A β-sheet structure formed by C–H...O hydrogen bonds between the thia­zole rings and amide bonds of a dimeric desoxazoline ascidiacycl­amide analogue

A dimeric analogue of desoxazoline ascidiacycl­amide was synthesized to increase the conformational flexibility of the mol­ecule. The overall structure of this compound, C₇₂H₁₁₂N₁₆O₁₆S₄·3C₃H₇NO·H₂O, was relatively flat and was classified neither as the folded nor squared form, which have been observed in ascidiacycl­amide analogues. Rather, a unique β-sheet was formed in the 48-membered ring with pseudo-twofold symmetry. This was stabilized by hydrogen bonds including C—H...O interactions between thia­zole and carbonyl O atoms. This is the first structure of an ascidiacycl­amide analogue to exhibit a flat conformation composed of a β-sheet.

Key indicators

• Single-crystal synchrotron study
• T = 100 K
• Mean [sigma](C-C) = 0.015 Å
• Disorder in main residue
• R factor = 0.097
• wR factor = 0.259
• Data-to-parameter ratio = 8.0

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level B:



PLAT_420  Alert B D-H Without Acceptor       O(124) -   H(134)            ?


 Alert Level C:



DIFMN_02  Alert C The minimum difference density is < -0.1*ZMAX*0.75
          _refine_diff_density_min given =     -1.214
          Test value =     -1.200

DIFMN_03  Alert C The minimum difference density is < -0.1*ZMAX*0.75
          The relevant atom site should be identified.

DIFMX_01  Alert C The maximum difference density is > 0.1*ZMAX*0.75
          _refine_diff_density_max given =      1.515
          Test value =      1.200

DIFMX_02  Alert C The minimum difference density is > 0.1*ZMAX*0.75
          The relevant atom site should be identified.

REFLT_03
         From the CIF: _diffrn_reflns_theta_max           30.25
         From the CIF: _reflns_number_total               8977
         TEST2: Reflns within _diffrn_reflns_theta_max
         Count of symmetry unique reflns         9641
         Completeness (_total/calc)             93.11%
          Alert C: < 95% complete

RFACR_01  Alert C The value of the weighted R factor is > 0.25
          Weighted R factor given   0.259

PLAT_202  Alert C Isotropic non-H Atoms in Anion/Solvent       =          2

PLAT_213  Alert C Atom  O39    has ADP max/min Ratio ...........       3.10

PLAT_213  Alert C Atom  C5     has ADP max/min Ratio ...........       3.50

PLAT_213  Alert C Atom  C31    has ADP max/min Ratio ...........       3.60

PLAT_213  Alert C Atom  C45    has ADP max/min Ratio ...........       3.20

PLAT_213  Alert C Atom  C57    has ADP max/min Ratio ...........       3.30

PLAT_213  Alert C Atom  C58    has ADP max/min Ratio ...........       3.10

PLAT_213  Alert C Atom  C67    has ADP max/min Ratio ...........       3.20

PLAT_214  Alert C Atom  N121   (Anion/Solvent) ADP max/min Ratio       4.30

PLAT_301  Alert C Main Residue Disorder ........................       1.00 Perc.

PLAT_320  Alert C Check Hybridisation of  S(25)  in main residue          ?

PLAT_320  Alert C Check Hybridisation of  S(52)  in main residue          ?

PLAT_320  Alert C Check Hybridisation of  S(79)  in main residue          ?

PLAT_320  Alert C Check Hybridisation of  S(106) in main residue          ?

PLAT_367  Alert C Long?  C(sp?)-C(sp?) Bond  C(45)  -   C(46)  =       1.70 Ang.

General Notes



ABSMU_01  Radiation type not identified. Calculation of
          _exptl_absorpt_correction_mu not performed.

REFLT_03
         From the CIF: _diffrn_reflns_theta_max           30.25
         From the CIF: _reflns_number_total               8977
         Count of symmetry unique reflns         9641
         Completeness (_total/calc)             93.11%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured         0
         Fraction of Friedel pairs measured     0.000
         Are heavy atom types Z>Si present          yes
          WARNING: Large fraction of Friedel related reflns may
                   be needed to determine absolute structure


 0 Alert Level A = Potentially serious problem

 1 Alert Level B = Potential problem

 21 Alert Level C = Please check

---

S1. Comment

Ascidiacyclamide (ASC) is a cytotoxic peptide isolated from marine organisms (Ireland et al., 1982; Hamamoto et al., 1983), and includes unusualamino acids (Fig. 1), thiazole (Thz) and oxazoline (Oxz). Two major structures are known for this peptide (Ishida et al., 1989). We have attempted to control its structure by chemical modification, e.g. substitution of amino acids or changing the chirality (Doi et al., 1999). The conformations of ASC analogues seem to be restricted by the rigid blocks composed of Thz and Oxz, since these blocks limit the rotations of peptide backbones (N—Cα and Cα-C bonds). Therefore, we tried to break the Oxz blocks to increase backbone flexibility. The Oxz block is synthesized from threonine and modification would result in threonine residues in place of the Oxz blocks. Threonine has two chiral C atoms at the α and β positions, and both C atoms could be targets of the chiral modifications (a diastereomer of threonine at the Cβ position is named allo-threonine, aThr). Such desoxazoline-ASC analogues (dASC) prefer a single conformation, viz. a folded form (Asano et al., 2001). It was postulated that the molecular size of these cyclic peptides (24-membered ring) could limit the conformational variations.

Thus, we attempted a dimerization of these dASC diastereomers to give more conformational freedom to the peptide backbone (Fig. 1). The dimeric desoxazoline-ASC (dASC2) analogues have a 48-membered ring in place of the 24-membered ring of ASC in dASC analogues. Crystals of [Thr,D-aThr]-dASC2 were obtained from the dASC2 diastereomers. The structure of this analogue is completely different from the folded or squared structure of ASC and a related peptide, patellamide (Schmitz et al., 1989). We report here the crystal structure of [D-aThr,Thr]-dASC2.

Crystals of [D-aThr,Thr]-dASC2 were grown in aqueous dimethylformamide (DMF) solution and the X-ray diffraction data were measured on s synchrotron source. The structure is shown in Fig. 2. The peptide is slightly twisted, but no large folding is observed. In dASC analogues, the peptide molecules are folded such that the Thz rings face each other (Asano et al., 2001), and the Thz-Thz stacking is a notable feature of a folded dASC. In this structure, the four Thz rings are separated from each other and no stacking is observed. The Thz4 and Thz12 rings are both roughly perpendicular to the Thz8 and Thz16 rings; the angles between the least-squares planes are Thz4···Thz8 = 85.7°, Thz4···Thz16 = 84.2°, Thz12···Thz8 = 78.2° and Thz12···Thz16 = 76.9°. The conformation of the peptide backbone is shown in Figs. 3 and 4. The peptide backbone forms a unique β-sheet structure (Fig. 3). In this β-sheet, C—H···O hydrogen bonds are formed between the Thz and carbonyl O atoms (Table 2): C24(Thz4)···O96(Thr14) = 3.158 (11) Å and C78(Thz12)···O42(Thr6) = 3.190 (12) Å. Such hydrogen bonds lead to a parallel arrangement of Thz4 and Thz12; the angle between the least-squares planes of Thz4 and Thz12 is 23.2°. Consequently, the 48-membered ring is relatively flat (Fig. 4). Furthermore, the peptide has a repeated sequence, and structural symmetry is found in the torsion angles of the backbone (Table 1). Although this implies the existence of a pseudo-twofold axis in the molecule, the crystallographic symmetry is distorted by local conformations and interactions with the solvent molecules (Fig. 1); O39(Thr6)···O119(DMF) = 2.579 (24) Å, N70(D-Val11)···O114(DMF) = 2.963 (13) Å, N16(D-Val3)···O109(DMF) = 2.965 (9) Å and O93(Thr14)···O124(W) = 2.717 (22) Å.

The conformational properties which were found in the folded and squared structures of ASC and dASC analogues are not found in the structure of [D-aThr,Thr]-dASC2. The molecule is relatively flat, with accompanying slight twisting, and a unique β-sheet is formed, involving C—H···O hydrogen bonds. Dimerization gives conformational flexibility to the peptide molecule, and the resulting novel flat structure is the first such example in ASC analogues.

