Streptidinium sulfate monohydrate

In streptidinium sulfate monohydrate {systematic name: 1,1′-[(1S,3R,4S,6R)-2,4,5,6-tetra­hydroxy­cyclo­hexane-1,3-di­yl]di­guan­idinium sulfate monohydrate}, C₈H₂₀N₆O₄²⁺·SO₄²⁻·H₂O, at 100 (2) K, the components are arranged in double helices based on hydrogen bonds. One helix contains streptidinium cations and the other contains disordered sulfate anions and solvent water mol­ecules. The helices are linked into a three-dimensional hydrogen-bonded network by O—H...O and N—H...O hydrogen bonds.

S1. Comment

Streptidine {N,N'''-[(1S,3R,4S,6R)-2,4,5,6-tetrahydroxycyclohexane-1,3-diyl]diguanidine} is a substrate in the biosynthesis of aminoglycosides as streptomycin, dihydrostreptomycin and bluensomycin. Streptidine is a derivative of cyclohexane which is substituted with four hydroxyl groups and two basic guanidine groups, and it has been shown to be one of the eight meso forms of 1,3-diguanido-2,4,5,6-tetrahydroxycyclohexane (Carter et al., 1947). Streptidine is responsible for the Sakaguchi reaction given by streptomycin, whereby guanidines in alkaline solution develop an intense red colour when treated with α-naphthol and sodium hypochlorite; this is a qualitative test for arginine, whether free or combined within a protein. Electrometric titration of streptidine dihydrochloride showed it to be a very strong base (Fried et al., 1946).

Streptidine is a `decoy acceptor' which allows the antibiotic activity of streptomycin to recover against the Escherichia coli strain overexpressing the aminoglycoside-modifying enzyme 6-O-adenyl transferase. It could be a good starting compound for the design of more efficient `decoy acceptors' of aminoglycoside-modifying enzymes (Latorre et al., 2007). Streptidine is a metabolite but not the antibiotic itself. It is a potential contributor to ototoxicity after prolonged antibiotic administration since it acts as a damaging agent for the inner ear (Meza & Granados, 2005). The only previous structural study of this compound employed X-ray powder diffraction (Rose, 1954). Here, we report a single-crystal study of the title compound, (I) (Fig. 1), at 100 K.

The sulfate anions of (I) are doubly charged but the water molecule is not protonated. The stoichoimetry of the crystal structure requires the streptidinium cation to carry two positive charges, which are located on the guanidine groups. The planarity of these groups and their relative closeness to the sulfate anions suggest that they must in fact be protonated. The sulfate anion is disordered over two sets of atomic sites, with occupancies of 0.795 (4) and 0.205 (5).

The central cyclohexane ring adopts a classical chair conformation. All H atoms occupy axial positions, while hydroxyl groups and protonated guanidine groups occupy equatorial positions. Streptidine is present in a cationic form and the protonation is on the C═NH N atom in both guanidine fragments. The same type of protonation was found in the crystal structure of streptomycin oxime selenate tetrahydrate (Neidle et al., 1978). From this result, the protonation on the C—NH₂ group of streptidine, as proposed by Latorre et al. (2007), seems to be incorrect.

In both guanidine moieties, the N atoms have a planar geometry. The C—N bond lengths are in the range 1.320–1.347 Å, intermediate between double (1.28 Å; Reference for standard value?) and single (1.47 Å; Reference for standard value?) bonds, indicating the delocalization of the double C═N bond over all three C—N bonds. Both guanidine groups, N1–N3/C7 and N4–N6/C8, are planar to within 0.003 (3) and 0.006 (3) Å, respectively. The dihedral angles between the central cyclohexane ring (C1–C6) and the guanidine moieties are 112.3 (1) (plane of N1–N3/C7) and 100.8 (1)° (plane of N4–N6/C8). For comparison, the respective dihedral angles in streptomycin oxime selenate tetrahydrate are 97.5 and 109.2° (Neidle et al., 1978).

