0.0219 (6)	0.0206 (6)	0.0280 (6)	0.0004 (5)	0.0029 (5)	0.0033 (5)
O8	0.0185 (6)	0.0193 (6)	0.0329 (7)	−0.0018 (5)	0.0007 (5)	−0.0025 (5)
O9	0.0220 (6)	0.0267 (6)	0.0236 (6)	0.0032 (5)	0.0039 (5)	−0.0030 (5)
O10	0.0203 (6)	0.0220 (6)	0.0323 (7)	0.0033 (5)	0.0014 (5)	−0.0025 (5)
O11	0.0199 (6)	0.0201 (5)	0.0214 (6)	0.0037 (5)	−0.0001 (5)	−0.0029 (5)
N1	0.0155 (6)	0.0160 (6)	0.0230 (7)	0.0016 (5)	−0.0004 (5)	−0.0011 (5)
N2	0.0176 (7)	0.0168 (6)	0.0201 (7)	0.0017 (5)	0.0009 (5)	0.0001 (5)
N3	0.0204 (7)	0.0160 (6)	0.0210 (7)	0.0010 (5)	0.0032 (5)	−0.0001 (5)
N4	0.0174 (6)	0.0141 (6)	0.0246 (7)	0.0001 (5)	−0.0009 (6)	−0.0032 (5)
N5	0.0217 (7)	0.0156 (6)	0.0205 (7)	0.0001 (5)	0.0005 (6)	−0.0023 (5)
N6	0.0171 (7)	0.0178 (7)	0.0246 (7)	−0.0007 (5)	0.0002 (6)	0.0022 (6)
N7	0.0163 (7)	0.0157 (6)	0.0241 (7)	−0.0010 (5)	0.0025 (6)	−0.0003 (5)
N8	0.0158 (7)	0.0194 (7)	0.0229 (7)	0.0013 (5)	0.0019 (6)	0.0002 (5)
N9	0.0170 (7)	0.0160 (6)	0.0222 (7)	0.0025 (6)	0.0005 (5)	0.0006 (5)
C1	0.0190 (8)	0.0151 (7)	0.0202 (8)	0.0004 (6)	−0.0004 (6)	−0.0024 (6)
C2	0.0190 (8)	0.0155 (7)	0.0235 (8)	−0.0002 (6)	0.0003 (6)	−0.0001 (6)
C3	0.0218 (8)	0.0152 (7)	0.0225 (8)	−0.0011 (6)	0.0009 (6)	−0.0003 (6)
C4	0.0374 (10)	0.0231 (9)	0.0253 (9)	−0.0056 (8)	−0.0084 (8)	0.0053 (7)
C5	0.0220 (8)	0.0154 (7)	0.0144 (7)	−0.0003 (6)	0.0015 (6)	−0.0037 (6)
C6	0.0230 (8)	0.0186 (8)	0.0189 (8)	0.0007 (6)	0.0023 (6)	0.0025 (6)
C7	0.0277 (9)	0.0356 (10)	0.0180 (8)	0.0003 (8)	0.0035 (7)	0.0001 (7)
C8	0.0376 (11)	0.0292 (9)	0.0237 (9)	−0.0043 (8)	0.0095 (8)	−0.0055 (7)
C9	0.078 (2)	0.080 (2)	0.0394 (13)	−0.0420 (17)	0.0269 (13)	−0.0311 (14)
C10	0.0383 (11)	0.0341 (10)	0.0262 (9)	−0.0027 (9)	0.0080 (8)	−0.0004 (8)
C11	0.0255 (8)	0.0188 (7)	0.0225 (8)	0.0031 (7)	0.0035 (7)	0.0033 (6)
C12	0.0187 (8)	0.0157 (7)	0.0243 (8)	0.0012 (6)	0.0036 (6)	−0.0026 (6)
C13	0.0221 (8)	0.0182 (8)	0.0239 (8)	−0.0013 (6)	0.0059 (7)	−0.0013 (6)
C14	0.0310 (10)	0.0235 (9)	0.0328 (10)	−0.0010 (8)	0.0115 (8)	−0.0046 (7)
C15	0.0238 (8)	0.0194 (8)	0.0293 (9)	−0.0026 (7)	0.0050 (7)	0.0004 (7)
C16	0.0393 (11)	0.0260 (9)	0.0349 (11)	−0.0017 (8)	0.0117 (9)	0.0059 (8)
C17	0.0189 (8)	0.0170 (7)	0.0198 (8)	0.0007 (6)	0.0042 (6)	−0.0004 (6)
C18	0.0181 (8)	0.0196 (8)	0.0348 (10)	0.0005 (6)	−0.0065 (7)	−0.0035 (7)
C19	0.0193 (8)	0.0229 (9)	0.0343 (10)	0.0039 (7)	−0.0056 (7)	−0.0031 (7)
C20	0.0252 (8)	0.0205 (8)	0.0238 (8)	0.0024 (7)	−0.0030 (7)	−0.0006 (7)
C21	0.0186 (8)	0.0135 (7)	0.0227 (8)	−0.0001 (6)	−0.0004 (6)	−0.0005 (6)
C22	0.0174 (7)	0.0188 (8)	0.0211 (8)	0.0013 (6)	−0.0007 (6)	0.0003 (6)
C23	0.0279 (9)	0.0240 (9)	0.0226 (8)	−0.0001 (7)	0.0013 (7)	−0.0070 (7)
C24	0.0276 (9)	0.0196 (8)	0.0311 (9)	0.0022 (7)	−0.0022 (7)	−0.0063 (7)
C25	0.0240 (8)	0.0143 (7)	0.0311 (9)	0.0039 (6)	−0.0019 (7)	−0.0023 (6)
