Tuning solubility and stability of hydrochloro­thiazide co-crystals

Hydrochlorothiazide (HCT), C₇H₈ClN₃O₄S₂, is a diuretic BCS (Biopharmaceutics Classification System) class IV drug which has primary and secondary sulfonamide groups. To modify the aqueous solubility of the drug, co-crystals with biologically safe co-formers were screened. Multi-component molecular crystals of HCT were prepared with nicotinic acid, nicotin­amide, succinamide, p-aminobenzoic acid, resorcinol and pyrogallol using liquid-assisted grinding. The co-crystals were characterized by FT-IR spectroscopy, powder X-ray diffraction (PXRD) and differential scanning calorimetry. Single crystal structures were obtained for four of them. The N—H...O sulfonamide catemer synthons found in the stable polymorph of pure HCT are replaced in the co-crystals by drug-co-former heterosynthons. Isostructural co-crystals with nicotinic acid and nicotinamide are devoid of the common sulfonamide dimer/catemer synthons. Solubility and stability experiments were carried out for the co-crystals in water (neutral pH) under ambient conditions. Among the six binary systems, the co-crystal with p-aminobenzoic acid showed a sixfold increase in solubility compared with pure HCT, and stability up to 24 h in an aqueous medium. The co-crystals with nicotinamide, resorcinol and pyrogallol showed only a 1.5–2-fold increase in solubility and transformed to HCT within 1 h of the dissolution experiment. An inverse correlation is observed between the melting points of the co-crystals and their solubilities.

Computing details

For all compounds, data collection: CrystalClear (Rigaku, 2009); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: PLATON (Spek, 2009).

Figures

(HCT-NIC)

Crystal data

C7H8ClN3O4S2·C6H5NO2	Dx = 1.780 Mg m^−3
Mr = 420.84	Melting point: 530.8 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 5097 reflections
a = 7.368 (2) Å	θ = 2.5–27.5°
b = 13.121 (4) Å	µ = 0.55 mm^−1
c = 16.247 (4) Å	T = 150 K
V = 1570.6 (8) Å^3	Needle, colourless
Z = 4	0.28 × 0.12 × 0.08 mm
F(000) = 864

Data collection

Rigaku XtaLAB mini diffractometer	3584 independent reflections
Radiation source: fine-focus sealed tube	3504 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.107
ω–scans	θmax = 27.4°, θmin = 2.0°
Absorption correction: multi-scan SADABS (Sheldrick, 2008)	h = −9→9
Tmin = 0.828, Tmax = 1.000	k = −17→16
16679 measured reflections	l = −21→20

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)] = 0.037	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.107	w = 1/[σ^2(Fo^2) + (0.0449P)^2 + 0.7156P] where P = (Fo^2 + 2Fc^2)/3
S = 1.14	(Δ/σ)max < 0.001
3584 reflections	Δρmax = 0.33 e Å^−3
251 parameters	Δρmin = −0.43 e Å^−3
3 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.09 (7)

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
H3A	0.203 (3)	0.658 (3)	−0.023 (2)	0.040 (12)*
H1N	0.329 (7)	0.595 (4)	0.425 (3)	0.046 (12)*
H3B	0.073 (7)	0.7381 (18)	0.005 (3)	0.061 (14)*
S1	−0.00567 (8)	0.59206 (5)	0.05115 (4)	0.01570 (15)
S2	−0.18549 (9)	0.63204 (5)	0.37635 (4)	0.01574 (15)
Cl1	0.42298 (9)	0.58834 (6)	0.10972 (4)	0.02076 (16)
O5	0.4549 (3)	0.63577 (17)	0.92104 (12)	0.0230 (4)
C1	−0.0681 (4)	0.61725 (19)	0.21611 (16)	0.0139 (5)
H1	−0.1898	0.6220	0.2013	0.017*
N2	−0.0841 (3)	0.58250 (19)	0.45670 (14)	0.0183 (5)
O6	0.2934 (3)	0.65087 (18)	0.80396 (13)	0.0250 (5)
C6	−0.0188 (3)	0.62164 (19)	0.29986 (15)	0.0137 (5)
O4	−0.3381 (3)	0.56864 (17)	0.35580 (12)	0.0219 (4)
O2	0.0538 (3)	0.49270 (16)	0.02454 (12)	0.0220 (4)
C3	0.2470 (3)	0.5976 (2)	0.18030 (16)	0.0159 (5)
C4	0.2958 (4)	0.5996 (2)	0.26229 (16)	0.0176 (5)
H4	0.4174	0.5927	0.2766	0.021*
O1	−0.1966 (3)	0.61489 (17)	0.04967 (12)	0.0218 (4)
C9	0.6136 (4)	0.6436 (2)	0.79338 (17)	0.0162 (5)
C2	0.0631 (4)	0.60598 (19)	0.15537 (15)	0.0145 (5)
O3	−0.2178 (3)	0.73792 (16)	0.39429 (13)	0.0248 (5)
C8	0.4377 (4)	0.6436 (2)	0.84389 (17)	0.0179 (5)
N4	0.9350 (3)	0.65074 (18)	0.78890 (17)	0.0221 (5)
H4N	1.0372	0.6560	0.8141	0.027*
N1	0.2196 (3)	0.6147 (2)	0.40469 (14)	0.0195 (5)
C7	0.0925 (4)	0.6307 (2)	0.47148 (16)	0.0202 (5)
H7A	0.0749	0.7033	0.4792	0.024*
H7B	0.1440	0.6034	0.5218	0.024*
C12	0.9343 (4)	0.6430 (2)	0.7059 (2)	0.0255 (6)
H12	1.0434	0.6433	0.6772	0.031*
C5	0.1651 (4)	0.61200 (19)	0.32456 (16)	0.0154 (5)
N3	0.0937 (4)	0.6747 (2)	−0.00578 (15)	0.0207 (5)
C11	0.7729 (4)	0.6348 (2)	0.66377 (18)	0.0246 (6)
H11	0.7723	0.6283	0.6068	0.029*
C10	0.6103 (4)	0.6365 (2)	0.70768 (17)	0.0214 (6)
H10	0.5000	0.6328	0.6799	0.026*
C13	0.7806 (4)	0.6504 (2)	0.83334 (18)	0.0198 (6)
H13	0.7854	0.6547	0.8904	0.024*
H2N	−0.084 (5)	0.5167 (14)	0.454 (2)	0.029 (9)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0141 (3)	0.0218 (3)	0.0111 (3)	0.0002 (3)	0.0004 (2)	−0.0013 (2)
S2	0.0156 (3)	0.0192 (3)	0.0124 (3)	0.0022 (3)	0.0009 (2)	−0.0003 (2)
Cl1	0.0155 (3)	0.0297 (3)	0.0171 (3)	0.0021 (3)	0.0039 (2)	0.0008 (3)
O5	0.0235 (10)	0.0293 (10)	0.0162 (9)	−0.0008 (9)	0.0031 (8)	0.0011 (8)
C1	0.0121 (11)	0.0154 (11)	0.0141 (11)	0.0000 (9)	−0.0016 (10)	0.0012 (9)
N2	0.0202 (11)	0.0208 (11)	0.0137 (10)	−0.0008 (10)	−0.0017 (9)	0.0018 (9)
O6	0.0139 (9)	0.0377 (12)	0.0235 (10)	−0.0010 (9)	0.0000 (8)	0.0024 (9)
C6	0.0135 (11)	0.0145 (11)	0.0129 (11)	−0.0004 (9)	0.0004 (9)	0.0005 (9)
O4	0.0154 (9)	0.0324 (12)	0.0180 (9)	−0.0030 (9)	−0.0004 (7)	0.0022 (8)
O2	0.0233 (10)	0.0239 (10)	0.0188 (9)	0.0035 (9)	0.0008 (8)	−0.0063 (8)
C3	0.0146 (12)	0.0173 (12)	0.0158 (12)	−0.0002 (10)	0.0022 (9)	−0.0005 (10)
C4	0.0130 (11)	0.0215 (13)	0.0183 (12)	0.0000 (11)	−0.0016 (10)	−0.0001 (10)
O1	0.0135 (9)	0.0360 (12)	0.0159 (9)	−0.0002 (8)	−0.0007 (8)	0.0000 (8)
C9	0.0138 (11)	0.0150 (12)	0.0198 (12)	0.0015 (10)	0.0011 (10)	0.0009 (10)
C2	0.0142 (11)	0.0167 (13)	0.0127 (11)	0.0014 (10)	0.0009 (9)	−0.0004 (9)
O3	0.0319 (12)	0.0201 (10)	0.0223 (10)	0.0090 (9)	0.0059 (9)	−0.0015 (8)
C8	0.0165 (12)	0.0153 (12)	0.0218 (13)	−0.0024 (10)	0.0013 (10)	0.0020 (10)
N4	0.0167 (11)	0.0193 (12)	0.0304 (13)	0.0006 (9)	0.0007 (10)	0.0012 (10)
N1	0.0171 (11)	0.0277 (13)	0.0137 (10)	−0.0003 (10)	−0.0028 (9)	−0.0003 (9)
C7	0.0212 (13)	0.0257 (13)	0.0138 (11)	−0.0019 (12)	−0.0028 (11)	−0.0032 (11)
C12	0.0213 (13)	0.0256 (14)	0.0297 (15)	0.0021 (12)	0.0070 (12)	−0.0001 (12)
C5	0.0157 (12)	0.0159 (13)	0.0146 (12)	−0.0002 (9)	−0.0028 (10)	0.0012 (9)
N3	0.0190 (12)	0.0258 (12)	0.0173 (11)	0.0027 (10)	0.0031 (10)	0.0030 (10)
C11	0.0302 (15)	0.0243 (14)	0.0192 (13)	0.0023 (13)	0.0080 (12)	−0.0007 (12)
C10	0.0229 (14)	0.0205 (13)	0.0207 (13)	0.0006 (12)	−0.0010 (12)	−0.0006 (11)
C13	0.0174 (12)	0.0182 (13)	0.0239 (13)	−0.0018 (11)	0.0006 (11)	0.0004 (10)