The crystal structure of (I) is stabilized by N—H···O and O—H···O hydrogen bonds and electrostatic interactions. The molecules are arranged in double helices based on hydrogen bonds, one of streptidinium cations, and the second of sulfate anions and water molecules (Fig. 2). Between the helices, O—H···O and N—H···O hydrogen bonds occur, and a three-dimensional hydrogen-bonding network is built up through the entire crystal structure. Hydrogen bonds linking the sulfate anion, the streptidinium cation and the water molecule are summarized in Table 1 and shown in Fig. 3. The geometries of all the hydrogen bonds are within accepted limits (Desiraju & Steiner, 1999). The streptidinium cation is involved in 156 [15 ?] hydrogen bonds of O—H···O and N—H···O types with adjacent streptidinium cations (three bonds), water molecules (two bonds) and sulfate ions (ten bonds). The sulfate anion accepts eight hydrogen bonds from the streptidinium cation and one from the water molecule. Finally, the water molecule is involved in four O—H···O bonds, two to a streptidinium cation as an acceptor and two to a sulfate anion as a donor. There are no intramolecular hydrogen bonds in the streptidinium cation.

S2. Experimental

Streptidine crystals were obtained while attempting to crystallize a molecular complex of streptomycin sulfate with p-sulfonatocalix[4]arene from an aqueous solution [Please give brief details of quantities, reaction conditions etc.]. Due to acidic hydrolysis of streptomycin to streptidine and dihydrostreptobiosaminidine, instead of the desired complex crystals of streptidinium sulfate monohydrate, (I), were obtained.

S3. Refinement

Due to the not very satisfactory geometry of sulfate anion the SADI instruction in SHELXL program was applied in order to rationalize the bond lengths. The anisotropic displacement parameters of oxygen atoms of the minor component in disordered anion were kept the same as the corresponding atoms of the major component. All H atoms were located in difference maps. H atoms attached to C atoms were then treated as riding atoms in geometrically calculated positions, with C—H = 1.00 Å, and U_iso(H) = 1.5U_eq(C). For H atoms bonded to N or O atoms, the atomic corrdinates were refined with U_iso(H) = 1.2U_eq(N) and 1.5U_eq(O), to give distances in the ranges N—H = 0.79 (4)–0.94 (4) Å and O—H = 0.78 (5)–0.93 (5) Å. Friedel opposites were kept unmerged, and the value of the Flack x parameter (Flack, 1983) confirmed that the space group was P3₂.

Computing details

Data collection: COLLECT (Nonius, 1998); cell refinement: DENZO (Otwinowski & Minor 1997) and SCALEPACK (Otwinowski & Minor 1997); data reduction: DENZO (Otwinowski & Minor 1997) and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Burnett & Johnson,1996); software used to prepare material for publication: publCIF (Westrip, 2009).

Figures

	Fig. 1. The molecular structure of (I), showing the atom-labelling scheme. Only the major component of the sulfate anion is shown. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The double helical arrangement of streptidinium cations (white), sulfate anions (grey) and water molecules (black) around the 32 crystallographic axis.
	Fig. 3. The packing of (I) along the c axis, with hydrogen bonds shown as dashed lines. Water molecules are represented as spheres.

{[(1S,3R,4S,6R)-2,4,5,6-tetrahydroxycyclohexane- 1,3-diyl]diimino}bis(aminomethaniminium) sulfate monohydrate

Crystal data

C8H20N6O4^2+·SO4^2^−·H2O	Dx = 1.614 Mg m^−3
Mr = 378.38	Mo Kα radiation, λ = 0.71073 Å
Trigonal, P32	Cell parameters from 1276 reflections
Hall symbol: P 32	θ = 2.6–27.5°
a = 9.1105 (5) Å	µ = 0.27 mm^−1
c = 16.2506 (7) Å	T = 100 K
V = 1168.1 (1) Å^3	Trigonal pyramid, colourless
Z = 3	0.50 × 0.40 × 0.35 mm
F(000) = 600

