The hydrogen-bonding network in deacetyl­cephalothin

The structural analysis of deacetyl­cephalothin [systematic name: (6R,7R)-3-hydroxy­methyl-8-oxo-7-(2-thio­phen-2-yl­acetyl­amino)-5-thia-1-aza­bicyclo­[4.2.0]oct-2-ene-2-carboxylic acid], C₁₄H₁₄N₂O₅S₂, shows that the geometry of the central bicyclic moiety is close to the geometry exhibited by other biologically active cephalosporin antibiotics. The mol­ecules are arranged in a helical chain running parallel to the 2₁ axis via a strong O—H...O hydrogen bond. The main helices are zipped together via N—H...O inter­actions, forming infinite layers. The supramolecular architecture is stabilized by O—H...S and C—H...O hydrogen bonds.

S1. Comment

The cephalosporins are widely used broad-spectrum antibiotics, exhibiting antibacterial activity against both Gram-positive and Gram-negative bacteria (Dollery, 1999). In humans and animals, after parenteral administration of cephalothin [systematic name: (6R,7R)-3-acetoxymethyl-8-oxo-7-(2-thiophen-2-ylacetylamino)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid], the metabolite deacetylcephalothin, DACT, (I), is formed (Katzung, 2001). Microbiological tests showed that DACT exhibits lower activity than the parent drug (Lee et al., 1963). In general, the decrease of biological activity was attributed to the blocking of the carboxyl substituent (Flynn, 1972). On the basis of NMR and IR studies, it was proposed that, in solution, the O1—H hydroxyl group in DACT can form an intramolecular hydrogen bond with the O2 carbonyl atom and in this manner protect the COOH group (Zimniak et al., 1998). In order to elucidate the nature of the hydrogen bonds in DACT in the solid state, this crystallographic study has been performed. The structure of the sodium salt of cephalothin was determined by van Meerssche et al. (1979).

The asymmetric unit of the title compound contains one DACT molecule, confirmed as the (R,R) isomer (Fig. 1). The analysis of the bicyclic [4.2.0] ring shows that the dihydrothiazine six-membered ring displays an envelope conformation, with atom S1 lying 0.9027 (6) Å out of the plane defined by the remaining atoms of the ring, and the C3—S1—C4—N1 torsion angle being 56.5 (2)°. The β-lactam four-membered ring is folded along the C8—N1 line, and the C4—C8—N1—C7 torsion angle is 166.9 (3)°. The geometry of the Δ³-cephem core (cephem is 5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-8-one) in DACT was compared with that observed for other structurally characterized active cephalosporins derived from the Cambridge Structural Database (CSD, Version 5.26, August 2005; Allen, 2002). It was found that the overall geometry and conformation of the Δ³-cephem core in DACT are close to those in retrieved structures (Table 1).

Some geometric parameters were found to correlate with the antimicrobial activity of cephalosporins. The most commonly reported are the pyramidality of atom N1 (Woodward, 1980), the distance between atom C6 of the carboxyl group and the β-lactam atom O4 (Cohen, 1983) and the O4—N1—C5—C6 torsion angle (Nangia et al., 1996). In the DACT molecule, atom N1 is displaced from the plane defined by atoms C4/C5/C8 by 0.214 (3) Å and Cohen's and Nangia's parameters are 3.186 (4) Å and 40.1 (3)°, respectively. These values are within the ranges postulated for active cephalosporins of 0.15–0.25 Å, 3.1–3.6 Å and 30–160°, respectively (Nangia et al., 1996).