Geometric parameters (Å, º)

S1—O1	1.439 (2)	C4—H4	0.9300
S1—O2	1.442 (2)	C9—C13	1.394 (4)
S1—N3	1.602 (3)	C9—C10	1.396 (4)
S1—C2	1.777 (3)	C9—C8	1.534 (4)
S2—O4	1.438 (2)	N4—C13	1.348 (4)
S2—O3	1.439 (2)	N4—C12	1.352 (4)
S2—N2	1.638 (2)	N4—H4N	0.8600
S2—C6	1.753 (3)	N1—C5	1.363 (3)
Cl1—C3	1.735 (3)	N1—C7	1.449 (4)
O5—C8	1.264 (3)	N1—H1N	0.91 (5)
C1—C2	1.389 (4)	C7—H7A	0.9700
C1—C6	1.410 (3)	C7—H7B	0.9700
C1—H1	0.9300	C12—C11	1.377 (5)
N2—C7	1.467 (4)	C12—H12	0.9300
N2—H2N	0.864 (19)	N3—H3A	0.882 (19)
O6—C8	1.249 (4)	N3—H3B	0.865 (19)
C6—C5	1.419 (4)	C11—C10	1.395 (4)
C3—C4	1.380 (4)	C11—H11	0.9300
C3—C2	1.418 (4)	C10—H10	0.9300
C4—C5	1.406 (4)	C13—H13	0.9300
O1—S1—O2	118.73 (13)	O6—C8—O5	127.4 (3)
O1—S1—N3	107.24 (14)	O6—C8—C9	116.2 (2)
O2—S1—N3	107.44 (13)	O5—C8—C9	116.5 (2)
O1—S1—C2	105.88 (12)	C13—N4—C12	122.0 (3)
O2—S1—C2	106.97 (12)	C13—N4—H4N	119.0
N3—S1—C2	110.49 (13)	C12—N4—H4N	119.0
O4—S2—O3	118.42 (14)	C5—N1—C7	121.9 (2)
O4—S2—N2	108.18 (13)	C5—N1—H1N	127 (3)
O3—S2—N2	107.28 (13)	C7—N1—H1N	110 (3)
O4—S2—C6	109.78 (12)	N1—C7—N2	112.9 (2)
O3—S2—C6	109.56 (13)	N1—C7—H7A	109.0
N2—S2—C6	102.39 (12)	N2—C7—H7A	109.0
C2—C1—C6	120.7 (2)	N1—C7—H7B	109.0
C2—C1—H1	119.7	N2—C7—H7B	109.0
C6—C1—H1	119.7	H7A—C7—H7B	107.8
C7—N2—S2	111.35 (19)	N4—C12—C11	120.4 (3)
C7—N2—H2N	116 (2)	N4—C12—H12	119.8
S2—N2—H2N	111 (2)	C11—C12—H12	119.8
C1—C6—C5	121.0 (2)	N1—C5—C4	119.3 (2)
C1—C6—S2	120.5 (2)	N1—C5—C6	123.3 (2)
C5—C6—S2	118.41 (19)	C4—C5—C6	117.4 (2)
C4—C3—C2	121.5 (2)	S1—N3—H3A	116 (3)
C4—C3—Cl1	116.4 (2)	S1—N3—H3B	117 (4)
C2—C3—Cl1	122.0 (2)	H3A—N3—H3B	118 (4)
C3—C4—C5	121.2 (3)	C12—C11—C10	119.1 (3)
C3—C4—H4	119.4	C12—C11—H11	120.4
C5—C4—H4	119.4	C10—C11—H11	120.4
C13—C9—C10	119.0 (3)	C11—C10—C9	119.8 (3)
C13—C9—C8	119.8 (2)	C11—C10—H10	120.1
C10—C9—C8	121.3 (2)	C9—C10—H10	120.1
C1—C2—C3	118.1 (2)	N4—C13—C9	119.7 (3)
C1—C2—S1	119.3 (2)	N4—C13—H13	120.1
C3—C2—S1	122.5 (2)	C9—C13—H13	120.1

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O2^i	0.91 (5)	2.17 (5)	2.927 (3)	141 (4)
N2—H2N···O5^ii	0.87 (2)	2.28 (2)	3.073 (3)	153 (3)
N3—H3A···O5^iii	0.88 (2)	2.09 (3)	2.959 (4)	171 (3)
N3—H3B···O5^iv	0.86 (3)	2.22 (4)	3.021 (4)	154 (4)
N4—H4N···O6^v	0.86	1.90	2.652 (3)	146

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

(HCT-NCT)

Crystal data

C7H8ClN3O4S2·C6H6N2O	Dx = 1.707 Mg m^−3
Mr = 419.86	Melting point: 446.6 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 5118 reflections
a = 7.6531 (10) Å	θ = 2.5–27.5°
b = 13.2192 (16) Å	µ = 0.53 mm^−1
c = 16.148 (2) Å	T = 150 K
V = 1633.6 (4) Å^3	Plate, colourless
Z = 4	0.30 × 0.20 × 0.20 mm
F(000) = 864

Data collection

Rigaku XtaLAB mini diffractometer	3729 independent reflections
Radiation source: fine-focus sealed tube	3642 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.102
ω–scans	θmax = 27.5°, θmin = 2.0°
Absorption correction: multi-scan SADABS (Sheldrick, 2008)	h = −9→9
Tmin = 0.773, Tmax = 1.000	k = −17→17
16245 measured reflections	l = −20→20