S2. Experimental

dASC and dASC2 analogues were synthesized by a previously reported method (Hamada et al., 1987). Dimerization of dASC was controlled by the concentration of starting linear peptides. The cyclization reaction was performed in 10mM of the linear peptide, but dimerization mainly occurred above this concentration. dASC2 analogues (ca 20 mg) were dissolved in DMF (0.2 ml), and water was added to the solution just before the solution became unclear. The aqueous DMF solution was sealed in vials at room temperature. A crystal was mounted on a nylon loop in the mother liquor, and frozen under a nitrogen stream (100 K).

S3. Refinement

A total of 90 images with oscillation-angle of 2° were measured on a synchrotron using RAXIS-IV, and the first 87 frames were processed by MOSFLM (Leslie, 1999). The 37199 observed reflections were successively processed by the CCP4 program suite (1994), and the reflections were merged to 17325 reflections with an R_merg value of 0.060. The structure was solved using all reflections. H atoms of the peptide were positioned at calculated positions and constrained during the refinement. H atoms of the water molecules were positioned by considering the hydrogen-bonding networks and fixed during the refinement. The resolution of the diffraction data was 0.80 Å, but reflections of 0.83–0.80 Å resolution were omitted in the final refinement stage because of the higher R value of that shell. Disorder was observed in the D-Val7 side chain, relating to the rotation of the Cα-Cβ bond. The occupancies of the two disordered sites were 0.59 and 0.41.

Computing details

Data collection: PROCESS (Higashi, 1996); cell refinement: MOSFLM (Leslie, 1999); data reduction: MOSFLM; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1998); software used to prepare material for publication: PARST (Nardelli, 1995).

Figures

	Fig. 1. A view of dASC2 with the atomic numbering scheme. Displacement ellipsoids are drawn at the 40% probability level. Dotted lines represent hydrogen bonds. The solvent molecules are shaded.
	Fig. 2. Top view of the peptide backbone. Side chains have been omitted for clarity (Cβ atoms only are drawn). Dotted lines represent hydrogen bonds.
	Fig. 3. Side view of the peptide backbone. Side chains have been omitted for clarity (Cβ atoms only are drawn).

desoxazoline-ascidiacyclamide dimer (DMF & H2O solvated) cyclo(–Ile-Thr-D-Val-Thz-Ile-D-alloIle-D-Val-Thz-)2 [Thz = thiazole, Thr = (2S,3R), D-alloThr = (2R,3R)]

Crystal data

C72H112N16O16S4·3C3H7NO·H2O	Z = 2
Mr = 1823.32	F(000) = 1956
Monoclinic, P21	Dx = 1.222 Mg m^−3
a = 11.5563 (1) Å	Synchrotron radiation, λ = 0.83600 Å
b = 9.9957 (2) Å	µ = 0.17 mm^−1
c = 42.9208 (10) Å	T = 100 K
β = 91.3492 (15)°	Cubic, colorless
V = 4956.55 (16) Å^3	0.01 × 0.01 × 0.01 mm

Data collection

Rigaku RAXIS-IV diffractometer	8977 independent reflections
Radiation source: double monochromated beam	8890 reflections with I > 2σ(I)
Diamond monochromator	Rint = 0.038
Detector resolution: 10 pixels mm^-1	θmax = 30.3°, θmin = 2.6°
oscillation scans	h = −13→13
Absorption correction: for a cylinder mounted on the ϕ axis (CYLABS; Nardelli, 1998)	k = −11→12
Tmin = 0.657, Tmax = 0.661	l = 0→51
15629 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.097	H-atom parameters constrained
wR(F^2) = 0.259	w = 1/[σ^2(Fo^2) + (0.1312P)^2 + 5.0564P] where P = (Fo^2 + 2Fc^2)/3
S = 1.25	(Δ/σ)max = 0.017
8977 reflections	Δρmax = 1.52 e Å^−3
1119 parameters	Δρmin = −1.21 e Å^−3
4 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.17 (14)

