Crystallographic evidence of Gly-D,L-Met oxidation to its sulfoxide in the presence of gold(III): solid solution of the racemic mixture of two diastereo­isomers

Crystallographic analysis of a solid solution of two diastereoisomers, i.e. ({(1S,R)-1-carb­oxy-3-[(R,S)-methyl­sul­fin­yl]propyl}amino­carbonyl)methanaminium tetra­chlorido­aur­ate(III) and ({(1S,R)-1-carb­oxy-3-[(S,R)-methyl­sulfinyl]propyl}amino­carbonyl)methanaminium tetra­chloridoaurate(III), (C₇H₁₅N₂O₄S)[AuCl₄], has shown that in the presence of gold(III), the methio­nine part of the Gly-D,L-Met dipeptide is oxidized to sulfoxide, and no coordination to the Au^III cation through the S atom of the sulfoxide is observed. In view of our observation, literature reports that methio­nine acts as an N,S-bidentate donor ligand forming stable gold(III) complexes require verification. Moreover, it has been demonstrated that crystallization of the oxidation product leads to a substantial 77:23 excess of both S-methio­nine/R-sulfoxide and R-methio­nine/S-sulfoxide over S-methio­nine/S-sulfoxide and R-methio­nine/R-sulfoxide. The presence of two different di­astereoisomers at the same crystallographic site is a source of static disorder at this site.

S1. Comment

The prominent role of methionine oxidation/reduction in aging and age-related degenerative diseases and in the regulation of cell function (Hoshi & Heinemann, 2001) stimulated our interest in the role of gold(III) halides in the oxidative process of the amino acid methionine and methionine-containing peptides. By reacting hydrogen tetrachloroaurate(III) with the Gly-D,L-Met dipeptide and subjecting the final product of this reaction to X-ray analysis, we wished to verify the literature reports on the ability of gold(III) halides to oxidize methionine to its sulfoxide, and furthermore to find out whether the newly formed sulfoxide group has the ability to replace chloride ligands in the first coordination sphere of the gold(III) cation, in a manner similar to the coordination of methionine sulfoxide to platinum(II) (Freeman, 1977; Bruhn et al., 1999; Ling et al., 1993). It has been known for some time that gold(III) halides are able to oxidize sulfides (Natile et al., 1976), disulfide bridges in albumin and insulin (Witkiewicz & Shaw, 1981), and methionine residues of ribonuclease (Isab & Sadler, 1977). The mechanism of this redox reaction has been investigated (Natile et al., 1976; Vujačić et al., 2009) but so far no crystallographic evidence for the reaction has been provided. Herein, we report the synthesis, isolation and X-ray analysis of the product of the reaction of hydrogen tetrachloroaurate(III) with the Gly-D,L-Met dipeptide.

The product turned out to be the tetrachloridoaurate(III) salt, (I), of H⁺Gly-Met sulfoxide. The crystal structure consists of discrete square-planar [AuCl₄]^- anions and glycyl-methionine sulfoxide cations (Fig. 1, Table 1). The cations are disordered at the methionine side chain due to the presence, at the same crystallographic site, of two diastereomers differing in their configuration at the triply-bonded S atom. Consequently, the Gly-Met sulfoxide cations contain two asymmetric centres, one at a peptide C^α atom and the other at the S atom. The oxidation and/or crystallization process is partially diastereoselective, leading to an excess of one of the two possible diastereoisomers, i.e. glycyl-S-methionine-R-sulfoxide over glycyl-S-methionine-S-sulfoxide, the ratio being 77:23. Data collected for another crystal selected from the same sample provided a similar ratio of stereoisomers, 0.70:0.30. This crystallographic finding is in contrast with the report (Natile et al., 1976) that the reaction of equimolar amounts of (S)-methionine and hydrogen tetrachloridoaurate(III) in water proceeds with total stereospecificity, providing S-methionine-S-sulfoxide as the sole product. The Gly-Met sulfoxide units of (I) exist as cations, with the N- and C- termini protonated. For the predominant conformer, the relative orientation of the linked units can be described by a set of three torsion angles, ψ₁ = 172.2 (3), ω₁ = 173.8 (4) and Φ₂ = -118.8 (5)°. The S-methionine side chain in the prevalent R-sulfoxide isomer adopts a gauche,gauche,trans conformation (described by the set of torsion angles γ¹ = N2—C3—C5—C6, γ² = C3—C5—C6—S1 and γ³ = C5—C6—S1—C7 listed in Table 1), while the minor S-sulfoxide isomer (defined by the corresponding primed atoms) adopts a gauche,trans,trans conformation.