C26	0.0209 (8)	0.0152 (7)	0.0239 (8)	−0.0006 (6)	−0.0014 (7)	0.0000 (6)
C27	0.0211 (8)	0.0134 (7)	0.0239 (8)	0.0007 (6)	−0.0012 (7)	−0.0020 (6)
C28	0.0180 (8)	0.0156 (7)	0.0247 (8)	0.0012 (6)	−0.0020 (6)	0.0005 (6)
C29	0.0289 (9)	0.0207 (8)	0.0228 (8)	0.0044 (7)	−0.0014 (7)	0.0020 (7)
C30	0.0275 (9)	0.0269 (9)	0.0204 (8)	0.0050 (7)	−0.0033 (7)	0.0005 (7)
C31	0.0357 (10)	0.0286 (10)	0.0318 (10)	−0.0020 (8)	0.0018 (8)	−0.0063 (8)
C32	0.0514 (14)	0.0319 (11)	0.0437 (12)	0.0019 (10)	−0.0018 (10)	−0.0141 (9)
C33	0.0570 (14)	0.0497 (14)	0.0288 (11)	0.0218 (12)	−0.0016 (10)	−0.0130 (10)
C34	0.0513 (14)	0.0628 (16)	0.0277 (10)	0.0218 (13)	0.0092 (10)	0.0041 (10)
C35	0.0373 (11)	0.0379 (11)	0.0308 (10)	0.0084 (9)	0.0054 (8)	0.0092 (9)
C36	0.0215 (8)	0.0169 (8)	0.0221 (8)	0.0003 (6)	−0.0004 (6)	0.0017 (6)
C37	0.0210 (8)	0.0165 (7)	0.0213 (8)	0.0006 (6)	0.0021 (6)	0.0000 (6)
C38	0.0245 (8)	0.0259 (9)	0.0216 (8)	0.0008 (7)	0.0030 (7)	0.0021 (7)
C39	0.0260 (8)	0.0217 (8)	0.0186 (8)	−0.0021 (7)	0.0020 (7)	0.0004 (7)
C40	0.0477 (12)	0.0190 (9)	0.0346 (11)	−0.0013 (8)	−0.0064 (9)	−0.0025 (8)
C41	0.0526 (14)	0.0336 (11)	0.0433 (12)	−0.0055 (10)	−0.0207 (11)	−0.0062 (9)
C42	0.0344 (10)	0.0382 (11)	0.0341 (10)	0.0009 (9)	−0.0120 (9)	0.0008 (9)
C43	0.0324 (10)	0.0243 (9)	0.0313 (10)	0.0013 (8)	0.0028 (8)	0.0017 (7)
C44	0.0252 (8)	0.0209 (8)	0.0272 (9)	−0.0037 (7)	0.0028 (7)	−0.0023 (7)
C45	0.0196 (8)	0.0156 (7)	0.0225 (8)	−0.0034 (6)	−0.0007 (6)	−0.0027 (6)
C46	0.0175 (8)	0.0189 (7)	0.0216 (8)	−0.0007 (6)	−0.0011 (6)	−0.0017 (6)
C47	0.0197 (8)	0.0314 (9)	0.0224 (8)	0.0027 (7)	−0.0008 (7)	−0.0066 (7)
C48	0.0462 (12)	0.0271 (10)	0.0413 (12)	0.0068 (9)	−0.0163 (10)	−0.0155 (9)
C49	0.0267 (9)	0.0344 (10)	0.0218 (8)	−0.0036 (8)	−0.0026 (7)	−0.0005 (7)
C50	0.0203 (8)	0.0200 (8)	0.0162 (7)	−0.0002 (6)	−0.0017 (6)	−0.0018 (6)
C51	0.0191 (8)	0.0154 (7)	0.0180 (8)	0.0009 (6)	−0.0005 (6)	−0.0001 (6)
C52	0.0223 (8)	0.0189 (8)	0.0193 (8)	−0.0001 (7)	−0.0008 (6)	0.0009 (6)
C53	0.0335 (10)	0.0217 (9)	0.0246 (9)	−0.0057 (7)	0.0005 (7)	0.0024 (7)
C54	0.0306 (10)	0.0259 (9)	0.0230 (9)	−0.0034 (7)	−0.0047 (7)	0.0028 (7)
C55	0.0521 (13)	0.0361 (11)	0.0220 (9)	−0.0121 (10)	−0.0057 (9)	0.0018 (8)
C56	0.0182 (7)	0.0153 (7)	0.0169 (7)	−0.0015 (6)	0.0013 (6)	0.0021 (6)
O60	0.0260 (7)	0.0390 (8)	0.0240 (7)	0.0023 (6)	0.0003 (5)	0.0047 (6)
C61	0.0364 (11)	0.0348 (11)	0.0348 (11)	0.0001 (9)	0.0036 (9)	0.0015 (8)
C62	0.0385 (11)	0.0292 (9)	0.0307 (10)	0.0008 (8)	0.0027 (8)	−0.0001 (8)
C63	0.0502 (13)	0.0375 (11)	0.0351 (11)	0.0014 (10)	0.0015 (10)	−0.0061 (9)
C64	0.0701 (17)	0.0427 (13)	0.0301 (11)	−0.0020 (12)	−0.0021 (11)	−0.0019 (9)
O70A	0.0668 (15)	0.0371 (10)	0.0263 (8)	−0.0151 (10)	−0.0020 (9)	0.0046 (7)
C71A	0.077 (2)	0.0348 (14)	0.0267 (12)	−0.0196 (15)	−0.0023 (14)	0.0052 (10)