Special details

Geometry. Mean-plane data from final SHELXL refinement run:-

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

- 0.3629 x + 9.7478 y + 9.4330 z = 10.7033

* -0.0033 C21 * 0.0057 N22 * -0.0058 C23 * 0.0033 C24 * 0.0000 S25

Rms deviation of fitted atoms = 0.0042

- 10.6859 x - 0.3847 y + 17.1882 z = 10.9015

Angle to previous plane = 85.73 Thz4-Thz8

* -0.0022 C48 * 0.0093 N49 * -0.0136 C50 * 0.0107 C51 * -0.0043 S52

Rms deviation of fitted atoms = 0.0091

- 3.4107 x + 9.5134 y - 3.3086 z = 6.5795

Angle to previous plane = 78.20 Thz8-Thz12

* -0.0075 C75 * -0.0055 N76 * 0.0202 C77 * -0.0216 C78 * 0.0144 S79

Rms deviation of fitted atoms = 0.0153

- 0.3629 x + 9.7478 y + 9.4330 z = 10.7033

Angle to previous plane = 23.22 Thz12-Thz4

* -0.0033 C21 * 0.0057 N22 * -0.0058 C23 * 0.0033 C24 * 0.0000 S25

Rms deviation of fitted atoms = 0.0042

10.6609 x + 0.1294 y - 17.4834 z = 2.4178

Angle to previous plane = 84.21 Thz4-Thz16

* -0.0053 C102 * 0.0054 N103 * -0.0024 C104 * -0.0007 C105 * 0.0029 S106

Rms deviation of fitted atoms = 0.0038

- 3.4107 x + 9.5134 y - 3.3086 z = 6.5795

Angle to previous plane = 76.85 Thz16-Thz12

* -0.0075 C75 * -0.0055 N76 * 0.0202 C77 * -0.0216 C78 * 0.0144 S79

Rms deviation of fitted atoms = 0.0153

- 10.6859 x - 0.3847 y + 17.1882 z = 10.9015

Angle to previous plane = 78.20 Thz12-Thz8

* -0.0022 C48 * 0.0093 N49 * -0.0136 C50 * 0.0107 C51 * -0.0043 S52

Rms deviation of fitted atoms = 0.0091

10.6609 x + 0.1294 y - 17.4834 z = 2.4178

Angle to previous plane = 1.52 Thz8-Thz16

* -0.0053 C102 * 0.0054 N103 * -0.0024 C104 * -0.0007 C105 * 0.0029 S106

Rms deviation of fitted atoms = 0.0038

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
N1	0.3244 (4)	1.1096 (5)	0.06135 (14)	0.0349 (12)
H1	0.3440	1.0266	0.0607	0.042*
C2	0.2624 (5)	1.1671 (6)	0.03467 (19)	0.0385 (16)
H2	0.2326	1.2546	0.0409	0.046*
C3	0.3359 (7)	1.1875 (11)	0.0059 (2)	0.064 (3)
H3	0.2868	1.2321	−0.0098	0.077*
C4	0.3744 (9)	1.0584 (15)	−0.0079 (2)	0.083 (4)
H4	0.3095	0.9969	−0.0086	0.099*
H5	0.4340	1.0197	0.0056	0.099*
C5	0.4368 (7)	1.2776 (13)	0.0126 (4)	0.098 (5)
H6	0.4100	1.3596	0.0216	0.098*
H7	0.4754	1.2968	−0.0065	0.098*
H8	0.4898	1.2344	0.0269	0.098*
C6	0.4221 (12)	1.073 (2)	−0.0410 (3)	0.131 (8)
H9	0.4452	0.9865	−0.0485	0.131*
H10	0.4878	1.1316	−0.0404	0.131*
H11	0.3631	1.1089	−0.0547	0.131*
C7	0.1594 (5)	1.0770 (6)	0.02725 (13)	0.0269 (12)
O8	0.1611 (4)	0.9568 (4)	0.03542 (9)	0.0294 (9)
N9	0.0721 (4)	1.1309 (5)	0.01103 (11)	0.0255 (10)
H12	0.0750	1.2142	0.0061	0.031*
C10	−0.0278 (5)	1.0527 (6)	0.00139 (13)	0.0249 (11)
H13	−0.0019	0.9845	−0.0133	0.030*
C11	−0.1147 (5)	1.1446 (6)	−0.01612 (13)	0.0293 (12)
H14	−0.0757	1.1848	−0.0339	0.035*
O12	−0.1452 (4)	1.2483 (4)	0.00487 (10)	0.0307 (9)
H15	−0.1543	1.3181	−0.0050	0.031*
C13	−0.2232 (6)	1.0727 (8)	−0.02822 (16)	0.0407 (15)
H16	−0.2734	1.1356	−0.0386	0.041*
H17	−0.2626	1.0333	−0.0110	0.041*
H18	−0.2017	1.0038	−0.0426	0.041*
C14	−0.0847 (4)	0.9809 (5)	0.02840 (11)	0.0191 (10)
O15	−0.1202 (3)	0.8648 (4)	0.02536 (9)	0.0260 (8)
N16	−0.0972 (4)	1.0524 (5)	0.05514 (10)	0.0213 (9)
H19	−0.0683	1.1315	0.0566	0.026*
C17	−0.1592 (4)	0.9960 (6)	0.08137 (12)	0.0246 (11)
H20	−0.1771	0.9033	0.0756	0.030*
C18	−0.2759 (6)	1.0641 (8)	0.08651 (16)	0.0419 (17)
H21	−0.3079	1.0281	0.1057	0.050*
C19	−0.3589 (7)	1.0274 (16)	0.05931 (18)	0.076 (4)
H22	−0.3638	0.9318	0.0575	0.076*
H23	−0.3303	1.0641	0.0403	0.076*
H24	−0.4342	1.0634	0.0631	0.076*
C20	−0.2637 (11)	1.2135 (11)	0.0902 (3)	0.082 (4)
H25	−0.3386	1.2523	0.0933	0.082*
H26	−0.2306	1.2506	0.0718	0.082*
H27	−0.2143	1.2326	0.1080	0.082*
C21	−0.0809 (5)	0.9882 (6)	0.11003 (12)	0.0258 (11)
N22	−0.1183 (5)	0.9611 (6)	0.13760 (11)	0.0347 (12)
C23	−0.0259 (6)	0.9436 (10)	0.15802 (14)	0.0458 (19)
C24	0.0797 (6)	0.9600 (10)	0.14601 (14)	0.049 (2)
H28	0.1491	0.9524	0.1573	0.059*
S25	0.06873 (13)	0.9967 (2)	0.10733 (3)	0.0381 (4)
C26	−0.0474 (7)	0.9103 (12)	0.19168 (16)	0.058 (3)
O27	0.0363 (5)	0.8948 (10)	0.20993 (11)	0.078 (3)
N28	−0.1567 (6)	0.9076 (10)	0.20027 (13)	0.060 (2)
H29	−0.2103	0.9148	0.1861	0.072*
C29	−0.1899 (8)	0.8931 (14)	0.23256 (16)	0.068 (3)
H30	−0.1242	0.8550	0.2444	0.081*
C30	−0.2200 (12)	1.0276 (17)	0.2470 (2)	0.090 (4)
H31	−0.2769	1.0735	0.2335	0.107*
C31	−0.268 (3)	1.014 (3)	0.2795 (3)	0.190 (12)
H32	−0.3336	0.9554	0.2789	0.190*
H33	−0.2911	1.1006	0.2868	0.190*
H34	−0.2092	0.9782	0.2933	0.190*
C32	−0.113 (2)	1.120 (3)	0.2523 (5)	0.154 (9)
H35	−0.0467	1.0688	0.2600	0.184*
H36	−0.0926	1.1648	0.2332	0.184*
C33	−0.152 (2)	1.220 (3)	0.2767 (5)	0.164 (10)
H37	−0.0993	1.2938	0.2775	0.164*
H38	−0.1534	1.1770	0.2967	0.164*
H39	−0.2283	1.2514	0.2712	0.164*
C34	−0.2928 (6)	0.7976 (14)	0.23504 (14)	0.063 (3)
O35	−0.3766 (6)	0.7999 (12)	0.21688 (12)	0.086 (3)
N36	−0.2840 (6)	0.7119 (10)	0.25932 (14)	0.057 (2)
H40	−0.2183	0.7044	0.2690	0.069*
C37	−0.3803 (7)	0.6318 (12)	0.26982 (19)	0.060 (2)
H41	−0.4528	0.6735	0.2626	0.072*
C38	−0.3758 (11)	0.4933 (18)	0.2577 (3)	0.104 (5)
H42	−0.2986	0.4561	0.2619	0.125*
O39	−0.3963 (12)	0.502 (2)	0.2235 (3)	0.178 (8)
H43	−0.3677	0.4321	0.2158	0.178*
C40	−0.4656 (13)	0.4025 (16)	0.2717 (4)	0.103 (5)
H44	−0.4573	0.3137	0.2636	0.103*
H45	−0.5417	0.4355	0.2666	0.103*
H46	−0.4549	0.4006	0.2940	0.103*