The molecular packing of DACT involves strong intermolecular hydrogen bonds (Table 2), resulting in a two-dimensional supramolecular structure that has been examined using graph-set descriptors (Etter, 1990; Bernstein et al., 1995). The molecules of DACT are linked head-to-tail via strong O3—H3O···O5ⁱ hydrogen bonds, forming a helix with a C(10) pattern around the 2₁ screw axis [symmetry code: (i) −x, y + 1/2, 1 − z Please check added symmetry code; motif a in Fig. 2]. These main helices are further zipped together via the hydroxymethyl group, acting as both hydrogen-bond acceptor and donor. An O1ⁱⁱ···H—N1 [O1ⁱⁱ···H2N—N2 in Table 2?] bond [the C(9) motif b] is formed by the peptide N1—H [N2—H2N?] group and, simultaneously, the O1—H1O group is engaged in a hydrogen bond with atom S1ⁱⁱ of the dihydrothiazine ring, resulting in the C(6) motif c [symmetry code: (ii) 1 − x, y + 1/2, 1 − z Please check added symmetry code]. Motif a and motifs b or c combine to form layers of fused rings parallel to the (001) plane, with the second-level graph descriptors N₂(ab) = C₂²(11)[R₄⁴(38)] and N₂(ac) = C₂²(14)[R₄⁴(30)].

The two-dimensional structure is additionally stabilized by weak C—H···O hydrogen bonds between molecules related by translation symmetry in the [010] direction, as shown schematically in Fig. 3 (motifs d and e) (Steiner, 2002). These bonds are formed by two H atoms of the dihydrothiazine ring (H3A and H4) and the lactam atom O4ⁱⁱⁱ [symmetry code: (iii) x, y − 1, z Please check added symmetry code], acting as a double acceptor, and tighten the helix, joining consecutive coils. Adjacent sheets are linked by very weak hydrogen-bond type interactions between aromatic C—H donors of the thiophene ring and atom O2 of the carboxyl group, leading to a three-dimensional supramolecular network (Fig. 3).

Thus, in the solid state, all the potential strong hydrogen-bonding donor centres of DACT are engaged in the intermolecular interactions that are decisive for supramolecular assembly. They do not form the O—H···O intramolecular bonds that were previously postulated for solutions (Zimniak et al., 1998). The only intramolecular interaction observed in DACT is the weak C1—H1A···O2 interaction, depicted as motif f in Fig. 1.

S2. Experimental

The preparation method and properties of DACT were reported previously by Zimniak et al. (1998). Single crystals of DACT were obtained from anhydrous EtOH.

S3. Refinement

Since the absorption coefficient was comparatively low, no absorption correction was applied. The thiophene ring was found to be disordered over two positions related by rotation about the C10—C11 bond, with site-occupancy factors of 0.626 (4) and 0.374 (4) for the major and minor components, respectively. The alternative atoms C11 and C11B were fixed at the same sites with identical displacement parameters. The positions of H atoms attached to N and O atoms were refined freely but their isotropic displacement parameters were fixed to 1.2 and 1.5 times U_eq of the parent atom, respectively. The remaining H atoms were positioned geometrically and refined using a riding model, with U_iso(H) = 1.2 or 1.3U_eq(C). The absolute structure was established based on anomalous dispersion (1279 Friedel pairs) using Flack's parameter x (Flack, 1983; Flack & Bernardinelli, 1999, 2000).

Computing details

Data collection: P3/P4-PC Diffractometer Program (Siemens, 1991); cell refinement: P3/P4-PC Diffractometer Program; data reduction: XDISK (Siemens, 1991); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996; Farrugia, 1997); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).

Figures

	Fig. 1. A drawing of the DACT molecule with the atom-numbering scheme. Only the major orientation of the disordered thiophene ring is shown. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii. The intramolecular hydrogen bond (motif f) is shown by a dashed line.
	Fig. 2. A packing diagram, showing the layered hydrogen-bond structure of DACT with assigned graph motifs, viewed along the c axis. Thiophene rings and the remaining H atoms have been omitted for clarity.
	Fig. 3. The topology of the hydrogen-bonded structure of DACT, represented by connections of molecule centres of gravity (motif a solid lines; motifs b and c dotted lines; motifs d and e dashed lines). Thin dotted lines indicate C—H···O interlayer interactions.

