Novel heterocyclic inhibitors of matrix metalloproteinases: three 6H-1,3,4-thiadiazines

The title compounds, (2S)-N-[5-(4-chloro­phenyl)-2,3-di­hydro-6H-1,3,4-thia­diazin-2-yl­idene]-2-[(phenyl­sulfonyl)­amino]­pro­pan­amide, C₁₈H₁₇ClN₄O₃S₂, (I), (2R)-N-[5-(4-fluoro­phenyl)-6H-1,3,4-thia­diazin-2-yl]-2-[(phenyl­sulfonyl)amino]­propan­amide, C₁₈H₁₇FN₄O₃S₂, (II), and (2S)-N-[5-(5-chloro-2-thienyl)-6H-1,3,4-thia­diazin-2-yl]-2-[(phenyl­sulfonyl)­amino]­propan­amide, C₁₆H₁₅ClN₄O₃S₃, (III), are potent inhibitors of matrix metalloproteinases. In all three compounds, the thia­diazine ring adopts a screw-boat conformation. The mol­ecules of compound (I) show a short intramolecular N_Ala—H...N_exo hydrogen bond [N...N 2.661 (3) Å] and are linked into a chain along the c axis by N_endo—H...S_endo and N_endo—H...O_Ala hydrogen bonds [N...S 3.236 (3) and N...O 3.375 (3) Å] between neighbouring mol­ecules. In compound (II), the mol­ecules are connected antiparallel into a chain along the a axis by N_exo—H...O_Ala and N_Ala—H...N_endo hydrogen bonds [N...O 2.907 (6) and N...N 2.911 (6) Å]. The mol­ecules of compound (III) are dimerized antiparallel through N_exo—H...N_endo hydrogen bonds [N...N 2.956 (7) and 2.983 (7) Å]. The different hydrogen-bonding patterns can be explained by an amido–imino tautomerism (prototropic shift) shown by different bond lengths within the 6H-1,3,4-thia­diazine moiety.

S1. Comment

Inhibitors of matrix metalloproteinases (MMPs) can provide useful treatments for diseases associated with excessive degradation of the extracellular matrix, such as osteoarthritis (Cawston, 1996), rheumatoid arthritis (Bläser et al., 1996), periodontal disease (Overall et al., 1987), multiple sclerosis (Yong, 1999), and tumour metastasis (Chambers & Matrisian, 1997). Recent efforts by a number of laboratories working in the area have provided several classes of MMP inhibitors, which have been extensively reviewed by Becket & Whittaker (1998). The value of thiadiazines as MMP inhibitors has, however, not hitherto been recognized. To investigate this heterocyclic system further and to establish the inhibitor structures for ligand-protein docking experiments, single-crystal X-ray diffraction studies were carried out on the three title compounds, (I), (II) and (III). \sch

The title compounds (Figs. 1, 2 and 3) consist of a 6H-1,3,4-thiadiazine system, a p-substituted phenyl ring or 5-chloro-substituted thiophene ring, and an amide-linked N-phenylsulfonyl-substituted D– or L-alanine residue. The three rings do not share a common plane and the thiadiazine ring deviates from planarity. The puckering of this ring system may be described by the amplitude and phase coordinates introduced by Cremer & Pople (1975) and Evans & Boeyens (1989). The puckering parameters for (I), (II) and molecules 1 and 2 of (III) are Q = 0.567 (3), 0.618 (2), 0.634 and 0.665 Å, θ = 70.6 (3), 69.9 (2), 109.5 and 70.5°, and ϕ = 39.9 (3), 33.1 (3), 217.1 and 35.9°, respectively. Thus, the thiadiazine moiety assumes a screw-boat conformation in all compounds (Boeyens, 1978). The large ϕ value for molecule 1 in the unit cell of (III) indicates that the direction of the ring distortion is towards an inverted screw-boat conformation.

In compounds (I) and (II) there are two distinct S1—C8 and S1—C9 bond lengths, which can be attributed to typical S-Csp³ and S-Csp² bonds [average values 1.819 (19) and 1.751 (17) Å; Allen et al., 1992]. The two molecules of compound (III) show similar S—C bond lengths. This corresponds to the 6H tautomeric form of the thiadiazine ring (Novikova et al., 1991). The endocyclic C9—N2 distance in (II) is shorter than the exocyclic C9—N3 distance and corresponds to an N═ Csp² bond. The same applies to the two molecules of compound (III). In contrast with this trend, the endocyclic C9—N2 distance in (I) is slightly longer than the exocyclic C9—N3 distance and corresponds to an N-Csp² bond. These systematic bond differences resemble the characteristic pattern of bond length changes introduced by an amido-imino tautomerism (prototropic shift) within the 6H-1,3,4-thiadiazine moiety.

As shown in Scheme 2, the geometry of compounds (II) and (III) is consistent with the tautomer on the left-hand side, while the geometry of (I) is closer to that of the tautomer on the right-hand side. Consequently, the endocyclic N atom close to the exocyclic N atom is a hydrogen-bond acceptor in (II) and (III) and a hydrogen-bond donor in (I). The opposite applies to the exocyclic N atom, which is a hydrogen-bond donor in (II) and (III) and a hydrogen-bond acceptor in (I). This contributes to the different hydrogen-bonding patterns in the crystal structures of the three compounds.

Related literature

For related literature, see: Allen et al. (1992); Becket & Whittaker (1998); Bläser et al. (1996); Boeyens (1978); Cawston (1996); Cremer & Pople (1975); Evans & Boeyens (1989); Novikova et al. (1991); Overall et al. (1987); Yong (1999).

S2. Experimental

The synthesis and spectroscopic data of the title compounds will be published elsewhere. Crystals of all three compounds suitable for diffraction analysis were obtained by slow crystallization from solution in methanol/acetonitrile (5:1).

S3. Refinement

H atoms on N in (I) and (II) were refined isotropically. Other H atoms in (I) and (II), and all H atoms in (III), were included in calculated positions using a riding model, with U(H) = 1.2U_eq for CH₂ and CH groups, and U(H) = 1.5U_eq for CH₃ groups, and C—H in the range 0.95–0.99 Å (Please check - no C—H data in CIF for (III). The torsion angles of the CH₃ groups were refined.

Computing details

For all compounds, data collection: P3/PC (Siemens, 1993); cell refinement: P3/PC; data reduction: SHELXTL-Plus (Sheldrick, 1990a); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990b); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 1990).

Figures

	Fig. 1. The molecular structure of (I) showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The molecular structure of (II) showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 3. The molecular structure of (III) showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.