O70B	0.0668 (15)	0.0371 (10)	0.0263 (8)	−0.0151 (10)	−0.0020 (9)	0.0046 (7)
C71B	0.077 (2)	0.0348 (14)	0.0267 (12)	−0.0196 (15)	−0.0023 (14)	0.0052 (10)
C72	0.0598 (15)	0.0380 (11)	0.0265 (10)	−0.0095 (10)	−0.0087 (10)	0.0084 (9)
C73	0.0518 (15)	0.0502 (14)	0.0476 (14)	0.0056 (12)	−0.0093 (12)	0.0144 (11)
C74	0.0496 (14)	0.0368 (12)	0.0602 (15)	0.0073 (11)	0.0145 (12)	0.0087 (11)
O80	0.0414 (8)	0.0280 (7)	0.0356 (8)	0.0076 (6)	0.0023 (7)	0.0023 (6)

S1—O2	1.4398 (14)	C25—H25B	0.9900
S1—O1	1.4509 (16)	C26—C27	1.532 (3)
S1—C4	1.756 (2)	C26—H26	0.99 (2)
S1—C3	1.7772 (18)	C28—C36	1.530 (2)
O3—C5	1.234 (2)	C28—C29	1.531 (2)
O4—C11	1.225 (2)	C28—H28	0.97 (2)
O5—C17	1.248 (2)	C29—C30	1.512 (3)
O6—C22	1.228 (2)	C29—H29A	0.9900
O7—C27	1.231 (2)	C29—H29B	0.9900
O8—C36	1.231 (2)	C30—C31	1.386 (3)
O9—C45	1.223 (2)	C30—C35	1.388 (3)
O10—C50	1.225 (2)	C31—C32	1.396 (3)
O11—C56	1.234 (2)	C31—H31	0.9500
N1—C56	1.352 (2)	C32—C33	1.384 (4)
N1—C1	1.469 (2)	C32—H32	0.9500
N1—H1D	0.85 (3)	C33—C34	1.370 (4)
N2—C5	1.341 (2)	C33—H33	0.9500
N2—C6	1.463 (2)	C34—C35	1.391 (3)
N2—H2D	0.81 (2)	C34—H34	0.9500
N3—C11	1.345 (2)	C35—H35	0.9500
N3—C12	1.462 (2)	C37—C38	1.534 (2)
N3—H3D	0.91 (3)	C37—C45	1.538 (2)
N4—C17	1.327 (2)	C37—H37	0.98 (2)
N4—C21	1.468 (2)	C38—C39	1.505 (3)
N4—C18	1.479 (2)	C38—H38A	0.9900
N5—C22	1.352 (2)	C38—H38B	0.9900
N5—C26	1.465 (2)	C39—C40	1.386 (3)
N5—C23	1.485 (2)	C39—C44	1.390 (3)
N6—C27	1.343 (2)	C40—C41	1.385 (3)
N6—C28	1.456 (2)	C40—H40	0.9500
N6—H6D	0.84 (3)	C41—C42	1.386 (3)
N7—C36	1.342 (2)	C41—H41	0.9500
N7—C37	1.463 (2)	C42—C43	1.382 (3)
N7—H7D	0.84 (2)	C42—H42	0.9500
N8—C45	1.344 (2)	C43—C44	1.385 (3)
N8—C46	1.452 (2)	C43—H43	0.9500
N8—H8D	0.82 (2)	C44—H44	0.9500
N9—C50	1.352 (2)	C46—C50	1.529 (2)
N9—C51	1.455 (2)	C46—C47	1.544 (2)
N9—H9D	0.72 (2)	C46—H46	0.96 (2)
C1—C2	1.532 (2)	C47—C49	1.527 (3)
C1—C5	1.535 (2)	C47—C48	1.531 (3)
C1—H1	0.96 (2)	C47—H47	1.0000
C2—C3	1.523 (2)	C48—H48A	0.9800
C2—H2A	0.9900	C48—H48B	0.9800
C2—H2B	0.9900	C48—H48C	0.9800
C3—H3A	0.9900	C49—H49A	0.9800
C3—H3B	0.9900	C49—H49B	0.9800
C4—H4A	0.9800	C49—H49C	0.9800
C4—H4B	0.9800	C51—C56	1.523 (2)
C4—H4C	0.9800	C51—C52	1.549 (2)
C6—C7	1.524 (2)	C51—H51	1.01 (2)
C6—C11	1.539 (2)	C52—C53	1.526 (2)
C6—H6	0.95 (2)	C52—C54	1.531 (3)
C7—C8	1.533 (3)	C52—H52	1.0000
C7—H7A	0.9900	C53—H53A	0.9800
C7—H7B	0.9900	C53—H53B	0.9800
C8—C10	1.510 (3)	C53—H53C	0.9800
C8—C9	1.537 (3)	C54—C55	1.521 (3)
C8—H8	1.0000	C54—H54A	0.9900
C9—H9A	0.9800	C54—H54B	0.9900
C9—H9B	0.9800	C55—H55A	0.9800
C9—H9C	0.9800	C55—H55B	0.9800
C10—H10A	0.9800	C55—H55C	0.9800
C10—H10B	0.9800	O60—C61	1.426 (3)
C10—H10C	0.9800	O60—H60	0.86 (3)
C12—C13	1.538 (2)	C61—C62	1.510 (3)
C12—C17	1.538 (2)	C61—H61A	0.9900
C12—H12	1.003 (19)	C61—H61B	0.9900
C13—C14	1.526 (2)	C62—C63	1.514 (3)
C13—C15	1.542 (2)	C62—H62A	0.9900