The extended structure of (I) consists of alternating inorganic ([AuCl₄]^-) and organic (H⁺Gly-Met sulfoxide) layers parallel to the (001) lattice planes and situated at, respectively, 0 and 1/2 along the c axis (Fig. 2a). Within the inorganic layer the closest interanionic Au···Cl distance [3.3890 (10) A%] is less than the sum of the van der Waals radii of the two atoms (3.41 Å; Standard reference?). Thus, the square-planar arrangement of the AuCl₄^- anionic core is complemented into an elongated square pyramid. Two such square-pyramidal units related by a centre of symmetry at (1/2, 1/2, 0) share two Cl^- anions, forming an [Au₂Cl₈]^2- dimer with an Au···Au separation of 3.8862 (3) Å (Fig. 2b), similar to reported examples (Bourosh et al., 2007; Schimansky et al., 1998). These dimeric units, related by a unit translation along the a direction, form close Cl···Cl contacts of 3.3015 (14) Å (shorter than the sum of the van der Waals radii for Cl atoms, 3.50 Å). The ladders thus formed, repeated by a unit translation along the b direction, extend into layers parallel to the (001) lattice plane (Fig. 2a). In between these layers one finds undulating bimolecular layers consisting of H⁺Gly-Met sulfoxide cations (Fig. 2a and c).

The crystal structure of (I) is stabilized by various types of hydrogen bonds (Table 2). The presence of competitive hydrogen-bond acceptors, such as Cl^- anions and sulfoxide O atoms, perturbs the hydrogen-bond pattern typical for dipeptides. The amino···carboxyl hydrogen bond, known in dipeptides as the C(8) motif, now forms the centrosymmetric R₂²(16) ring motif (for graph-set notation, see, for example, Bernstein et al., 1995). In addition, it constitutes part of the R₃²(8) ring pattern, the other constituents being the carboxyl···sulfoxide and the amine···sulfoxide hydrogen bonds. Furthermore, pairs of centrosymmetrically related amine···amide and carboxyl···sulfoxide hydrogen bonds lead to the formation of R₂²(8) and R₂²(16) motifs. Only the amine···sulfoxide C(10) chain joins molecules situated at the same c level. The other hydrogen bonds operate between molecules situated in two neighbouring organic layers, the components of a single bilayer (Fig. 2c). The above-mentioned hydrogen bonds not only hold together molecules constituting the double-molecular organic layer, but also join together the organic and inorganic layers. Intermolecular interactions occur between the protonated N-terminus and the peptide N—H group, and three of the four Cl^- anions.

In conclusion, we have provided crystallographic evidence that the methionine part of the Gly-D,L-Met dipeptide is oxidized to sulfoxide in the presence of gold(III), and no coordination to the gold(III) centre through the S atom of the sulfoxide is observed. In view of these findings, the reported coordination of gold(III) by sulfur in methionine-containing peptides (Ivanova & Mitewa, 2004) requires verification, preferably by crystallographic methods. We have also demonstrated that the oxidative process leads to a substantial excess of one of the two possible diastereoisomers, i.e. S-methionine-R-sulfoxide over S-methionine-S-sulfoxide.