(6R,7R)-3-hydroxymethyl-8-oxo-7-(2-thiophen-2-ylacetylamino) −5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid]

Crystal data

C14H14N2O5S2	F(000) = 368
Mr = 354.36	Dx = 1.469 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 30 reflections
a = 9.6992 (18) Å	θ = 12–35°
b = 6.4069 (12) Å	µ = 0.36 mm^−1
c = 12.919 (2) Å	T = 293 K
β = 93.974 (14)°	Prism, colourless
V = 800.9 (2) Å^3	0.35 × 0.25 × 0.20 mm
Z = 2

Data collection

Siemens P3 diffractometer	Rint = 0.034
Radiation source: fine-focus sealed tube	θmax = 25.0°, θmin = 2.1°
Graphite monochromator	h = −11→11
profile data from ω/2θ scans	k = −7→7
3986 measured reflections	l = −15→15
2834 independent reflections	2 standard reflections every 70 reflections
2623 reflections with I > 2σ(I)	intensity decay: 4.8%

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)] = 0.038	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.090	w = 1/[σ^2(Fo^2) + (0.0457P)^2 + 0.2079P] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max < 0.001
2834 reflections	Δρmax = 0.18 e Å^−3
254 parameters	Δρmin = −0.18 e Å^−3
101 restraints	Absolute structure: Flack (1983), with 1279 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.02 (9)

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. The final INS file consists the following commands used for the disorder modeling:.. FVAR 0.74006 0.62590.. EXYZ C11 C11B EADP C11 C11B SIMU 0.01 C12 > C14B PART 1 C11 1 0.248025 0.535527 0.048752 21.00000 0.04728 0.06776 = 0.03732 0.00464 0.01135 − 0.01780 S2 5 0.187420 0.399948 − 0.056591 21.00000 0.06606 0.09550 = 0.05519 − 0.01974 − 0.00492 − 0.01144 C12 1 0.321358 0.223034 − 0.038721 21.00000 0.07422 0.08112 = 0.05731 − 0.00069 0.01855 0.00386 AFIX 43 H12 2 0.331184 0.109531 − 0.082476 21.00000 − 1.20000 AFIX 0 C13 1 0.409962 0.262301 0.043170 21.00000 0.07112 0.08522 = 0.05287 0.00329 0.00702 0.00212 AFIX 43 H13 2 0.487275 0.183635 0.064720 21.00000 − 1.20000 AFIX 0 C14 1 0.362088 0.452475 0.092339 21.00000 0.07120 0.09576 = 0.05398 0.00910 0.00259 0.00420 AFIX 43 H14 2 0.409082 0.510841 0.150511 21.00000 − 1.20000 AFIX 0 PART 2 SAME 0.01 0.01 C11 > C14 C11B 1 0.248025 0.535527 0.048752 − 21.00000 0.04728 0.06776 = 0.03732 0.00464 0.01135 − 0.01780 S2B 5 0.380840 0.429973 0.119799 − 21.00000 0.06099 0.08744 = 0.05530 0.01098 0.00766 0.01385 C12B 1 0.390183 0.230218 0.029443 − 21.00000 0.07166 0.08192 = 0.05190 − 0.00032 0.01524 0.00246 AFIX 43 H12B 2 0.452711 0.120532 0.038175 − 21.00000 − 1.20000 AFIX 0 C13B 1 0.300204 0.246551 − 0.053861 − 21.00000 0.07040 0.08684 = 0.05072 − 0.00687 0.01591 − 0.00218 AFIX 43 H13B 2 0.291940 0.156371 − 0.110360 − 21.00000 − 1.20000 AFIX 0 C14B 1 0.217613 0.433737 − 0.038580 − 21.00000 0.07083 0.08563 = 0.05678 − 0.00125 0.00919 − 0.01386 AFIX 43 H14B 2 0.148441 0.477886 − 0.087109 − 21.00000 − 1.20000 PART 0