Data collection

Nonius Kappa APEXII diffractometer	2547 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.028
Graphite monochromator	θmax = 27.5°, θmin = 2.9°
Detector resolution: 8.3 pixels mm^-1	h = −11→11
ϕ and ω scans	k = 0→11
4125 measured reflections	l = −15→21
2645 independent reflections

Refinement

Refinement on F^2	Hydrogen site location: geom and difmap
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.046	w = 1/[σ^2(Fo^2) + (0.0172P)^2 + 2.4698P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.100	(Δ/σ)max = 0.002
S = 1.05	Δρmax = 0.67 e Å^−3
2645 reflections	Δρmin = −0.59 e Å^−3
279 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
29 restraints	Extinction coefficient: 0.007 (2)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983)
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.08 (12)

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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	Occ. (<1)
C1	0.4926 (5)	0.4670 (4)	0.8515 (2)	0.0173 (7)
H1	0.4685	0.5543	0.8750	0.021*
C2	0.6612 (5)	0.5597 (5)	0.8052 (2)	0.0184 (7)
H2	0.6929	0.4753	0.7854	0.022*
C3	0.6461 (4)	0.6551 (4)	0.7317 (2)	0.0145 (7)
H3	0.6147	0.7394	0.7521	0.017*
C4	0.5089 (4)	0.5338 (5)	0.6728 (2)	0.0165 (7)
H4	0.5362	0.4460	0.6534	0.020*
C5	0.3393 (4)	0.4481 (4)	0.7193 (2)	0.0160 (7)
H5	0.3117	0.5366	0.7371	0.019*
C6	0.3447 (5)	0.3514 (5)	0.7950 (3)	0.0186 (8)
H6	0.3647	0.2587	0.7754	0.022*
C7	0.5080 (4)	0.4061 (5)	0.9983 (2)	0.0177 (7)
C8	0.9247 (5)	0.9068 (5)	0.7015 (3)	0.0206 (8)
O1	0.7849 (4)	0.6716 (3)	0.86210 (18)	0.0229 (6)
H1O	0.874 (7)	0.684 (6)	0.852 (3)	0.034*
O2	0.5009 (3)	0.6269 (3)	0.60419 (19)	0.0217 (6)
H2O	0.452 (7)	0.553 (7)	0.566 (3)	0.033*
O3	0.2097 (3)	0.3318 (3)	0.66622 (18)	0.0232 (6)
H3O	0.141 (7)	0.365 (6)	0.659 (3)	0.035*
O4	0.1874 (4)	0.2743 (3)	0.83795 (19)	0.0242 (6)
H4O	0.178 (7)	0.348 (7)	0.853 (3)	0.036*
N1	0.5027 (5)	0.3684 (4)	0.9196 (2)	0.0230 (7)
H1A	0.509 (6)	0.267 (6)	0.902 (3)	0.028*
N2	0.5040 (6)	0.5414 (5)	1.0236 (3)	0.0333 (9)
H2A	0.510 (7)	0.639 (7)	0.992 (3)	0.040*
H2B	0.516 (7)	0.566 (7)	1.079 (3)	0.040*
N3	0.5165 (4)	0.3002 (4)	1.0542 (2)	0.0202 (7)
H3A	0.503 (6)	0.206 (6)	1.036 (3)	0.024*
H3B	0.496 (6)	0.309 (6)	1.110 (3)	0.024*
N4	0.8068 (4)	0.7456 (4)	0.6879 (2)	0.0171 (7)
H4A	0.825 (5)	0.697 (6)	0.647 (3)	0.021*
N5	1.0663 (4)	0.9756 (5)	0.6586 (3)	0.0265 (8)
H5A	1.128 (6)	1.095 (6)	0.663 (3)	0.032*
H5B	1.075 (7)	0.915 (7)	0.622 (3)	0.032*
N6	0.8990 (4)	0.9996 (4)	0.7570 (2)	0.0239 (7)
H6A	0.812 (6)	0.945 (6)	0.794 (3)	0.029*
H6B	0.994 (6)	1.110 (6)	0.774 (3)	0.029*
S1	0.43923 (11)	0.46653 (11)	0.24761 (4)	0.0219 (2)
O1S	0.5553 (5)	0.6048 (4)	0.1917 (2)	0.0347 (9)	0.786 (3)