(I) (2S)-N-[5-(4-chlorophenyl)-2,3-dihydro-6H-1,3,4-thiadiazin-2-ylidene]-2- (phenylsulfonyl)amino]propanamide

Crystal data

C18H17ClN4O3S2	Dx = 1.538 Mg m^−3
Mr = 436.93	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P21212	Cell parameters from 21 reflections
a = 15.600 (4) Å	θ = 2.3–11.3°
b = 20.764 (6) Å	µ = 0.45 mm^−1
c = 5.826 (3) Å	T = 173 K
V = 1887.1 (12) Å^3	Needle, colourless
Z = 4	1.00 × 0.30 × 0.15 mm
F(000) = 904

Data collection

Siemens P21 diffractometer	Rint = 0.031
Radiation source: normal-focus sealed tube	θmax = 30.0°, θmin = 2.0°
Graphite monochromator	h = −21→21
Wyckoff scan	k = −29→29
6296 measured reflections	l = −8→8
5491 independent reflections	3 standard reflections every 100 reflections
4278 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.051	w = 1/[σ^2(Fo^2) + (0.0588P)^2 + 0.3217P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.123	(Δ/σ)max = 0.001
S = 1.02	Δρmax = 0.33 e Å^−3
5491 reflections	Δρmin = −0.29 e Å^−3
263 parameters	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0119 (13)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: −0.09 (9)

Special details

Experimental. A large crystal was taken to obtain sufficient scattering

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

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

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

	x	y	z	Uiso*/Ueq
Cl1	0.11511 (5)	0.02529 (5)	0.58490 (19)	0.0520 (2)
S1	0.59765 (4)	0.10699 (4)	0.01091 (11)	0.03229 (18)
S2	0.88067 (4)	0.24019 (3)	0.42578 (12)	0.02781 (16)
O1	0.76848 (13)	0.11095 (12)	−0.1246 (3)	0.0368 (5)
O2	0.93380 (13)	0.27590 (10)	0.2705 (4)	0.0366 (5)
O3	0.89429 (14)	0.24560 (11)	0.6671 (3)	0.0366 (5)
N1	0.53506 (15)	0.08429 (12)	0.5034 (4)	0.0314 (5)
N2	0.61864 (16)	0.10364 (13)	0.4584 (4)	0.0330 (5)
H2N	0.652 (3)	0.1030 (19)	0.567 (7)	0.055 (12)*
N3	0.74395 (14)	0.10914 (12)	0.2667 (4)	0.0271 (5)
N4	0.89356 (15)	0.16405 (12)	0.3655 (4)	0.0286 (5)
H4N	0.865 (2)	0.1395 (15)	0.468 (6)	0.028 (8)*
C1	0.3227 (2)	0.08555 (18)	0.2499 (7)	0.0446 (9)
H1	0.3350	0.1033	0.1033	0.054*
C2	0.2383 (2)	0.0691 (2)	0.3037 (7)	0.0500 (10)
H2	0.1938	0.0753	0.1947	0.060*
C3	0.22054 (18)	0.04408 (14)	0.5135 (6)	0.0335 (7)
C4	0.2847 (2)	0.03333 (17)	0.6697 (6)	0.0416 (8)
H4	0.2719	0.0150	0.8151	0.050*
C5	0.3687 (2)	0.04931 (17)	0.6139 (5)	0.0380 (7)
H5	0.4132	0.0413	0.7216	0.046*
C6	0.38849 (17)	0.07664 (12)	0.4045 (5)	0.0251 (5)
C7	0.47799 (17)	0.09696 (12)	0.3512 (4)	0.0239 (5)
C8	0.49870 (19)	0.13464 (15)	0.1401 (5)	0.0335 (7)
H8A	0.5041	0.1808	0.1800	0.040*
H8B	0.4514	0.1302	0.0281	0.040*
C9	0.65946 (17)	0.10633 (13)	0.2565 (5)	0.0239 (5)
C10	0.79127 (17)	0.11970 (13)	0.0754 (5)	0.0262 (5)
C11	0.88237 (17)	0.14299 (14)	0.1261 (5)	0.0286 (6)
H11	0.8946	0.1806	0.0240	0.034*
C12	0.9475 (2)	0.08998 (16)	0.0706 (7)	0.0444 (8)
H12A	1.0056	0.1057	0.1025	0.067*
H12B	0.9430	0.0783	−0.0919	0.067*
H12C	0.9358	0.0521	0.1656	0.067*
C13	0.77307 (18)	0.26187 (14)	0.3706 (5)	0.0289 (6)
C14	0.7503 (2)	0.28643 (17)	0.1605 (6)	0.0421 (8)
H14	0.7922	0.2918	0.0437	0.051*
C15	0.6655 (2)	0.30333 (18)	0.1204 (7)	0.0503 (9)
H15	0.6494	0.3205	−0.0244	0.060*
C16	0.6049 (2)	0.29535 (16)	0.2886 (6)	0.0429 (8)
H16	0.5473	0.3079	0.2611	0.052*
C17	0.6274 (2)	0.26935 (17)	0.4961 (7)	0.0445 (8)
H17	0.5850	0.2630	0.6108	0.053*
C18	0.7120 (2)	0.25213 (17)	0.5398 (5)	0.0399 (7)
H18	0.7277	0.2340	0.6835	0.048*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0271 (4)	0.0570 (5)	0.0718 (6)	−0.0076 (4)	0.0075 (4)	0.0054 (5)
S1	0.0246 (3)	0.0544 (4)	0.0179 (3)	0.0047 (3)	−0.0008 (3)	−0.0002 (3)
S2	0.0240 (3)	0.0313 (3)	0.0281 (3)	−0.0085 (3)	−0.0027 (3)	0.0017 (3)
O1	0.0293 (10)	0.0547 (14)	0.0264 (10)	0.0002 (10)	0.0004 (8)	−0.0089 (10)
O2	0.0315 (11)	0.0356 (12)	0.0428 (12)	−0.0092 (9)	0.0016 (10)	0.0060 (10)
O3	0.0315 (11)	0.0459 (13)	0.0324 (10)	−0.0093 (10)	−0.0062 (9)	−0.0051 (10)
N1	0.0264 (11)	0.0440 (14)	0.0238 (11)	−0.0122 (10)	0.0007 (10)	0.0049 (10)
N2	0.0275 (11)	0.0516 (15)	0.0197 (11)	−0.0161 (11)	−0.0027 (9)	0.0049 (11)
N3	0.0257 (11)	0.0286 (12)	0.0270 (11)	−0.0052 (9)	−0.0044 (9)	0.0039 (10)
N4	0.0263 (12)	0.0305 (12)	0.0290 (12)	−0.0044 (10)	−0.0047 (10)	0.0047 (10)
C1	0.0259 (15)	0.070 (2)	0.0378 (17)	0.0028 (15)	−0.0004 (14)	0.0202 (17)
C2	0.0267 (16)	0.070 (3)	0.053 (2)	−0.0002 (16)	−0.0082 (15)	0.0186 (19)
C3	0.0267 (13)	0.0262 (13)	0.0475 (18)	−0.0024 (10)	0.0081 (13)	−0.0013 (13)
C4	0.0358 (16)	0.049 (2)	0.0401 (18)	−0.0136 (15)	0.0049 (14)	0.0092 (16)
C5	0.0337 (16)	0.0485 (18)	0.0319 (16)	−0.0090 (14)	−0.0051 (13)	0.0057 (14)
C6	0.0266 (13)	0.0223 (11)	0.0264 (12)	0.0001 (10)	0.0014 (12)	−0.0001 (10)
C7	0.0291 (13)	0.0211 (12)	0.0213 (11)	0.0002 (10)	0.0018 (10)	0.0011 (10)
C8	0.0268 (13)	0.0389 (16)	0.0348 (16)	0.0081 (12)	0.0064 (12)	0.0129 (13)
C9	0.0273 (12)	0.0227 (12)	0.0217 (12)	−0.0024 (10)	−0.0048 (10)	0.0017 (11)
C10	0.0242 (12)	0.0265 (13)	0.0279 (12)	0.0037 (10)	−0.0006 (11)	−0.0008 (12)
C11	0.0232 (12)	0.0337 (14)	0.0289 (14)	0.0008 (11)	−0.0007 (11)	0.0004 (11)
C12	0.0281 (15)	0.0490 (19)	0.056 (2)	0.0106 (13)	−0.0002 (15)	−0.0101 (18)
C13	0.0277 (13)	0.0245 (13)	0.0344 (15)	−0.0036 (11)	−0.0032 (11)	−0.0028 (12)
C14	0.0400 (17)	0.047 (2)	0.0390 (17)	0.0073 (15)	0.0030 (14)	0.0105 (16)
C15	0.0460 (19)	0.058 (2)	0.047 (2)	0.0183 (17)	−0.0065 (17)	0.0144 (18)
C16	0.0352 (17)	0.0372 (17)	0.056 (2)	0.0038 (14)	−0.0058 (16)	−0.0005 (15)
C17	0.0278 (15)	0.053 (2)	0.053 (2)	−0.0055 (14)	0.0048 (15)	0.0001 (17)
C18	0.0323 (15)	0.0519 (19)	0.0354 (17)	−0.0062 (13)	−0.0009 (12)	0.0065 (16)