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
S1	0.34512 (6)	0.42171 (10)	0.39715 (5)	0.03643 (17)
O1	0.5993 (2)	0.4588 (3)	0.70333 (18)	0.0502 (6)
H1O	0.616 (4)	0.584 (7)	0.687 (3)	0.075*
O2	0.3286 (2)	0.8445 (5)	0.7476 (2)	0.0753 (8)
O3	0.1076 (2)	0.7683 (4)	0.70668 (17)	0.0507 (6)
H3O	0.073 (4)	0.856 (7)	0.748 (3)	0.076*
O4	0.1383 (2)	0.9813 (3)	0.48534 (17)	0.0437 (5)
O5	−0.0068 (2)	0.5487 (4)	0.17060 (16)	0.0589 (7)
N1	0.1820 (2)	0.6264 (3)	0.52097 (18)	0.0318 (5)
N2	0.1509 (2)	0.7267 (4)	0.27214 (18)	0.0365 (5)
H2N	0.223 (3)	0.787 (5)	0.274 (2)	0.044*
C1	0.4577 (3)	0.4143 (6)	0.7132 (2)	0.0461 (7)
H1A	0.4249	0.4966	0.7695	0.060*
H1B	0.4477	0.2681	0.7308	0.060*
C2	0.3705 (2)	0.4607 (4)	0.6154 (2)	0.0348 (6)
C3	0.3997 (3)	0.3232 (5)	0.5248 (2)	0.0411 (6)
H3A	0.3549	0.1897	0.5338	0.053*
H3B	0.4984	0.2979	0.5271	0.053*
C4	0.1724 (3)	0.4853 (4)	0.4323 (2)	0.0314 (6)
H4	0.1139	0.3630	0.4418	0.041*
C5	0.2702 (3)	0.6060 (4)	0.6110 (2)	0.0325 (6)
C6	0.2409 (3)	0.7540 (5)	0.6961 (2)	0.0396 (7)
C7	0.1386 (2)	0.7990 (4)	0.4636 (2)	0.0311 (6)
C8	0.0983 (3)	0.6634 (4)	0.3685 (2)	0.0329 (6)
H8	−0.0018	0.6405	0.3608	0.043*
C9	0.0966 (3)	0.6594 (5)	0.1809 (2)	0.0407 (7)
C10	0.1737 (3)	0.7210 (6)	0.0870 (2)	0.0525 (8)
H10A	0.1089	0.7732	0.0325	0.068*
H10B	0.2393	0.8311	0.1058	0.068*
C11	0.2480 (3)	0.5355 (6)	0.0488 (2)	0.0504 (8)	0.626 (4)
S2	0.1874 (3)	0.3999 (5)	−0.0566 (2)	0.0727 (8)	0.626 (4)
C12	0.3214 (16)	0.223 (2)	−0.0387 (10)	0.070 (2)	0.626 (4)
H12	0.3312	0.1095	−0.0825	0.084*	0.626 (4)
C13	0.4100 (15)	0.262 (2)	0.0432 (10)	0.070 (2)	0.626 (4)
H13	0.4873	0.1836	0.0647	0.084*	0.626 (4)
C14	0.3621 (14)	0.452 (3)	0.0923 (9)	0.074 (3)	0.626 (4)
H14	0.4091	0.5108	0.1505	0.088*	0.626 (4)
C11B	0.2480 (3)	0.5355 (6)	0.0488 (2)	0.0504 (8)	0.374 (4)
S2B	0.3808 (6)	0.4300 (10)	0.1198 (3)	0.0677 (11)	0.374 (4)
C12B	0.390 (2)	0.230 (3)	0.0294 (15)	0.068 (3)	0.374 (4)
H12B	0.4527	0.1205	0.0382	0.082*	0.374 (4)
C13B	0.300 (3)	0.247 (4)	−0.0539 (15)	0.069 (3)	0.374 (4)
H13B	0.2919	0.1564	−0.1104	0.083*	0.374 (4)
C14B	0.2176 (18)	0.434 (3)	−0.0386 (12)	0.071 (3)	0.374 (4)