O2S	0.2591 (3)	0.4094 (5)	0.2327 (3)	0.0316 (9)	0.786 (3)
O3S	0.4931 (5)	0.5230 (5)	0.33338 (15)	0.0261 (8)	0.786 (3)
O4S	0.4715 (5)	0.3241 (4)	0.2324 (2)	0.0278 (9)	0.786 (3)
O1S'	0.4024 (18)	0.5609 (15)	0.1843 (6)	0.0347 (9)	0.214 (3)
O2S'	0.3081 (13)	0.4522 (18)	0.3063 (7)	0.0316 (9)	0.214 (3)
O3S'	0.6076 (8)	0.5825 (14)	0.2834 (8)	0.0261 (8)	0.214 (3)
O4S'	0.3720 (19)	0.2907 (7)	0.2180 (8)	0.0278 (9)	0.214 (3)
O1W	0.3210 (4)	0.4019 (4)	0.4808 (2)	0.0271 (7)
H1W	0.229 (7)	0.397 (7)	0.493 (4)	0.041*
H2W	0.365 (7)	0.427 (7)	0.426 (4)	0.041*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0278 (19)	0.0147 (16)	0.0138 (17)	0.0139 (15)	−0.0001 (15)	0.0006 (14)
C2	0.0239 (19)	0.0173 (17)	0.0151 (18)	0.0112 (15)	−0.0032 (15)	−0.0037 (15)
C3	0.0136 (16)	0.0130 (16)	0.0148 (18)	0.0051 (13)	0.0042 (14)	0.0013 (13)
C4	0.0178 (16)	0.0147 (16)	0.0142 (18)	0.0061 (14)	0.0030 (14)	0.0044 (14)
C5	0.0161 (16)	0.0091 (15)	0.0195 (19)	0.0037 (13)	0.0026 (15)	0.0017 (14)
C6	0.0190 (17)	0.0120 (16)	0.0196 (19)	0.0038 (14)	0.0021 (15)	−0.0014 (14)
C7	0.0138 (16)	0.0225 (18)	0.0153 (18)	0.0078 (14)	−0.0002 (14)	−0.0035 (15)
C8	0.0171 (17)	0.0178 (17)	0.024 (2)	0.0069 (15)	−0.0005 (15)	0.0023 (16)
O1	0.0197 (13)	0.0275 (14)	0.0208 (15)	0.0112 (12)	−0.0056 (12)	−0.0058 (12)
O2	0.0226 (14)	0.0177 (13)	0.0180 (14)	0.0049 (11)	−0.0024 (12)	0.0041 (11)
O3	0.0175 (13)	0.0190 (13)	0.0249 (15)	0.0031 (11)	−0.0042 (12)	0.0008 (11)
O4	0.0253 (14)	0.0147 (13)	0.0263 (16)	0.0053 (11)	0.0117 (12)	0.0002 (11)
N1	0.041 (2)	0.0194 (16)	0.0137 (16)	0.0189 (15)	0.0011 (15)	0.0006 (13)
N2	0.059 (3)	0.038 (2)	0.0171 (19)	0.034 (2)	−0.0095 (18)	−0.0122 (17)
N3	0.0253 (17)	0.0225 (16)	0.0123 (16)	0.0115 (14)	0.0011 (13)	−0.0022 (13)
N4	0.0178 (15)	0.0154 (14)	0.0178 (17)	0.0080 (12)	0.0048 (13)	0.0000 (13)
N5	0.0183 (16)	0.0226 (18)	0.033 (2)	0.0060 (14)	0.0055 (15)	0.0001 (16)
N6	0.0209 (16)	0.0150 (15)	0.031 (2)	0.0054 (13)	0.0012 (15)	−0.0045 (14)
S1	0.0245 (5)	0.0203 (5)	0.0144 (4)	0.0062 (4)	−0.0012 (4)	−0.0009 (4)
O1S	0.039 (2)	0.0243 (18)	0.025 (2)	0.0037 (16)	0.0045 (18)	−0.0049 (16)
O2S	0.0236 (18)	0.034 (2)	0.038 (2)	0.0152 (16)	−0.0080 (16)	−0.0030 (17)
O3S	0.0314 (19)	0.0327 (19)	0.018 (2)	0.0186 (16)	−0.0034 (15)	−0.0068 (15)
O4S	0.041 (2)	0.035 (2)	0.0161 (18)	0.026 (2)	0.0007 (18)	−0.0021 (16)
O1S'	0.039 (2)	0.0243 (18)	0.025 (2)	0.0037 (16)	0.0045 (18)	−0.0049 (16)
O2S'	0.0236 (18)	0.034 (2)	0.038 (2)	0.0152 (16)	−0.0080 (16)	−0.0030 (17)
O3S'	0.0314 (19)	0.0327 (19)	0.018 (2)	0.0186 (16)	−0.0034 (15)	−0.0068 (15)
O4S'	0.041 (2)	0.035 (2)	0.0161 (18)	0.026 (2)	0.0007 (18)	−0.0021 (16)
O1W	0.0337 (16)	0.0267 (15)	0.0216 (16)	0.0155 (13)	0.0014 (13)	−0.0025 (13)