S2. Experimental

Distilled water was demineralized and purified to a resistance greater than 10 MΩ cm^-1. All common chemicals were of reagent grade and used without further purification. The title compound was obtained by mixing together in water equimolar amounts of H[AuCl₄].3H₂O (Aldrich) and glycyl-D,L-methionine (Sigma) in the pH range 1.5-2.0 (achieved by adding a few drops of nitric acid) at room temperature. The resulting solution was filtered and the filtrate left to stand at room temperature, allowing crystals of (I) to precipitate. These crystals were filtered off and dried. Elemental microanalysis was performed by the Microanalytical Laboratory, Faculty of Chemistry, University of Belgrade. Analysis found: C 15.31, H 2.70, N 4.96, S 5.52%; C₇H₁₅N₂O₄SCl₄Au requires: C 14.96, H 2.69, N 4.98, S 5.71%. Yield ca. 40%. Not all products present in the reaction mixture have been identified, but deposits of metallic gold were clearly visible on the walls of the reaction vessel.

The ¹H NMR spectrum of a D₂O solution of (I) containing TSP (sodium trimethylsilylpropane-3-sulfonate) as the internal reference was recorded with a Varian Gemini 200 spectrometer; δ (p.p.m.): 3.91 (GlyCH₂, s), 2.71 (MetδCH₃, s), ~2.40 (MetβCH₂, m), ~3.00 (MetγCH₂, m). As the chemical shift of the singlet of the Gly-Met methyl H atoms is 2.11 p.p.m., the observed very intense singlet at 2.71 p.p.m. was assigned to the methyl H atoms of the Gly-Met sulfoxide. The remaining part of the ¹H NMR spectrum resembled that of the Gly-Met dipeptide measured under the same experimental conditions. That the singlet at 2.71 p.p.m. belongs to the methyl H atoms of the Gly-Met sulfoxide was confirmed by measuring the ¹H NMR spectrum for the pure dimethylsulfoxide in D₂O in acidic solution.

In order to verify whether the presence of nitric acid could have played a role in oxidation of the methionine, the whole synthetic procedure has been repeated using hydrochloric acid instead of nitric acid. On the basis of ¹H NMR and preliminary X-ray data, the reaction product has been identified as that obtained in the presence of nitric acid.

S3. Refinement

The hydroxyl H atom was positioned using the HFIX 147 facility in SHELXL97 (Sheldrick, 2008). The other H atoms were also positioned geometrically and refined using the riding-model technique, with the following distance constraints: tertiary C—H = 1.00, secondary C—H = 0.99, methyl C—H = 0.98, ammonium N—H = 0.91, peptide N—H = 0.88 and hydroxyl O—H = 0.84 Å. U_iso(H) = 1.2U_eq(parent), or 1.5U_eq(parent) for methyl and ammonium groups. The side chain of the methionine sulfoxide was found to be disordered over two sites, representing stereoisomers differing in the configuration at the triply-bonded S atom (R_S or S_S). The occupancy factors refined to 0.77 and 0.23 for the unprimed (R_S) and primed (S_S) fragments, respectively. For the major component, all non-H atoms were refined anisotropically, while for the minor component only the S atom was refined anisotropically. The remaing non-H atoms (C3', C5', C6', C7' and O7') were given a common isotropic displacement parameter which refined to a value of 0.037 (3) Ų.

In order to evaluate whether the stereoselelectivity was maintained across the bulk of the sample, we have performed data collection and the X-ray analysis for another crystal selected from the same sample. For the second data set, the obtained ratio of R_S and S_S stereoisomers was 0.70:0.30.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2007); cell refinement: CrysAlis RED (Oxford Diffraction, 2007); data reduction: CrysAlis RED (Oxford Diffraction, 2007); program(s) used to solve structure: SHELXS86 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Stereochemical Workstation Operation Manual (Siemens, 1989) and Mercury (Bruno et al., 2002); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

Fig. 1. The asymmetric unit of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 40% probability level and H atoms are shown as small spheres of arbitrary radii. Primed and unprimed atoms connected by open and filled bonds, respectively, illustrate the disorder of the methionine sulfoxide side chain, caused by the presence at the same crystallographic site of both RS and SS isomers.