Geometric parameters (Å, º)

Cl1—C3	1.741 (3)	C5—C6	1.381 (4)
S1—C9	1.726 (3)	C5—H5	0.9500
S1—C8	1.811 (3)	C6—C7	1.491 (4)
S2—O3	1.426 (2)	C7—C8	1.493 (4)
S2—O2	1.433 (2)	C8—H8A	0.9900
S2—N4	1.632 (3)	C8—H8B	0.9900
S2—C13	1.767 (3)	C10—C11	1.530 (4)
O1—C10	1.231 (4)	C11—C12	1.533 (4)
N1—C7	1.284 (4)	C11—H11	1.0000
N1—N2	1.389 (3)	C12—H12A	0.9800
N2—C9	1.338 (3)	C12—H12B	0.9800
N2—H2N	0.82 (4)	C12—H12C	0.9800
N3—C9	1.321 (3)	C13—C14	1.373 (4)
N3—C10	1.355 (4)	C13—C18	1.385 (4)
N4—C11	1.472 (4)	C14—C15	1.388 (5)
N4—H4N	0.90 (3)	C14—H14	0.9500
C1—C6	1.378 (4)	C15—C16	1.372 (5)
C1—C2	1.396 (5)	C15—H15	0.9500
C1—H1	0.9500	C16—C17	1.370 (5)
C2—C3	1.356 (5)	C16—H16	0.9500
C2—H2	0.9500	C17—C18	1.391 (4)
C3—C4	1.371 (5)	C17—H17	0.9500
C4—C5	1.390 (4)	C18—H18	0.9500
C4—H4	0.9500
C9—S1—C8	97.71 (15)	C7—C8—H8B	109.4
O3—S2—O2	119.69 (14)	S1—C8—H8B	109.4
O3—S2—N4	105.65 (14)	H8A—C8—H8B	108.0
O2—S2—N4	107.11 (14)	N3—C9—N2	115.9 (2)
O3—S2—C13	107.50 (14)	N3—C9—S1	126.5 (2)
O2—S2—C13	107.62 (14)	N2—C9—S1	117.6 (2)
N4—S2—C13	108.94 (13)	O1—C10—N3	126.7 (3)
C7—N1—N2	117.5 (2)	O1—C10—C11	119.8 (3)
C9—N2—N1	128.6 (2)	N3—C10—C11	113.5 (2)
C9—N2—H2N	112 (3)	N4—C11—C10	112.8 (2)
N1—N2—H2N	117 (3)	N4—C11—C12	109.5 (2)
C9—N3—C10	120.9 (2)	C10—C11—C12	110.4 (2)
C11—N4—S2	118.48 (19)	N4—C11—H11	108.0
C11—N4—H4N	114 (2)	C10—C11—H11	108.0
S2—N4—H4N	110 (2)	C12—C11—H11	108.0
C6—C1—C2	121.5 (3)	C11—C12—H12A	109.5
C6—C1—H1	119.2	C11—C12—H12B	109.5
C2—C1—H1	119.2	H12A—C12—H12B	109.5
C3—C2—C1	119.3 (3)	C11—C12—H12C	109.5
C3—C2—H2	120.4	H12A—C12—H12C	109.5
C1—C2—H2	120.4	H12B—C12—H12C	109.5
C2—C3—C4	120.7 (3)	C14—C13—C18	120.7 (3)
C2—C3—Cl1	119.6 (3)	C14—C13—S2	120.2 (2)
C4—C3—Cl1	119.7 (3)	C18—C13—S2	119.1 (2)
C3—C4—C5	119.6 (3)	C13—C14—C15	119.4 (3)
C3—C4—H4	120.2	C13—C14—H14	120.3
C5—C4—H4	120.2	C15—C14—H14	120.3
C6—C5—C4	121.0 (3)	C16—C15—C14	120.4 (3)
C6—C5—H5	119.5	C16—C15—H15	119.8
C4—C5—H5	119.5	C14—C15—H15	119.8
C1—C6—C5	117.8 (3)	C17—C16—C15	120.1 (3)
C1—C6—C7	121.6 (3)	C17—C16—H16	119.9
C5—C6—C7	120.6 (3)	C15—C16—H16	119.9
N1—C7—C6	116.6 (2)	C16—C17—C18	120.4 (3)
N1—C7—C8	121.7 (2)	C16—C17—H17	119.8
C6—C7—C8	121.5 (2)	C18—C17—H17	119.8
C7—C8—S1	111.14 (19)	C13—C18—C17	119.0 (3)
C7—C8—H8A	109.4	C13—C18—H18	120.5
S1—C8—H8A	109.4	C17—C18—H18	120.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···S1^i	0.82 (4)	2.72 (4)	3.236 (3)	122 (3)
N2—H2N···O1^i	0.82 (4)	2.56 (4)	3.375 (3)	173 (4)
N4—H4N···N3	0.90 (3)	2.31 (3)	2.661 (3)	103 (2)

Symmetry code: (i) x, y, z+1.