C41	−0.3747 (6)	0.6354 (9)	0.30591 (17)	0.0479 (18)
O42	−0.2819 (5)	0.6183 (10)	0.31941 (14)	0.072 (2)
N43	−0.4729 (5)	0.6618 (7)	0.31967 (13)	0.0444 (15)
H47	−0.5352	0.6729	0.3086	0.053*
C44	−0.4762 (8)	0.6724 (9)	0.35366 (17)	0.0501 (19)
H48	−0.4072	0.6265	0.3620	0.060*
C45	−0.5805 (19)	0.604 (2)	0.3679 (4)	0.146 (10)
H49	−0.6458	0.6165	0.3532	0.175*
C46	−0.5503 (18)	0.4379 (15)	0.3683 (4)	0.112 (5)
H50	−0.6153	0.3896	0.3761	0.112*
H51	−0.4835	0.4217	0.3815	0.112*
H52	−0.5348	0.4085	0.3475	0.112*
C47	−0.620 (2)	0.624 (2)	0.3957 (4)	0.091 (7)	0.59 (3)
H53	−0.6914	0.5748	0.3979	0.091*	0.59 (3)
H54	−0.6347	0.7173	0.3987	0.091*	0.59 (3)
H55	−0.5647	0.5931	0.4110	0.091*	0.59 (3)
C47'	−0.6833 (18)	0.625 (2)	0.3582 (4)	0.043 (6)	0.41 (3)
H53'	−0.7359	0.5736	0.3703	0.043*	0.41 (3)
H54'	−0.6907	0.6001	0.3367	0.043*	0.41 (3)
H55'	−0.7010	0.7187	0.3604	0.043*	0.41 (3)
C48	−0.4651 (6)	0.8186 (8)	0.36330 (15)	0.0402 (15)
N49	−0.4245 (5)	0.8579 (6)	0.39010 (13)	0.0365 (12)
C50	−0.4246 (6)	0.9966 (8)	0.39179 (17)	0.0430 (16)
C51	−0.4699 (10)	1.0608 (10)	0.3665 (2)	0.065 (3)
H56	−0.4782	1.1530	0.3646	0.079*
S52	−0.5092 (3)	0.9470 (3)	0.33864 (5)	0.0663 (7)
C53	−0.3778 (7)	1.0676 (8)	0.42048 (17)	0.0424 (16)
O54	−0.3719 (7)	1.1901 (6)	0.42159 (16)	0.0681 (18)
N55	−0.3467 (4)	0.9860 (6)	0.44366 (12)	0.0350 (12)
H57	−0.3637	0.9026	0.4418	0.042*
C56	−0.2853 (6)	1.0293 (8)	0.47217 (16)	0.0399 (16)
H58	−0.2562	1.1203	0.4690	0.048*
C57	−0.3617 (9)	1.0291 (18)	0.5011 (2)	0.108 (7)
H59	−0.3089	1.0560	0.5182	0.130*
C58	−0.4495 (9)	1.1380 (18)	0.4996 (3)	0.113 (7)
H60	−0.4152	1.2174	0.4913	0.113*
H61	−0.4766	1.1561	0.5202	0.113*
H62	−0.5134	1.1108	0.4864	0.113*
C59	−0.4137 (13)	0.900 (2)	0.5122 (3)	0.117 (6)
H63	−0.4921	0.9130	0.5193	0.140*
H64	−0.4132	0.8319	0.4962	0.140*
C60	−0.3349 (16)	0.869 (2)	0.5378 (3)	0.133 (7)
H65	−0.3572	0.7858	0.5471	0.133*
H66	−0.3372	0.9388	0.5531	0.133*
H67	−0.2578	0.8612	0.5301	0.133*
C61	−0.1829 (5)	0.9363 (7)	0.47664 (13)	0.0286 (12)
O62	−0.1861 (4)	0.8190 (5)	0.46723 (10)	0.0353 (10)
N63	−0.0903 (4)	0.9887 (5)	0.49189 (11)	0.0283 (10)
H68	−0.0894	1.0731	0.4959	0.034*
C64	0.0086 (5)	0.9068 (7)	0.50188 (13)	0.0295 (12)
H69	−0.0188	0.8345	0.5152	0.035*
C65	0.0916 (7)	0.9958 (7)	0.52100 (15)	0.0425 (16)
H70	0.0481	1.0382	0.5377	0.051*
O66	0.1297 (4)	1.0984 (5)	0.50017 (11)	0.0390 (11)
H71	0.1467	1.1656	0.5104	0.039*
C67	0.1921 (10)	0.9200 (11)	0.5357 (3)	0.078 (4)
H72	0.2409	0.9809	0.5472	0.078*
H73	0.2360	0.8782	0.5196	0.078*
H74	0.1633	0.8527	0.5494	0.078*
C68	0.0716 (5)	0.8459 (6)	0.47454 (12)	0.0259 (12)
O69	0.1223 (4)	0.7369 (5)	0.47813 (11)	0.0394 (11)
N70	0.0740 (4)	0.9157 (5)	0.44821 (10)	0.0265 (10)
H75	0.0340	0.9880	0.4466	0.032*
C71	0.1431 (5)	0.8725 (8)	0.42167 (12)	0.0344 (14)
H76	0.1747	0.7845	0.4272	0.041*
C72	0.2471 (7)	0.9631 (12)	0.41591 (17)	0.058 (2)
H77	0.2873	0.9261	0.3980	0.070*
C73	0.3317 (8)	0.9574 (19)	0.4438 (2)	0.091 (5)
H78	0.3504	0.8658	0.4484	0.091*
H79	0.2967	0.9976	0.4616	0.091*
H80	0.4010	1.0052	0.4389	0.091*
C74	0.2152 (12)	1.1039 (15)	0.4079 (3)	0.089 (4)
H81	0.2842	1.1549	0.4045	0.089*
H82	0.1732	1.1427	0.4247	0.089*
H83	0.1676	1.1047	0.3892	0.089*
C75	0.0653 (6)	0.8511 (8)	0.39358 (14)	0.0383 (15)
N76	0.1034 (5)	0.8551 (8)	0.36525 (12)	0.0436 (15)
C77	0.0140 (7)	0.8185 (12)	0.34446 (16)	0.058 (2)
C78	−0.0874 (7)	0.7822 (14)	0.35704 (16)	0.065 (3)
H84	−0.1518	0.7508	0.3459	0.078*
S79	−0.07962 (16)	0.8025 (3)	0.39670 (4)	0.0538 (6)
C80	0.0395 (7)	0.8194 (13)	0.31066 (15)	0.059 (3)
O81	−0.0342 (5)	0.7849 (12)	0.29068 (12)	0.085 (3)
N82	0.1460 (5)	0.8616 (10)	0.30400 (13)	0.0545 (19)
H85	0.1942	0.8718	0.3194	0.065*
C83	0.1875 (7)	0.8919 (11)	0.27283 (15)	0.055 (2)
H86	0.1206	0.9028	0.2586	0.066*
C84	0.2555 (9)	1.0218 (13)	0.2737 (2)	0.068 (3)
H87	0.3190	1.0099	0.2890	0.081*
C85	0.3103 (12)	1.0470 (15)	0.2422 (2)	0.085 (4)
H88	0.3560	0.9709	0.2366	0.085*
H89	0.3590	1.1248	0.2436	0.085*
H90	0.2506	1.0613	0.2267	0.085*
C86	0.1853 (14)	1.1412 (14)	0.2844 (3)	0.090 (4)
H91	0.1501	1.1839	0.2662	0.108*
H92	0.1232	1.1092	0.2973	0.108*
C87	0.252 (2)	1.242 (2)	0.3020 (5)	0.148 (8)
H93	0.2015	1.3123	0.3083	0.148*
H94	0.3113	1.2776	0.2891	0.148*
H95	0.2872	1.2006	0.3201	0.148*
C88	0.2607 (6)	0.7785 (11)	0.26133 (16)	0.051 (2)
O89	0.3421 (5)	0.7322 (9)	0.27728 (12)	0.068 (2)
N90	0.2366 (6)	0.7350 (9)	0.23214 (14)	0.0521 (17)
H96	0.1754	0.7650	0.2228	0.062*
C91	0.3088 (9)	0.6393 (10)	0.21548 (18)	0.055 (2)
H97	0.3847	0.6309	0.2259	0.066*
C92	0.2474 (17)	0.5002 (15)	0.2137 (4)	0.114 (5)
H98	0.1715	0.5146	0.2036	0.136*
O93	0.2280 (13)	0.4456 (14)	0.2422 (3)	0.138 (5)
H99	0.1639	0.4762	0.2481	0.138*
C94	0.3128 (19)	0.4040 (14)	0.1932 (4)	0.122 (6)
H100	0.2722	0.3202	0.1921	0.122*
H101	0.3891	0.3897	0.2019	0.122*
H102	0.3184	0.4410	0.1727	0.122*
C95	0.3219 (7)	0.6934 (8)	0.18265 (16)	0.0446 (17)
O96	0.2364 (5)	0.7152 (8)	0.16664 (12)	0.0610 (17)
N97	0.4278 (5)	0.7105 (7)	0.17234 (12)	0.0400 (13)
H103	0.4864	0.6982	0.1847	0.048*
C98	0.4463 (7)	0.7504 (8)	0.13985 (17)	0.0422 (16)
H104	0.3809	0.7134	0.1277	0.051*
C99	0.5548 (9)	0.6884 (10)	0.1263 (3)	0.066 (3)
H105	0.5566	0.7173	0.1045	0.079*
C100	0.5456 (13)	0.5367 (11)	0.1257 (4)	0.087 (4)
H106	0.4735	0.5111	0.1158	0.087*
H107	0.5488	0.5030	0.1466	0.087*