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)] = 0.034	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.100	w = 1/[σ^2(Fo^2) + (0.0549P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max < 0.001
3729 reflections	Δρmax = 0.39 e Å^−3
259 parameters	Δρmin = −0.35 e Å^−3
3 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.07 (6)

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
H4A	−0.189 (5)	0.678 (3)	0.2591 (13)	0.047 (10)*
H4B	−0.299 (5)	0.659 (3)	0.185 (2)	0.036 (9)*
H3B	0.090 (5)	0.767 (3)	0.011 (2)	0.038 (9)*
H3A	0.222 (6)	0.838 (3)	−0.024 (2)	0.050 (11)*
H2	−0.080 (4)	0.9753 (14)	0.4472 (17)	0.028 (8)*
H1N	0.315 (3)	0.897 (3)	0.422 (2)	0.043 (10)*
S1	0.01096 (7)	0.90436 (5)	0.04541 (3)	0.01671 (14)
S2	−0.17478 (8)	0.86518 (4)	0.36854 (3)	0.01623 (14)
Cl1	0.42358 (8)	0.91277 (5)	0.10733 (3)	0.02230 (14)
O4	−0.2001 (3)	0.75883 (13)	0.38361 (10)	0.0238 (4)
O1	0.0668 (2)	1.00198 (14)	0.01633 (10)	0.0248 (4)
C6	−0.0092 (3)	0.87943 (16)	0.29444 (13)	0.0146 (4)
C3	0.2520 (3)	0.90350 (17)	0.17734 (13)	0.0158 (4)
O3	−0.3234 (2)	0.92516 (14)	0.34658 (10)	0.0236 (4)
C4	0.2965 (3)	0.90243 (18)	0.25956 (14)	0.0174 (4)
H4	0.4126	0.9107	0.2750	0.021*
N2	−0.0834 (3)	0.91306 (16)	0.45132 (12)	0.0191 (4)
O2	−0.1720 (2)	0.88010 (15)	0.04411 (10)	0.0232 (4)
C1	−0.0529 (3)	0.88397 (16)	0.21010 (13)	0.0142 (4)
H1	−0.1693	0.8797	0.1940	0.017*
C5	0.1668 (3)	0.88884 (16)	0.32104 (13)	0.0162 (4)
C2	0.0766 (3)	0.89481 (17)	0.15076 (13)	0.0148 (4)
N1	0.2131 (3)	0.88665 (17)	0.40275 (12)	0.0207 (4)
C7	0.0882 (3)	0.8679 (2)	0.46811 (13)	0.0222 (5)
H7A	0.1334	0.8952	0.5196	0.027*
H7B	0.0744	0.7955	0.4751	0.027*
N3	0.1115 (3)	0.82098 (19)	−0.00884 (13)	0.0232 (4)
O5	−0.0379 (2)	0.62984 (15)	0.08724 (10)	0.0244 (4)
C9	0.1170 (3)	0.64114 (17)	0.21545 (14)	0.0162 (4)
N5	0.4304 (3)	0.65609 (17)	0.21639 (13)	0.0247 (5)
C8	−0.0450 (3)	0.64231 (17)	0.16412 (14)	0.0171 (4)
N4	−0.1956 (3)	0.65702 (17)	0.20406 (14)	0.0220 (4)
C10	0.1167 (3)	0.62836 (19)	0.30164 (14)	0.0197 (5)
H10	0.0120	0.6194	0.3300	0.024*
C12	0.4248 (4)	0.6434 (2)	0.29903 (16)	0.0259 (5)
H12	0.5299	0.6442	0.3279	0.031*
C11	0.2731 (3)	0.6292 (2)	0.34380 (15)	0.0248 (5)
H11	0.2764	0.6204	0.4009	0.030*
C13	0.2789 (3)	0.65377 (18)	0.17601 (14)	0.0195 (5)
H13	0.2804	0.6609	0.1187	0.023*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0132 (3)	0.0239 (3)	0.0130 (2)	−0.0016 (2)	0.0000 (2)	0.00132 (19)
S2	0.0140 (3)	0.0212 (3)	0.0134 (2)	−0.0023 (2)	0.00138 (19)	−0.0005 (2)
Cl1	0.0130 (3)	0.0317 (3)	0.0222 (3)	−0.0033 (2)	0.0050 (2)	−0.0014 (2)
O4	0.0255 (10)	0.0241 (9)	0.0218 (8)	−0.0071 (7)	0.0037 (7)	0.0007 (7)
O1	0.0220 (9)	0.0282 (9)	0.0244 (8)	−0.0033 (8)	0.0015 (7)	0.0067 (7)
C6	0.0126 (10)	0.0159 (10)	0.0155 (10)	−0.0017 (8)	−0.0002 (8)	−0.0006 (8)
C3	0.0102 (10)	0.0167 (10)	0.0206 (10)	−0.0021 (9)	0.0017 (8)	−0.0013 (8)
O3	0.0136 (8)	0.0356 (10)	0.0217 (8)	0.0044 (8)	0.0009 (7)	−0.0008 (7)
C4	0.0094 (10)	0.0212 (11)	0.0217 (10)	−0.0017 (9)	−0.0039 (8)	−0.0030 (9)
N2	0.0190 (11)	0.0218 (10)	0.0165 (9)	−0.0014 (9)	−0.0003 (8)	−0.0017 (8)
O2	0.0135 (8)	0.0379 (10)	0.0184 (8)	−0.0024 (8)	−0.0009 (6)	0.0000 (7)
C1	0.0109 (10)	0.0150 (10)	0.0168 (10)	−0.0005 (8)	−0.0009 (8)	−0.0005 (7)
C5	0.0140 (11)	0.0180 (11)	0.0165 (10)	−0.0006 (9)	−0.0024 (8)	−0.0018 (8)
C2	0.0123 (11)	0.0188 (10)	0.0132 (10)	−0.0012 (9)	−0.0009 (8)	0.0003 (7)
N1	0.0137 (10)	0.0328 (12)	0.0155 (9)	−0.0010 (9)	−0.0045 (7)	−0.0023 (8)
C7	0.0212 (13)	0.0312 (12)	0.0143 (10)	−0.0002 (11)	−0.0042 (9)	0.0017 (9)
N3	0.0207 (12)	0.0305 (12)	0.0183 (10)	−0.0012 (10)	0.0035 (8)	−0.0029 (9)
O5	0.0216 (10)	0.0320 (9)	0.0196 (8)	0.0011 (8)	−0.0047 (6)	−0.0049 (7)
C9	0.0124 (11)	0.0159 (10)	0.0203 (11)	0.0002 (9)	−0.0030 (8)	−0.0022 (8)
N5	0.0146 (10)	0.0312 (12)	0.0282 (11)	−0.0014 (9)	−0.0025 (9)	0.0041 (8)
C8	0.0126 (11)	0.0155 (10)	0.0233 (11)	0.0001 (9)	0.0002 (8)	−0.0014 (8)
N4	0.0088 (10)	0.0309 (11)	0.0264 (10)	−0.0015 (9)	0.0001 (8)	−0.0030 (9)
C10	0.0159 (12)	0.0218 (11)	0.0215 (11)	0.0015 (10)	0.0019 (9)	0.0007 (9)
C12	0.0170 (12)	0.0328 (14)	0.0280 (13)	0.0001 (11)	−0.0066 (10)	0.0024 (10)
C11	0.0234 (14)	0.0319 (12)	0.0190 (10)	0.0019 (12)	−0.0060 (9)	0.0032 (9)
C13	0.0134 (12)	0.0260 (12)	0.0191 (10)	−0.0007 (10)	−0.0003 (8)	0.0015 (9)