H14B	0.1484	0.4779	−0.0871	0.085*	0.374 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0332 (3)	0.0313 (3)	0.0456 (3)	0.0019 (3)	0.0093 (3)	−0.0051 (3)
O1	0.0355 (10)	0.0390 (13)	0.0746 (14)	0.0064 (9)	−0.0067 (9)	0.0086 (11)
O2	0.0499 (13)	0.094 (2)	0.0802 (17)	0.0075 (13)	−0.0043 (12)	−0.0445 (16)
O3	0.0378 (11)	0.0636 (15)	0.0512 (13)	0.0176 (10)	0.0072 (9)	−0.0119 (11)
O4	0.0472 (11)	0.0259 (11)	0.0587 (12)	0.0033 (8)	0.0080 (10)	0.0006 (9)
O5	0.0539 (13)	0.0796 (17)	0.0425 (12)	−0.0323 (12)	−0.0012 (10)	0.0130 (11)
N1	0.0270 (10)	0.0277 (11)	0.0408 (12)	0.0053 (9)	0.0038 (9)	−0.0028 (10)
N2	0.0265 (11)	0.0404 (13)	0.0430 (13)	−0.0067 (10)	0.0059 (10)	0.0047 (11)
C1	0.0392 (14)	0.0505 (16)	0.0489 (15)	0.0119 (16)	0.0043 (12)	0.0085 (17)
C2	0.0283 (12)	0.0329 (16)	0.0439 (14)	0.0031 (10)	0.0083 (10)	0.0048 (12)
C3	0.0357 (14)	0.0327 (14)	0.0548 (17)	0.0075 (12)	0.0021 (12)	−0.0001 (13)
C4	0.0283 (12)	0.0254 (13)	0.0410 (14)	−0.0011 (10)	0.0050 (10)	−0.0027 (11)
C5	0.0269 (13)	0.0309 (14)	0.0401 (14)	0.0014 (11)	0.0060 (11)	0.0006 (12)
C6	0.0357 (15)	0.0418 (16)	0.0413 (16)	0.0074 (13)	0.0012 (12)	−0.0026 (13)
C7	0.0200 (12)	0.0295 (15)	0.0444 (15)	0.0005 (10)	0.0063 (10)	0.0025 (12)
C8	0.0291 (13)	0.0318 (14)	0.0383 (14)	−0.0037 (11)	0.0058 (11)	0.0017 (12)
C9	0.0347 (15)	0.0457 (17)	0.0416 (16)	−0.0066 (13)	0.0022 (12)	0.0106 (13)
C10	0.0539 (19)	0.060 (2)	0.0447 (18)	−0.0158 (16)	0.0084 (14)	0.0123 (16)
C11	0.0473 (17)	0.068 (2)	0.0373 (15)	−0.0178 (15)	0.0114 (13)	0.0046 (15)
S2	0.0661 (13)	0.0955 (17)	0.0552 (11)	−0.0114 (12)	−0.0049 (8)	−0.0197 (11)
C12	0.074 (5)	0.081 (4)	0.057 (4)	0.004 (3)	0.019 (4)	−0.001 (4)
C13	0.071 (4)	0.085 (4)	0.053 (4)	0.002 (4)	0.007 (3)	0.003 (3)
C14	0.071 (4)	0.096 (5)	0.054 (5)	0.004 (4)	0.003 (4)	0.009 (4)
C11B	0.0473 (17)	0.068 (2)	0.0373 (15)	−0.0178 (15)	0.0114 (13)	0.0046 (15)
S2B	0.0610 (19)	0.087 (2)	0.055 (2)	0.0139 (18)	0.0077 (15)	0.011 (2)
C12B	0.072 (5)	0.082 (5)	0.052 (5)	0.002 (5)	0.015 (5)	0.000 (4)
C13B	0.070 (6)	0.087 (5)	0.051 (5)	−0.002 (4)	0.016 (5)	−0.007 (5)
C14B	0.071 (6)	0.086 (6)	0.057 (6)	−0.014 (5)	0.009 (5)	−0.001 (5)