Fig. 2. (a) Alternating cationic and anionic (001) layers situated at, respectively, 1/2 and 0 along c. Hydrogen-bonding interactions are shown as dotted lines. The view is along the a axis. (b) The arrangement of the anionic [AuCl4]^- species within the (001) layer, with close Au···Cl and Cl···Cl interactions indicated by arrows. Dotted lines indicate what? The view is along the c axis. (c) The undulating double molecular cationic layer in (001), viewed along the c axis. Thick and thin lines differentiate molecules situated at different c levels. Hydrogen-bonding interactions are shown as dotted lines.

({(1S,R)-1-carboxy-3-[(R,S)-methylsulfinyl]propyl}aminocarbonyl)methanaminium tetrachloridoaurate(III)

Crystal data

(C7H15N2O4S)[AuCl4]	Z = 2
Mr = 562.04	F(000) = 532
Triclinic, P1	Dx = 2.347 Mg m^−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 7.6250 (5) Å	Cell parameters from 10055 reflections
b = 10.2576 (4) Å	θ = 2.0–27.6°
c = 10.7160 (7) Å	µ = 10.06 mm^−1
α = 95.281 (4)°	T = 130 K
β = 107.222 (6)°	Plate, yellow
γ = 92.001 (4)°	0.30 × 0.20 × 0.03 mm
V = 795.46 (8) Å^3

Data collection

Kuma KM-4 CCD κ-geometry diffractometer	2756 independent reflections
Radiation source: fine-focus sealed tube	2650 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.015
ω scans	θmax = 25.0°, θmin = 2.7°
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2007)	h = −9→9
Tmin = 0.092, Tmax = 1.000	k = −12→12
5656 measured reflections	l = −12→12

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)] = 0.016	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.042	H-atom parameters constrained
S = 1.12	w = 1/[σ^2(Fo^2) + (0.0223P)^2 + 1.1866P] where P = (Fo^2 + 2Fc^2)/3
2756 reflections	(Δ/σ)max = 0.002
201 parameters	Δρmax = 0.53 e Å^−3
34 restraints	Δρmin = −0.91 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	Occ. (<1)
Au1	0.437403 (18)	0.679448 (13)	0.032005 (13)	0.01635 (6)
Cl1	0.15424 (14)	0.72917 (11)	0.04329 (11)	0.0290 (2)
Cl2	0.33202 (13)	0.67455 (10)	−0.19127 (9)	0.0237 (2)
Cl3	0.54176 (14)	0.68106 (12)	0.25560 (10)	0.0295 (2)
Cl4	0.72384 (13)	0.63911 (10)	0.01723 (9)	0.0230 (2)
N1	−0.0180 (5)	0.5924 (3)	0.3259 (3)	0.0240 (7)
H11N	−0.1338	0.5533	0.2946	0.036*
H12N	−0.0183	0.6750	0.3013	0.036*
H13N	0.0206	0.5965	0.4152	0.036*
C1	0.1080 (6)	0.5151 (4)	0.2717 (4)	0.0232 (9)
H11	0.2179	0.5714	0.2754	0.028*
H12	0.0453	0.4826	0.1786	0.028*
C2	0.1663 (5)	0.3999 (4)	0.3504 (4)	0.0223 (9)
O2	0.0941 (4)	0.3706 (3)	0.4326 (3)	0.0311 (7)
N2	0.2970 (5)	0.3336 (4)	0.3197 (4)	0.0281 (8)
H2N	0.3459	0.3624	0.2618	0.034*
C4	0.5671 (6)	0.2324 (5)	0.4509 (4)	0.0289 (10)
O3	0.6539 (4)	0.3361 (3)	0.4829 (3)	0.0316 (7)
O4	0.6382 (5)	0.1179 (4)	0.4763 (4)	0.0488 (10)
H4O	0.7405	0.1305	0.5347	0.073*
C3	0.3608 (7)	0.2124 (6)	0.3737 (5)	0.0225 (13)	0.77
H3A	0.2944	0.1968	0.4392	0.027*	0.77
C5	0.3143 (8)	0.0920 (6)	0.2721 (6)	0.0273 (13)	0.77
H51	0.3651	0.0148	0.3159	0.033*	0.77
H52	0.3756	0.1052	0.2043	0.033*	0.77
C6	0.1082 (7)	0.0624 (5)	0.2045 (5)	0.0277 (12)	0.77
H61	0.0907	−0.0071	0.1305	0.033*	0.77
H62	0.0546	0.1421	0.1676	0.033*	0.77
S1	−0.01353 (19)	0.00961 (14)	0.31427 (15)	0.0289 (3)	0.77
C7	−0.2359 (9)	−0.0187 (7)	0.1908 (8)	0.0343 (19)	0.77
H71	−0.2276	−0.0839	0.1203	0.051*	0.77
H72	−0.2739	0.0637	0.1545	0.051*	0.77
H73	−0.3267	−0.0513	0.2308	0.051*	0.77
O7	0.0469 (10)	−0.1271 (5)	0.3446 (6)	0.0315 (16)	0.77
C3'	0.3536 (16)	0.2337 (15)	0.405 (2)	0.037 (3)*	0.23
H3A'	0.3008	0.2409	0.4799	0.044*	0.23
C5'	0.285 (2)	0.1020 (15)	0.311 (2)	0.037 (3)*	0.23
H51'	0.3218	0.1028	0.2299	0.044*	0.23
H52'	0.3323	0.0247	0.3556	0.044*	0.23
S1'	−0.0288 (7)	−0.0543 (4)	0.2123 (5)	0.0352 (12)	0.23
C6'	0.077 (2)	0.1027 (15)	0.280 (2)	0.037 (3)*	0.23
H61'	0.0293	0.1676	0.2178	0.044*	0.23
H62'	0.0456	0.1291	0.3622	0.044*	0.23
C7'	−0.261 (2)	−0.023 (3)	0.222 (3)	0.037 (3)*	0.23
H71'	−0.3507	−0.0873	0.1604	0.055*	0.23
H72'	−0.2903	0.0656	0.1995	0.055*	0.23
H73'	−0.2648	−0.0311	0.3117	0.055*	0.23
O7'	0.042 (4)	−0.147 (2)	0.316 (3)	0.037 (3)*	0.23