Geometric parameters (Å, º)

S1—O2	1.4365 (19)	N1—H1N	0.851 (19)
S1—O1	1.4383 (18)	C7—H7A	0.9700
S1—N3	1.604 (2)	C7—H7B	0.9700
S1—C2	1.778 (2)	N3—H3B	0.80 (4)
S2—O3	1.4311 (19)	N3—H3A	0.91 (4)
S2—O4	1.4398 (18)	O5—C8	1.254 (3)
S2—N2	1.636 (2)	C9—C10	1.402 (3)
S2—C6	1.753 (2)	C9—C13	1.403 (3)
Cl1—C3	1.737 (2)	C9—C8	1.492 (3)
C6—C1	1.404 (3)	N5—C13	1.331 (3)
C6—C5	1.420 (3)	N5—C12	1.346 (3)
C3—C4	1.371 (3)	C8—N4	1.335 (3)
C3—C2	1.414 (3)	N4—H4A	0.932 (18)
C4—C5	1.415 (3)	N4—H4B	0.85 (4)
C4—H4	0.9300	C10—C11	1.377 (3)
N2—C7	1.467 (3)	C10—H10	0.9300
N2—H2	0.826 (18)	C12—C11	1.381 (4)
C1—C2	1.386 (3)	C12—H12	0.9300
C1—H1	0.9300	C11—H11	0.9300
C5—N1	1.366 (3)	C13—H13	0.9300
N1—C7	1.446 (3)
O2—S1—O1	119.03 (11)	C5—N1—H1N	126 (2)
O2—S1—N3	107.82 (12)	C7—N1—H1N	111 (2)
O1—S1—N3	107.19 (12)	N1—C7—N2	112.79 (19)
O2—S1—C2	105.86 (11)	N1—C7—H7A	109.0
O1—S1—C2	106.98 (11)	N2—C7—H7A	109.0
N3—S1—C2	109.77 (11)	N1—C7—H7B	109.0
O3—S2—O4	118.41 (12)	N2—C7—H7B	109.0
O3—S2—N2	109.14 (11)	H7A—C7—H7B	107.8
O4—S2—N2	107.29 (11)	S1—N3—H3B	108 (3)
O3—S2—C6	110.23 (11)	S1—N3—H3A	115 (2)
O4—S2—C6	108.52 (11)	H3B—N3—H3A	121 (4)
N2—S2—C6	101.96 (11)	C10—C9—C13	117.8 (2)
C1—C6—C5	121.1 (2)	C10—C9—C8	123.5 (2)
C1—C6—S2	119.65 (18)	C13—C9—C8	118.7 (2)
C5—C6—S2	119.26 (16)	C13—N5—C12	117.1 (2)
C4—C3—C2	121.9 (2)	O5—C8—N4	122.4 (2)
C4—C3—Cl1	116.33 (18)	O5—C8—C9	120.8 (2)
C2—C3—Cl1	121.73 (16)	N4—C8—C9	116.8 (2)
C3—C4—C5	120.5 (2)	C8—N4—H4A	117 (2)
C3—C4—H4	119.8	C8—N4—H4B	130 (2)
C5—C4—H4	119.8	H4A—N4—H4B	112 (3)
C7—N2—S2	112.09 (16)	C11—C10—C9	119.2 (2)
C7—N2—H2	113 (2)	C11—C10—H10	120.4
S2—N2—H2	109 (2)	C9—C10—H10	120.4
C2—C1—C6	120.3 (2)	N5—C12—C11	124.3 (2)
C2—C1—H1	119.8	N5—C12—H12	117.9
C6—C1—H1	119.8	C11—C12—H12	117.9
N1—C5—C4	119.9 (2)	C10—C11—C12	118.2 (2)
N1—C5—C6	122.4 (2)	C10—C11—H11	120.9
C4—C5—C6	117.7 (2)	C12—C11—H11	120.9
C1—C2—C3	118.52 (19)	N5—C13—C9	123.4 (2)
C1—C2—S1	117.83 (17)	N5—C13—H13	118.3
C3—C2—S1	123.55 (17)	C9—C13—H13	118.3
C5—N1—C7	122.5 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1^i	0.85 (3)	2.22 (3)	2.893 (3)	136 (3)
N2—H2···O5^ii	0.83 (2)	2.30 (2)	3.076 (3)	156 (3)
N3—H3A···O5^iii	0.91 (4)	2.15 (4)	3.037 (3)	167 (3)
N3—H3B···O5	0.80 (4)	2.40 (4)	3.178 (3)	165 (4)
N4—H4A···O4	0.93 (2)	2.28 (3)	3.197 (3)	168 (3)
N4—H4B···N5^iv	0.85 (4)	2.13 (4)	2.869 (3)	145 (3)

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

(HCT-SAM)

Crystal data

2(C7H8ClN3O4S2)·C4H8N2O2	F(000) = 1464
Mr = 711.60	Dx = 1.767 Mg m^−3
Monoclinic, C2/c	Melting point: 508.1 K
Hall symbol: -C 2yc	Mo Kα radiation, λ = 0.71073 Å
a = 17.857 (7) Å	Cell parameters from 3807 reflections
b = 10.363 (4) Å	θ = 2.3–27.5°
c = 14.548 (5) Å	µ = 0.63 mm^−1
β = 96.459 (4)°	T = 150 K
V = 2675.0 (17) Å^3	Block, colourless
Z = 4	0.20 × 0.20 × 0.20 mm

Data collection

Rigaku XtaLAB mini diffractometer	3066 independent reflections
Radiation source: fine-focus sealed tube	2952 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.056
ω–scans	θmax = 27.5°, θmin = 2.3°
Absorption correction: multi-scan SADABS (Sheldrick, 2008)	h = −23→23
Tmin = 0.915, Tmax = 1.000	k = −13→13
13760 measured reflections	l = −18→18

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.028	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.075	H atoms treated by a mixture of independent and constrained refinement
S = 1.09	w = 1/[σ^2(Fo^2) + (0.0301P)^2 + 3.6288P] where P = (Fo^2 + 2Fc^2)/3
3066 reflections	(Δ/σ)max = 0.001
214 parameters	Δρmax = 0.38 e Å^−3
0 restraints	Δρmin = −0.50 e Å^−3