(II) (2R)-N-[5-(4-fluoro-phenyl)-6H-1,3,4-thiadiazin-2-yl]-2- [(phenylsulfonyl)amino]propanamide

Crystal data

C18H17FN4O3S2	Dx = 1.456 Mg m^−3
Mr = 420.48	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 20 reflections
a = 9.675 (19) Å	θ = 2.6–11.5°
b = 12.704 (19) Å	µ = 0.32 mm^−1
c = 15.606 (15) Å	T = 173 K
V = 1918 (5) Å^3	Needle, colourless
Z = 4	1.0 × 0.6 × 0.6 mm
F(000) = 872

Data collection

Siemens P21 diffractometer	Rint = 0.045
Radiation source: normal-focus sealed tube	θmax = 30.1°, θmin = 2.1°
Graphite monochromator	h = −13→13
Wyckoff scan	k = −17→17
6306 measured reflections	l = −21→21
5271 independent reflections	3 standard reflections every 100 reflections
4615 reflections with I > 2σ(I)	intensity decay: none

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)] = 0.049	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.128	w = 1/[σ^2(Fo^2) + (0.0722P)^2 + 0.8564P] where P = (Fo^2 + 2Fc^2)/3
S = 1.01	(Δ/σ)max = 0.001
5271 reflections	Δρmax = 0.34 e Å^−3
262 parameters	Δρmin = −0.43 e Å^−3
0 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.12 (8)

Special details

Experimental. A large crystal was taken to obtain sufficient scattering

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

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

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

	x	y	z	Uiso*/Ueq
S1	0.09325 (6)	0.77278 (5)	0.31052 (4)	0.02420 (14)
S2	0.17513 (7)	0.50883 (5)	0.58954 (4)	0.02467 (14)
N1	0.3671 (2)	0.8371 (2)	0.22849 (14)	0.0289 (5)
N2	0.3699 (2)	0.8075 (2)	0.31511 (14)	0.0285 (5)
N3	0.2754 (2)	0.76999 (19)	0.44485 (13)	0.0224 (4)
H3N	0.363 (4)	0.759 (3)	0.463 (2)	0.037 (9)*
N4	0.1390 (2)	0.62762 (18)	0.62024 (13)	0.0232 (4)
H4N	0.052 (5)	0.634 (3)	0.637 (3)	0.051 (12)*
O1	0.04966 (18)	0.77390 (17)	0.48789 (12)	0.0279 (4)
O2	0.3221 (2)	0.49252 (17)	0.60224 (12)	0.0350 (5)
O3	0.0773 (3)	0.44185 (17)	0.63244 (13)	0.0352 (5)
F1	0.3034 (3)	0.9218 (2)	−0.16711 (12)	0.0593 (7)
C1	0.2067 (4)	0.7757 (2)	0.02291 (18)	0.0349 (6)
H1	0.1514	0.7170	0.0386	0.042*
C2	0.2143 (4)	0.8060 (3)	−0.06292 (19)	0.0425 (8)
H2	0.1649	0.7688	−0.1059	0.051*
C3	0.2953 (4)	0.8915 (3)	−0.08354 (18)	0.0375 (7)
C4	0.3687 (3)	0.9493 (3)	−0.02380 (18)	0.0335 (6)
H4	0.4228	1.0083	−0.0404	0.040*
C5	0.3604 (3)	0.9181 (2)	0.06178 (17)	0.0285 (5)
H5	0.4100	0.9562	0.1042	0.034*
C6	0.2797 (3)	0.8307 (2)	0.08625 (16)	0.0238 (5)
C7	0.2741 (3)	0.7991 (2)	0.17787 (16)	0.0228 (5)
C8	0.1631 (3)	0.7255 (2)	0.20965 (16)	0.0298 (5)
H8A	0.2024	0.6542	0.2177	0.036*
H8B	0.0882	0.7207	0.1666	0.036*
C9	0.2571 (3)	0.7875 (2)	0.35682 (15)	0.0212 (4)
C10	0.1728 (3)	0.75567 (19)	0.50393 (15)	0.0214 (4)
C11	0.2220 (3)	0.7174 (2)	0.59211 (15)	0.0236 (5)
H11	0.3211	0.6956	0.5881	0.028*
C12	0.2083 (4)	0.8058 (3)	0.6576 (2)	0.0392 (7)
H12A	0.1109	0.8259	0.6630	0.059*
H12B	0.2624	0.8668	0.6387	0.059*
H12C	0.2428	0.7816	0.7133	0.059*
C13	0.1483 (3)	0.4990 (2)	0.47732 (15)	0.0238 (5)
C14	0.0141 (3)	0.4948 (2)	0.44451 (17)	0.0278 (5)
H14	−0.0637	0.5002	0.4814	0.033*
C15	−0.0030 (3)	0.4825 (2)	0.35636 (18)	0.0316 (6)
H15	−0.0935	0.4809	0.3327	0.038*
C16	0.1113 (3)	0.4726 (2)	0.30260 (17)	0.0324 (6)
H16	0.0983	0.4627	0.2428	0.039*
C17	0.2444 (4)	0.4770 (3)	0.33623 (19)	0.0391 (7)
H17	0.3221	0.4703	0.2994	0.047*
C18	0.2639 (3)	0.4913 (3)	0.42403 (17)	0.0361 (6)
H18	0.3545	0.4958	0.4473	0.043*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0176 (2)	0.0352 (3)	0.0198 (3)	−0.0027 (2)	−0.0020 (2)	0.0014 (2)
S2	0.0276 (3)	0.0302 (3)	0.0162 (2)	0.0046 (3)	−0.0007 (2)	0.0030 (2)
N1	0.0253 (10)	0.0446 (13)	0.0170 (9)	−0.0067 (10)	−0.0006 (8)	0.0072 (9)
N2	0.0205 (9)	0.0471 (13)	0.0180 (9)	−0.0046 (9)	−0.0028 (8)	0.0079 (9)
N3	0.0173 (8)	0.0325 (11)	0.0173 (9)	−0.0011 (9)	−0.0008 (7)	0.0037 (8)
N4	0.0205 (9)	0.0310 (10)	0.0181 (9)	−0.0007 (9)	0.0041 (8)	0.0019 (8)
O1	0.0172 (7)	0.0428 (11)	0.0237 (8)	0.0023 (8)	0.0002 (6)	0.0060 (8)
O2	0.0312 (9)	0.0472 (11)	0.0266 (9)	0.0166 (10)	−0.0058 (8)	−0.0006 (9)
O3	0.0473 (12)	0.0334 (10)	0.0248 (9)	−0.0064 (10)	0.0043 (9)	0.0066 (8)
F1	0.0914 (18)	0.0667 (14)	0.0197 (9)	−0.0189 (14)	0.0008 (10)	0.0077 (9)
C1	0.0509 (18)	0.0305 (13)	0.0233 (12)	−0.0073 (13)	−0.0033 (11)	0.0011 (11)
C2	0.067 (2)	0.0407 (16)	0.0201 (12)	−0.0077 (16)	−0.0079 (13)	−0.0029 (11)
C3	0.0500 (19)	0.0445 (16)	0.0179 (12)	0.0002 (14)	0.0022 (12)	0.0061 (11)
C4	0.0329 (13)	0.0420 (15)	0.0257 (13)	−0.0041 (13)	0.0043 (11)	0.0071 (11)
C5	0.0239 (12)	0.0387 (14)	0.0228 (11)	−0.0048 (11)	0.0013 (10)	0.0032 (10)
C6	0.0250 (11)	0.0284 (11)	0.0181 (10)	0.0015 (10)	0.0017 (9)	0.0012 (9)
C7	0.0237 (11)	0.0262 (11)	0.0185 (10)	0.0016 (9)	−0.0001 (8)	0.0013 (8)
C8	0.0371 (14)	0.0320 (12)	0.0202 (11)	−0.0104 (12)	0.0012 (10)	−0.0028 (10)
C9	0.0217 (10)	0.0250 (11)	0.0169 (10)	−0.0002 (9)	−0.0013 (8)	0.0026 (8)
C10	0.0201 (10)	0.0278 (11)	0.0162 (9)	−0.0015 (9)	0.0001 (8)	0.0017 (8)
C11	0.0205 (10)	0.0339 (12)	0.0165 (9)	−0.0041 (10)	−0.0014 (8)	0.0033 (10)
C12	0.0525 (19)	0.0383 (15)	0.0267 (13)	−0.0128 (14)	−0.0015 (13)	−0.0076 (12)
C13	0.0275 (12)	0.0265 (11)	0.0176 (10)	0.0006 (10)	−0.0011 (8)	0.0007 (9)
C14	0.0271 (12)	0.0338 (14)	0.0225 (11)	−0.0012 (11)	0.0012 (9)	−0.0021 (10)
C15	0.0360 (14)	0.0348 (14)	0.0241 (12)	−0.0094 (12)	−0.0061 (10)	−0.0011 (11)
C16	0.0467 (16)	0.0328 (13)	0.0177 (11)	−0.0083 (12)	0.0003 (11)	−0.0011 (10)
C17	0.0418 (16)	0.0525 (19)	0.0229 (12)	−0.0022 (15)	0.0084 (11)	−0.0041 (12)
C18	0.0290 (13)	0.0563 (19)	0.0230 (13)	0.0036 (14)	0.0017 (10)	0.0010 (13)