C13—H13	1.0000	C62—H62B	0.9900
C14—H14A	0.9800	C63—C64	1.509 (3)
C14—H14B	0.9800	C63—H63A	0.9900
C14—H14C	0.9800	C63—H63B	0.9900
C15—C16	1.525 (3)	C64—H64A	0.9800
C15—H15A	0.9900	C64—H64B	0.9800
C15—H15B	0.9900	C64—H64C	0.9800
C16—H16A	0.9800	O70A—C71A	1.431 (3)
C16—H16B	0.9800	O70A—H70A	0.8400
C16—H16C	0.9800	C71A—C72	1.529 (4)
C18—C19	1.524 (2)	C71A—H71A	0.9900
C18—H18A	0.9900	C71A—H71B	0.9900
C18—H18B	0.9900	O70B—C71B	1.52 (2)
C19—C20	1.532 (3)	O70B—H70B	0.8400
C19—H19A	0.9900	C71B—C72	1.436 (19)
C19—H19B	0.9900	C71B—H71C	0.9900
C20—C21	1.542 (2)	C71B—H71D	0.9900
C20—H20A	0.9900	C72—C73	1.509 (3)
C20—H20B	0.9900	C72—H72A	0.9900
C21—C22	1.533 (2)	C72—H72B	0.9900
C21—H21	1.01 (2)	C73—C74	1.516 (4)
C23—C24	1.527 (3)	C73—H73A	0.9900
C23—H23A	0.9900	C73—H73B	0.9900
C23—H23B	0.9900	C74—H74A	0.9800
C24—C25	1.531 (3)	C74—H74B	0.9800
C24—H24A	0.9900	C74—H74C	0.9800
C24—H24B	0.9900	O80—H80A	0.99 (4)
C25—C26	1.543 (2)	O80—H80B	0.97 (3)
C25—H25A	0.9900
O2—S1—O1	117.22 (9)	C36—C28—H28	104.4 (11)
O2—S1—C4	108.57 (10)	C29—C28—H28	108.5 (11)
O1—S1—C4	109.25 (9)	C30—C29—C28	112.32 (14)
O2—S1—C3	108.92 (8)	C30—C29—H29A	109.1
O1—S1—C3	108.67 (9)	C28—C29—H29A	109.1
C4—S1—C3	103.32 (10)	C30—C29—H29B	109.1
C56—N1—C1	121.36 (14)	C28—C29—H29B	109.1
C56—N1—H1D	118.7 (17)	H29A—C29—H29B	107.9
C1—N1—H1D	118.0 (17)	C31—C30—C35	118.92 (18)
C5—N2—C6	121.61 (15)	C31—C30—C29	120.46 (17)
C5—N2—H2D	121.1 (16)	C35—C30—C29	120.60 (18)
C6—N2—H2D	117.3 (16)	C30—C31—C32	120.4 (2)
C11—N3—C12	120.45 (15)	C30—C31—H31	119.8
C11—N3—H3D	116.6 (16)	C32—C31—H31	119.8
C12—N3—H3D	121.1 (16)	C33—C32—C31	119.9 (2)
C17—N4—C21	120.75 (14)	C33—C32—H32	120.1
C17—N4—C18	127.14 (14)	C31—C32—H32	120.1
C21—N4—C18	112.10 (13)	C34—C33—C32	120.0 (2)
C22—N5—C26	125.77 (14)	C34—C33—H33	120.0
C22—N5—C23	121.32 (15)	C32—C33—H33	120.0
C26—N5—C23	112.02 (13)	C33—C34—C35	120.3 (2)
C27—N6—C28	120.66 (15)	C33—C34—H34	119.8
C27—N6—H6D	118.5 (17)	C35—C34—H34	119.8
C28—N6—H6D	119.7 (17)	C30—C35—C34	120.4 (2)
C36—N7—C37	120.78 (15)	C30—C35—H35	119.8
C36—N7—H7D	119.1 (14)	C34—C35—H35	119.8
C37—N7—H7D	119.8 (14)	O8—C36—N7	122.91 (16)
C45—N8—C46	121.69 (15)	O8—C36—C28	119.37 (15)
C45—N8—H8D	115.9 (16)	N7—C36—C28	117.70 (15)
C46—N8—H8D	121.2 (16)	N7—C37—C38	111.54 (14)
C50—N9—C51	121.94 (15)	N7—C37—C45	112.25 (14)
C50—N9—H9D	120.9 (17)	C38—C37—C45	112.20 (14)
C51—N9—H9D	117.0 (17)	N7—C37—H37	104.6 (11)
N1—C1—C2	111.78 (14)	C38—C37—H37	110.5 (11)
N1—C1—C5	113.02 (13)	C45—C37—H37	105.3 (11)
C2—C1—C5	109.65 (14)	C39—C38—C37	112.82 (15)
N1—C1—H1	107.4 (12)	C39—C38—H38A	109.0
C2—C1—H1	110.0 (12)	C37—C38—H38A	109.0
C5—C1—H1	104.7 (12)	C39—C38—H38B	109.0
C3—C2—C1	112.28 (14)	C37—C38—H38B	109.0
C3—C2—H2A	109.1	H38A—C38—H38B	107.8
C1—C2—H2A	109.1	C40—C39—C44	118.00 (17)
C3—C2—H2B	109.1	C40—C39—C38	119.48 (17)