Special details

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

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

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

	x	y	z	Uiso*/Ueq
O5	0.58958 (6)	0.73979 (11)	0.23837 (7)	0.0188 (2)
N4	0.62805 (8)	0.81035 (14)	0.38288 (9)	0.0205 (3)
C8	0.58360 (8)	0.81627 (14)	0.30324 (10)	0.0137 (3)
C9	0.52549 (8)	0.92315 (14)	0.29545 (9)	0.0143 (3)
H9A	0.5513	1.0055	0.3024	0.017*
H9B	0.4946	0.9149	0.3459	0.017*
H4A	0.6641 (12)	0.757 (2)	0.3882 (15)	0.027 (5)*
H4B	0.6253 (12)	0.869 (2)	0.4228 (15)	0.028 (5)*
H3A	0.2981 (12)	0.270 (2)	−0.0766 (14)	0.024 (5)*
H1N	0.6185 (12)	0.559 (2)	0.2115 (15)	0.030 (5)*
H3B	0.3582 (13)	0.219 (2)	−0.1256 (17)	0.035 (6)*
H2	0.6921 (12)	0.281 (2)	0.2910 (16)	0.032 (6)*
S1	0.371906 (17)	0.16424 (3)	0.01623 (2)	0.01135 (10)
S2	0.663071 (18)	0.20174 (3)	0.15605 (2)	0.01254 (10)
Cl1	0.350346 (19)	0.47281 (4)	0.06027 (3)	0.01974 (10)
O2	0.31583 (5)	0.16662 (11)	0.08070 (7)	0.0160 (2)
O3	0.70777 (6)	0.20209 (12)	0.07987 (7)	0.0198 (2)
O1	0.40726 (5)	0.04300 (10)	−0.00025 (7)	0.0157 (2)
C4	0.49658 (8)	0.46935 (14)	0.12677 (10)	0.0159 (3)
H4	0.4890	0.5554	0.1412	0.019*
N2	0.70431 (7)	0.29655 (13)	0.23594 (9)	0.0168 (3)
C1	0.51720 (7)	0.21110 (14)	0.08139 (9)	0.0124 (3)
H1	0.5244	0.1251	0.0663	0.015*
O4	0.64833 (6)	0.08112 (11)	0.19855 (8)	0.0191 (2)
N3	0.33254 (7)	0.21774 (14)	−0.07964 (9)	0.0170 (3)
C3	0.43754 (8)	0.39759 (14)	0.08455 (10)	0.0143 (3)
C2	0.44638 (7)	0.26692 (13)	0.06101 (9)	0.0125 (3)
N1	0.62632 (7)	0.48267 (13)	0.19294 (10)	0.0192 (3)
C5	0.56895 (8)	0.41299 (14)	0.14843 (10)	0.0141 (3)
C6	0.57733 (7)	0.28248 (14)	0.12399 (9)	0.0121 (3)
C7	0.70280 (8)	0.43225 (16)	0.20784 (11)	0.0204 (3)
H7A	0.7318	0.4829	0.2553	0.024*
H7B	0.7263	0.4408	0.1512	0.024*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O5	0.0214 (5)	0.0175 (5)	0.0178 (5)	0.0029 (4)	0.0042 (4)	−0.0039 (4)
N4	0.0205 (6)	0.0220 (7)	0.0179 (6)	0.0063 (5)	−0.0015 (5)	−0.0024 (5)
C8	0.0134 (6)	0.0136 (7)	0.0146 (6)	−0.0020 (5)	0.0042 (5)	0.0012 (5)
C9	0.0150 (6)	0.0119 (7)	0.0160 (7)	0.0002 (5)	0.0022 (5)	−0.0022 (5)
S1	0.00894 (15)	0.01345 (18)	0.01141 (17)	0.00104 (11)	0.00015 (12)	−0.00080 (11)
S2	0.00868 (16)	0.01553 (18)	0.01312 (17)	0.00032 (11)	−0.00003 (12)	−0.00045 (12)
Cl1	0.01550 (17)	0.01712 (19)	0.0258 (2)	0.00725 (12)	−0.00091 (13)	−0.00194 (13)
O2	0.0121 (5)	0.0218 (6)	0.0148 (5)	0.0003 (4)	0.0040 (4)	0.0004 (4)
O3	0.0131 (5)	0.0300 (6)	0.0166 (5)	0.0000 (4)	0.0034 (4)	−0.0031 (4)
O1	0.0132 (5)	0.0138 (5)	0.0197 (5)	0.0009 (4)	0.0000 (4)	−0.0035 (4)
C4	0.0182 (7)	0.0109 (7)	0.0189 (7)	0.0016 (5)	0.0026 (5)	−0.0019 (5)
N2	0.0142 (6)	0.0217 (7)	0.0137 (6)	−0.0020 (5)	−0.0022 (5)	−0.0022 (5)
C1	0.0122 (6)	0.0122 (6)	0.0128 (6)	0.0009 (5)	0.0014 (5)	−0.0004 (5)
O4	0.0160 (5)	0.0172 (5)	0.0234 (5)	0.0007 (4)	−0.0014 (4)	0.0045 (4)
N3	0.0133 (6)	0.0254 (7)	0.0121 (6)	0.0066 (5)	0.0008 (5)	0.0009 (5)
C3	0.0130 (6)	0.0147 (7)	0.0150 (6)	0.0047 (5)	0.0013 (5)	0.0008 (5)
C2	0.0111 (6)	0.0131 (7)	0.0128 (6)	0.0000 (5)	0.0001 (5)	−0.0009 (5)
N1	0.0166 (6)	0.0144 (7)	0.0260 (7)	−0.0024 (5)	0.0002 (5)	−0.0064 (5)
C5	0.0146 (6)	0.0139 (7)	0.0138 (6)	−0.0022 (5)	0.0020 (5)	−0.0009 (5)
C6	0.0100 (6)	0.0138 (7)	0.0126 (6)	0.0008 (5)	0.0012 (5)	0.0005 (5)
C7	0.0146 (7)	0.0201 (8)	0.0260 (8)	−0.0055 (6)	0.0003 (6)	−0.0041 (6)

Geometric parameters (Å, º)

O5—C8	1.2461 (18)	C4—C3	1.377 (2)
N4—C8	1.3301 (19)	C4—C5	1.421 (2)
N4—H4A	0.85 (2)	C4—H4	0.9300
N4—H4B	0.85 (2)	N2—C7	1.464 (2)
C8—C9	1.5132 (19)	N2—H2	0.87 (2)
C9—C9^i	1.519 (3)	C1—C6	1.3909 (19)
C9—H9A	0.9700	C1—C2	1.3920 (19)
C9—H9B	0.9700	C1—H1	0.9300
S1—O1	1.4384 (11)	N3—H3A	0.83 (2)
S1—O2	1.4472 (11)	N3—H3B	0.85 (2)
S1—N3	1.5894 (13)	C3—C2	1.410 (2)
S1—C2	1.7692 (14)	N1—C5	1.3569 (19)
S2—O4	1.4320 (12)	N1—C7	1.455 (2)
S2—O3	1.4368 (12)	N1—H1N	0.85 (2)
S2—N2	1.6328 (13)	C5—C6	1.411 (2)
S2—C6	1.7611 (14)	C7—H7A	0.9700
Cl1—C3	1.7415 (15)	C7—H7B	0.9700
C8—N4—H4A	118.9 (14)	S2—N2—H2	113.7 (15)
C8—N4—H4B	119.2 (14)	C6—C1—C2	120.74 (13)
H4A—N4—H4B	121 (2)	C6—C1—H1	119.6
O5—C8—N4	122.47 (14)	C2—C1—H1	119.6
O5—C8—C9	121.68 (13)	S1—N3—H3A	116.2 (14)
N4—C8—C9	115.85 (13)	S1—N3—H3B	118.0 (15)
C8—C9—C9^i	113.83 (11)	H3A—N3—H3B	120 (2)
C8—C9—H9A	108.8	C4—C3—C2	121.73 (13)
C9^i—C9—H9A	108.8	C4—C3—Cl1	118.10 (11)
C8—C9—H9B	108.8	C2—C3—Cl1	120.17 (11)
C9^i—C9—H9B	108.8	C1—C2—C3	118.12 (12)
H9A—C9—H9B	107.7	C1—C2—S1	117.11 (11)
O1—S1—O2	118.13 (6)	C3—C2—S1	124.54 (10)
O1—S1—N3	108.52 (7)	C5—N1—C7	121.69 (13)
O2—S1—N3	107.02 (7)	C5—N1—H1N	120.3 (14)
O1—S1—C2	105.12 (7)	C7—N1—H1N	118.0 (14)
O2—S1—C2	107.30 (7)	N1—C5—C6	122.33 (13)
N3—S1—C2	110.69 (7)	N1—C5—C4	120.40 (14)
O4—S2—O3	118.71 (7)	C6—C5—C4	117.25 (12)
O4—S2—N2	107.94 (7)	C1—C6—C5	121.59 (13)
O3—S2—N2	107.60 (7)	C1—C6—S2	118.03 (11)
O4—S2—C6	109.42 (7)	C5—C6—S2	120.17 (10)
O3—S2—C6	109.66 (7)	N1—C7—N2	111.96 (12)
N2—S2—C6	102.22 (7)	N1—C7—H7A	109.2
C3—C4—C5	120.57 (13)	N2—C7—H7A	109.2
C3—C4—H4	119.7	N1—C7—H7B	109.2
C5—C4—H4	119.7	N2—C7—H7B	109.2
C7—N2—S2	112.74 (10)	H7A—C7—H7B	107.9
C7—N2—H2	116.2 (15)