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Au1	0.01414 (9)	0.02028 (9)	0.01630 (9)	0.00131 (5)	0.00643 (6)	0.00419 (6)
Cl1	0.0208 (5)	0.0402 (6)	0.0323 (6)	0.0109 (4)	0.0141 (4)	0.0128 (4)
Cl2	0.0233 (5)	0.0310 (5)	0.0172 (5)	0.0008 (4)	0.0055 (4)	0.0067 (4)
Cl3	0.0230 (5)	0.0501 (6)	0.0168 (5)	0.0015 (5)	0.0077 (4)	0.0045 (4)
Cl4	0.0157 (4)	0.0340 (5)	0.0215 (5)	0.0033 (4)	0.0082 (4)	0.0047 (4)
N1	0.0201 (17)	0.0315 (19)	0.0221 (18)	0.0035 (14)	0.0067 (14)	0.0092 (14)
C1	0.019 (2)	0.035 (2)	0.018 (2)	0.0044 (17)	0.0070 (16)	0.0099 (17)
C2	0.0151 (18)	0.035 (2)	0.0166 (19)	0.0014 (17)	0.0025 (16)	0.0073 (17)
O2	0.0296 (16)	0.0437 (18)	0.0274 (16)	0.0093 (14)	0.0149 (14)	0.0183 (14)
N2	0.0223 (18)	0.041 (2)	0.0273 (19)	0.0088 (16)	0.0123 (15)	0.0164 (16)
C4	0.023 (2)	0.044 (3)	0.023 (2)	0.013 (2)	0.0083 (18)	0.0120 (19)
O3	0.0322 (17)	0.0379 (18)	0.0215 (16)	0.0053 (14)	0.0028 (13)	0.0029 (13)
O4	0.0273 (18)	0.047 (2)	0.064 (3)	0.0046 (16)	−0.0037 (17)	0.0206 (19)
C3	0.017 (3)	0.038 (3)	0.019 (3)	0.012 (2)	0.012 (2)	0.012 (2)
C5	0.026 (3)	0.034 (3)	0.026 (3)	0.004 (2)	0.012 (2)	0.012 (2)
C6	0.034 (3)	0.025 (3)	0.024 (3)	0.004 (2)	0.007 (2)	0.008 (2)
S1	0.0245 (7)	0.0255 (7)	0.0352 (8)	0.0044 (5)	0.0067 (6)	0.0021 (6)
C7	0.024 (3)	0.024 (3)	0.052 (6)	0.000 (2)	0.006 (3)	0.010 (3)
O7	0.028 (2)	0.030 (3)	0.037 (4)	0.012 (2)	0.005 (3)	0.014 (3)
S1'	0.039 (3)	0.018 (2)	0.032 (3)	0.0110 (19)	−0.014 (2)	−0.0064 (19)

