N-Amidino-4-hydroxy-L-proline monohydrate and N-amidino-L-methionine monohydrate

The title amidino-amino acids (a-Hpro), C₆H₁₁N₃O₃·H₂O, (I), and a-Met, C₆H₁₃N₃O₂S·H₂O, (II), respectively, exist in the form of zwitterions. The five-membered pyrrolidine ring in (I) adopts an envelope conformation, with the Cγ atom out of the plane defined by the rest of the ring atoms, and with the hydroxyl and carboxyl­ate groups in a trans configuration relative to the ring plane. The two crystallographically independent zwitterions in (II) reveal quite different conformations of their side chains and a slightly different orientation of the guanidine moiety with respect to the carboxyl­ate group. The crystal structures of both (I) and (II) are stabilized by extensive networks of O—H...O, N—H...O and C—H...O hydrogen bonds, the network being three-dimensional in (I) and two-dimensional in (II).

S1. Comment

The title compounds, α-guanidino acids, derived from 4-hydroxyproline and methionine, amidino-4-hydroxy-L-proline, a-Hpro, (I), and amidino-L-methionine, a-Met, (II), have been crystallized and structurally analysed by X-ray crystallography as a completion of broader studies on the chiro-optical properties of the guanidine chromophore (Siemion et al., 2004). We present here the complete geometric characterization of (I) and (II) in the solid state, together with a comparison of their molecular structures with related compounds and an analysis of their intermolecular interactions in the crystal network. \sch

Both (I) and (II) crystallize as hydrated zwitterions, with one zwitterion in the asymmetric unit of (I) and two crystallographically independent zwitterions [denoted (1) and (2)] in (II). All the zwitterions in both (I) and (II) exist with the carboxyl groups deprotonated and the amidine moieties protonated. The positive charge is delocalized into the whole amidine group; the π-electron pair is equally distributed between the three C—N bonds, which makes C0—N1, C0—N2 and C0—N3 equal in length (about 1.33 Å; Tables 1 and 3) and the whole guanidine group planar [atoms C0, N1, N2 and N3 lie in one plane to within 0.003 or 0.005 Å in (I) and (II), respectively].

A very interesting structural feature of α-guanidino acids, of relevance to studies on the chiro-optical properties of the guanidine chromophore, is the orientation of the amidine atom C0 relative to the carboxylate atom C1, and the mutual orientation of the planar guanidine and carboxylate moieties. In (I), the amidine group is in a gauche (-sc) orientation with respect to the carboxylate substituent, whereas in the two crystallographically independent zwitterions of (II), the respective C0—N1—C2—C1 torsion angles reveal ap and -ac conformations for (1) and (2), respectively. The dihedral angles between the two planes defined by the guanidine and carboxylate groups are 79.9 (2)° in (I), and 21.1 (1) and 44.3 (1)° in (1) and (2), respectively, of (II).

The Ψ¹ (O1—C1—C2—N1) and Ψ² (O2—C1—C2—N1) torsion angles are −24.9 (3) and 158.0 (2)° for (I), and −20.2 (2) and 159.6 (1)° and −29.4 (2) and 151.4 (1)° for zwitterions (1) and (2) in (II). Thus, atom N1 is displaced from the plane of the carboxylate group by about 0.43 Å in (I), and by 0.49 and −0.64 Å in (1) and (2) of (II), respectively.

The molecular structure of (I) and the conformation of the pyrrolidine ring are shown in Fig. 1. The five-membered pyrrolidine ring adopts an envelope conformation, with the Cγ atom (C4) lying out of the ring plane [the dihedral angle between the N1/C2/C3/C5 and C3/C4/C5 planes is 35.2 (2)°], and with the hydroxyl and carboxylate groups in a trans configuration relative to the plane of the pyrrolidine ring. A similar conformation of the ring and orientation of the –OH and –COOH substituents were found previously in 4-hydroxy-L-proline (Donohue & Trueblood, 1952; Koetzle et al., 1973) and its palladium complex (Patel et al., 1986). It is interesting to note that a different puckering of the pyrrolidine ring has sometimes been observed in hydroxyproline derivatives and analogues, such as allo-4-hydroxy-L-proline dihydrate (Shamala et al., 1976) and 2,3-cis-3,4-trans-3,4-dihydroxy-L-proline (Karle, 1970) (envelope with Cβ atom puckered), or N-methylated 4-hydroxyproline derivatives (Jones et al., 1988) (envelope with N atom puckered).

The ring substituents in (I), i.e. amidine, carboxylate and hydoxyl groups, are in equatorial, bisectional and axial positions, respectively. The guanidine group is nearly coplanar with the four plane-defining pyrrolidine ring atoms; the dihedral angle between the respective planes is 10.3 (2)°).

The molecular structures of the two crystallographically independent zwitterions in (II) are shown in Fig. 2. Zwitterions (1) and (2) reveal quite different conformations of their side-chains and, as described above, slightly different orientations of the guanidine moiety with respect to the rest of the molecule, especially to the carboxylate group, and this is readily observed in the superimposition of the two zwitterions shown in Fig. 2. The values of the C¹ (N1—C2—C3—C4), C² (C2—C3—C4—S) and C³ (C3—C4—S—C5) torsion angles (Table 3) indicate the +gauche, trans, -gauche and -gauche, trans, -gauche conformations of the side-chains in (1) and (2), respectively.