Geometric parameters (Å, º)

S1—C9	1.752 (4)	C5—C6	1.410 (4)
S1—C8	1.816 (3)	C5—H5	0.9500
S2—O3	1.438 (3)	C6—C7	1.486 (4)
S2—O2	1.451 (3)	C7—C8	1.508 (4)
S2—N4	1.621 (3)	C8—H8A	0.9900
S2—C13	1.775 (3)	C8—H8B	0.9900
N1—C7	1.291 (4)	C10—C11	1.535 (4)
N1—N2	1.404 (3)	C11—C12	1.524 (4)
N2—C9	1.296 (4)	C11—H11	1.0000
N3—C10	1.367 (3)	C12—H12A	0.9800
N3—C9	1.403 (3)	C12—H12B	0.9800
N3—H3N	0.90 (4)	C12—H12C	0.9800
N4—C11	1.463 (4)	C13—C14	1.397 (4)
N4—H4N	0.88 (5)	C13—C18	1.397 (4)
O1—C10	1.239 (4)	C14—C15	1.394 (4)
F1—C3	1.362 (3)	C14—H14	0.9500
C1—C2	1.396 (4)	C15—C16	1.394 (5)
C1—C6	1.401 (4)	C15—H15	0.9500
C1—H1	0.9500	C16—C17	1.392 (5)
C2—C3	1.377 (5)	C16—H16	0.9500
C2—H2	0.9500	C17—C18	1.395 (4)
C3—C4	1.383 (4)	C17—H17	0.9500
C4—C5	1.396 (4)	C18—H18	0.9500
C4—H4	0.9500
C9—S1—C8	93.21 (15)	C7—C8—H8B	109.6
O3—S2—O2	119.79 (16)	S1—C8—H8B	109.6
O3—S2—N4	105.73 (15)	H8A—C8—H8B	108.1
O2—S2—N4	107.70 (13)	N2—C9—N3	114.6 (2)
O3—S2—C13	108.76 (14)	N2—C9—S1	125.2 (2)
O2—S2—C13	105.54 (12)	N3—C9—S1	120.08 (18)
N4—S2—C13	109.01 (12)	O1—C10—N3	122.5 (2)
C7—N1—N2	120.2 (2)	O1—C10—C11	122.6 (2)
C9—N2—N1	121.3 (2)	N3—C10—C11	114.9 (2)
C10—N3—C9	126.1 (2)	N4—C11—C12	109.0 (2)
C10—N3—H3N	117 (2)	N4—C11—C10	110.2 (2)
C9—N3—H3N	116 (2)	C12—C11—C10	109.9 (2)
C11—N4—S2	121.23 (19)	N4—C11—H11	109.2
C11—N4—H4N	123 (3)	C12—C11—H11	109.2
S2—N4—H4N	112 (3)	C10—C11—H11	109.2
C2—C1—C6	120.9 (3)	C11—C12—H12A	109.5
C2—C1—H1	119.6	C11—C12—H12B	109.5
C6—C1—H1	119.6	H12A—C12—H12B	109.5
C3—C2—C1	118.1 (3)	C11—C12—H12C	109.5
C3—C2—H2	120.9	H12A—C12—H12C	109.5
C1—C2—H2	120.9	H12B—C12—H12C	109.5
F1—C3—C2	118.6 (3)	C14—C13—C18	121.5 (3)
F1—C3—C4	117.8 (3)	C14—C13—S2	120.01 (19)
C2—C3—C4	123.6 (3)	C18—C13—S2	118.4 (2)
C3—C4—C5	117.7 (3)	C15—C14—C13	118.5 (2)
C3—C4—H4	121.2	C15—C14—H14	120.8
C5—C4—H4	121.2	C13—C14—H14	120.8
C4—C5—C6	121.0 (3)	C16—C15—C14	120.6 (3)
C4—C5—H5	119.5	C16—C15—H15	119.7
C6—C5—H5	119.5	C14—C15—H15	119.7
C1—C6—C5	118.7 (2)	C17—C16—C15	120.2 (3)
C1—C6—C7	121.7 (2)	C17—C16—H16	119.9
C5—C6—C7	119.6 (2)	C15—C16—H16	119.9
N1—C7—C6	117.5 (2)	C16—C17—C18	120.0 (3)
N1—C7—C8	121.8 (2)	C16—C17—H17	120.0
C6—C7—C8	120.7 (2)	C18—C17—H17	120.0
C7—C8—S1	110.18 (19)	C17—C18—C13	119.1 (3)
C7—C8—H8A	109.6	C17—C18—H18	120.5
S1—C8—H8A	109.6	C13—C18—H18	120.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3N···O1^i	0.90 (4)	2.01 (4)	2.907 (6)	174 (3)
N4—H4N···N2^ii	0.88 (5)	2.06 (5)	2.911 (6)	163 (4)

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

(III) (2S)-N-[5-(5-chloro-2-thienyl)-6H-1,3,4-thiadiazin-2-yl]-2- [(phenylsulfonyl)amino]propanamide