Geometric parameters (Å, º)

C1—N1	1.456 (5)	O1—H1O	0.78 (6)
C1—C2	1.531 (5)	O2—H2O	0.85 (5)
C1—C6	1.533 (5)	O3—H3O	0.83 (5)
C1—H1	1.0000	O4—H4O	0.76 (6)
C2—O1	1.420 (4)	N1—H1A	1.00 (5)
C2—C3	1.523 (5)	N2—H2A	1.01 (6)
C2—H2	1.0000	N2—H2B	0.92 (6)
C3—N4	1.457 (4)	N3—H3A	0.85 (5)
C3—C4	1.523 (5)	N3—H3B	0.93 (5)
C3—H3	1.0000	N4—H4A	0.86 (5)
C4—O2	1.425 (4)	N5—H5A	0.95 (5)
C4—C5	1.537 (5)	N5—H5B	0.84 (5)
C4—H4	1.0000	N6—H6A	0.91 (5)
C5—O3	1.418 (4)	N6—H6B	0.99 (5)
C5—C6	1.527 (5)	S1—O2S	1.473 (2)
C5—H5	1.0000	S1—O3S'	1.479 (2)
C6—O4	1.424 (5)	S1—O4S'	1.480 (2)
C6—H6	1.0000	S1—O3S	1.482 (2)
C7—N2	1.318 (5)	S1—O1S	1.483 (2)
C7—N1	1.319 (5)	S1—O1S'	1.483 (2)
C7—N3	1.355 (5)	S1—O2S'	1.483 (2)
C8—N5	1.318 (5)	S1—O4S	1.487 (2)
C8—N4	1.334 (5)	O1W—H1W	0.85 (6)
C8—N6	1.335 (5)	O1W—H2W	0.95 (6)
N1—C1—C2	111.0 (3)	N5—C8—N4	119.6 (4)
N1—C1—C6	109.6 (3)	N5—C8—N6	119.8 (4)
C2—C1—C6	112.3 (3)	N4—C8—N6	120.6 (3)
N1—C1—H1	107.9	C2—O1—H1O	111 (4)
C2—C1—H1	107.9	C4—O2—H2O	105 (3)
C6—C1—H1	107.9	C5—O3—H3O	108 (4)
O1—C2—C3	111.5 (3)	C6—O4—H4O	105 (4)
O1—C2—C1	107.0 (3)	C7—N1—C1	125.5 (3)
C3—C2—C1	110.4 (3)	C7—N1—H1A	120 (3)
O1—C2—H2	109.3	C1—N1—H1A	114 (3)
C3—C2—H2	109.3	C7—N2—H2A	131 (3)
C1—C2—H2	109.3	C7—N2—H2B	119 (3)
N4—C3—C2	110.7 (3)	H2A—N2—H2B	110 (4)
N4—C3—C4	109.3 (3)	C7—N3—H3A	117 (3)
C2—C3—C4	110.7 (3)	C7—N3—H3B	120 (3)
N4—C3—H3	108.7	H3A—N3—H3B	119 (4)
C2—C3—H3	108.7	C8—N4—C3	124.7 (3)
C4—C3—H3	108.7	C8—N4—H4A	116 (3)
O2—C4—C3	109.1 (3)	C3—N4—H4A	119 (3)
O2—C4—C5	110.5 (3)	C8—N5—H5A	113 (3)
C3—C4—C5	108.1 (3)	C8—N5—H5B	117 (4)