C1—C2—H2B	109.1	C44—C39—C38	122.51 (16)
H2A—C2—H2B	107.9	C41—C40—C39	121.30 (19)
C2—C3—S1	108.93 (12)	C41—C40—H40	119.3
C2—C3—H3A	109.9	C39—C40—H40	119.3
S1—C3—H3A	109.9	C40—C41—C42	119.86 (19)
C2—C3—H3B	109.9	C40—C41—H41	120.1
S1—C3—H3B	109.9	C42—C41—H41	120.1
H3A—C3—H3B	108.3	C43—C42—C41	119.66 (19)
S1—C4—H4A	109.5	C43—C42—H42	120.2
S1—C4—H4B	109.5	C41—C42—H42	120.2
H4A—C4—H4B	109.5	C42—C43—C44	119.90 (18)
S1—C4—H4C	109.5	C42—C43—H43	120.1
H4A—C4—H4C	109.5	C44—C43—H43	120.1
H4B—C4—H4C	109.5	C43—C44—C39	121.27 (17)
O3—C5—N2	121.66 (16)	C43—C44—H44	119.4
O3—C5—C1	121.24 (15)	C39—C44—H44	119.4
N2—C5—C1	117.06 (15)	O9—C45—N8	123.35 (16)
N2—C6—C7	113.03 (14)	O9—C45—C37	122.02 (16)
N2—C6—C11	112.05 (14)	N8—C45—C37	114.53 (15)
C7—C6—C11	111.91 (15)	N8—C46—C50	111.81 (14)
N2—C6—H6	108.6 (12)	N8—C46—C47	110.13 (14)
C7—C6—H6	110.6 (12)	C50—C46—C47	111.71 (14)
C11—C6—H6	99.8 (12)	N8—C46—H46	107.8 (12)
C6—C7—C8	114.57 (16)	C50—C46—H46	104.8 (12)
C6—C7—H7A	108.6	C47—C46—H46	110.4 (13)
C8—C7—H7A	108.6	C49—C47—C48	110.37 (16)
C6—C7—H7B	108.6	C49—C47—C46	112.55 (15)
C8—C7—H7B	108.6	C48—C47—C46	109.58 (16)
H7A—C7—H7B	107.6	C49—C47—H47	108.1
C10—C8—C7	112.46 (17)	C48—C47—H47	108.1
C10—C8—C9	108.81 (18)	C46—C47—H47	108.1
C7—C8—C9	108.83 (19)	C47—C48—H48A	109.5
C10—C8—H8	108.9	C47—C48—H48B	109.5
C7—C8—H8	108.9	H48A—C48—H48B	109.5
C9—C8—H8	108.9	C47—C48—H48C	109.5
C8—C9—H9A	109.5	H48A—C48—H48C	109.5
C8—C9—H9B	109.5	H48B—C48—H48C	109.5
H9A—C9—H9B	109.5	C47—C49—H49A	109.5
C8—C9—H9C	109.5	C47—C49—H49B	109.5
H9A—C9—H9C	109.5	H49A—C49—H49B	109.5
H9B—C9—H9C	109.5	C47—C49—H49C	109.5
C8—C10—H10A	109.5	H49A—C49—H49C	109.5
C8—C10—H10B	109.5	H49B—C49—H49C	109.5
H10A—C10—H10B	109.5	O10—C50—N9	123.05 (16)
C8—C10—H10C	109.5	O10—C50—C46	120.92 (15)
H10A—C10—H10C	109.5	N9—C50—C46	115.99 (15)
H10B—C10—H10C	109.5	N9—C51—C56	108.42 (13)
O4—C11—N3	122.69 (17)	N9—C51—C52	112.31 (13)
O4—C11—C6	121.04 (16)	C56—C51—C52	109.55 (14)
N3—C11—C6	116.06 (15)	N9—C51—H51	107.2 (11)
N3—C12—C13	110.50 (14)	C56—C51—H51	108.9 (11)
N3—C12—C17	108.76 (13)	C52—C51—H51	110.4 (11)
C13—C12—C17	112.12 (14)	C53—C52—C54	112.50 (15)
N3—C12—H12	107.9 (11)	C53—C52—C51	109.27 (14)
C13—C12—H12	110.3 (11)	C54—C52—C51	110.55 (14)
C17—C12—H12	107.1 (10)	C53—C52—H52	108.1
C14—C13—C12	111.31 (15)	C54—C52—H52	108.1
C14—C13—C15	111.63 (15)	C51—C52—H52	108.1
C12—C13—C15	108.82 (14)	C52—C53—H53A	109.5
C14—C13—H13	108.3	C52—C53—H53B	109.5
C12—C13—H13	108.3	H53A—C53—H53B	109.5
C15—C13—H13	108.3	C52—C53—H53C	109.5
C13—C14—H14A	109.5	H53A—C53—H53C	109.5
C13—C14—H14B	109.5	H53B—C53—H53C	109.5
H14A—C14—H14B	109.5	C55—C54—C52	114.49 (16)
C13—C14—H14C	109.5	C55—C54—H54A	108.6
H14A—C14—H14C	109.5	C52—C54—H54A	108.6
H14B—C14—H14C	109.5	C55—C54—H54B	108.6
C16—C15—C13	113.53 (16)	C52—C54—H54B	108.6
C16—C15—H15A	108.9	H54A—C54—H54B	107.6