Similar gauche, trans, gauche side-chain conformations are quite commonly present in methionine residues and have been observed previously, for example in the methioninium cations in crystalline L-methioninium nitrate (Pandirajan et al., 2002) and DL-methioninium trichloroacetate (Rajagopal et al., 2003), or in the methionine zwitterions in L-methionine L-methioninium perchlorate monohydrate (Sridhar et al., 2002), and even in one of the methionine moieties in the L-methionyl-L-methionine dipeptide (Stenkamp & Jensen, 1975). However, in the crystal of L-methionine, two different conformations of the side-chain were observed, neither of them being as described above (Torii & Iitaka, 1973).

The main difference in the side-chain conformations of (1) and (2) is the orientation of their Cγ atom (C4) relative to the carboxylate atom C1, which is -sc in (1) and ap in (2). Three of the four side-chain atoms in (2), namely C32, C42 and S2, together with atoms C12 and C22 from the main chain, lie in one plane (to within 0.04 Å), from which methyl atom C52 deviates by about 1.67 Å. This is reflected in the C12—C22—C32—C42 and C22—C32—C42—S2 torsion angles, which are both close to 180° (Table 3).

The crystal structure of (I) is stabilized by a network of O—H···O and N—H···O hydrogen bonds, in which hydroxyl, amidine and carboxylate groups, as well as the water molecules, are involved (Fig. 3, Table 2). Additionally, there are also close C—H···O contacts. The strongest O—H···O interaction is formed between the hydroxyl and carboxylate groups of adjacent a-Hpro zwitterions. The water molecules act as donors of medium-strength O—H···O hydrogen bonds to the carboxylate O atoms from two different zwitterions. Simultaneously, a water O atom is an acceptor of one N—H···O contact from the amidine group, which also acts as a donor of three additional N—H···O hydrogen bonds to the hydroxyl and carboxylate groups from three different adjacent zwitterions. The carboxylate moiety is involved as acceptor in five different hydrogen-bond interactions, hence three- or four-centred contacts are formed. Thus, the hydrogen-bond network linking adjacent zwitterions and water molecules in the crystal of (I) is three-dimensional (Fig. 3).

The packing of (II) is quite different from that observed in (I) (Figs. 4 and 5; Table 4). As can be seen in Fig. 4, the crystal has a layer architecture. The two crystallographically independent zwitterions have almost identical hydrogen-bonding features. Zwitterions (1) and (2) are linked to each other by two three-centred N—H···O contacts formed by their guanidine and carboxylate groups. This results in (1)-(2) dimers, in which guanidine –NH and one of the –NH₂ groups are involved. The other –NH₂ group acts as a linker to the adjacent (1)-(2) dimer by acting in an N—H···O hydrogen-bond to the carboxylate O atom from an adjacent dimer, to form infinite ribbons along the a axis. Pairs of adjacent ribbons are linked by water molecules to form layers parallel to the (001) plane, in which the a-Met side-chains of both (1) and (2) are located on one side of the plane defined by the two-dimensional O—H···O and N—H···O hydrogen-bond network. The arrangement of the zwitterions and water molecules within the layer is shown in Fig. 5. Both water molecules are involved in additional O—H···O interactions with the adjacent head-to-head layer and act as the linkers between each such pair of adjacent layers. This assembly of a-Met zwitterions and water molecules leads to the double-layer architecture of the crystal of (II). The result of this arrangement of the individual zwitterions in the crystal network is the aggregation of the hydrophilic and hydrophobic groups into two distinct regions in the crystal, which is very often observed in crystals containing the methionine moiety (Mathieson, 1952; Torii & Iitaka, 1973; Alagar et al., 2002; Pandirajan et al., 2002; Sridhar et al., 2002; Rajagopal et al., 2003).

Table 2. Hydrogen-bonding and close C—H···O contact geometry for (I) (Å, °)

S2. Experimental

The synthesis of guanidino acids (amidino-aminoacids) and their purification and characterization by high-pressure liquid chromatography and ESI-MS, along with the CD and UV spectra peculiarities, are described in detail by Siemion et al., 2004. Crystals of (I) (II), were obtained by recrystallization of the synthesized compounds. Slow evaporation of aqueous solutions at 277 K gave long thin colourless plates of (I), and very fragile colourless parallelepipeds of (II), with a tendency to twinning.

S3. Refinement

All H atoms were found in a difference Fourier map and were refined isotropically, except for atom H22 in (II), which, due to the rather low value of its displacement parameter, was refined with U_iso = U_eq(C22). Friedel opposites for (I) were merged and the absolute configuration was established on the basis of the known stereochemistry of the molecule.