Geometric parameters (Å, º)

S1—C3	1.810 (3)	C4—H4	0.9800
S1—C4	1.813 (3)	C5—C6	1.494 (4)
O1—C1	1.417 (3)	C7—C8	1.533 (4)
O1—H1O	0.85 (5)	C8—H8	0.9800
O2—C6	1.193 (4)	C9—C10	1.521 (4)
O3—C6	1.312 (3)	C10—C11	1.491 (5)
O3—H3O	0.85 (4)	C10—H10A	0.9700
O4—C7	1.201 (3)	C10—H10B	0.9700
O5—C9	1.228 (3)	C11—C14	1.318 (12)
N1—C7	1.381 (3)	C11—S2	1.686 (4)
N1—C5	1.402 (3)	S2—C12	1.727 (11)
N1—C4	1.457 (3)	C12—C13	1.340 (8)
N2—C9	1.329 (4)	C12—H12	0.9300
N2—C8	1.437 (4)	C13—C14	1.464 (18)
N2—H2N	0.80 (3)	C13—H13	0.9300
C1—C2	1.501 (4)	C14—H14	0.9300
C1—H1A	0.9700	S2B—C12B	1.739 (14)
C1—H1B	0.9700	C12B—C13B	1.342 (9)
C2—C5	1.344 (4)	C12B—H12B	0.9300
C2—C3	1.508 (4)	C13B—C14B	1.46 (2)
C3—H3A	0.9700	C13B—H13B	0.9300
C3—H3B	0.9700	C14B—H14B	0.9300
C4—C8	1.554 (4)
C3—S1—C4	93.86 (12)	O4—C7—C8	137.2 (3)
C1—O1—H1O	115 (3)	N1—C7—C8	91.6 (2)
C6—O3—H3O	123 (3)	N2—C8—C7	116.6 (2)
C7—N1—C5	131.8 (2)	N2—C8—C4	119.2 (2)
C7—N1—C4	94.3 (2)	C7—C8—C4	84.77 (19)
C5—N1—C4	126.7 (2)	N2—C8—H8	111.3
C9—N2—C8	122.3 (2)	C7—C8—H8	111.3
C9—N2—H2N	119 (2)	C4—C8—H8	111.3
C8—N2—H2N	118 (2)	O5—C9—N2	123.7 (3)
O1—C1—C2	112.2 (2)	O5—C9—C10	120.4 (3)
O1—C1—H1A	109.2	N2—C9—C10	115.9 (2)
C2—C1—H1A	109.2	C11—C10—C9	109.5 (3)
O1—C1—H1B	109.2	C11—C10—H10A	109.8
C2—C1—H1B	109.2	C9—C10—H10A	109.8
H1A—C1—H1B	107.9	C11—C10—H10B	109.8
C5—C2—C1	122.5 (3)	C9—C10—H10B	109.8
C5—C2—C3	123.1 (2)	H10A—C10—H10B	108.2
C1—C2—C3	114.4 (2)	C14—C11—C10	126.2 (7)
C2—C3—S1	116.4 (2)	C14—C11—S2	111.9 (6)
C2—C3—H3A	108.2	C10—C11—S2	121.9 (3)
S1—C3—H3A	108.2	C11—S2—C12	90.8 (5)
C2—C3—H3B	108.2	C13—C12—S2	114.7 (13)
S1—C3—H3B	108.2	C13—C12—H12	122.7
H3A—C3—H3B	107.3	S2—C12—H12	122.7
N1—C4—C8	87.91 (19)	C12—C13—C14	107.1 (13)
N1—C4—S1	109.03 (17)	C12—C13—H13	126.5
C8—C4—S1	115.72 (18)	C14—C13—H13	126.5
N1—C4—H4	113.8	C11—C14—C13	115.6 (11)
C8—C4—H4	113.8	C11—C14—H14	122.2
S1—C4—H4	113.8	C13—C14—H14	122.2