C13—C15—H15A	108.9	C54—C55—H55A	109.5
C16—C15—H15B	108.9	C54—C55—H55B	109.5
C13—C15—H15B	108.9	H55A—C55—H55B	109.5
H15A—C15—H15B	107.7	C54—C55—H55C	109.5
C15—C16—H16A	109.5	H55A—C55—H55C	109.5
C15—C16—H16B	109.5	H55B—C55—H55C	109.5
H16A—C16—H16B	109.5	O11—C56—N1	122.02 (15)
C15—C16—H16C	109.5	O11—C56—C51	120.54 (15)
H16A—C16—H16C	109.5	N1—C56—C51	117.44 (14)
H16B—C16—H16C	109.5	C61—O60—H60	111 (2)
O5—C17—N4	121.67 (15)	O60—C61—C62	111.15 (17)
O5—C17—C12	120.22 (15)	O60—C61—H61A	109.4
N4—C17—C12	118.10 (15)	C62—C61—H61A	109.4
N4—C18—C19	103.72 (14)	O60—C61—H61B	109.4
N4—C18—H18A	111.0	C62—C61—H61B	109.4
C19—C18—H18A	111.0	H61A—C61—H61B	108.0
N4—C18—H18B	111.0	C61—C62—C63	112.68 (18)
C19—C18—H18B	111.0	C61—C62—H62A	109.1
H18A—C18—H18B	109.0	C63—C62—H62A	109.1
C18—C19—C20	103.97 (14)	C61—C62—H62B	109.1
C18—C19—H19A	111.0	C63—C62—H62B	109.1
C20—C19—H19A	111.0	H62A—C62—H62B	107.8
C18—C19—H19B	111.0	C64—C63—C62	114.02 (19)
C20—C19—H19B	111.0	C64—C63—H63A	108.7
H19A—C19—H19B	109.0	C62—C63—H63A	108.7
C19—C20—C21	102.90 (14)	C64—C63—H63B	108.7
C19—C20—H20A	111.2	C62—C63—H63B	108.7
C21—C20—H20A	111.2	H63A—C63—H63B	107.6
C19—C20—H20B	111.2	C63—C64—H64A	109.5
C21—C20—H20B	111.2	C63—C64—H64B	109.5
H20A—C20—H20B	109.1	H64A—C64—H64B	109.5
N4—C21—C22	109.56 (13)	C63—C64—H64C	109.5
N4—C21—C20	102.95 (13)	H64A—C64—H64C	109.5
C22—C21—C20	110.84 (13)	H64B—C64—H64C	109.5
N4—C21—H21	108.6 (11)	C71A—O70A—H70A	109.5
C22—C21—H21	112.2 (11)	O70A—C71A—C72	109.9 (2)
C20—C21—H21	112.2 (11)	O70A—C71A—H71A	109.7
O6—C22—N5	121.66 (16)	C72—C71A—H71A	109.7
O6—C22—C21	121.19 (15)	O70A—C71A—H71B	109.7
N5—C22—C21	117.13 (14)	C72—C71A—H71B	109.7
N5—C23—C24	103.72 (14)	H71A—C71A—H71B	108.2
N5—C23—H23A	111.0	C71B—O70B—H70B	109.5
C24—C23—H23A	111.0	C72—C71B—O70B	100.5 (13)
N5—C23—H23B	111.0	C72—C71B—H71C	111.7
C24—C23—H23B	111.0	O70B—C71B—H71C	111.7
H23A—C23—H23B	109.0	C72—C71B—H71D	111.7
C23—C24—C25	103.64 (14)	O70B—C71B—H71D	111.7
C23—C24—H24A	111.0	H71C—C71B—H71D	109.4
C25—C24—H24A	111.0	C71B—C72—C73	94.6 (10)
C23—C24—H24B	111.0	C73—C72—C71A	114.8 (2)
C25—C24—H24B	111.0	C71B—C72—H72A	141.9
H24A—C24—H24B	109.0	C73—C72—H72A	108.6
C24—C25—C26	103.04 (14)	C71A—C72—H72A	108.6
C24—C25—H25A	111.2	C71B—C72—H72B	92.3
C26—C25—H25A	111.2	C73—C72—H72B	108.6
C24—C25—H25B	111.2	C71A—C72—H72B	108.6
C26—C25—H25B	111.2	H72A—C72—H72B	107.5
H25A—C25—H25B	109.1	C72—C73—C74	113.7 (2)
N5—C26—C27	113.61 (14)	C72—C73—H73A	108.8
N5—C26—C25	102.78 (14)	C74—C73—H73A	108.8
C27—C26—C25	109.21 (14)	C72—C73—H73B	108.8
N5—C26—H26	109.7 (12)	C74—C73—H73B	108.8
C27—C26—H26	107.6 (12)	H73A—C73—H73B	107.7
C25—C26—H26	114.0 (12)	C73—C74—H74A	109.5
O7—C27—N6	123.03 (16)	C73—C74—H74B	109.5
O7—C27—C26	119.81 (15)	H74A—C74—H74B	109.5
N6—C27—C26	117.15 (15)	C73—C74—H74C	109.5
N6—C28—C36	113.61 (14)	H74A—C74—H74C	109.5