Computing details

For both compounds, data collection: CrysAlis CCD (Oxford Diffraction, 2003); cell refinement: CrysAlis RED (Oxford Diffraction, 2003); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. (a) The molecular structure of the zwitterion in (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 40% probability level and H atoms are shown as small spheres of arbitrary radii. (b) The conformation of the pyrrolidine ring in (I).
	Fig. 2. The molecular structure of the two crystallographically independent zwitterions in (II). (a) (1) and (b) (2). The dashed line in (b) indicates the superimposed structure of (1), allowing a comparison of (1) and (2). The common reference points are atoms C1, O1 and O2. Displacement ellipsoids are drawn at the 40% probability level and H atoms are shown as small spheres of arbitrary radii.
	Fig. 3. A view of the three-dimensional network of O—H···O and N—H···O hydrogen bonds linking adjacent zwitterions and water molecules in the crystal of (I). [Symmetry codes are as listed in Table 2.]
	Fig. 4. A crystal packing diagram of (II), viewed down the a axis, showing the layer architecture.
	Fig. 5. A packing diagram for (II), showing the arrangement of the zwitterions and water molecules within the layer formed by O—H···O and N—H···O hydrogen bonds, viewed down the c axis. The a-Met side-chains are shown as thin lines. [Symmetry codes are as listed in Table 4.]

(I) N-Amidino-4-hydroxy-L-proline monohydrate

Crystal data

C6H11N3O3·H2O	F(000) = 408
Mr = 191.19	Dx = 1.528 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 6400 reflections
a = 4.604 (2) Å	θ = 3.3–28.3°
b = 12.514 (4) Å	µ = 0.13 mm^−1
c = 14.422 (4) Å	T = 100 K
V = 830.9 (5) Å^3	Plate, colourless
Z = 4	0.50 × 0.10 × 0.03 mm

Data collection

Kuma KM4 CCD κ-geometry diffractometer	923 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.077
Graphite monochromator	θmax = 27.0°, θmin = 3.3°
ω scans	h = −5→5
5278 measured reflections	k = −15→7
1066 independent reflections	l = −18→18

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)] = 0.039	All H-atom parameters refined
wR(F^2) = 0.081	w = 1/[σ^2(Fo^2) + (0.0469P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.03	(Δ/σ)max < 0.001
1066 reflections	Δρmax = 0.20 e Å^−3
170 parameters	Δρmin = −0.21 e Å^−3
0 restraints	Absolute structure: known absolute configuration
Primary atom site location: structure-invariant direct methods

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
O1	−0.1823 (4)	0.0600 (2)	0.2950 (2)	0.0167 (4)
O2	0.1533 (4)	0.1207 (2)	0.3950 (2)	0.0168 (4)
O3	0.2106 (4)	0.3812 (2)	0.1082 (2)	0.0169 (4)
O1W	−0.0050 (5)	0.1963 (2)	0.5706 (2)	0.0242 (5)
N1	0.0993 (5)	0.1549 (2)	0.1465 (2)	0.0141 (5)
N2	0.0864 (5)	0.0278 (2)	0.0311 (2)	0.0168 (5)
N3	0.4007 (5)	0.0070 (2)	0.1532 (2)	0.0168 (5)
C0	0.1968 (6)	0.0633 (2)	0.1107 (2)	0.0147 (5)
C1	0.0348 (6)	0.1158 (2)	0.3167 (2)	0.0145 (5)
C2	0.1608 (6)	0.1897 (2)	0.2423 (2)	0.0136 (5)
C3	0.0098 (6)	0.3000 (2)	0.2481 (2)	0.0158 (5)
C4	−0.0431 (6)	0.3335 (2)	0.1477 (2)	0.0145 (6)
C5	−0.0981 (6)	0.2282 (2)	0.0990 (2)	0.0151 (6)
H2	0.378 (6)	0.194 (2)	0.250 (2)	0.015 (7)*
H21	0.148 (7)	−0.026 (2)	0.001 (2)	0.029 (9)*
H22	−0.048 (8)	0.067 (2)	−0.001 (2)	0.026 (8)*
H3	0.209 (7)	0.450 (3)	0.136 (2)	0.037 (9)*
H31	0.437 (7)	−0.062 (2)	0.125 (2)	0.028 (8)*
H32	0.498 (7)	0.033 (2)	0.195 (2)	0.021 (8)*
H3A	−0.165 (7)	0.291 (2)	0.280 (2)	0.025 (8)*
H3B	0.123 (7)	0.358 (2)	0.285 ()	0.027 (8)*
H4	−0.205 (6)	0.380 (2)	0.138 (2)	0.013 (7)*
H5A	−0.310 (6)	0.210 (2)	0.102 (2)	0.016 (7)*
H5B	−0.064 (6)	0.235 (2)	0.034 (2)	0.018 (7)*
H1W	−0.108 (10)	0.256 (3)	0.586 (3)	0.07 (2)*
H2W	−0.011 (9)	0.181 (3)	0.513 (3)	0.06 (2)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0128 (9)	0.0211 (9)	0.0163 (9)	−0.0028 (9)	−0.0022 (8)	0.0014 (8)
O2	0.0175 (9)	0.0199 (8)	0.0130 (8)	−0.0004 (9)	−0.0033 (8)	0.0011 (8)
O3	0.0151 (9)	0.0168 (9)	0.0190 (9)	−0.0034 (8)	0.0046 (8)	−0.0005 (8)
O1W	0.0286 (11)	0.0286 (11)	0.0155 (10)	0.0091 (11)	0.0011 (10)	0.0001 (9)
N1	0.0145 (11)	0.0180 (10)	0.0098 (9)	0.0024 (9)	−0.0027 (10)	−0.0001 (9)
N2	0.0163 (12)	0.0191 (12)	0.0151 (11)	0.0033 (10)	−0.0026 (11)	−0.0029 (10)
N3	0.0172 (12)	0.0191 (12)	0.0140 (11)	0.0037 (10)	−0.0046 (11)	−0.0029 (9)
C0	0.0118 (11)	0.0173 (12)	0.0151 (11)	−0.0013 (11)	0.0052 (12)	0.0038 (11)
C1	0.0125 (12)	0.0156 (12)	0.0155 (12)	0.0019 (12)	0.0021 (11)	−0.0007 (11)
C2	0.0148 (13)	0.0155 (12)	0.0105 (11)	−0.0001 (12)	−0.0010 (11)	−0.0024 (10)
C3	0.0157 (12)	0.0167 (12)	0.0152 (12)	0.0004 (12)	0.0034 (12)	−0.0012 (11)
C4	0.0101 (12)	0.0188 (12)	0.0147 (12)	0.0012 (11)	0.0030 (11)	0.0018 (10)
C5	0.0104 (12)	0.0203 (13)	0.0147 (12)	0.0019 (10)	−0.0015 (12)	0.0030 (11)