H108	0.6086	0.5002	0.1142	0.087*
C101	0.6621 (11)	0.7322 (12)	0.1405 (3)	0.078 (3)
H109	0.7256	0.6894	0.1305	0.078*
H110	0.6635	0.7089	0.1622	0.078*
H111	0.6690	0.8275	0.1384	0.078*
C102	0.4384 (6)	0.9012 (7)	0.13602 (16)	0.0389 (15)
N103	0.3975 (5)	0.9565 (6)	0.11087 (12)	0.0332 (11)
C104	0.3992 (6)	1.0958 (8)	0.11336 (18)	0.0416 (15)
C105	0.4437 (9)	1.1431 (9)	0.1407 (2)	0.056 (2)
H112	0.4508	1.2332	0.1458	0.067*
S106	0.4849 (3)	1.0140 (3)	0.16474 (4)	0.0682 (7)
C107	0.3523 (5)	1.1810 (7)	0.08709 (19)	0.0393 (15)
O108	0.3435 (5)	1.3010 (6)	0.08957 (17)	0.0605 (16)
O109	0.0104 (7)	0.3136 (7)	0.07110 (17)	0.0718 (19)
C110	0.0581 (7)	0.4000 (9)	0.0848 (2)	0.0537 (19)
H113	0.1323	0.3809	0.0924	0.064*
N111	0.0179 (8)	0.5228 (8)	0.0908 (2)	0.070 (2)
C112	−0.0943 (15)	0.5616 (18)	0.0788 (4)	0.148 (10)
H114	−0.1109	0.6514	0.0852	0.148*
H115	−0.1519	0.5021	0.0866	0.148*
H116	−0.0951	0.5573	0.0564	0.148*
C113	0.077 (3)	0.626 (2)	0.1065 (4)	0.183 (13)
H117	0.0268	0.7024	0.1079	0.183*
H118	0.1444	0.6498	0.0952	0.183*
H119	0.0991	0.5965	0.1270	0.183*
O114	−0.0518 (10)	1.1520 (12)	0.4231 (3)	0.118 (4)
C115	−0.107 (2)	1.189 (2)	0.4000 (5)	0.153 (10)
H120	−0.1727	1.1460	0.3921	0.184*
N116	−0.058 (2)	1.311 (3)	0.3859 (6)	0.179 (8)*
C117	0.055 (2)	1.407 (3)	0.3973 (5)	0.171 (11)
H121	0.0620	1.4810	0.3832	0.171*
H122	0.1243	1.3550	0.3974	0.171*
H123	0.0419	1.4407	0.4179	0.171*
C118	−0.130 (2)	1.371 (4)	0.3615 (6)	0.180 (10)*
H124	−0.0951	1.4532	0.3547	0.180*
H125	−0.2053	1.3899	0.3694	0.180*
H126	−0.1371	1.3107	0.3442	0.180*
O119	−0.3309 (14)	0.317 (2)	0.1859 (3)	0.163 (6)
C120	−0.2342 (16)	0.287 (2)	0.1764 (4)	0.120 (6)
H127	−0.2267	0.2025	0.1674	0.145*
N121	−0.1332 (15)	0.3678 (15)	0.1779 (3)	0.146 (7)
C122	−0.140 (2)	0.509 (3)	0.1937 (6)	0.160 (9)
H128	−0.0671	0.5550	0.1915	0.160*
H129	−0.1551	0.4988	0.2155	0.160*
H130	−0.2004	0.5609	0.1840	0.160*
C123	−0.0247 (19)	0.313 (2)	0.1639 (4)	0.152 (9)
H131	0.0331	0.3820	0.1635	0.152*
H132	−0.0414	0.2829	0.1431	0.152*
H133	0.0035	0.2395	0.1763	0.152*
O124	0.0280 (14)	0.5350 (18)	0.2669 (4)	0.178 (7)
H134	0.0030	0.4891	0.2830	0.214*
H135	0.0125	0.6103	0.2752	0.214*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.018 (3)	0.024 (3)	0.063 (3)	0.0003 (19)	−0.010 (2)	0.002 (2)
C2	0.012 (3)	0.025 (3)	0.078 (5)	0.001 (2)	−0.005 (3)	0.016 (3)
C3	0.024 (4)	0.084 (7)	0.086 (6)	0.009 (4)	0.004 (4)	0.052 (5)
C4	0.050 (5)	0.144 (12)	0.055 (5)	0.033 (6)	0.018 (4)	0.054 (6)
C5	0.020 (4)	0.099 (9)	0.176 (12)	0.001 (4)	0.005 (5)	0.094 (9)
C6	0.079 (8)	0.26 (2)	0.059 (6)	0.049 (11)	0.024 (5)	0.067 (10)
C7	0.023 (3)	0.025 (3)	0.033 (3)	0.002 (2)	0.002 (2)	0.002 (2)
O8	0.033 (2)	0.023 (2)	0.0318 (19)	0.0022 (17)	−0.0059 (16)	0.0022 (16)
N9	0.020 (2)	0.019 (2)	0.037 (2)	0.0024 (18)	−0.0004 (18)	0.0047 (19)
C10	0.026 (3)	0.021 (3)	0.027 (2)	−0.002 (2)	−0.003 (2)	0.004 (2)
C11	0.031 (3)	0.027 (3)	0.030 (3)	0.002 (2)	−0.007 (2)	0.006 (2)
O12	0.030 (2)	0.025 (2)	0.036 (2)	0.0048 (17)	−0.0040 (16)	0.0064 (17)
C13	0.037 (4)	0.043 (4)	0.041 (3)	−0.004 (3)	−0.019 (3)	0.005 (3)
C14	0.012 (2)	0.020 (3)	0.026 (2)	−0.0016 (19)	−0.0057 (17)	0.0003 (19)
O15	0.025 (2)	0.0220 (19)	0.0310 (19)	−0.0024 (15)	−0.0034 (15)	−0.0010 (15)
N16	0.020 (2)	0.020 (2)	0.024 (2)	−0.0040 (17)	0.0002 (16)	0.0005 (17)
C17	0.018 (3)	0.030 (3)	0.026 (2)	−0.002 (2)	−0.0015 (19)	0.000 (2)
C18	0.029 (3)	0.061 (5)	0.036 (3)	0.015 (3)	0.006 (2)	0.011 (3)
C19	0.033 (4)	0.155 (12)	0.040 (4)	0.025 (6)	−0.001 (3)	0.003 (6)
C20	0.088 (8)	0.063 (6)	0.097 (7)	0.042 (6)	0.042 (6)	0.012 (6)
C21	0.021 (3)	0.032 (3)	0.024 (2)	0.006 (2)	−0.0037 (19)	−0.006 (2)
N22	0.028 (3)	0.050 (3)	0.025 (2)	0.007 (2)	−0.0045 (18)	−0.004 (2)
C23	0.033 (4)	0.080 (6)	0.024 (3)	0.014 (3)	−0.013 (2)	−0.009 (3)
C24	0.031 (4)	0.092 (6)	0.024 (3)	0.013 (4)	−0.015 (2)	−0.003 (3)
S25	0.0204 (7)	0.0655 (11)	0.0281 (7)	0.0063 (7)	−0.0055 (5)	−0.0034 (7)
C26	0.038 (4)	0.110 (8)	0.026 (3)	0.019 (5)	−0.008 (3)	−0.003 (4)
O27	0.043 (3)	0.169 (8)	0.023 (2)	0.028 (4)	−0.0080 (19)	0.001 (3)
N28	0.043 (4)	0.116 (7)	0.022 (3)	0.009 (4)	−0.004 (2)	0.002 (3)
C29	0.048 (5)	0.132 (10)	0.023 (3)	0.000 (5)	−0.004 (3)	−0.001 (4)
C30	0.095 (8)	0.127 (11)	0.047 (5)	0.007 (8)	0.005 (5)	−0.011 (6)
C31	0.37 (4)	0.146 (17)	0.055 (7)	−0.01 (2)	0.083 (14)	−0.026 (10)
C32	0.155 (19)	0.20 (3)	0.106 (12)	0.005 (19)	−0.016 (12)	−0.024 (16)
C33	0.17 (2)	0.21 (3)	0.115 (14)	0.00 (2)	−0.002 (13)	−0.023 (17)
C34	0.032 (4)	0.139 (9)	0.018 (3)	0.000 (5)	−0.001 (2)	−0.013 (4)
O35	0.047 (4)	0.180 (9)	0.031 (2)	−0.011 (5)	−0.009 (2)	−0.010 (4)
N36	0.030 (3)	0.104 (6)	0.038 (3)	0.006 (3)	0.000 (2)	−0.007 (4)
C37	0.038 (4)	0.097 (7)	0.044 (4)	−0.002 (4)	−0.002 (3)	−0.023 (5)
C38	0.075 (7)	0.132 (12)	0.105 (9)	0.000 (8)	0.026 (6)	−0.072 (10)
O39	0.151 (10)	0.27 (2)	0.115 (8)	−0.080 (12)	0.054 (7)	−0.131 (12)
C40	0.093 (9)	0.102 (10)	0.116 (10)	−0.001 (8)	0.006 (7)	−0.062 (9)
C41	0.034 (4)	0.067 (5)	0.043 (4)	−0.007 (3)	−0.002 (3)	−0.011 (4)
O42	0.032 (3)	0.123 (6)	0.060 (3)	−0.004 (3)	−0.007 (2)	−0.004 (4)
N43	0.031 (3)	0.065 (4)	0.038 (3)	−0.001 (3)	−0.003 (2)	−0.019 (3)
C44	0.058 (5)	0.059 (5)	0.033 (3)	−0.011 (4)	0.003 (3)	−0.011 (3)
C45	0.178 (18)	0.144 (14)	0.121 (11)	−0.114 (14)	0.107 (13)	−0.097 (11)