C2—C5—N1	119.8 (2)	C13B—C12B—S2B	114.8 (15)
C2—C5—C6	125.6 (2)	C13B—C12B—H12B	122.6
N1—C5—C6	114.5 (2)	S2B—C12B—H12B	122.6
O2—C6—O3	125.3 (3)	C12B—C13B—C14B	106.7 (15)
O2—C6—C5	123.6 (3)	C12B—C13B—H13B	126.6
O3—C6—C5	111.1 (2)	C14B—C13B—H13B	126.6
O4—C7—N1	131.2 (3)	C13B—C14B—H14B	122.3
O1—C1—C2—C5	−117.2 (3)	C9—N2—C8—C7	−161.9 (2)
O1—C1—C2—C3	66.0 (4)	C9—N2—C8—C4	98.7 (3)
C5—C2—C3—S1	23.6 (4)	O4—C7—C8—N2	49.6 (4)
C1—C2—C3—S1	−159.6 (2)	N1—C7—C8—N2	−129.2 (2)
C4—S1—C3—C2	−49.3 (2)	O4—C7—C8—C4	169.7 (3)
C7—N1—C4—C8	−9.60 (19)	N1—C7—C8—C4	−9.13 (18)
C5—N1—C4—C8	−162.3 (2)	N1—C4—C8—N2	126.3 (2)
C7—N1—C4—S1	106.94 (18)	S1—C4—C8—N2	16.2 (3)
C5—N1—C4—S1	−45.7 (3)	N1—C4—C8—C7	8.65 (17)
C3—S1—C4—N1	56.49 (19)	S1—C4—C8—C7	−101.50 (19)
C3—S1—C4—C8	153.6 (2)	C8—N2—C9—O5	4.4 (5)
C1—C2—C5—N1	−172.9 (3)	C8—N2—C9—C10	−173.4 (3)
C3—C2—C5—N1	3.7 (4)	O5—C9—C10—C11	−71.8 (4)
C1—C2—C5—C6	6.7 (4)	N2—C9—C10—C11	106.1 (3)
C3—C2—C5—C6	−176.7 (3)	C9—C10—C11—C14	−74.9 (9)
C7—N1—C5—C2	−132.7 (3)	C9—C10—C11—S2	102.4 (3)
C4—N1—C5—C2	9.4 (4)	C14—C11—S2—C12	0.8 (11)
C7—N1—C5—C6	47.7 (4)	C10—C11—S2—C12	−176.8 (7)
C4—N1—C5—C6	−170.2 (2)	C11—S2—C12—C13	−0.2 (14)
C2—C5—C6—O2	43.0 (5)	S2—C12—C13—C14	−0.4 (18)
N1—C5—C6—O2	−137.4 (3)	C10—C11—C14—C13	176.3 (9)
C2—C5—C6—O3	−136.4 (3)	S2—C11—C14—C13	−1.2 (15)
N1—C5—C6—O3	43.2 (3)	C12—C13—C14—C11	1.1 (19)
C5—N1—C7—O4	−18.8 (5)	S2B—C12B—C13B—C14B	−2 (3)
C4—N1—C7—O4	−169.2 (3)	O4—N1—C5—C6	40.1 (3)
C5—N1—C7—C8	160.1 (3)	C4—C8—N1—C7	166.9 (3)
C4—N1—C7—C8	9.73 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3O···O5^i	0.86 (4)	1.77 (4)	2.629 (3)	177 (4)
N2—H2N···O1^ii	0.80 (3)	2.05 (3)	2.841 (3)	172 (2)
O1—H1O···S1^ii	0.85 (4)	2.46 (4)	3.297 (2)	168 (4)
C3—H3A···O4^iii	0.97	2.53	3.362 (4)	144
C4—H4···O4^iii	0.98	2.52	3.322 (3)	139
C1—H1A···O2	0.97	2.43	3.072 (5)	124

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