Crystal data

C16H15ClN4O3S3	F(000) = 912
Mr = 442.95	Dx = 1.547 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 10.613 (4) Å	Cell parameters from 19 reflections
b = 11.193 (4) Å	θ = 2.2–12.0°
c = 16.399 (5) Å	µ = 0.56 mm^−1
β = 102.48 (3)°	T = 173 K
V = 1902.0 (11) Å^3	Needle, colourless
Z = 4	0.40 × 0.15 × 0.15 mm

Data collection

Siemens P21 diffractometer	Rint = 0.054
Radiation source: normal-focus sealed tube	θmax = 25.1°, θmin = 2.0°
Graphite monochromator	h = −12→12
Wyckoff scan	k = −13→13
7536 measured reflections	l = −19→19
6749 independent reflections	3 standard reflections every 100 reflections
4676 reflections with I > 2σ(I)	intensity decay: none

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)] = 0.061	H-atom parameters constrained
wR(F^2) = 0.125	w = 1/[σ^2(Fo^2) + (0.0364P)^2 + 0.5602P] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max < 0.001
6749 reflections	Δρmax = 0.30 e Å^−3
489 parameters	Δρmin = −0.35 e Å^−3
1 restraint	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.03 (11)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

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

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

	x	y	z	Uiso*/Ueq
S1	0.40775 (15)	0.81849 (19)	0.58846 (10)	0.0259 (4)
S2	0.16364 (15)	0.81560 (19)	0.26446 (10)	0.0235 (4)
S3	0.28040 (18)	0.57269 (18)	−0.00242 (12)	0.0290 (5)
Cl1	0.3719 (2)	0.8724 (3)	0.75937 (14)	0.0604 (8)
O1	0.1612 (4)	0.8569 (5)	0.1016 (3)	0.0304 (14)
O2	0.3633 (5)	0.4811 (5)	−0.0219 (4)	0.0458 (17)
O3	0.1639 (5)	0.6035 (5)	−0.0615 (3)	0.0395 (15)
N1	0.4014 (5)	0.7993 (5)	0.4035 (3)	0.0197 (13)
N2	0.4201 (5)	0.7802 (5)	0.3221 (3)	0.0174 (13)
N3	0.3557 (5)	0.8041 (5)	0.1809 (3)	0.0192 (13)
H3N	0.4371	0.7925	0.1793	0.023*
N4	0.3711 (5)	0.6881 (5)	0.0177 (3)	0.0229 (14)
H4N	0.4543	0.6759	0.0227	0.028*
C1	0.3059 (7)	0.8449 (7)	0.6556 (4)	0.0274 (18)
C2	0.1796 (7)	0.8390 (7)	0.6185 (5)	0.0289 (19)
H2A	0.1112	0.8523	0.6464	0.035*
C3	0.1619 (6)	0.8107 (7)	0.5332 (4)	0.0218 (16)
H3A	0.0796	0.8004	0.4972	0.026*
C4	0.2763 (6)	0.7994 (6)	0.5075 (4)	0.0174 (15)
C5	0.2920 (6)	0.7771 (6)	0.4220 (4)	0.0168 (16)
C6	0.1815 (6)	0.7287 (7)	0.3590 (4)	0.0227 (16)
H6A	0.1015	0.7333	0.3807	0.027*
H6B	0.1975	0.6439	0.3474	0.027*
C7	0.3258 (6)	0.7990 (6)	0.2596 (4)	0.0160 (15)
C8	0.2727 (6)	0.8251 (7)	0.1059 (4)	0.0210 (15)
C9	0.3318 (6)	0.8119 (7)	0.0290 (4)	0.0236 (16)
H9A	0.4126	0.8608	0.0401	0.028*
C10	0.2422 (7)	0.8672 (7)	−0.0479 (4)	0.0341 (19)
H10A	0.2789	0.8546	−0.0972	0.051*
H10B	0.2335	0.9531	−0.0389	0.051*
H10C	0.1571	0.8292	−0.0567	0.051*
C11	0.2328 (7)	0.5306 (7)	0.0920 (5)	0.0242 (17)
C12	0.3282 (7)	0.5117 (8)	0.1620 (5)	0.038 (2)
H12A	0.4165	0.5235	0.1611	0.045*
C13	0.2908 (9)	0.4745 (8)	0.2350 (5)	0.046 (2)
H13A	0.3545	0.4614	0.2846	0.055*
C14	0.1626 (8)	0.4568 (8)	0.2353 (5)	0.037 (2)
H14A	0.1382	0.4306	0.2848	0.044*
C15	0.0705 (7)	0.4767 (7)	0.1644 (5)	0.035 (2)
H15A	−0.0179	0.4659	0.1656	0.042*
C16	0.1036 (7)	0.5128 (7)	0.0904 (5)	0.0288 (19)
H16A	0.0397	0.5246	0.0407	0.035*
S4	0.62260 (17)	0.65968 (19)	−0.08416 (12)	0.0313 (5)
S5	0.87898 (15)	0.69831 (18)	0.23384 (11)	0.0262 (4)
S6	0.74209 (17)	0.95360 (17)	0.49967 (11)	0.0226 (4)
Cl2	0.6468 (2)	0.6173 (2)	−0.25930 (12)	0.0426 (6)
O4	0.8880 (4)	0.6490 (5)	0.3946 (3)	0.0303 (13)
O5	0.8576 (5)	0.9368 (5)	0.5643 (3)	0.0351 (14)
O6	0.6437 (5)	1.0353 (5)	0.5131 (4)	0.0344 (14)
N5	0.6363 (5)	0.7027 (6)	0.0977 (3)	0.0211 (14)
N6	0.6218 (5)	0.7269 (5)	0.1804 (3)	0.0209 (14)
N7	0.6929 (5)	0.7152 (5)	0.3229 (3)	0.0200 (13)
H7N	0.6139	0.7322	0.3279	0.024*
N8	0.6715 (5)	0.8263 (5)	0.4790 (3)	0.0204 (12)
H8N	0.5867	0.8233	0.4685	0.025*
C17	0.7171 (7)	0.6540 (7)	−0.1580 (5)	0.0284 (19)
C18	0.8396 (7)	0.6827 (7)	−0.1274 (5)	0.031 (2)
H18A	0.9042	0.6840	−0.1595	0.037*
C19	0.8625 (6)	0.7114 (7)	−0.0409 (5)	0.0274 (18)
H19A	0.9450	0.7334	−0.0090	0.033*
C20	0.7558 (6)	0.7044 (7)	−0.0085 (4)	0.0221 (16)
C21	0.7438 (6)	0.7284 (7)	0.0769 (4)	0.0206 (17)
C22	0.8535 (6)	0.7838 (8)	0.1375 (4)	0.031 (2)
H22A	0.8331	0.8679	0.1482	0.037*
H22B	0.9325	0.7825	0.1145	0.037*
C23	0.7179 (6)	0.7134 (7)	0.2428 (4)	0.0195 (16)
C24	0.7823 (6)	0.6924 (7)	0.3934 (5)	0.0220 (17)
C25	0.7438 (6)	0.7162 (6)	0.4773 (4)	0.0188 (15)