C46	0.172 (16)	0.066 (8)	0.098 (9)	−0.011 (9)	−0.037 (10)	0.003 (7)
C47	0.14 (2)	0.073 (13)	0.063 (11)	−0.022 (13)	0.009 (11)	0.001 (9)
C47'	0.043 (12)	0.044 (10)	0.045 (9)	−0.001 (8)	0.014 (7)	−0.001 (7)
C48	0.034 (4)	0.052 (4)	0.034 (3)	0.003 (3)	−0.005 (2)	−0.004 (3)
N49	0.030 (3)	0.042 (3)	0.037 (3)	0.000 (2)	−0.005 (2)	−0.006 (2)
C50	0.044 (4)	0.041 (4)	0.044 (3)	0.005 (3)	−0.006 (3)	−0.004 (3)
C51	0.098 (8)	0.046 (5)	0.051 (5)	0.014 (5)	−0.015 (5)	0.000 (4)
S52	0.0941 (18)	0.0644 (14)	0.0392 (9)	0.0167 (13)	−0.0223 (10)	−0.0008 (9)
C53	0.046 (4)	0.036 (4)	0.045 (4)	0.001 (3)	−0.004 (3)	−0.004 (3)
O54	0.102 (5)	0.030 (3)	0.071 (4)	0.000 (3)	−0.015 (4)	−0.004 (3)
N55	0.029 (3)	0.035 (3)	0.041 (3)	−0.003 (2)	−0.008 (2)	−0.009 (2)
C56	0.024 (3)	0.047 (4)	0.048 (4)	0.003 (3)	−0.011 (3)	−0.020 (3)
C57	0.042 (5)	0.23 (2)	0.050 (5)	0.060 (9)	−0.003 (4)	−0.032 (8)
C58	0.034 (5)	0.170 (15)	0.136 (11)	0.018 (6)	−0.004 (5)	−0.112 (11)
C59	0.099 (11)	0.163 (17)	0.090 (9)	−0.026 (12)	0.024 (8)	−0.025 (11)
C60	0.155 (15)	0.172 (19)	0.073 (8)	0.009 (15)	0.035 (9)	0.024 (11)
C61	0.019 (3)	0.040 (3)	0.027 (3)	−0.005 (2)	−0.002 (2)	−0.007 (2)
O62	0.032 (2)	0.037 (3)	0.036 (2)	−0.0063 (19)	−0.0061 (17)	−0.0078 (19)
N63	0.023 (2)	0.032 (3)	0.030 (2)	−0.003 (2)	−0.0024 (18)	−0.004 (2)
C64	0.028 (3)	0.036 (3)	0.024 (2)	−0.005 (2)	−0.005 (2)	0.003 (2)
C65	0.058 (4)	0.034 (3)	0.034 (3)	−0.006 (3)	−0.025 (3)	0.008 (3)
O66	0.034 (3)	0.035 (2)	0.048 (3)	−0.0077 (19)	−0.0114 (19)	0.002 (2)
C67	0.089 (8)	0.057 (6)	0.085 (6)	0.012 (5)	−0.070 (6)	−0.002 (5)
C68	0.014 (3)	0.038 (3)	0.025 (2)	−0.002 (2)	−0.0071 (18)	0.004 (2)
O69	0.028 (2)	0.044 (3)	0.046 (2)	0.007 (2)	0.0051 (18)	0.019 (2)
N70	0.022 (2)	0.034 (3)	0.023 (2)	0.005 (2)	−0.0022 (17)	0.0052 (19)
C71	0.022 (3)	0.059 (4)	0.022 (2)	0.008 (3)	−0.002 (2)	0.002 (3)
C72	0.037 (4)	0.105 (8)	0.034 (3)	−0.023 (4)	0.004 (3)	−0.003 (4)
C73	0.042 (5)	0.189 (15)	0.043 (4)	−0.032 (7)	−0.004 (3)	−0.017 (7)
C74	0.101 (9)	0.095 (9)	0.072 (6)	−0.055 (8)	0.015 (6)	0.003 (6)
C75	0.026 (3)	0.066 (5)	0.023 (3)	0.005 (3)	−0.001 (2)	0.000 (3)
N76	0.028 (3)	0.080 (5)	0.023 (2)	0.004 (3)	−0.0039 (19)	0.001 (3)
C77	0.034 (4)	0.109 (8)	0.029 (3)	−0.003 (4)	−0.009 (3)	−0.003 (4)
C78	0.033 (4)	0.134 (9)	0.028 (3)	−0.005 (5)	−0.006 (3)	−0.012 (5)
S79	0.0296 (9)	0.1023 (17)	0.0296 (7)	−0.0099 (10)	0.0006 (6)	−0.0059 (9)
C80	0.032 (4)	0.119 (8)	0.026 (3)	0.004 (4)	−0.006 (2)	−0.009 (4)
O81	0.047 (3)	0.180 (9)	0.029 (2)	−0.021 (5)	−0.008 (2)	−0.014 (4)
N82	0.032 (3)	0.107 (6)	0.024 (2)	0.002 (3)	−0.005 (2)	0.003 (3)
C83	0.037 (4)	0.103 (7)	0.025 (3)	0.009 (4)	−0.003 (3)	0.001 (4)
C84	0.061 (6)	0.101 (8)	0.041 (4)	0.003 (5)	−0.007 (4)	0.003 (5)
C85	0.092 (8)	0.106 (10)	0.056 (5)	−0.023 (7)	0.001 (5)	0.014 (6)
C86	0.118 (11)	0.077 (8)	0.074 (7)	0.014 (7)	−0.016 (7)	0.006 (6)
C87	0.20 (2)	0.091 (12)	0.147 (16)	−0.010 (14)	−0.001 (15)	−0.018 (12)
C88	0.033 (4)	0.091 (7)	0.029 (3)	−0.004 (4)	0.000 (3)	0.010 (4)
O89	0.042 (3)	0.127 (6)	0.034 (2)	0.019 (4)	−0.006 (2)	0.013 (3)
N90	0.037 (3)	0.090 (5)	0.029 (3)	−0.003 (3)	0.000 (2)	0.002 (3)
C91	0.069 (6)	0.059 (5)	0.038 (4)	0.002 (4)	0.000 (3)	0.003 (4)
C92	0.163 (15)	0.068 (8)	0.112 (10)	−0.016 (9)	0.051 (10)	0.016 (8)
O93	0.164 (11)	0.103 (8)	0.151 (10)	0.026 (8)	0.068 (9)	0.022 (8)
C94	0.183 (17)	0.052 (7)	0.133 (12)	0.012 (9)	0.054 (12)	0.002 (8)
C95	0.051 (4)	0.049 (4)	0.034 (3)	0.004 (3)	−0.002 (3)	−0.008 (3)
O96	0.043 (3)	0.103 (5)	0.037 (2)	0.003 (3)	−0.005 (2)	−0.015 (3)
N97	0.034 (3)	0.053 (4)	0.032 (3)	−0.001 (3)	−0.007 (2)	−0.002 (3)
C98	0.047 (4)	0.040 (4)	0.039 (3)	0.003 (3)	0.000 (3)	0.002 (3)
C99	0.069 (6)	0.050 (5)	0.079 (6)	0.009 (4)	0.035 (5)	0.003 (4)
C100	0.101 (9)	0.046 (6)	0.117 (9)	0.019 (5)	0.043 (7)	0.004 (6)
C101	0.093 (8)	0.064 (6)	0.078 (6)	0.000 (6)	0.025 (6)	−0.007 (5)
C102	0.041 (4)	0.036 (4)	0.040 (3)	−0.004 (3)	0.013 (3)	−0.009 (3)
N103	0.027 (3)	0.032 (3)	0.040 (3)	0.004 (2)	0.000 (2)	−0.005 (2)
C104	0.038 (4)	0.034 (4)	0.054 (4)	−0.001 (3)	0.008 (3)	−0.010 (3)
C105	0.077 (6)	0.043 (4)	0.049 (4)	0.003 (4)	0.002 (4)	−0.017 (4)
S106	0.119 (2)	0.0530 (12)	0.0329 (9)	−0.0009 (13)	0.0008 (10)	−0.0157 (9)
C107	0.019 (3)	0.030 (3)	0.069 (4)	0.000 (2)	0.001 (3)	−0.008 (3)
O108	0.050 (3)	0.029 (3)	0.102 (5)	0.003 (2)	−0.012 (3)	−0.009 (3)
O109	0.088 (5)	0.044 (3)	0.084 (4)	−0.016 (3)	0.005 (4)	−0.030 (3)
C110	0.045 (5)	0.046 (5)	0.070 (5)	0.002 (4)	−0.005 (4)	−0.004 (4)
N111	0.088 (6)	0.043 (4)	0.080 (5)	−0.005 (4)	0.014 (4)	−0.027 (4)
C112	0.143 (14)	0.131 (14)	0.176 (16)	0.102 (12)	0.108 (13)	0.089 (13)
C113	0.36 (4)	0.095 (13)	0.099 (11)	−0.097 (18)	0.010 (16)	−0.043 (10)
O114	0.115 (8)	0.108 (8)	0.133 (8)	0.051 (7)	0.024 (6)	0.053 (7)
C115	0.18 (2)	0.133 (16)	0.151 (16)	0.075 (15)	0.072 (15)	0.067 (14)
C117	0.19 (2)	0.20 (3)	0.129 (14)	−0.10 (2)	0.009 (14)	−0.043 (17)
O119	0.156 (12)	0.219 (18)	0.114 (8)	0.023 (13)	−0.011 (8)	−0.006 (11)
C120	0.110 (12)	0.122 (13)	0.131 (13)	0.017 (11)	0.048 (10)	−0.028 (11)
N121	0.190 (14)	0.115 (10)	0.140 (11)	−0.015 (10)	0.139 (12)	−0.047 (9)
C122	0.18 (2)	0.138 (18)	0.158 (18)	−0.051 (17)	−0.021 (16)	0.047 (17)
C123	0.196 (19)	0.126 (14)	0.133 (14)	0.049 (14)	−0.038 (13)	−0.100 (13)
O124	0.192 (13)	0.159 (13)	0.190 (13)	−0.032 (11)	0.132 (11)	−0.038 (11)