Symmetry code: (i) −x+1, y, −z+1/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O5	0.85 (2)	1.99 (2)	2.840 (2)	172 (2)
N2—H2···O2^i	0.87 (2)	2.23 (2)	3.045 (2)	157 (2)
N3—H3A···O2^ii	0.82 (2)	2.13 (2)	2.906 (2)	156 (2)
N3—H3B···O5^iii	0.85 (2)	2.02 (2)	2.861 (2)	168 (2)
N4—H4A···O3^iv	0.85 (2)	2.35 (2)	3.129 (2)	153 (2)
N4—H4B···O1^v	0.85 (2)	2.24 (2)	3.061 (2)	164 (2)

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

(HCT-PABA)

Crystal data

C7H8ClN3O4S2·2(C7H7NO2)	F(000) = 1184
Mr = 572.01	Dx = 1.587 Mg m^−3
Monoclinic, P21/c	Melting point: 448.9 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 12.7042 (13) Å	Cell parameters from 6230 reflections
b = 10.8626 (7) Å	θ = 1.7–27.5°
c = 18.5745 (18) Å	µ = 0.39 mm^−1
β = 110.905 (6)°	T = 150 K
V = 2394.6 (4) Å^3	Rod, colourless
Z = 4	0.40 × 0.20 × 0.20 mm

Data collection

Rigaku XtaLAB mini diffractometer	5505 independent reflections
Radiation source: fine-focus sealed tube	4896 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.107
ω–scans	θmax = 27.5°, θmin = 1.7°
Absorption correction: multi-scan SADABS (Sheldrick, 2008)	h = −16→16
Tmin = 0.985, Tmax = 1.000	k = −14→14
24989 measured reflections	l = −24→24

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.139	H atoms treated by a mixture of independent and constrained refinement
S = 1.13	w = 1/[σ^2(Fo^2) + (0.0688P)^2 + 0.5786P] where P = (Fo^2 + 2Fc^2)/3
5505 reflections	(Δ/σ)max = 0.001
374 parameters	Δρmax = 0.39 e Å^−3
0 restraints	Δρmin = −0.56 e Å^−3