O2—C4—H4	109.7	H5A—N5—H5B	127 (5)
C3—C4—H4	109.7	C8—N6—H6A	118 (3)
C5—C4—H4	109.7	C8—N6—H6B	120 (3)
O3—C5—C6	108.3 (3)	H6A—N6—H6B	116 (4)
O3—C5—C4	109.3 (3)	O3S'—S1—O4S'	128.4 (8)
C6—C5—C4	112.0 (3)	O2S—S1—O3S	113.2 (2)
O3—C5—H5	109.1	O2S—S1—O1S	113.3 (2)
C6—C5—H5	109.1	O3S—S1—O1S	108.1 (2)
C4—C5—H5	109.1	O3S'—S1—O1S'	108.3 (8)
O4—C6—C5	111.4 (3)	O4S'—S1—O1S'	108.1 (8)
O4—C6—C1	111.5 (3)	O3S'—S1—O2S'	108.2 (8)
C5—C6—C1	110.9 (3)	O4S'—S1—O2S'	103.6 (8)
O4—C6—H6	107.6	O1S'—S1—O2S'	95.3 (8)
C5—C6—H6	107.6	O2S—S1—O4S	109.6 (2)
C1—C6—H6	107.6	O3S—S1—O4S	106.5 (2)
N2—C7—N1	122.2 (4)	O1S—S1—O4S	105.8 (2)
N2—C7—N3	119.6 (4)	H1W—O1W—H2W	121 (5)
N1—C7—N3	118.2 (3)
N1—C1—C2—O1	−61.3 (4)	O3—C5—C6—O4	−60.1 (4)
C6—C1—C2—O1	175.6 (3)	C4—C5—C6—O4	179.3 (3)
N1—C1—C2—C3	177.2 (3)	O3—C5—C6—C1	175.1 (3)
C6—C1—C2—C3	54.1 (4)	C4—C5—C6—C1	54.5 (4)
O1—C2—C3—N4	60.4 (4)	N1—C1—C6—O4	59.8 (4)
C1—C2—C3—N4	179.2 (3)	C2—C1—C6—O4	−176.4 (3)
O1—C2—C3—C4	−178.2 (3)	N1—C1—C6—C5	−175.5 (3)
C1—C2—C3—C4	−59.3 (4)	C2—C1—C6—C5	−51.6 (4)
N4—C3—C4—O2	−56.6 (4)	N2—C7—N1—C1	0.3 (6)
C2—C3—C4—O2	−178.8 (3)	N3—C7—N1—C1	179.7 (4)
N4—C3—C4—C5	−176.7 (3)	C2—C1—N1—C7	107.6 (4)
C2—C3—C4—C5	61.0 (4)	C6—C1—N1—C7	−127.9 (4)
O2—C4—C5—O3	61.8 (4)	N5—C8—N4—C3	179.5 (4)
C3—C4—C5—O3	−178.9 (3)	N6—C8—N4—C3	−1.8 (6)
O2—C4—C5—C6	−178.2 (3)	C2—C3—N4—C8	−93.3 (4)
C3—C4—C5—C6	−58.9 (4)	C4—C3—N4—C8	144.4 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O1W^i	0.78 (6)	2.00 (6)	2.775 (4)	170 (5)
O2—H2O···O1W	0.85 (5)	1.90 (5)	2.748 (4)	171 (5)