Geometric parameters (Å, º)

N1—C107	1.348 (10)	C59—C60	1.443 (16)
N1—C2	1.455 (9)	C61—O62	1.240 (8)
C2—C7	1.520 (8)	C61—N63	1.347 (7)
C2—C3	1.528 (11)	N63—C64	1.463 (8)
C3—C4	1.491 (19)	C64—C68	1.522 (8)
C3—C5	1.496 (15)	C64—C65	1.532 (9)
C4—C6	1.544 (12)	C65—O66	1.437 (9)
C7—O8	1.251 (8)	C65—C67	1.511 (10)
C7—N9	1.327 (8)	C68—O69	1.245 (8)
N9—C10	1.446 (7)	C68—N70	1.329 (7)
C10—C14	1.525 (7)	N70—C71	1.471 (7)
C10—C11	1.543 (8)	C71—C75	1.502 (8)
C11—O12	1.424 (8)	C71—C72	1.530 (11)
C11—C13	1.526 (9)	C72—C74	1.49 (2)
C14—O15	1.237 (7)	C72—C73	1.529 (11)
C14—N16	1.363 (7)	C75—N76	1.304 (8)
N16—C17	1.462 (7)	C75—S79	1.752 (7)
C17—C21	1.511 (7)	N76—C77	1.398 (9)
C17—C18	1.531 (8)	C77—C78	1.351 (12)
C18—C20	1.508 (15)	C77—C80	1.487 (9)
C18—C19	1.538 (11)	C78—S79	1.715 (7)
C21—N22	1.297 (8)	C80—O81	1.243 (9)
C21—S25	1.738 (6)	C80—N82	1.338 (11)
N22—C23	1.376 (8)	N82—C83	1.463 (9)
C23—C24	1.346 (11)	C83—C88	1.504 (14)
C23—C26	1.509 (10)	C83—C84	1.518 (16)
C24—S25	1.702 (6)	C84—C86	1.520 (18)
C26—O27	1.240 (9)	C84—C85	1.526 (13)
C26—N28	1.325 (11)	C86—C87	1.47 (2)
N28—C29	1.454 (9)	C88—O89	1.240 (10)
C29—C30	1.52 (2)	C88—N90	1.349 (10)
C29—C34	1.531 (15)	N90—C91	1.466 (12)
C30—C31	1.520 (16)	C91—C95	1.520 (10)
C30—C32	1.55 (3)	C91—C92	1.562 (18)
C32—C33	1.52 (3)	C92—O93	1.363 (18)
C34—O35	1.229 (9)	C92—C94	1.52 (2)
C34—N36	1.351 (13)	C95—O96	1.210 (10)
N36—C37	1.451 (13)	C95—N97	1.322 (10)
C37—C38	1.480 (19)	N97—C98	1.471 (9)
C37—C41	1.549 (10)	C98—C102	1.519 (11)
C38—O39	1.48 (2)	C98—C99	1.527 (11)
C38—C40	1.51 (2)	C99—C101	1.438 (17)
C41—O42	1.219 (10)	C99—C100	1.520 (15)
C41—N43	1.318 (10)	C102—N103	1.292 (10)
N43—C44	1.464 (9)	C102—S106	1.746 (7)
C44—C48	1.523 (12)	N103—C104	1.397 (10)
C44—C45	1.526 (14)	C104—C105	1.357 (11)
C45—C47'	1.27 (3)	C104—C107	1.503 (11)
C45—C47	1.30 (2)	C105—S106	1.711 (10)
C45—C46	1.70 (3)	C107—O108	1.208 (9)
C48—N49	1.293 (9)	O109—C110	1.175 (11)
C48—S52	1.733 (8)	C110—N111	1.339 (12)
N49—C50	1.388 (11)	N111—C113	1.398 (18)
C50—C51	1.356 (12)	N111—C112	1.438 (19)
C50—C53	1.511 (10)	O114—C115	1.23 (2)
C51—S52	1.704 (10)	C115—N116	1.48 (4)
C53—O54	1.227 (10)	N116—C118	1.45 (3)
C53—N55	1.329 (10)	N116—C117	1.68 (3)
N55—C56	1.466 (8)	O119—C120	1.24 (2)
C56—C61	1.514 (9)	C120—N121	1.42 (2)
C56—C57	1.542 (12)	N121—C123	1.51 (2)
C57—C58	1.489 (19)	N121—C122	1.57 (3)
C57—C59	1.503 (17)
C107—N1—C2	122.6 (6)	C58—C57—C56	111.5 (12)
N1—C2—C7	107.4 (5)	C59—C57—C56	119.9 (11)
N1—C2—C3	114.6 (5)	C60—C59—C57	100.2 (13)
C7—C2—C3	110.9 (7)	O62—C61—N63	122.9 (6)
C4—C3—C5	111.0 (9)	O62—C61—C56	121.5 (5)
C4—C3—C2	112.4 (7)	N63—C61—C56	115.6 (6)
C5—C3—C2	111.8 (10)	C61—N63—C64	122.1 (5)
C3—C4—C6	113.6 (12)	N63—C64—C68	112.5 (5)
O8—C7—N9	122.9 (6)	N63—C64—C65	107.9 (5)
O8—C7—C2	120.2 (5)	C68—C64—C65	109.9 (5)
N9—C7—C2	116.9 (5)	O66—C65—C67	111.9 (8)
C7—N9—C10	121.6 (5)	O66—C65—C64	106.1 (5)
N9—C10—C14	113.1 (4)	C67—C65—C64	113.4 (7)
N9—C10—C11	108.9 (5)	O69—C68—N70	123.1 (5)
C14—C10—C11	111.3 (5)	O69—C68—C64	119.1 (5)
O12—C11—C13	110.2 (5)	N70—C68—C64	117.7 (5)
O12—C11—C10	107.0 (4)	C68—N70—C71	121.8 (5)
C13—C11—C10	113.9 (5)	N70—C71—C75	109.7 (5)
O15—C14—N16	122.7 (5)	N70—C71—C72	113.2 (6)
O15—C14—C10	120.6 (5)	C75—C71—C72	114.3 (6)
N16—C14—C10	116.7 (5)	C74—C72—C73	111.5 (11)
C14—N16—C17	120.6 (4)	C74—C72—C71	113.9 (8)
N16—C17—C21	110.6 (4)	C73—C72—C71	110.0 (8)
N16—C17—C18	112.9 (5)	N76—C75—C71	122.4 (6)
C21—C17—C18	114.7 (5)	N76—C75—S79	115.1 (5)
C20—C18—C17	112.1 (7)	C71—C75—S79	122.2 (4)
C20—C18—C19	111.8 (9)	C75—N76—C77	109.1 (6)
C17—C18—C19	108.7 (6)	C78—C77—N76	116.8 (6)
N22—C21—C17	123.2 (5)	C78—C77—C80	125.8 (7)
N22—C21—S25	115.1 (4)	N76—C77—C80	117.4 (7)
C17—C21—S25	121.3 (4)	C77—C78—S79	109.8 (6)
C21—N22—C23	109.7 (5)	C78—S79—C75	89.1 (3)
C24—C23—N22	115.9 (6)	O81—C80—N82	124.0 (7)
C24—C23—C26	124.4 (6)	O81—C80—C77	121.5 (7)
N22—C23—C26	119.7 (6)	N82—C80—C77	114.5 (6)
C23—C24—S25	110.7 (5)	C80—N82—C83	125.7 (6)
C24—S25—C21	88.6 (3)	N82—C83—C88	110.1 (8)
O27—C26—N28	123.8 (7)	N82—C83—C84	109.6 (7)
O27—C26—C23	119.3 (7)	C88—C83—C84	111.0 (7)
N28—C26—C23	116.8 (6)	C83—C84—C86	113.6 (9)
C26—N28—C29	122.8 (6)	C83—C84—C85	110.2 (9)
N28—C29—C30	111.5 (10)	C86—C84—C85	111.9 (11)
N28—C29—C34	110.6 (7)	C87—C86—C84	114.5 (15)