Special details

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

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

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

	x	y	z	Uiso*/Ueq
Cl1	0.54311 (4)	0.98431 (5)	0.59525 (3)	0.02861 (14)
S1	0.78391 (4)	0.93073 (4)	0.57049 (3)	0.02260 (14)
S2	0.96912 (4)	0.83564 (4)	0.87657 (3)	0.02217 (14)
O1	0.89760 (13)	0.89278 (14)	0.58331 (8)	0.0303 (3)
O2	0.69328 (14)	0.87103 (13)	0.51175 (8)	0.0321 (3)
O3	1.03409 (12)	0.74102 (14)	0.85759 (8)	0.0306 (3)
O4	1.02489 (13)	0.94838 (14)	0.90824 (9)	0.0328 (4)
N1	0.73297 (16)	0.86940 (17)	0.87536 (10)	0.0263 (4)
H1A	0.675 (3)	0.863 (3)	0.8795 (18)	0.045 (8)*
N2	0.91681 (15)	0.77752 (17)	0.93698 (10)	0.0242 (3)
H2	0.905 (2)	0.710 (3)	0.9289 (16)	0.037 (8)*
N3	0.77732 (18)	1.07567 (16)	0.54761 (10)	0.0269 (4)
H3A	0.834 (3)	1.121 (3)	0.5743 (17)	0.041 (8)*
H3B	0.715 (2)	1.108 (2)	0.5423 (14)	0.027 (6)*
C1	0.85794 (16)	0.88280 (16)	0.72392 (10)	0.0207 (4)
H1	0.9284	0.8686	0.7183	0.025*
C2	0.76514 (16)	0.91518 (16)	0.65984 (11)	0.0207 (4)
C3	0.66188 (16)	0.93532 (16)	0.67032 (11)	0.0217 (4)
C4	0.65159 (16)	0.91995 (17)	0.74124 (11)	0.0227 (4)
H4	0.5803	0.9319	0.7461	0.027*
C5	0.74532 (16)	0.88667 (16)	0.80680 (10)	0.0203 (4)
C6	0.84951 (16)	0.87079 (16)	0.79616 (11)	0.0199 (4)
C7	0.82793 (17)	0.85309 (18)	0.94724 (11)	0.0252 (4)
H7A	0.8013	0.8136	0.9857	0.030*
H7B	0.8592	0.9347	0.9676	0.030*
O5	0.36984 (13)	0.78704 (14)	0.93242 (9)	0.0289 (3)
H5	0.418 (3)	0.816 (3)	0.9780 (18)	0.044 (8)*
O6	0.51525 (12)	0.83489 (13)	0.89678 (8)	0.0284 (3)
N4	0.1554 (2)	0.6710 (2)	0.57380 (12)	0.0421 (5)
H4A	0.080 (3)	0.661 (3)	0.561 (2)	0.064 (10)*
H4B	0.184 (3)	0.659 (3)	0.542 (2)	0.048 (9)*
C8	0.41772 (17)	0.79651 (17)	0.87988 (11)	0.0226 (4)
C9	0.34785 (17)	0.75939 (17)	0.80156 (11)	0.0222 (4)
C10	0.39743 (17)	0.74947 (19)	0.74583 (12)	0.0264 (4)
H10	0.4759	0.7642	0.7599	0.032*
C11	0.33462 (19)	0.71859 (19)	0.67065 (12)	0.0292 (4)
H11	0.3703	0.7107	0.6338	0.035*
C12	0.21853 (18)	0.69878 (18)	0.64846 (12)	0.0281 (4)
C13	0.16818 (17)	0.70697 (18)	0.70463 (12)	0.0279 (4)
H13	0.0898	0.6914	0.6907	0.033*
C14	0.23210 (17)	0.73750 (17)	0.78000 (12)	0.0250 (4)
H14	0.1971	0.7436	0.8173	0.030*
O7	0.64972 (14)	0.59504 (15)	0.53563 (9)	0.0325 (3)
H7O	0.604 (3)	0.612 (3)	0.494 (2)	0.075 (12)*
O8	0.50291 (13)	0.64480 (16)	0.56920 (9)	0.0358 (4)
N5	0.87033 (18)	0.50847 (17)	0.89727 (11)	0.0299 (4)
H5A	0.935 (3)	0.471 (3)	0.9068 (19)	0.054 (9)*
H5B	0.839 (3)	0.478 (2)	0.9260 (18)	0.042 (8)*
C15	0.60146 (18)	0.61083 (17)	0.58688 (11)	0.0253 (4)
C16	0.67374 (17)	0.58307 (17)	0.66703 (11)	0.0237 (4)
C17	0.78858 (18)	0.56006 (18)	0.68765 (12)	0.0258 (4)
H17	0.8224	0.5620	0.6496	0.031*
C18	0.85355 (18)	0.53439 (18)	0.76365 (12)	0.0266 (4)
H18	0.9320	0.5198	0.7776	0.032*
C19	0.80391 (18)	0.52988 (17)	0.82028 (11)	0.0247 (4)
C20	0.68879 (19)	0.55347 (19)	0.79923 (12)	0.0281 (4)
H20	0.6545	0.5516	0.8370	0.034*
C21	0.62492 (18)	0.57954 (18)	0.72343 (12)	0.0272 (4)
H21	0.5466	0.5953	0.7095	0.033*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl1	0.0208 (3)	0.0379 (3)	0.0220 (3)	0.00102 (18)	0.00136 (19)	0.00392 (18)
S1	0.0263 (3)	0.0260 (2)	0.0159 (2)	−0.00045 (17)	0.00809 (19)	−0.00101 (16)
S2	0.0167 (2)	0.0321 (3)	0.0167 (2)	−0.00148 (17)	0.00476 (18)	0.00198 (17)
O1	0.0301 (8)	0.0410 (8)	0.0237 (7)	0.0069 (6)	0.0144 (6)	0.0019 (6)
O2	0.0381 (9)	0.0348 (7)	0.0203 (7)	−0.0063 (6)	0.0065 (6)	−0.0073 (6)
O3	0.0213 (7)	0.0455 (8)	0.0254 (7)	0.0082 (6)	0.0087 (6)	0.0051 (6)
O4	0.0295 (8)	0.0409 (8)	0.0238 (7)	−0.0129 (6)	0.0044 (6)	−0.0009 (6)
N1	0.0202 (9)	0.0402 (9)	0.0212 (8)	0.0005 (7)	0.0108 (7)	0.0035 (7)
N2	0.0232 (9)	0.0300 (9)	0.0196 (8)	−0.0009 (7)	0.0078 (6)	0.0033 (7)
N3	0.0293 (10)	0.0279 (8)	0.0239 (9)	−0.0005 (7)	0.0100 (7)	0.0026 (7)
C1	0.0195 (9)	0.0244 (8)	0.0194 (9)	−0.0003 (7)	0.0083 (7)	0.0007 (7)
C2	0.0221 (10)	0.0232 (8)	0.0170 (8)	−0.0013 (7)	0.0071 (7)	−0.0004 (7)
C3	0.0200 (9)	0.0230 (8)	0.0198 (9)	−0.0009 (7)	0.0043 (7)	0.0004 (7)
C4	0.0173 (9)	0.0277 (9)	0.0237 (9)	−0.0015 (7)	0.0080 (7)	0.0002 (7)
C5	0.0192 (9)	0.0235 (8)	0.0197 (9)	−0.0021 (7)	0.0088 (7)	0.0000 (7)
C6	0.0178 (9)	0.0242 (8)	0.0190 (8)	−0.0015 (7)	0.0079 (7)	0.0001 (7)
C7	0.0255 (10)	0.0328 (9)	0.0188 (9)	−0.0009 (8)	0.0100 (8)	0.0010 (7)
O5	0.0267 (8)	0.0406 (8)	0.0223 (7)	−0.0086 (6)	0.0121 (6)	−0.0062 (6)
O6	0.0219 (7)	0.0400 (8)	0.0233 (7)	−0.0064 (6)	0.0082 (6)	−0.0043 (6)
N4	0.0388 (13)	0.0529 (12)	0.0251 (10)	−0.0029 (10)	−0.0001 (9)	−0.0066 (9)
C8	0.0224 (9)	0.0239 (8)	0.0222 (9)	−0.0005 (7)	0.0090 (7)	−0.0018 (7)
C9	0.0219 (9)	0.0233 (8)	0.0211 (9)	−0.0008 (7)	0.0075 (7)	−0.0003 (7)
C10	0.0218 (10)	0.0330 (10)	0.0247 (10)	−0.0038 (8)	0.0087 (8)	−0.0029 (8)
C11	0.0318 (11)	0.0354 (10)	0.0225 (10)	−0.0032 (9)	0.0125 (8)	−0.0043 (8)
C12	0.0302 (11)	0.0253 (9)	0.0231 (10)	0.0005 (8)	0.0028 (8)	−0.0010 (7)
C13	0.0199 (10)	0.0303 (9)	0.0301 (11)	−0.0004 (8)	0.0047 (8)	−0.0002 (8)
C14	0.0218 (10)	0.0277 (9)	0.0259 (10)	−0.0007 (7)	0.0089 (8)	−0.0006 (7)
O7	0.0306 (9)	0.0478 (9)	0.0207 (8)	0.0070 (7)	0.0110 (6)	0.0068 (6)
O8	0.0277 (8)	0.0566 (10)	0.0232 (8)	0.0097 (7)	0.0093 (6)	0.0078 (7)
N5	0.0307 (10)	0.0356 (9)	0.0212 (9)	0.0016 (8)	0.0067 (8)	0.0023 (7)
C15	0.0278 (10)	0.0258 (9)	0.0239 (10)	0.0002 (8)	0.0113 (8)	0.0022 (7)
C16	0.0253 (10)	0.0240 (8)	0.0211 (9)	0.0000 (7)	0.0072 (8)	0.0011 (7)
C17	0.0274 (11)	0.0282 (9)	0.0239 (10)	−0.0005 (8)	0.0116 (8)	−0.0009 (7)
C18	0.0233 (10)	0.0300 (9)	0.0251 (10)	0.0029 (8)	0.0071 (8)	−0.0011 (8)
C19	0.0291 (11)	0.0229 (9)	0.0207 (9)	−0.0017 (7)	0.0071 (8)	−0.0020 (7)
C20	0.0298 (11)	0.0343 (10)	0.0223 (10)	−0.0019 (8)	0.0116 (8)	−0.0010 (8)
C21	0.0245 (10)	0.0325 (10)	0.0261 (10)	−0.0003 (8)	0.0108 (8)	−0.0003 (8)

Geometric parameters (Å, º)