O3—H3O···O3S′^ii	0.83 (5)	1.79 (5)	2.590 (12)	162 (5)
O3—H3O···O3S^ii	0.83 (5)	2.00 (5)	2.801 (5)	160 (5)
O3—H3O···O1S^ii	0.83 (5)	2.56 (5)	3.155 (5)	130 (4)
O4—H4O···O2^ii	0.76 (6)	2.15 (6)	2.876 (4)	158 (5)
N1—H1A···O3S′^iii	1.00 (5)	2.07 (5)	2.863 (12)	135 (4)
N1—H1A···O4S^iii	1.00 (5)	2.27 (5)	3.136 (5)	145 (4)
N2—H2B···O1S^iv	0.92 (6)	1.87 (6)	2.782 (5)	174 (5)
N2—H2B···O1S′^iv	0.92 (6)	1.99 (6)	2.805 (14)	147 (5)
N2—H2A···O2S′^v	1.01 (6)	1.85 (6)	2.811 (8)	158 (4)
N2—H2A···O2S^v	1.01 (6)	2.25 (6)	3.220 (6)	161 (4)
N3—H3A···O3S′^iii	0.85 (5)	2.00 (5)	2.774 (12)	150 (4)
N3—H3A···O3S^iii	0.85 (5)	2.12 (5)	2.978 (5)	176 (4)
N3—H3B···O4S^iv	0.93 (5)	2.02 (5)	2.949 (5)	174 (4)
N3—H3B···O4S′^iv	0.93 (5)	2.05 (5)	2.952 (14)	161 (4)
N4—H4A···O4S′^i	0.86 (5)	2.02 (5)	2.865 (14)	168 (4)
N4—H4A···O4S^i	0.86 (5)	2.14 (5)	2.976 (5)	167 (4)
N5—H5A···O3^vi	0.95 (5)	1.90 (5)	2.831 (5)	169 (4)
N5—H5B···O2S^i	0.84 (5)	2.22 (5)	3.009 (5)	157 (5)
N5—H5B···O2S′^i	0.84 (5)	2.43 (5)	3.019 (14)	127 (4)
N5—H5B···O4S′^i	0.84 (5)	2.54 (6)	3.258 (15)	144 (5)
N6—H6B···O4^vi	0.99 (5)	1.94 (5)	2.884 (4)	159 (4)
N6—H6B···O3^vi	0.99 (5)	2.66 (5)	3.284 (4)	122 (3)
N6—H6A···O4S′^v	0.91 (5)	2.40 (5)	3.021 (13)	125 (4)
N6—H6A···O2S^v	0.91 (5)	2.45 (5)	3.358 (5)	170 (4)
O1W—H1W···O1S^ii	0.85 (6)	1.95 (6)	2.784 (5)	166 (5)
O1W—H1W···O1S′^ii	0.85 (6)	2.25 (6)	2.894 (12)	133 (5)
O1W—H2W···O3S	0.95 (6)	1.84 (6)	2.772 (5)	166 (5)
O1W—H2W···O2S′	0.95 (6)	2.06 (6)	2.884 (12)	144 (5)

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