C30—C29—C34	109.7 (9)	O89—C88—N90	121.9 (9)
C31—C30—C29	112.8 (14)	O89—C88—C83	121.7 (7)
C31—C30—C32	102.8 (15)	N90—C88—C83	116.3 (7)
C29—C30—C32	113.2 (13)	C88—N90—C91	123.8 (7)
C33—C32—C30	104.0 (19)	N90—C91—C95	106.9 (7)
O35—C34—N36	123.0 (10)	N90—C91—C92	110.0 (9)
O35—C34—C29	123.1 (10)	C95—C91—C92	109.1 (9)
N36—C34—C29	113.9 (6)	O93—C92—C94	111.2 (14)
C34—N36—C37	123.0 (7)	O93—C92—C91	113.4 (14)
N36—C37—C38	111.9 (8)	C94—C92—C91	111.2 (12)
N36—C37—C41	106.5 (6)	O96—C95—N97	122.5 (7)
C38—C37—C41	111.8 (10)	O96—C95—C91	119.5 (7)
C37—C38—O39	106.5 (15)	N97—C95—C91	118.0 (7)
C37—C38—C40	113.0 (9)	C95—N97—C98	120.5 (6)
O39—C38—C40	109.6 (12)	N97—C98—C102	111.2 (6)
O42—C41—N43	124.9 (7)	N97—C98—C99	113.0 (7)
O42—C41—C37	119.2 (7)	C102—C98—C99	114.1 (7)
N43—C41—C37	115.9 (7)	C101—C99—C100	111.7 (11)
C41—N43—C44	120.3 (6)	C101—C99—C98	115.0 (9)
N43—C44—C48	109.6 (7)	C100—C99—C98	110.7 (9)
N43—C44—C45	114.0 (9)	N103—C102—C98	122.3 (7)
C48—C44—C45	112.6 (8)	N103—C102—S106	114.5 (5)
C47'—C45—C47	85.7 (17)	C98—C102—S106	123.2 (6)
C47'—C45—C44	122 (2)	C102—N103—C104	111.0 (6)
C47—C45—C44	126.8 (15)	C105—C104—N103	114.7 (8)
C47'—C45—C46	111.1 (14)	C105—C104—C107	125.1 (7)
C47—C45—C46	102.4 (19)	N103—C104—C107	120.2 (6)
C44—C45—C46	106.2 (15)	C104—C105—S106	110.7 (7)
N49—C48—C44	124.0 (7)	C105—S106—C102	89.2 (4)
N49—C48—S52	114.4 (6)	O108—C107—N1	125.4 (8)
C44—C48—S52	121.5 (5)	O108—C107—C104	121.7 (8)
C48—N49—C50	110.4 (7)	N1—C107—C104	112.9 (6)
C51—C50—N49	115.6 (7)	O109—C110—N111	127.5 (9)
C51—C50—C53	123.6 (8)	C110—N111—C113	127.0 (16)
N49—C50—C53	120.7 (7)	C110—N111—C112	119.5 (11)
C50—C51—S52	109.7 (7)	C113—N111—C112	113.4 (17)
C51—S52—C48	89.8 (4)	O114—C115—N116	113 (3)
O54—C53—N55	124.7 (7)	C118—N116—C115	115 (2)
O54—C53—C50	121.3 (8)	C118—N116—C117	114 (3)
N55—C53—C50	114.0 (6)	C115—N116—C117	131 (2)
C53—N55—C56	124.1 (6)	O119—C120—N121	126.5 (19)
N55—C56—C61	106.7 (5)	C120—N121—C123	117.8 (14)
N55—C56—C57	113.4 (7)	C120—N121—C122	119.1 (14)
C61—C56—C57	111.0 (7)	C123—N121—C122	123.1 (17)
C58—C57—C59	111.3 (12)
C107—N1—C2—C7	−128.0 (6)	C53—N55—C56—C61	−129.8 (7)
N1—C2—C7—N9	158.6 (5)	N55—C56—C61—N63	151.6 (5)
C2—C7—N9—C10	177.0 (5)	C56—C61—N63—C64	171.2 (5)
C7—N9—C10—C14	54.2 (7)	C61—N63—C64—C68	63.9 (7)
N9—C10—C14—N16	43.0 (6)	N63—C64—C68—N70	32.5 (7)
C10—C14—N16—C17	174.9 (5)	C64—C68—N70—C71	173.2 (5)
C14—N16—C17—C21	120.2 (5)	C68—N70—C71—C75	120.5 (6)
N16—C17—C21—N22	169.3 (5)	N70—C71—C75—N76	157.4 (6)
C17—C21—N22—C23	172.1 (6)	C71—C75—N76—C77	174.1 (7)
C21—N22—C23—C26	−179.7 (7)	C75—N76—C77—C80	178.8 (8)
N22—C23—C26—N28	−4.0 (12)	N76—C77—C80—N82	−2.8 (12)
C23—C26—N28—C29	−172.4 (8)	C77—C80—N82—C83	−170.0 (8)
C26—N28—C29—C34	−138.5 (9)	C80—N82—C83—C88	−102.1 (10)
N28—C29—C34—N36	138.3 (9)	N82—C83—C88—N90	132.2 (8)
C29—C34—N36—C37	167.3 (8)	C83—C88—N90—C91	170.9 (8)
C34—N36—C37—C41	−138.6 (9)	C88—N90—C91—C95	−134.9 (8)
N36—C37—C41—N43	132.2 (8)	N90—C91—C95—N97	125.0 (8)
C37—C41—N43—C44	−177.8 (7)	C91—C95—N97—C98	174.2 (7)
C41—N43—C44—C48	95.4 (8)	C95—N97—C98—C102	84.8 (8)
N43—C44—C48—N49	−154.2 (7)	N97—C98—C102—N103	−146.4 (7)
C44—C48—N49—C50	179.6 (7)	C98—C102—N103—C104	179.7 (6)
C48—N49—C50—C53	−178.1 (7)	C102—N103—C104—C107	−178.2 (6)
N49—C50—C53—N55	−4.8 (10)	N103—C104—C107—N1	−7.4 (10)
C50—C53—N55—C56	171.7 (6)	C2—N1—C107—C104	171.0 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N9—H12···O12	0.86	2.57	2.779 (7)	95
N16—H19···O12	0.86	2.64	2.957 (6)	103
C24—H28···O96	0.93	2.60	3.158 (11)	119
N36—H40···O81	0.86	2.44	3.240 (9)	155
O39—H43···O119	0.844	1.782	2.58 (2)	156.8
N63—H68···O66	0.86	2.55	2.784 (7)	97
N70—H75···O66	0.86	2.76	2.942 (7)	94
N70—H75···O114	0.86	2.15	2.963 (13)	157
C78—H84···O42	0.93	2.29	3.190 (12)	164
N90—H96···O27	0.86	2.13	2.952 (10)	161
O93—H99···O124	0.846	1.877	2.72 (2)	171.8
O124—H135···O81	0.854	1.948	2.80 (2)	174.2
N16—H19···O109^i	0.86	2.12	2.965 (9)	167
O12—H15···O8^ii	0.822	1.905	2.712 (6)	166.9
N9—H12···O15^ii	0.86	2.10	2.873 (6)	150
N43—H47···O89^iii	0.86	2.02	2.862 (8)	166
O66—H71···O62^iv	0.824	1.860	2.684 (7)	178.8
N63—H68···O69^iv	0.86	2.02	2.823 (7)	154
N97—H103···O35^v	0.86	2.31	3.059 (9)	146

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