H25A	0.8252	0.7229	0.5211	0.023*
C26	0.6667 (7)	0.6109 (6)	0.5012 (4)	0.0328 (19)
H26A	0.6527	0.6232	0.5578	0.049*
H26B	0.7149	0.5366	0.4995	0.049*
H26C	0.5832	0.6057	0.4618	0.049*
C27	0.7938 (7)	1.0000 (6)	0.4091 (4)	0.0196 (16)
C28	0.9248 (7)	1.0217 (6)	0.4133 (5)	0.0272 (18)
H28A	0.9856	1.0142	0.4649	0.033*
C29	0.9648 (8)	1.0542 (7)	0.3419 (5)	0.037 (2)
H29A	1.0537	1.0684	0.3441	0.045*
C30	0.8765 (8)	1.0664 (7)	0.2669 (5)	0.038 (2)
H30A	0.9047	1.0901	0.2182	0.046*
C31	0.7466 (8)	1.0441 (8)	0.2628 (5)	0.037 (2)
H31A	0.6862	1.0516	0.2110	0.044*
C32	0.7048 (7)	1.0108 (6)	0.3342 (5)	0.0274 (19)
H32A	0.6159	0.9956	0.3316	0.033*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0224 (9)	0.0408 (12)	0.0148 (9)	−0.0048 (9)	0.0044 (7)	−0.0030 (9)
S2	0.0132 (8)	0.0401 (12)	0.0167 (9)	0.0008 (9)	0.0023 (7)	0.0040 (9)
S3	0.0295 (10)	0.0368 (12)	0.0221 (10)	−0.0056 (9)	0.0091 (8)	−0.0076 (9)
Cl1	0.0623 (14)	0.101 (2)	0.0210 (12)	−0.0311 (15)	0.0158 (10)	−0.0204 (13)
O1	0.020 (3)	0.048 (4)	0.022 (3)	0.011 (3)	0.001 (2)	0.010 (3)
O2	0.051 (4)	0.042 (4)	0.053 (4)	−0.003 (3)	0.031 (3)	−0.013 (3)
O3	0.033 (3)	0.060 (4)	0.020 (3)	−0.017 (3)	−0.007 (2)	0.002 (3)
N1	0.021 (3)	0.026 (4)	0.012 (3)	−0.001 (3)	0.005 (2)	0.001 (3)
N2	0.015 (3)	0.023 (3)	0.013 (3)	0.000 (2)	0.001 (2)	−0.001 (2)
N3	0.018 (3)	0.031 (4)	0.010 (3)	0.003 (3)	0.006 (2)	0.001 (3)
N4	0.017 (3)	0.034 (4)	0.017 (3)	−0.001 (3)	0.003 (2)	−0.009 (3)
C1	0.046 (5)	0.025 (5)	0.015 (4)	−0.006 (4)	0.014 (3)	−0.001 (3)
C2	0.026 (4)	0.033 (5)	0.033 (5)	−0.003 (4)	0.019 (3)	−0.001 (4)
C3	0.017 (3)	0.024 (4)	0.026 (4)	−0.001 (3)	0.009 (3)	0.000 (4)
C4	0.021 (3)	0.016 (4)	0.014 (3)	0.000 (3)	0.001 (3)	0.004 (3)
C5	0.016 (3)	0.019 (4)	0.015 (4)	0.002 (3)	0.002 (3)	0.004 (3)
C6	0.021 (3)	0.028 (4)	0.018 (4)	−0.010 (3)	0.003 (3)	0.004 (3)
C7	0.019 (3)	0.014 (4)	0.015 (4)	0.001 (3)	0.004 (3)	−0.003 (3)
C8	0.024 (4)	0.022 (4)	0.016 (4)	−0.003 (3)	0.003 (3)	0.005 (3)
C9	0.018 (3)	0.041 (5)	0.011 (3)	0.004 (4)	0.003 (3)	−0.003 (4)
C10	0.044 (5)	0.039 (5)	0.019 (4)	0.010 (4)	0.007 (3)	0.003 (3)
C11	0.030 (4)	0.021 (4)	0.022 (4)	−0.001 (3)	0.007 (3)	−0.008 (3)
C12	0.024 (4)	0.054 (6)	0.034 (5)	−0.002 (4)	0.002 (4)	−0.002 (4)
C13	0.058 (6)	0.051 (7)	0.023 (5)	0.000 (5)	−0.003 (4)	0.003 (4)
C14	0.062 (6)	0.028 (5)	0.026 (5)	−0.011 (5)	0.023 (4)	0.000 (4)
C15	0.033 (4)	0.033 (5)	0.043 (5)	−0.004 (4)	0.019 (4)	−0.010 (4)
C16	0.025 (4)	0.032 (5)	0.032 (5)	−0.002 (4)	0.011 (3)	−0.002 (4)
S4	0.0222 (9)	0.0529 (14)	0.0189 (10)	−0.0040 (9)	0.0044 (8)	−0.0066 (9)
S5	0.0135 (8)	0.0452 (13)	0.0206 (10)	0.0016 (9)	0.0053 (7)	0.0007 (9)
S6	0.0259 (10)	0.0238 (10)	0.0198 (10)	−0.0071 (8)	0.0088 (8)	−0.0071 (8)
Cl2	0.0547 (13)	0.0571 (15)	0.0157 (10)	−0.0008 (11)	0.0069 (9)	−0.0062 (10)
O4	0.025 (3)	0.041 (3)	0.027 (3)	0.012 (3)	0.010 (2)	0.001 (3)
O5	0.040 (3)	0.045 (4)	0.020 (3)	−0.019 (3)	0.005 (2)	−0.002 (3)
O6	0.048 (3)	0.019 (3)	0.047 (4)	0.002 (3)	0.032 (3)	−0.009 (3)
N5	0.013 (3)	0.034 (4)	0.017 (3)	0.002 (3)	0.004 (2)	−0.006 (3)
N6	0.019 (3)	0.034 (4)	0.011 (3)	0.000 (3)	0.007 (2)	−0.006 (3)
N7	0.013 (3)	0.029 (4)	0.019 (3)	0.003 (3)	0.005 (2)	−0.001 (3)
N8	0.013 (3)	0.020 (3)	0.028 (3)	−0.002 (3)	0.006 (2)	−0.007 (3)
C17	0.032 (4)	0.035 (5)	0.021 (4)	0.001 (4)	0.014 (3)	−0.002 (4)
C18	0.034 (4)	0.040 (5)	0.026 (4)	0.001 (4)	0.021 (3)	0.004 (4)
C19	0.023 (4)	0.036 (5)	0.025 (4)	0.002 (4)	0.009 (3)	0.006 (4)
C20	0.018 (3)	0.030 (4)	0.020 (4)	0.002 (3)	0.005 (3)	0.002 (4)
C21	0.015 (3)	0.024 (4)	0.023 (4)	0.005 (3)	0.005 (3)	−0.002 (3)
C22	0.019 (4)	0.057 (6)	0.016 (4)	−0.007 (4)	0.003 (3)	−0.007 (4)
C23	0.009 (3)	0.031 (4)	0.019 (4)	0.001 (3)	0.003 (3)	0.004 (3)
C24	0.018 (4)	0.020 (4)	0.029 (4)	0.003 (3)	0.006 (3)	0.000 (3)
C25	0.020 (4)	0.018 (4)	0.017 (3)	0.002 (3)	0.000 (3)	−0.002 (3)
C26	0.045 (5)	0.023 (4)	0.038 (5)	−0.002 (4)	0.026 (4)	0.006 (4)
C27	0.027 (4)	0.020 (4)	0.011 (4)	−0.002 (3)	0.003 (3)	−0.002 (3)
C28	0.025 (4)	0.021 (4)	0.034 (5)	0.000 (3)	0.005 (3)	−0.007 (4)
C29	0.042 (5)	0.037 (5)	0.041 (5)	−0.004 (4)	0.023 (4)	0.002 (4)
C30	0.060 (6)	0.029 (5)	0.028 (5)	0.000 (4)	0.016 (4)	−0.004 (4)
C31	0.054 (5)	0.027 (5)	0.023 (5)	−0.010 (4)	−0.005 (4)	0.004 (4)
C32	0.033 (4)	0.019 (4)	0.029 (5)	−0.002 (3)	0.004 (4)	0.005 (4)