Geometric parameters (Å, º)

C1—O1	1.258 (3)	C3—H3B	1.04 (3)
C1—O2	1.255 (3)	C4—C5	1.514 (4)
C2—N1	1.476 (3)	C4—H4	0.96 (3)
C5—N1	1.462 (3)	C5—H5A	1.00 (3)
C4—O3	1.430 (3)	C5—H5B	0.96 (3)
C0—N1	1.335 (3)	O3—H3	0.95 (3)
C0—N2	1.332 (3)	N3—H31	0.96 (3)
C0—N3	1.324 (3)	N3—H32	0.82 (3)
C1—C2	1.530 (4)	N2—H21	0.84 (3)
C2—C3	1.548 (4)	N2—H22	0.92 (4)
C2—H2	1.01 (3)	O1W—H1W	0.92 (4)
C3—C4	1.527 (4)	O1W—H2W	0.86 (4)
C3—H3A	0.93 (3)
O2—C1—O1	126.6 (2)	O3—C4—C5	108.4 (2)
O1—C1—C2	117.5 (2)	O3—C4—C3	111.2 (2)
O2—C1—C2	115.9 (2)	C5—C4—C3	103.2 (2)
N1—C0—N2	119.4 (2)	O3—C4—H4	109 (2)
N1—C0—N3	121.0 (2)	C5—C4—H4	109 (2)
N2—C0—N3	119.5 (2)	C3—C4—H4	116 (2)
C0—N1—C2	123.5 (2)	N1—C5—C4	103.0 (2)
C0—N1—C5	124.5 (2)	N1—C5—H5A	116 (2)
C2—N1—C5	111.9 (2)	C4—C5—H5A	110 (2)
N1—C2—C1	113.9 (2)	N1—C5—H5B	115 (2)
N1—C2—C3	103.1 (2)	C4—C5—H5B	111 (2)
C1—C2—C3	109.3 (2)	H5A—C5—H5B	103 (2)
N1—C2—H2	108 (2)	C4—O3—H3	102 (2)
C1—C2—H2	109 (2)	C0—N3—H31	114 (2)
C3—C2—H2	113 (2)	C0—N3—H32	121 (2)
C4—C3—C2	105.4 (2)	H31—N3—H32	125 (3)
C4—C3—H3A	111 (2)	C0—N2—H21	125 (2)
C2—C3—H3A	108 (2)	C0—N2—H22	121 (2)
C4—C3—H3B	112 (2)	H21—N2—H22	113 (3)
C2—C3—H3B	115 (2)	H1W—O1W—H2W	114 (3)
H3A—C3—H3B	105 (2)
O1—C1—C2—N1	−24.9 (3)	N2—C0—N1—C2	166.9 (2)
O2—C1—C2—N1	158.0 (2)	N3—C0—N1—C2	−12.9 (4)
O1—C1—C2—C3	89.9 (3)	N2—C0—N1—C5	−8.0 (4)
O2—C1—C2—C3	−87.2 (3)	N3—C0—N1—C5	172.1 (2)
N1—C2—C3—C4	−17.0 (3)	C1—C2—N1—C0	−63.2 (3)
C1—C2—C3—C4	−138.6 (2)	C3—C2—N1—C0	178.4 (2)
C2—C3—C4—O3	−82.8 (3)	C1—C2—N1—C5	112.2 (2)
C2—C3—C4—C5	33.1 (3)	C3—C2—N1—C5	−6.1 (3)
O3—C4—C5—N1	81.9 (2)	C4—C5—N1—C0	−157.7 (2)
C3—C4—C5—N1	−36.0 (3)	C4—C5—N1—C2	26.9 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H21···O2^i	0.84 (3)	2.15 (3)	2.957 (3)	161 (3)
N2—H22···O3^ii	0.92 (4)	2.01 (4)	2.885 (3)	159 (3)
N3—H31···O1W^i	0.96 (3)	1.89 (3)	2.850 (3)	180 (3)
N3—H32···O1^iii	0.82 (3)	2.08 (3)	2.882 (3)	163 (3)
O3—H3···O1^iv	0.95 (3)	1.70 (3)	2.642 (3)	169 (3)
O1W—H1W···O2^v	0.92 (4)	1.91 (5)	2.823 (3)	173 (4)
O1W—H2W···O2	0.86 (4)	2.00 (4)	2.800 (3)	154 (4)
C2—H2···O1^iii	1.01 (3)	2.71 (3)	3.515 (3)	138 (2)
C3—H3A···O1W^v	0.93 (3)	2.67 (3)	3.531 (4)	154 (2)
C4—H4···O3^vi	0.96 (3)	2.72 (3)	3.533 (4)	143 (2)
C5—H5B···O3^ii	0.96 (3)	2.72 (3)	3.402 (3)	129 (2)