N6—C28—C29	110.30 (14)	H74B—C74—H74C	109.5
C36—C28—C29	110.23 (14)	H80A—O80—H80B	92 (2)
N6—C28—H28	109.5 (11)
C56—N1—C1—C2	−69.93 (18)	C25—C26—C27—N6	109.82 (17)
C56—N1—C1—C5	54.3 (2)	C27—N6—C28—C36	−94.07 (18)
N1—C1—C2—C3	−68.07 (17)	C27—N6—C28—C29	141.59 (16)
C5—C1—C2—C3	165.78 (13)	N6—C28—C29—C30	−59.00 (19)
C1—C2—C3—S1	168.11 (11)	C36—C28—C29—C30	174.75 (15)
O2—S1—C3—C2	−60.58 (14)	C28—C29—C30—C31	−59.7 (2)
O1—S1—C3—C2	68.19 (13)	C28—C29—C30—C35	121.90 (19)
C4—S1—C3—C2	−175.86 (12)	C35—C30—C31—C32	0.4 (3)
C6—N2—C5—O3	−2.1 (2)	C29—C30—C31—C32	−178.02 (19)
C6—N2—C5—C1	175.65 (14)	C30—C31—C32—C33	1.5 (3)
N1—C1—C5—O3	−142.96 (15)	C31—C32—C33—C34	−1.4 (4)
C2—C1—C5—O3	−17.5 (2)	C32—C33—C34—C35	−0.6 (4)
N1—C1—C5—N2	39.23 (19)	C31—C30—C35—C34	−2.4 (3)
C2—C1—C5—N2	164.67 (14)	C29—C30—C35—C34	176.02 (19)
C5—N2—C6—C7	−71.9 (2)	C33—C34—C35—C30	2.6 (4)
C5—N2—C6—C11	55.7 (2)	C37—N7—C36—O8	−7.5 (3)
N2—C6—C7—C8	−68.8 (2)	C37—N7—C36—C28	174.28 (14)
C11—C6—C7—C8	163.58 (15)	N6—C28—C36—O8	160.55 (16)
C6—C7—C8—C10	−68.9 (2)	C29—C28—C36—O8	−75.1 (2)
C6—C7—C8—C9	170.50 (19)	N6—C28—C36—N7	−21.2 (2)
C12—N3—C11—O4	7.0 (3)	C29—C28—C36—N7	103.17 (18)
C12—N3—C11—C6	−178.29 (14)	C36—N7—C37—C38	−72.1 (2)
N2—C6—C11—O4	−149.19 (17)	C36—N7—C37—C45	54.8 (2)
C7—C6—C11—O4	−21.0 (2)	N7—C37—C38—C39	−67.15 (19)
N2—C6—C11—N3	36.0 (2)	C45—C37—C38—C39	165.93 (14)
C7—C6—C11—N3	164.14 (15)	C37—C38—C39—C40	−88.6 (2)
C11—N3—C12—C13	146.05 (15)	C37—C38—C39—C44	91.7 (2)
C11—N3—C12—C17	−90.48 (18)	C44—C39—C40—C41	0.3 (3)
N3—C12—C13—C14	163.62 (14)	C38—C39—C40—C41	−179.4 (2)
C17—C12—C13—C14	42.1 (2)	C39—C40—C41—C42	0.6 (4)
N3—C12—C13—C15	−72.95 (18)	C40—C41—C42—C43	−0.7 (4)
C17—C12—C13—C15	165.55 (14)	C41—C42—C43—C44	−0.2 (3)
C14—C13—C15—C16	−69.6 (2)	C42—C43—C44—C39	1.1 (3)
C12—C13—C15—C16	167.21 (15)	C40—C39—C44—C43	−1.2 (3)
C21—N4—C17—O5	0.8 (2)	C38—C39—C44—C43	178.52 (17)
C18—N4—C17—O5	−178.07 (16)	C46—N8—C45—O9	−2.3 (2)
C21—N4—C17—C12	−179.28 (14)	C46—N8—C45—C37	174.08 (14)
C18—N4—C17—C12	1.8 (3)	N7—C37—C45—O9	−138.38 (16)
N3—C12—C17—O5	−63.5 (2)	C38—C37—C45—O9	−11.8 (2)
C13—C12—C17—O5	59.0 (2)	N7—C37—C45—N8	45.15 (19)
N3—C12—C17—N4	116.64 (17)	C38—C37—C45—N8	171.69 (14)
C13—C12—C17—N4	−120.86 (17)	C45—N8—C46—C50	−89.61 (19)
C17—N4—C18—C19	171.41 (16)	C45—N8—C46—C47	145.58 (15)
C21—N4—C18—C19	−7.56 (19)	N8—C46—C47—C49	175.97 (15)
N4—C18—C19—C20	28.20 (18)	C50—C46—C47—C49	51.1 (2)
C18—C19—C20—C21	−38.05 (18)	N8—C46—C47—C48	−60.82 (19)
C17—N4—C21—C22	−77.03 (19)	C50—C46—C47—C48	174.31 (15)
C18—N4—C21—C22	102.01 (16)	C51—N9—C50—O10	4.2 (3)
C17—N4—C21—C20	164.98 (15)	C51—N9—C50—C46	−173.40 (14)
C18—N4—C21—C20	−15.97 (18)	N8—C46—C50—O10	140.00 (16)
C19—C20—C21—N4	32.78 (16)	C47—C46—C50—O10	−96.07 (19)
C19—C20—C21—C22	−84.29 (16)	N8—C46—C50—N9	−42.4 (2)