Geometric parameters (Å, º)

S1—C4	1.718 (7)	S4—C17	1.732 (7)
S1—C1	1.727 (7)	S4—C20	1.741 (7)
S2—C7	1.750 (6)	S5—C23	1.755 (6)
S2—C6	1.805 (7)	S5—C22	1.817 (7)
S3—O2	1.431 (6)	S6—O6	1.440 (5)
S3—O3	1.439 (5)	S6—O5	1.449 (5)
S3—N4	1.602 (6)	S6—N8	1.611 (6)
S3—C11	1.792 (8)	S6—C27	1.769 (7)
Cl1—C1	1.722 (8)	Cl2—C17	1.718 (8)
O1—C8	1.223 (7)	O4—C24	1.218 (8)
N1—C5	1.286 (8)	N5—C21	1.292 (8)
N1—N2	1.407 (7)	N5—N6	1.423 (7)
N2—C7	1.286 (8)	N6—C23	1.288 (8)
N3—C8	1.369 (8)	N7—C24	1.351 (9)
N3—C7	1.395 (8)	N7—C23	1.396 (8)
N4—C9	1.470 (9)	N8—C25	1.456 (8)
C1—C2	1.349 (10)	C17—C18	1.328 (11)
C2—C3	1.406 (10)	C18—C19	1.423 (10)
C3—C4	1.375 (8)	C19—C20	1.354 (9)
C4—C5	1.469 (9)	C20—C21	1.458 (9)
C5—C6	1.487 (9)	C21—C22	1.492 (9)
C8—C9	1.533 (8)	C24—C25	1.540 (9)
C9—C10	1.536 (9)	C25—C26	1.533 (9)
C11—C12	1.373 (10)	C27—C32	1.384 (10)
C11—C16	1.380 (9)	C27—C28	1.399 (9)
C12—C13	1.404 (11)	C28—C29	1.379 (10)
C13—C14	1.376 (11)	C29—C30	1.382 (11)
C14—C15	1.366 (11)	C30—C31	1.388 (11)
C15—C16	1.395 (10)	C31—C32	1.390 (11)
C4—S1—C1	89.9 (3)	C17—S4—C20	90.3 (3)
C7—S2—C6	93.4 (3)	C23—S5—C22	93.3 (3)
O2—S3—O3	120.1 (4)	O6—S6—O5	119.8 (3)
O2—S3—N4	104.6 (3)	O6—S6—N8	105.9 (3)
O3—S3—N4	109.7 (3)	O5—S6—N8	108.7 (3)
O2—S3—C11	107.8 (4)	O6—S6—C27	108.0 (3)
O3—S3—C11	106.5 (3)	O5—S6—C27	106.6 (3)
N4—S3—C11	107.6 (3)	N8—S6—C27	107.3 (3)
C5—N1—N2	120.9 (5)	C21—N5—N6	119.5 (5)
C7—N2—N1	119.1 (5)	C23—N6—N5	120.3 (5)
C8—N3—C7	127.4 (5)	C24—N7—C23	124.1 (5)
C9—N4—S3	127.7 (4)	C25—N8—S6	122.0 (4)
C2—C1—Cl1	127.4 (6)	C18—C17—Cl2	127.5 (6)
C2—C1—S1	113.7 (6)	C18—C17—S4	113.3 (6)
Cl1—C1—S1	118.9 (4)	Cl2—C17—S4	119.2 (4)
C1—C2—C3	111.5 (6)	C17—C18—C19	111.9 (6)
C4—C3—C2	112.9 (6)	C20—C19—C18	113.7 (7)
C3—C4—C5	126.7 (6)	C19—C20—C21	128.3 (7)
C3—C4—S1	112.1 (5)	C19—C20—S4	110.8 (6)
C5—C4—S1	121.2 (5)	C21—C20—S4	120.8 (5)
N1—C5—C4	119.1 (6)	N5—C21—C20	118.5 (6)
N1—C5—C6	121.5 (6)	N5—C21—C22	121.6 (6)
C4—C5—C6	119.3 (6)	C20—C21—C22	119.9 (6)
C5—C6—S2	108.7 (5)	C21—C22—S5	107.9 (5)
N2—C7—N3	116.8 (5)	N6—C23—N7	117.8 (5)
N2—C7—S2	125.8 (5)	N6—C23—S5	124.3 (5)
N3—C7—S2	117.4 (5)	N7—C23—S5	117.8 (5)
O1—C8—N3	121.9 (6)	O4—C24—N7	124.3 (7)
O1—C8—C9	122.9 (6)	O4—C24—C25	118.3 (6)
N3—C8—C9	115.1 (5)	N7—C24—C25	117.3 (6)
N4—C9—C8	111.8 (6)	N8—C25—C26	109.4 (5)
N4—C9—C10	114.8 (6)	N8—C25—C24	114.0 (6)
C8—C9—C10	110.2 (5)	C26—C25—C24	110.8 (6)
C12—C11—C16	122.9 (8)	C32—C27—C28	120.7 (7)
C12—C11—S3	118.0 (6)	C32—C27—S6	119.7 (6)
C16—C11—S3	119.1 (6)	C28—C27—S6	119.6 (6)
C11—C12—C13	117.8 (8)	C29—C28—C27	119.2 (8)
C14—C13—C12	120.5 (8)	C28—C29—C30	120.5 (8)
C15—C14—C13	120.0 (7)	C29—C30—C31	120.1 (8)
C14—C15—C16	121.3 (7)	C30—C31—C32	120.1 (8)
C11—C16—C15	117.5 (8)	C27—C32—C31	119.3 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3N···N6	0.88	2.09	2.956 (7)	168
N4—H4N···S4	0.88	2.77	3.456 (5)	136
N4—H4N···N5	0.88	2.08	2.842 (7)	145
N7—H7N···N2	0.88	2.11	2.983 (7)	172
N8—H8N···N1	0.88	2.04	2.882 (7)	160