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

(II) N-amidino-L-methionine monohydrate

Crystal data

C6H13N3O2S·H2O	F(000) = 448
Mr = 209.27	Dx = 1.353 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 18427 reflections
a = 8.982 (3) Å	θ = 3.1–36.6°
b = 9.844 (3) Å	µ = 0.30 mm^−1
c = 12.066 (4) Å	T = 100 K
β = 105.64 (3)°	Parallelepiped, colourless
V = 1027.4 (6) Å^3	0.30 × 0.10 × 0.10 mm
Z = 4

Data collection

Kuma KM4 CCD κ-geometry diffractometer	7275 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.036
Graphite monochromator	θmax = 36.0°, θmin = 3.1°
ω scans	h = −14→14
21484 measured reflections	k = −15→16
8879 independent reflections	l = −19→17

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)] = 0.039	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.078	w = 1/[σ^2(Fo^2) + (0.0399P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.98	(Δ/σ)max = 0.001
8879 reflections	Δρmax = 0.35 e Å^−3
354 parameters	Δρmin = −0.23 e Å^−3
1 restraint	Absolute structure: known absolute configuration confirmed by anomalous dispersion effects (Flack, 1983) with how many Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.02 (4)

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	0.94101 (4)	0.50568 (4)	1.03889 (3)	0.02469 (8)
S2	0.46058 (4)	0.23271 (4)	1.08970 (3)	0.02891 (8)
O11	0.77277 (9)	0.21446 (9)	0.65866 (7)	0.0159 (2)
O12	0.52003 (10)	0.47343 (9)	0.65140 (8)	0.0191 (2)
O21	1.02248 (10)	0.15741 (9)	0.70187 (8)	0.0164 (2)
O22	0.27924 (9)	0.52598 (8)	0.65441 (7)	0.0152 (2)
O1W	0.35522 (12)	−0.22899 (10)	0.57595 (9)	0.0210 (2)
O2W	0.88979 (11)	0.93637 (9)	0.56948 (9)	0.0206 (2)
N11	0.83253 (12)	0.47833 (10)	0.65204 (9)	0.0139 (2)
N12	0.48149 (11)	0.21256 (10)	0.70620 (9)	0.0148 (2)
N21	0.72029 (12)	0.68607 (11)	0.59634 (10)	0.0173 (2)
N22	0.54351 (12)	0.00644 (12)	0.64286 (10)	0.0185 (2)
N31	0.98387 (12)	0.66325 (11)	0.63070 (10)	0.0165 (2)
N32	0.30246 (13)	0.03436 (11)	0.67038 (11)	0.0189 (2)
C01	0.84695 (13)	0.60876 (11)	0.62699 (10)	0.0130 (2)
C02	0.44111 (13)	0.08558 (12)	0.67294 (10)	0.0140 (2)
C11	0.91564 (12)	0.24223 (12)	0.68850 (9)	0.0119 (2)
C12	0.39705 (13)	0.44856 (11)	0.67573 (9)	0.0121 (2)
C21	0.96236 (13)	0.39179 (11)	0.70969 (10)	0.0126 (2)
C22	0.38356 (13)	0.31501 (12)	0.73820 (10)	0.0130 (2)
C31	1.01853 (13)	0.42511 (13)	0.83939 (10)	0.0157 (2)
C32	0.43105 (15)	0.33898 (12)	0.86910 (11)	0.0159 (2)
C41	0.8908 (15)	0.42094 (15)	0.90065 (11)	0.0202 (2)
C42	0.40892 (15)	0.21132 (14)	0.93510 (11)	0.0212 (2)
C51	1.0842 (2)	0.3911 (2)	1.12186 (14)	0.0383 (4)
C52	0.6667 (2)	0.2505 (2)	1.11843 (14)	0.0319 (3)
H11	0.742 (2)	0.455 (2)	0.6571 (14)	0.019 (4)*
H12	0.569 (2)	0.239 (2)	0.7014 (15)	0.026 (4)*
H21	1.048 (2)	0.407 (2)	0.6777 (13)	0.012 (3)*
H22	0.276 (2)	0.286 (2)	0.7135 (13)	0.013*
H211	0.636 (2)	0.654 (2)	0.6035 (14)	0.018 (4)*
H212	0.730 (2)	0.770 (2)	0.5856 (15)	0.022 (4)*
H221	0.629 (2)	0.040 (2)	0.6378 (14)	0.022 (4)*
H222	0.517 (2)	−0.069 (2)	0.6214 (15)	0.027 (5)*