Cl1—C3	1.733 (2)	N4—H4A	0.91 (4)
S1—O2	1.4283 (15)	N4—H4B	0.81 (3)
S1—O1	1.4379 (16)	C8—C9	1.465 (3)
S1—N3	1.6251 (18)	C9—C10	1.395 (3)
S1—C2	1.7670 (19)	C9—C14	1.400 (3)
S2—O4	1.4319 (15)	C10—C11	1.380 (3)
S2—O3	1.4387 (15)	C10—H10	0.9500
S2—N2	1.6222 (17)	C11—C12	1.399 (3)
S2—C6	1.7511 (19)	C11—H11	0.9500
N1—C5	1.351 (2)	C12—C13	1.408 (3)
N1—C7	1.456 (3)	C13—C14	1.385 (3)
N1—H1A	0.77 (3)	C13—H13	0.9500
N2—C7	1.462 (3)	C14—H14	0.9500
N2—H2	0.75 (3)	O7—C15	1.315 (2)
N3—H3A	0.87 (3)	O7—H7O	0.81 (4)
N3—H3B	0.84 (3)	O8—C15	1.232 (3)
C1—C2	1.389 (3)	N5—C19	1.396 (3)
C1—C6	1.390 (2)	N5—H5A	0.88 (4)
C1—H1	0.9500	N5—H5B	0.84 (3)
C2—C3	1.410 (3)	C15—C16	1.475 (3)
C3—C4	1.380 (3)	C16—C17	1.392 (3)
C4—C5	1.413 (3)	C16—C21	1.396 (3)
C4—H4	0.9500	C17—C18	1.386 (3)
C5—C6	1.417 (3)	C17—H17	0.9500
C7—H7A	0.9900	C18—C19	1.407 (3)
C7—H7B	0.9900	C18—H18	0.9500
O5—C8	1.325 (2)	C19—C20	1.396 (3)
O5—H5	0.91 (3)	C20—C21	1.380 (3)
O6—C8	1.237 (2)	C20—H20	0.9500
N4—C12	1.365 (3)	C21—H21	0.9500
O2—S1—O1	118.99 (9)	H4A—N4—H4B	120 (3)
O2—S1—N3	106.73 (10)	O6—C8—O5	121.38 (17)
O1—S1—N3	106.02 (10)	O6—C8—C9	122.81 (17)
O2—S1—C2	109.38 (9)	O5—C8—C9	115.80 (17)
O1—S1—C2	106.34 (9)	C10—C9—C14	118.76 (18)
N3—S1—C2	109.06 (9)	C10—C9—C8	118.97 (18)
O4—S2—O3	117.95 (10)	C14—C9—C8	122.24 (18)
O4—S2—N2	108.27 (9)	C11—C10—C9	121.24 (19)
O3—S2—N2	107.69 (9)	C11—C10—H10	119.4
O4—S2—C6	108.39 (9)	C9—C10—H10	119.4
O3—S2—C6	110.24 (9)	C10—C11—C12	120.24 (19)
N2—S2—C6	103.29 (9)	C10—C11—H11	119.9
C5—N1—C7	122.99 (17)	C12—C11—H11	119.9
C5—N1—H1A	123 (2)	N4—C12—C11	120.6 (2)
C7—N1—H1A	114 (2)	N4—C12—C13	120.6 (2)
C7—N2—S2	113.43 (13)	C11—C12—C13	118.81 (18)
C7—N2—H2	118 (2)	C14—C13—C12	120.44 (19)
S2—N2—H2	110 (2)	C14—C13—H13	119.8
S1—N3—H3A	116.7 (19)	C12—C13—H13	119.8
S1—N3—H3B	113.4 (17)	C13—C14—C9	120.47 (19)
H3A—N3—H3B	113 (2)	C13—C14—H14	119.8
C2—C1—C6	121.13 (18)	C9—C14—H14	119.8
C2—C1—H1	119.4	C15—O7—H7O	108 (3)
C6—C1—H1	119.4	C19—N5—H5A	118 (2)
C1—C2—C3	117.89 (17)	C19—N5—H5B	118 (2)
C1—C2—S1	118.13 (14)	H5A—N5—H5B	108 (3)
C3—C2—S1	123.97 (15)	O8—C15—O7	122.56 (19)
C4—C3—C2	121.52 (18)	O8—C15—C16	122.53 (18)
C4—C3—Cl1	116.97 (15)	O7—C15—C16	114.90 (18)
C2—C3—Cl1	121.49 (15)	C17—C16—C21	119.42 (18)
C3—C4—C5	121.07 (18)	C17—C16—C15	121.89 (18)
C3—C4—H4	119.5	C21—C16—C15	118.69 (18)
C5—C4—H4	119.5	C18—C17—C16	120.08 (19)
N1—C5—C4	120.16 (18)	C18—C17—H17	120.0
N1—C5—C6	122.90 (18)	C16—C17—H17	120.0
C4—C5—C6	116.93 (17)	C17—C18—C19	120.37 (19)
C1—C6—C5	121.39 (17)	C17—C18—H18	119.8
C1—C6—S2	120.11 (15)	C19—C18—H18	119.8
C5—C6—S2	118.50 (14)	C20—C19—N5	120.47 (19)
N1—C7—N2	111.99 (16)	C20—C19—C18	119.23 (18)
N1—C7—H7A	109.2	N5—C19—C18	120.2 (2)
N2—C7—H7A	109.2	C21—C20—C19	119.94 (19)
N1—C7—H7B	109.2	C21—C20—H20	120.0
N2—C7—H7B	109.2	C19—C20—H20	120.0
H7A—C7—H7B	107.9	C20—C21—C16	121.0 (2)
C8—O5—H5	109.0 (19)	C20—C21—H21	119.5
C12—N4—H4A	118 (2)	C16—C21—H21	119.5
C12—N4—H4B	122 (2)
O4—S2—N2—C7	65.13 (16)	N2—S2—C6—C5	22.10 (17)
O3—S2—N2—C7	−166.31 (14)	C5—N1—C7—N2	−39.1 (3)
C6—S2—N2—C7	−49.67 (16)	S2—N2—C7—N1	60.4 (2)
C6—C1—C2—C3	−0.1 (3)	O6—C8—C9—C10	9.6 (3)
C6—C1—C2—S1	179.03 (14)	O5—C8—C9—C10	−170.63 (17)
O2—S1—C2—C1	135.13 (15)	O6—C8—C9—C14	−168.18 (19)
O1—S1—C2—C1	5.45 (17)	O5—C8—C9—C14	11.6 (3)
N3—S1—C2—C1	−108.48 (16)	C14—C9—C10—C11	−0.1 (3)
O2—S1—C2—C3	−45.79 (18)	C8—C9—C10—C11	−177.96 (19)
O1—S1—C2—C3	−175.47 (15)	C9—C10—C11—C12	1.2 (3)
N3—S1—C2—C3	70.60 (18)	C10—C11—C12—N4	178.5 (2)
C1—C2—C3—C4	−2.0 (3)	C10—C11—C12—C13	−2.1 (3)
S1—C2—C3—C4	178.96 (14)	N4—C12—C13—C14	−178.8 (2)
C1—C2—C3—Cl1	176.37 (14)	C11—C12—C13—C14	1.8 (3)
S1—C2—C3—Cl1	−2.7 (2)	C12—C13—C14—C9	−0.7 (3)
C2—C3—C4—C5	1.8 (3)	C10—C9—C14—C13	−0.2 (3)
Cl1—C3—C4—C5	−176.58 (14)	C8—C9—C14—C13	177.60 (18)
C7—N1—C5—C4	−170.63 (18)	O8—C15—C16—C17	−171.66 (19)
C7—N1—C5—C6	10.5 (3)	O7—C15—C16—C17	9.2 (3)
C3—C4—C5—N1	−178.53 (18)	O8—C15—C16—C21	8.6 (3)
C3—C4—C5—C6	0.4 (3)	O7—C15—C16—C21	−170.60 (18)
C2—C1—C6—C5	2.3 (3)	C21—C16—C17—C18	−0.2 (3)
C2—C1—C6—S2	−177.55 (14)	C15—C16—C17—C18	179.96 (18)
N1—C5—C6—C1	176.46 (17)	C16—C17—C18—C19	0.8 (3)
C4—C5—C6—C1	−2.4 (3)	C17—C18—C19—C20	−1.0 (3)
N1—C5—C6—S2	−3.7 (3)	C17—C18—C19—N5	−177.64 (18)
C4—C5—C6—S2	177.46 (13)	N5—C19—C20—C21	177.32 (19)
O4—S2—C6—C1	87.26 (16)	C18—C19—C20—C21	0.7 (3)
O3—S2—C6—C1	−43.21 (17)	C19—C20—C21—C16	−0.2 (3)
N2—S2—C6—C1	−158.03 (15)	C17—C16—C21—C20	−0.1 (3)
O4—S2—C6—C5	−92.61 (16)	C15—C16—C21—C20	179.73 (19)
O3—S2—C6—C5	136.92 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O6	0.77 (3)	2.19 (3)	2.955 (2)	176 (3)
N2—H2···N5	0.75 (3)	2.27 (3)	3.020 (3)	176 (3)
N3—H3A···O3^i	0.87 (3)	2.14 (3)	3.009 (2)	176 (3)
N3—H3B···O5^ii	0.84 (3)	2.35 (3)	3.066 (2)	144 (2)
N4—H4A···N2^iii	0.91 (4)	2.58 (4)	3.235 (3)	129 (3)
O5—H5···O8^iv	0.91 (3)	1.70 (3)	2.607 (2)	172 (3)
N5—H5A···O1^v	0.88 (4)	2.23 (4)	3.105 (3)	171 (3)
N5—H5B···N3^iv	0.84 (3)	2.71 (3)	3.519 (3)	164 (3)
O7—H7O···O6^vi	0.81 (4)	1.85 (4)	2.647 (2)	172 (4)

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