Geometric parameters (Å, º)

Au1—Cl1	2.2709 (10)	C5—H51	0.9900
Au1—Cl2	2.2824 (10)	C5—H52	0.9900
Au1—Cl4	2.2852 (9)	C6—S1	1.808 (6)
Au1—Cl3	2.2885 (10)	C6—H61	0.9900
N1—C1	1.479 (5)	C6—H62	0.9900
N1—H11N	0.9100	S1—O7	1.525 (5)
N1—H12N	0.9100	S1—C7	1.810 (7)
N1—H13N	0.9100	C7—H71	0.9800
C1—C2	1.517 (5)	C7—H72	0.9800
C1—H11	0.9900	C7—H73	0.9800
C1—H12	0.9900	C3'—C5'	1.582 (17)
C2—O2	1.222 (5)	C3'—H3A'	1.0000
C2—N2	1.328 (5)	C5'—C6'	1.521 (17)
N2—C3'	1.427 (18)	C5'—H51'	0.9900
N2—C3	1.457 (6)	C5'—H52'	0.9900
N2—H2N	0.8800	S1'—O7'	1.519 (17)
C4—O3	1.199 (5)	S1'—C6'	1.766 (14)
C4—O4	1.328 (6)	S1'—C7'	1.840 (17)
C4—C3	1.542 (6)	C6'—H61'	0.9900
C4—C3'	1.556 (12)	C6'—H62'	0.9900
O4—H4O	0.8400	C7'—H71'	0.9800
C3—C5	1.527 (7)	C7'—H72'	0.9800
C3—H3A	1.0000	C7'—H73'	0.9800
C5—C6	1.529 (7)
Cl1—Au1—Cl2	89.53 (4)	C6—C5—H51	108.7
Cl1—Au1—Cl4	177.23 (4)	C3—C5—H52	108.7
Cl2—Au1—Cl4	89.40 (4)	C6—C5—H52	108.7
Cl1—Au1—Cl3	90.47 (4)	H51—C5—H52	107.6
Cl2—Au1—Cl3	179.14 (4)	C5—C6—S1	112.9 (4)
Cl4—Au1—Cl3	90.64 (4)	C5—C6—H61	109.0
C1—N1—H11N	109.5	S1—C6—H61	109.0
C1—N1—H12N	109.5	C5—C6—H62	109.0
H11N—N1—H12N	109.5	S1—C6—H62	109.0
C1—N1—H13N	109.5	H61—C6—H62	107.8
H11N—N1—H13N	109.5	O7—S1—C6	106.3 (3)
H12N—N1—H13N	109.5	O7—S1—C7	104.7 (3)
N1—C1—C2	109.9 (3)	C6—S1—C7	95.7 (3)
N1—C1—H11	109.7	N2—C3'—C4	110.3 (12)
C2—C1—H11	109.7	N2—C3'—C5'	103.6 (14)
N1—C1—H12	109.7	C4—C3'—C5'	105.0 (10)
C2—C1—H12	109.7	N2—C3'—H3A'	112.4
H11—C1—H12	108.2	C4—C3'—H3A'	112.4
O2—C2—N2	123.9 (4)	C5'—C3'—H3A'	112.4
O2—C2—C1	121.7 (4)	C6'—C5'—C3'	102.3 (12)
N2—C2—C1	114.4 (3)	C6'—C5'—H51'	111.3
C2—N2—C3'	110.8 (8)	C3'—C5'—H51'	111.3
C2—N2—C3	123.5 (4)	C6'—C5'—H52'	111.3
C2—N2—H2N	118.8	C3'—C5'—H52'	111.3
C3'—N2—H2N	129.8	H51'—C5'—H52'	109.2
C3—N2—H2N	117.7	O7'—S1'—C6'	106.6 (11)
O3—C4—O4	123.9 (4)	O7'—S1'—C7'	103.8 (12)
O3—C4—C3	125.4 (4)	C6'—S1'—C7'	97.4 (10)
O4—C4—C3	110.7 (4)	C5'—C6'—S1'	110.6 (11)
O3—C4—C3'	117.6 (7)	C5'—C6'—H61'	109.5
O4—C4—C3'	117.1 (7)	S1'—C6'—H61'	109.5
C4—O4—H4O	109.5	C5'—C6'—H62'	109.5
N2—C3—C5	113.8 (4)	S1'—C6'—H62'	109.5
N2—C3—C4	109.5 (4)	H61'—C6'—H62'	108.1
C5—C3—C4	113.3 (4)	S1'—C7'—H71'	109.5
N2—C3—H3A	106.6	S1'—C7'—H72'	109.5
C5—C3—H3A	106.6	H71'—C7'—H72'	109.5
C4—C3—H3A	106.6	S1'—C7'—H73'	109.5
C3—C5—C6	114.1 (5)	H71'—C7'—H73'	109.5
C3—C5—H51	108.7	H72'—C7'—H73'	109.5
N1—C1—C2—O2	9.4 (5)	C3—C5—C6—S1	−68.1 (5)
N1—C1—C2—N2	−172.2 (3)	C5—C6—S1—O7	−70.3 (5)
O2—C2—N2—C3'	−6.1 (8)	C5—C6—S1—C7	−177.5 (5)
C1—C2—N2—C3'	175.5 (7)	C2—N2—C3'—C4	−135.7 (9)
O2—C2—N2—C3	4.5 (7)	C2—N2—C3'—C5'	112.4 (11)
C1—C2—N2—C3	−173.8 (4)	O3—C4—C3'—N2	43.1 (15)
C2—N2—C3—C5	113.2 (5)	O4—C4—C3'—N2	−149.7 (8)
C2—N2—C3—C4	−118.8 (5)	O3—C4—C3'—C5'	154.1 (12)
O3—C4—C3—N2	12.9 (7)	O4—C4—C3'—C5'	−38.7 (17)
O4—C4—C3—N2	−166.3 (4)	N2—C3'—C5'—C6'	−69.7 (17)
O3—C4—C3—C5	141.1 (5)	C4—C3'—C5'—C6'	174.6 (15)
O4—C4—C3—C5	−38.1 (6)	C3'—C5'—C6'—S1'	−164.6 (15)
N2—C3—C5—C6	−60.0 (6)	O7'—S1'—C6'—C5'	62 (2)
C4—C3—C5—C6	174.0 (4)	C7'—S1'—C6'—C5'	169.1 (18)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H11N···Cl2^i	0.91	2.69	3.476 (4)	145
N1—H11N···Cl3^ii	0.91	2.78	3.392 (3)	126
N1—H12N···O7^iii	0.91	2.05	2.881 (7)	151
N1—H13N···O2^iv	0.91	2.07	2.811 (4)	137
N1—H13N···O3^v	0.91	2.44	2.942 (5)	115
N2—H2N···Cl2^vi	0.88	2.80	3.493 (4)	136
N2—H2N···Cl4^vi	0.88	2.88	3.604 (4)	141
O4—H4O···O7^vii	0.84	1.75	2.585 (7)	170

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