H311	1.066 (2)	0.613 (2)	0.6459 (15)	0.026 (4)*
H312	0.980 (2)	0.742 (2)	0.6060 (16)	0.032 (5)*
H321	0.229 (2)	0.077 (2)	0.6850 (15)	0.030 (5)*
H322	0.283 (2)	−0.044 (2)	0.6448 (15)	0.019 (4)*
H31A	1.102 (2)	0.358 (2)	0.8774 (14)	0.022 (4)*
H31B	1.066 (2)	0.516 (2)	0.8462 (13)	0.022 (4)*
H32A	0.539 (2)	0.367 (2)	0.8923 (13)	0.015 (4)*
H32B	0.372 (2)	0.414 (2)	0.8875 (14)	0.019 (4)*
H41A	0.863 (2)	0.332 (2)	0.9109 (15)	0.026 (4)*
H41B	0.798 (2)	0.468 (2)	0.8600 (15)	0.026 (4)*
H42A	0.462 (2)	0.134 (2)	0.9179 (13)	0.016 (4)*
H42B	0.300 (2)	0.185 (2)	0.9140 (15)	0.024 (4)*
H51A	1.114 (2)	0.426 (2)	1.199 (2)	0.040 (5)*
H51B	1.177 (3)	0.391 (3)	1.095 (2)	0.059 (7)*
H51C	1.041 (3)	0.299 (3)	1.113 (2)	0.046 (6)*
H52A	0.709 (2)	0.248 (3)	1.200 (2)	0.048 (6)*
H52B	0.698 (2)	0.328 (2)	1.090 (2)	0.040 (6)*
H52C	0.701 (2)	0.177 (2)	1.089 (2)	0.037 (5)*
H1W	0.336 (2)	−0.300 (2)	0.602 (2)	0.036 (5)*
H2W	0.323 (2)	−0.235 (2)	0.506 (2)	0.039 (6)*
H3W	0.927 (2)	1.004 (2)	0.616 (2)	0.027 (4)*
H4W	0.850 (2)	0.971 (2)	0.506 (2)	0.035 (5)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0284 (2)	0.0249 (2)	0.0217 (2)	0.00530 (14)	0.00833 (12)	−0.00508 (13)
S2	0.0322 (2)	0.0348 (2)	0.0242 (2)	0.00854 (16)	0.01535 (13)	0.01053 (14)
O11	0.0101 (3)	0.0118 (4)	0.0261 (4)	−0.0008 (3)	0.0053 (3)	−0.0008 (3)
O12	0.0119 (4)	0.0162 (4)	0.0317 (5)	0.0021 (3)	0.0105 (3)	0.0069 (3)
O21	0.0127 (4)	0.0119 (4)	0.0246 (4)	0.0027 (3)	0.0049 (3)	0.0002 (3)
O22	0.0109 (3)	0.0134 (4)	0.0219 (4)	0.0015 (3)	0.0055 (3)	0.0016 (3)
O1W	0.0265 (5)	0.0123 (4)	0.0227 (5)	−0.0035 (3)	0.0041 (4)	0.0009 (3)
O2W	0.0263 (5)	0.0111 (4)	0.0223 (4)	−0.0010 (4)	0.0029 (4)	0.0010 (4)
N11	0.0087 (4)	0.0104 (4)	0.0231 (5)	−0.0006 (3)	0.0052 (3)	0.0007 (3)
N12	0.0102 (4)	0.0102 (4)	0.0252 (5)	−0.0011 (3)	0.0070 (4)	−0.0006 (4)
N21	0.0125 (4)	0.0104 (4)	0.0293 (6)	0.0009 (4)	0.0060 (4)	0.0022 (4)
N22	0.0142 (4)	0.0106 (4)	0.0329 (6)	−0.0009 (4)	0.0103 (4)	−0.0036 (4)
N31	0.0120 (4)	0.0094 (4)	0.0294 (5)	−0.0003 (4)	0.0076 (4)	0.0027 (4)
N32	0.0137 (4)	0.0103 (5)	0.0351 (6)	−0.0020 (4)	0.0107 (4)	−0.0035 (4)
C01	0.0113 (5)	0.0110 (5)	0.0172 (5)	−0.0006 (4)	0.0048 (4)	−0.0017 (4)
C02	0.0123 (5)	0.0101 (5)	0.0195 (5)	−0.0003 (4)	0.0040 (4)	0.0014 (4)
C11	0.0114 (4)	0.0107 (4)	0.0148 (4)	−0.0001 (4)	0.0056 (4)	0.0004 (4)
C12	0.0101 (5)	0.0104 (5)	0.0153 (5)	0.0000 (4)	0.0024 (4)	−0.0001 (4)
C21	0.0092 (4)	0.0094 (4)	0.0199 (5)	0.0000 (4)	0.0053 (4)	0.0002 (4)
C22	0.0094 (5)	0.0093 (4)	0.0211 (5)	0.0010 (4)	0.0056 (4)	0.0016 (4)
C31	0.0116 (5)	0.0140 (5)	0.0214 (5)	−0.0014 (4)	0.0040 (4)	−0.0025 (4)
C32	0.0150 (5)	0.0140 (5)	0.0199 (5)	0.0013 (4)	0.0070 (4)	0.0024 (4)
C41	0.0153 (5)	0.0266 (7)	0.0192 (5)	0.0001 (5)	0.0055 (4)	−0.0031 (5)
C42	0.0203 (6)	0.0202 (6)	0.0241 (6)	−0.0008 (5)	0.0080 (5)	0.0073 (5)
C51	0.0369 (9)	0.0507 (11)	0.0225 (7)	0.0159 (8)	−0.0002 (6)	−0.0022 (7)
C52	0.0321 (8)	0.0347 (9)	0.0263 (7)	0.0017 (7)	0.0036 (6)	0.0068 (6)

Geometric parameters (Å, º)

S1—C41	1.810 (2)	C21—H21	0.96 (2)
S1—C51	1.798 (2)	N11—H11	0.86 (2)
C21—N11	1.460 (2)	N21—H211	0.85 (2)
C11—O11	1.266 (2)	N21—H212	0.84 (2)
C11—O21	1.249 (2)	N31—H311	0.87 (2)
C01—N11	1.333 (2)	N31—H312	0.83 (2)
C01—N21	1.335 (2)	C52—H52A	0.95 (2)
C01—N31	1.331 (2)	C52—H52B	0.91 (2)
S2—C42	1.809 (2)	C52—H52C	0.90 (2)
S2—C52	1.798 (2)	C42—C32	1.529 (2)
C22—N12	1.457 (2)	C42—H42A	0.95 (2)
C12—O12	1.241 (2)	C42—H42B	0.98 (2)
C12—O22	1.273 (2)	C32—C22	1.539 (2)
C02—N12	1.333 (2)	C32—H32A	0.97 (2)
C02—N22	1.328 (2)	C32—H32B	0.97 (2)
C02—N32	1.336 (2)	C22—C12	1.536 (2)
C51—H51A	0.96 (2)	C22—H22	0.98 (2)
C51—H51B	0.98 (2)	N12—H12	0.84 (2)
C51—H51C	0.98 (3)	N22—H221	0.85 (2)
C41—C31	1.524 (2)	N22—H222	0.80 (2)
C41—H41A	0.93 (2)	N32—H321	0.83 (2)
C41—H41B	0.96 (2)	N32—H322	0.83 (2)
C31—C21	1.545 (2)	O1W—H1W	0.81 (2)
C31—H31A	1.02 (2)	O1W—H2W	0.82 (2)
C31—H31B	0.98 (2)	O2W—H3W	0.87 (2)
C21—C11	1.533 (2)	O2W—H4W	0.83 (2)
C51—S1—C41	100.79 (8)	C11—C21—C31	111.89 (9)
O11—C11—O21	125.24 (11)	N11—C21—H21	110.0 (9)
O11—C11—C21	117.75 (10)	C11—C21—H21	106.9 (10)
O21—C11—C21	117.01 (10)	C31—C21—H21	107.4 (9)
C31—C41—S1	113.65 (9)	C01—N21—H211	118.8 (12)
C01—N11—C21	123.77 (10)	C01—N21—H212	118.8 (12)
N31—C01—N11	121.71 (11)	H211—N21—H212	121 (2)
N31—C01—N21	119.34 (11)	C01—N31—H311	119.9 (12)
N11—C01—N21	118.94 (11)	C01—N31—H312	114.9 (13)
C52—S2—C42	100.06 (8)	H311—N31—H312	124 (2)
O12—C12—O22	125.34 (11)	S2—C52—H52A	107.3 (13)
O12—C12—C22	118.53 (10)	S2—C52—H52B	114.3 (13)
O22—C12—C22	116.12 (10)	H52A—C52—H52B	110 (2)
C32—C42—S2	114.09 (10)	S2—C52—H52C	106.9 (13)
C02—N12—C22	126.46 (10)	H52A—C52—H52C	108 (2)
N12—C02—N22	118.69 (11)	H52B—C52—H52C	111 (2)
N12—C02—N32	122.48 (11)	C32—C42—H42A	113.6 (10)
N22—C02—N32	118.82 (11)	S2—C42—H42A	108.3 (9)
C01—N11—H11	115.2 (12)	C32—C42—H42B	110.2 (11)
C21—N11—H11	117.1 (11)	S2—C42—H42B	105.0 (10)
C02—N12—H12	116.5 (13)	H42A—C42—H42B	105 (2)
C22—N12—H12	116.7 (13)	C42—C32—C22	111.68 (10)
S1—C51—H51A	106.3 (13)	C42—C32—H32A	109.8 (10)
S1—C51—H51B	111.2 (15)	C22—C32—H32A	108.4 (9)
H51A—C51—H51B	107 (2)	C42—C32—H32B	110.6 (10)
S1—C51—H51C	109 (2)	C22—C32—H32B	109.6 (9)
H51A—C51—H51C	116 (2)	H32A—C32—H32B	106.5 (14)
H51B—C51—H51C	108 (2)	N12—C22—C12	109.22 (9)
C31—C41—H41A	110.8 (11)	N12—C22—C32	110.97 (10)
S1—C41—H41A	108.8 (11)	C12—C22—C32	109.61 (10)
C31—C41—H41B	113.4 (11)	N12—C22—H22	109.5 (9)
S1—C41—H41B	102.3 (11)	C12—C22—H22	107.8 (9)
H41A—C41—H41B	108 (2)	C32—C22—H22	109.6 (9)
C41—C31—C21	113.75 (10)	C02—N22—H221	120 (2)
C41—C31—H31A	108.9 (9)	C02—N22—H222	118 (2)
C21—C31—H31A	108.5 (9)	H221—N22—H222	122 (2)
C41—C31—H31B	110.5 (10)	C02—N32—H321	126 (2)
C21—C31—H31B	107.1 (9)	C02—N32—H322	117 (2)
H31A—C31—H31B	107.8 (14)	H321—N32—H322	117 (2)
N11—C21—C11	109.47 (9)	H1W—O1W—H2W	106 (2)
N11—C21—C31	111.07 (10)	H3W—O2W—H4W	106 (2)
C51—S1—C41—C31	−70.0 (2)	C52—S2—C42—C32	−69.0 (1)
S1—C41—C31—C21	−163.1 (1)	S2—C42—C32—C22	−179.4 (1)
O11—C11—C21—N11	−20.2 (2)	O12—C12—C22—N12	−29.4 (2)
O21—C11—C21—N11	159.6 (1)	O22—C12—C22—N12	151.4 (1)
O11—C11—C21—C31	103.4 (2)	O12—C12—C22—C32	92.4 (2)
O21—C11—C21—C31	−76.9 (2)	O22—C12—C22—C32	−86.8 (2)
N11—C21—C31—C41	53.6 (2)	N12—C22—C32—C42	−63.3 (2)
C11—C21—C31—C41	−69.1 (2)	C12—C22—C32—C42	176.0 (1)
C11—C21—N11—C01	−160.8 (1)	C12—C22—N12—C02	−132.2 (2)
C31—C21—N11—C01	75.1 (2)	C32—C22—N12—C02	106.9 (2)
N21—C01—N11—C21	−166.3 (1)	N22—C02—N12—C22	177.7 (1)
N31—C01—N11—C21	14.4 (2)	N32—C02—N12—C22	−3.3 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N11—H11···O12	0.86 (2)	1.99 (2)	2.805 (2)	158 (2)
N21—H211···O12	0.85 (2)	2.22 (2)	2.950 (2)	145 (2)
N21—H212···O2W	0.84 (2)	2.22 (2)	2.960 (2)	147 (2)
N31—H311···O22^i	0.87 (2)	2.08 (2)	2.922 (2)	165 (2)
N31—H312···O2W	0.83 (2)	2.08 (2)	2.855 (2)	156 (2)
N12—H12···O11	0.84 (2)	2.05 (1)	2.826 (2)	154 (2)
N22—H221···O11	0.85 (2)	2.12 (1)	2.874 (2)	147 (2)
N22—H222···O1W	0.80 (2)	2.12 (2)	2.854 (2)	154 (2)
N32—H321···O21^ii	0.83 (2)	2.08 (2)	2.907 (2)	170 (2)
N32—H322···O1W	0.83 (2)	2.18 (2)	2.921 (2)	150 (2)
O1W—H1W···O22^iii	0.81 (2)	1.94 (2)	2.744 (2)	176 (2)
O1W—H2W···O11^iv	0.82 (2)	2.00 (2)	2.809 (2)	169 (2)
O2W—H3W···O21^v	0.87 (2)	1.90 (2)	2.771 (2)	173 (2)
O2W—H3W···O11^v	0.87 (2)	2.62 (2)	3.220 (2)	126 (2)
O2W—H4W···O22^vi	0.83 (2)	2.04 (2)	2.858 (2)	168 (2)
C21—H21···O22^i	0.96 (2)	2.47 (2)	3.364 (2)	155 (2)
C22—H22···O21^ii	0.98 (2)	2.57 (2)	3.514 (2)	162 (2)

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