C26—N5—C22—O6	−176.63 (16)	C47—C46—C50—N9	81.56 (18)
C23—N5—C22—O6	−8.3 (2)	C50—N9—C51—C56	−131.06 (16)
C26—N5—C22—C21	1.7 (2)	C50—N9—C51—C52	107.76 (17)
C23—N5—C22—C21	170.00 (15)	N9—C51—C52—C53	−178.01 (14)
N4—C21—C22—O6	−19.1 (2)	C56—C51—C52—C53	61.46 (18)
C20—C21—C22—O6	93.81 (19)	N9—C51—C52—C54	−53.68 (19)
N4—C21—C22—N5	162.59 (14)	C56—C51—C52—C54	−174.22 (14)
C20—C21—C22—N5	−84.48 (18)	C53—C52—C54—C55	−57.6 (2)
C22—N5—C23—C24	−176.92 (15)	C51—C52—C54—C55	179.91 (16)
C26—N5—C23—C24	−7.11 (19)	C1—N1—C56—O11	−12.7 (2)
N5—C23—C24—C25	28.18 (18)	C1—N1—C56—C51	166.44 (14)
C23—C24—C25—C26	−38.51 (18)	N9—C51—C56—O11	−53.7 (2)
C22—N5—C26—C27	−89.54 (19)	C52—C51—C56—O11	69.17 (19)
C23—N5—C26—C27	101.19 (17)	N9—C51—C56—N1	127.18 (15)
C22—N5—C26—C25	152.60 (16)	C52—C51—C56—N1	−109.94 (16)
C23—N5—C26—C25	−16.67 (18)	O60—C61—C62—C63	172.53 (18)
C24—C25—C26—N5	33.60 (17)	C61—C62—C63—C64	179.8 (2)
C24—C25—C26—C27	−87.33 (17)	O70B—C71B—C72—C73	−72.0 (13)
C28—N6—C27—O7	9.6 (2)	O70B—C71B—C72—C71A	58.0 (13)
C28—N6—C27—C26	−169.37 (14)	O70A—C71A—C72—C71B	−122.2 (14)
N5—C26—C27—O7	176.69 (14)	O70A—C71A—C72—C73	−65.0 (4)
C25—C26—C27—O7	−69.2 (2)	C71B—C72—C73—C74	−155.3 (9)
N5—C26—C27—N6	−4.3 (2)	C71A—C72—C73—C74	177.1 (2)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1D···O3i	0.85 (3)	2.21 (3)	3.043 (3)	163 (2)
N2—H2D···O1i	0.81 (2)	2.29 (2)	2.972 (3)	141 (2)
N3—H3D···O11	0.91 (3)	2.16 (3)	3.005 (2)	154 (2)
N7—H7D···O5	0.84 (2)	2.14 (2)	2.862 (3)	144 (2)
N8—H8D···O60	0.82 (2)	2.07 (2)	2.847 (2)	161 (2)
N9—H9D···O60	0.72 (2)	2.49 (2)	3.203 (2)	169 (2)
O60—H60···O5	0.86 (3)	1.91 (3)	2.761 (2)	170 (3)
O70A—H70A···O6ii	0.84	2.18	2.795 (2)	130
O80—H80A···O7iii	0.99 (4)	1.95 (4)	2.906 (2)	159 (3)
O80—H80B···O8iv	0.97 (3)	1.95 (3)	2.869 (2)	157 (3)

	Met sulfone1	Leu2	Ile3	Pro4	Pro5	Phe6	Phe7	Val8	Ile9
φ	54.3 (2)	55.7 (2)	-90.48 (18)	-77.03 (19)	-89.54 (19)	-94.07 (18)	54.8 (2)	-89.61 (18)	-131.06 (16)
ψ	39.23 (19)	36.0 (2)	116.64 (17)	162.59 (14)	-4.3 (2)	-21.2 (2)	45.15 (19)	-42.4 (2)	127.18 (15)
ω	166.44 (14)	175.65 (14)	-178.29 (14)	-179.28 (14)	1.6 (2)	-169.37 (14)	174.28 (14)	174.08 (14)	-173.40 (14)
χ1	-68.07 (17)	-68.8 (2)	-72.95 (18)	32.78 (16)	33.60 (17)	-59.00 (19)	-67.15 (19)	-60.82 (19)	-53.68 (19)

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1D⋯O3i	0.85 (3)	2.21 (3)	3.043 (3)	163 (2)
N2—H2D⋯O1i	0.81 (2)	2.29 (2)	2.972 (3)	141 (2)
N3—H3D⋯O11	0.91 (3)	2.16 (3)	3.005 (2)	154 (2)
N7—H7D⋯O5	0.84 (2)	2.14 (2)	2.862 (3)	144 (2)
N8—H8D⋯O60	0.82 (2)	2.07 (2)	2.847 (2)	161 (2)
N9—H9D⋯O60	0.72 (2)	2.49 (2)	3.203 (2)	169 (2)
O60—H60⋯O5	0.86 (3)	1.91 (3)	2.761 (2)	170 (3)
O70A—H70A⋯O6ii	0.84	2.18	2.795 (2)	130
O80—H80A⋯O7iii	0.99 (4)	1.95 (4)	2.906 (2)	159 (3)
O80—H80B⋯O8iv	0.97 (3)	1.95 (3)	2.869 (2)	157 (3)

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .