Bis(DL-cysteinium) oxalate

In the title compound, 2C₃H₈NO₂S⁺·C₂O₄²⁻, the oxalate anion occupies an inversion centre and is coordinated to cysteine mol­ecules of different chirality (L and D) via O—H...O and N—H...O hydrogen bonds, the resulting cysteine–oxalate stoichiometry in the crystal structure being 2:1. The oxalate anion is completely deprotonated, whereas cysteine has a positively charged –NH₃⁺ group and a neutral protonated carboxyl group. The structure is built from infinite hydrogen-bonded triple layers, consisting of an oxalate layer in the middle with layers of L- and D-cysteine mol­ecules on either side. The thiol groups are at the external sides of the layers and form S—H...O hydrogen bonds with the carboxyl groups of neighbouring cysteine mol­ecules. An inter­esting feature of the structure is the occurrence of short S...S contacts between SH groups of mol­ecules in neighbouring layers, which form not S—H...S but S—H...O inter­molecular hydrogen bonds. Due to the effects of crystal packing and inter­molecular hydrogen-bond formation, the conformation of the cysteine cation in the title structure is different from that calculated theoretically for an individual cation, as well as from those of cysteine zwitterions in crystals of pure cysteine.

S1. Comment

Aminoacids co-crystallize easily with organic acids in general and with oxalic acid in particular. These systems are interesting as molecular materials; for example, many of them exhibit nonlinear optical properties. A comparative study of the conformations of the molecules, the packing motifs and the hydrogen-bond networks in crystals of pure amino acids and in their co-crystals with organic acids is interesting for crystal engineering and for understanding structure–property relationships. The systems can also serve as biomimetics, providing information on the interrelation between conformation and environment for the molecular fragments from which biopolymers are built. The Cambridge Structural Database (CSD, Version 5.29, January 2008; Allen, 2002) has 18 entries for the structures of oxalates of amino acids with the semi-oxalate ion and with the oxalate ion. The oxalate ion can occupy the inversion centre, as, for example, in the structures of bis(DL-asparic [aspartic?] acid) oxalate (Alagar et al., 2003), bis(glycinium) oxalate (Chitra et al., 2006) and bis(DL-serinium) oxalate dihydrate (Alagar et al., 2002). Such structures have a stoichiometry ratio of amino acid to oxalate ion of 2:1. They can be formed either by non-chiral (glycine) or by racemic amino acids, having an equal number of the L and D molecules in the crystal. In addition to the previously known examples, we describe here a new crystal structure, that of bis(DL-cysteinium) oxalate, (I). In this structure, the oxalate anion occupies the inversion centre and is coordinated to cysteine molecules of different chirality (L and D) via O—H···O and N—H···O hydrogen bonds, the resulting stoichiometry of cysteine to oxalate in the crystal structure being 2:1. The asymmetric unit of the structure is shown in Fig. 1.

The oxalate anion is flat and completely deprotonated, whereas cysteine has a positively charged NH₃ group and a neutral protonated carboxyl group, so that the co-crystal is an oxalic acid salt of cysteine. Three H atoms remain localized at the N atom, so that the NH₃ `tail' is positively charged, and cysteine can be considered as a cation. The C1—O1 and C1—O2 distances and O1—C1—C2 and O2—C1—C2 angles differ noticeably (Table 1). The conformation of the cysteine cation in (I) (see torsion angles in Table 1) is different both from those of the cysteine zwitterions (carboxylic acid group deprotonated) in the crystal structures of pure cysteine in both monoclinic (Harding & Long, 1968; Görbitz & Dalhus, 1996) and orthorhombic L-cysteine (Kerr & Ashmore, 1973; Kerr et al., 1975; Moggach et al., 2005) or in DL-cysteine (Luger & Weber, 1999), and from the conformation of neutral cysteine molecules (with neutral NH<sub>2</sub> `tails') (Dobrowolski et al., 2007). The cysteine molecules/zwitterions/cations are flexible and can easily change their conformation via a rotation around the C1—C2 and C2—C3 bonds. For neutral isolated molecules, the optimum conformation is determined by the possibility of forming intramolecular hydrogen bonds in which the carboxylic acid, amino and thiol groups are involved (Dobrowolski et al., 2007). In the crystal structures, instead of forming intramolecular hydrogen bonds, cysteine zwitterions (in pure cysteine) or cations (in cysteine salts) form intermolecular hydrogen bonds, the different conformations corresponding to different types of hydrogen bonding.

In the structure of (I), hydrogen bonds link cysteine cations with oxalate anions, and cysteine cations with each other (Table 2; Figs. 2 and 3). The structure is built from infinite hydrogen-bonded triple layers, consisting of an oxalate layer in the middle with layers of L- and D-cysteine molecules on either side (Fig. 2). The thiol groups are at the external sides of the layers. They are ordered and form S—H···O hydrogen bonds with the carboxyl groups of neighbouring cysteine molecules. Weak S1—H1s···O2^vi hydrogen bonds [symmetry code: (vi) x + 1, y - 1, z] link the cysteine cations into infinite chains along the [110] direction. For comparison, in the crystal structure of pure cysteine the S—H···O contacts are not the dominant ones: the thiol groups can be disordered over S—H···S and S—H···O contacts, as in orthorhombic L-cysteine, or one of the crystallographically independent zwitterions can form S—H···O contacts and another –S—H···S contacts, as in monoclinic L-cysteine, or the thiol groups are ordered and form S—H···S hydrogen bonds exclusively, as in DL-cysteine and in orthorhombic L-cysteine at low temperatures. Interestingly enough, the S···O distance in the hydrogen bonds in (I) [3.6200 (15) Å] is longer than the corresponding distances in the contacts, which are not hydrogen-bonds, in the crystal structures of pure cysteine [3.479 Å in orthorhombic L-cysteine at 30 K (Moggach et al., 2005), 3.404 Å in monoclinic cysteine (Görbitz & Dalhus, 1996) or 3.084 Å in DL-cysteine (Luger & Weber, 1999)].

Each oxalate anion of (I) is linked via N—H···O and O—H···O hydrogen bonds to eight cysteine cations (four L- and four D-isomers). In turn, each cysteine cation forms hydrogen bonds with four oxalate anions, four cations of the same chirality and a cysteine cation of the opposite chirality. A centrosymmetric dimer is formed by an L- and a D-cation linked by a long N1—H1n···O1ⁱⁱⁱ hydrogen bond [symmetry code: (iii) -x+2, -y+2, -z] (Table 2, Fig. 3). The geometric parameters characterizing this bond are quite comparable with those typically observed for three-centred/bifurcated or four-centred hydrogen bonds (Jeffrey, 1997). The shortest hydrogen bond, O1—H1o···O3^v [symmetry code: (v) x - 1, y + 1, z], links an oxalate anion with the COOH group of the cysteine cation (Table 2, Fig. 3). According to its geometric parameters, this hydrogen bond can be classified as an intermediate between a strong and a medium hydrogen bond (Jeffrey, 1997).

Another interesting feature of the structure of (I) is the presence of short S···S contacts [3.5176 (8) Å] between molecules in neighbouring layers. The H atom of the thiol group is involved in the formation of S—H···O bonds with the carboxylic acid group, so that no short S—H···S hydrogen bonds are formed. Such short S···S contacts are not observed in the structures of pure cysteine, the S···S distances being 3.851 Å between neighbouring molecules in orthorhombic L-cysteine (Kerr et al., 1975), 3.589 and 4.080 Å in monoclinic L-cysteine (Görbitz & Dalhus, 1996) and 3.855 Å in DL-cysteine (Luger & Weber, 1999). In the CSD, only seven structures could be retrieved having shorter S···S contacts between the SH groups than the S···S contact in the structure of (I). Six of these structures are n-alkylthiols (Thalladi et al., 2000) and are all built up of long-chain molecules with a variable number n of the methylene groups in the chain, (CH₂)_n, the thiol groups being located at the two ends of these molecules. [Details of the seventh structure?]

Two short C—H···O contacts can be found in the structure of (I) (Table 2). The longer contact is between layers while the shorter one links neighbouring molecules within a layer.

According to our unpublished observations, bis(DL-cysteinium) oxalate is more stable with respect to oxidation and the formation of the S—S covalent bond than is pure cysteine, despite the presence of the short S···S contact in the crystal structure of the salt. This may be due to proton transfer from the oxalic acid to cysteine during salt formation. At the same time, it can be noted that the crystal structure of DL-homocystine monohydrate oxalate has been described (Bigoli et al., 1981), in which one of the two crystallographically independent cysteine molecules has a charged deprotonated carboxyl group (COO^-) and another a neutral protonated group (COOH), linked to a semi-oxalate ion via an O—H···O hydrogen bond.

S2. Experimental

DL-Cysteine (252 mg, 2.1 mmol) and oxalic acid dihydrate (252 mg, 2.0 mmol) were dissolved in distilled water (4.5 ml). Crystals of (I) were grown by slow addition of propan-2-ol (5.5 ml) at 283 K. The solutions containing cysteine and oxalic acid were stable for an indefinite period with respect to oxidation in the air, in contrast with solutions of pure cysteine.

S3. Refinement

All H atoms were found in a difference Fourier map and were refined freely. Subsequently, H atoms bonded to O and S atoms were refined with U_iso(H) = 1.5U_eq(O) or 1.5U_eq(S).

Computing details

Data collection: STADI4 (Stoe & Cie, 1997); cell refinement: STADI4 (Stoe & Cie, 1997); data reduction: X-RED (Stoe & Cie, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-STEP (Stoe & Cie, 1998) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008), X-RED (Stoe & Cie, 1997), WinGX (Farrugia, 1999) and publCIF (Westrip, 2008).

Figures

	Fig. 1. The asymmetric unit of (I), with the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary radii. [Symmetry code: (iv) -x+2, -y+1, -z.]
	Fig. 2. A fragment of the crystal structure of (I), viewed along the a axis. Hydrogen bonds are shown as dashed lines.
	Fig. 3. Cations of L- and D-cysteine, related by an inversion centre. Hydrogen bonds linking the cysteine dimer to the oxalate anion are shown as dashed lines. [Symmetry codes: (iii) -x+2, -y+2, -z; (iv) -x+2, -y+1, -z.]

(I)

Crystal data

C3H8NO2S^+·0.5C2O4^2^−	Z = 2
Mr = 166.17	F(000) = 174
Triclinic, P1	Dx = 1.645 Mg m^−3
Hall symbol: -P 1	Melting point: 434 K
a = 5.2779 (6) Å	Mo Kα radiation, λ = 0.71073 Å
b = 6.6526 (7) Å	Cell parameters from 42 reflections
c = 10.4424 (15) Å	θ = 10.0–12.5°
α = 86.840 (11)°	µ = 0.44 mm^−1
β = 76.844 (11)°	T = 295 K
γ = 70.097 (10)°	Block, colourless
V = 335.60 (8) Å^3	0.31 × 0.20 × 0.14 mm

Data collection

Stoe STADI-4 four-circle D094 diffractometer	2215 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.036
Planar graphite monochromator	θmax = 35.0°, θmin = 2.0°
Scan width (ω) = 1.42 – 1.84, scan ratio 2θ:ω = 1.00 I(Net) and σ(I) calculated according to Blessing (1987) Blessing, R. H. (1987). Crystallogr. Rev. 1, 3–58.	h = −8→8
Absorption correction: ψ scan (X-RED; Stoe & Cie, 1997)	k = −10→10
Tmin = 0.833, Tmax = 0.939	l = −16→16
6198 measured reflections	3 standard reflections every 180 min
2946 independent reflections	intensity decay: none

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.117	All H-atom parameters refined
S = 1.08	w = 1/[σ^2(Fo^2) + (0.0453P)^2 + 0.1005P] where P = (Fo^2 + 2Fc^2)/3
2946 reflections	(Δ/σ)max < 0.001
121 parameters	Δρmax = 0.38 e Å^−3
0 restraints	Δρmin = −0.53 e Å^−3

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 > 2σ(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
C1	0.6685 (2)	1.11093 (19)	0.24412 (12)	0.0217 (2)
C2	0.9488 (2)	0.98646 (19)	0.27549 (12)	0.0212 (2)
C3	0.9329 (3)	0.8012 (2)	0.36586 (14)	0.0306 (3)
C4	1.1332 (2)	0.41424 (17)	0.01386 (12)	0.0193 (2)
N1	1.1612 (2)	0.90894 (17)	0.15154 (11)	0.02180 (19)
O1	0.68648 (19)	1.22642 (16)	0.14033 (10)	0.0288 (2)
O2	0.4547 (2)	1.1043 (2)	0.31523 (12)	0.0390 (3)
O3	1.2366 (2)	0.46987 (15)	0.09779 (11)	0.0292 (2)
O4	1.22300 (19)	0.23871 (14)	−0.04532 (11)	0.0269 (2)
S1	1.25868 (9)	0.66012 (7)	0.41238 (4)	0.04141 (13)
H1n	1.143 (5)	0.805 (4)	0.115 (2)	0.046 (6)*
H2n	1.158 (4)	1.015 (4)	0.096 (2)	0.044 (6)*
H3n	1.335 (4)	0.846 (3)	0.168 (2)	0.033 (5)*
H2	1.002 (3)	1.090 (3)	0.3163 (18)	0.023 (4)*
H31	0.875 (4)	0.698 (3)	0.329 (2)	0.040 (5)*
H32	0.796 (4)	0.859 (3)	0.448 (2)	0.043 (6)*
H1o	0.518 (4)	1.311 (3)	0.123 (2)	0.035*
H1s	1.283 (4)	0.487 (3)	0.396 (2)	0.035*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0169 (4)	0.0219 (5)	0.0247 (5)	−0.0041 (4)	−0.0053 (4)	0.0005 (4)
C2	0.0182 (4)	0.0230 (5)	0.0206 (5)	−0.0043 (4)	−0.0054 (4)	0.0012 (4)
C3	0.0274 (6)	0.0337 (6)	0.0273 (6)	−0.0072 (5)	−0.0069 (5)	0.0110 (5)
C4	0.0151 (4)	0.0171 (4)	0.0238 (5)	−0.0028 (3)	−0.0053 (3)	0.0037 (4)
N1	0.0172 (4)	0.0214 (4)	0.0245 (5)	−0.0040 (3)	−0.0042 (3)	0.0009 (4)
O1	0.0183 (4)	0.0318 (5)	0.0307 (5)	−0.0018 (3)	−0.0069 (3)	0.0100 (4)
O2	0.0199 (4)	0.0474 (6)	0.0434 (6)	−0.0087 (4)	−0.0017 (4)	0.0140 (5)
O3	0.0254 (4)	0.0249 (4)	0.0360 (5)	0.0004 (3)	−0.0175 (4)	−0.0019 (4)
O4	0.0221 (4)	0.0186 (4)	0.0364 (5)	−0.0006 (3)	−0.0084 (4)	−0.0029 (3)
S1	0.0407 (2)	0.0396 (2)	0.0428 (2)	−0.00535 (16)	−0.02263 (17)	0.01373 (16)

Geometric parameters (Å, º)

C1—O2	1.2147 (15)	C4—O4	1.2408 (14)
C1—O1	1.2981 (15)	C4—O3	1.2626 (15)
C1—C2	1.5294 (16)	C4—C4^i	1.555 (2)
C2—N1	1.4890 (16)	N1—H1n	0.85 (2)
C2—C3	1.5243 (18)	N1—H2n	0.89 (2)
C2—H2	0.976 (17)	N1—H3n	0.92 (2)
C3—S1	1.8180 (14)	O1—H1o	0.93 (2)
C3—H31	0.97 (2)	S1—H1s	1.135 (19)
C3—H32	0.99 (2)
O2—C1—O1	125.43 (11)	S1—C3—H31	108.5 (13)
O2—C1—C2	121.21 (11)	H32—C3—H31	107.1 (17)
O1—C1—C2	113.29 (10)	O4—C4—O3	126.12 (10)
N1—C2—C3	110.88 (10)	O4—C4—C4^i	118.84 (13)
N1—C2—C1	110.12 (9)	O3—C4—C4^i	115.03 (12)
C3—C2—C1	111.49 (10)	C2—N1—H1n	112.7 (16)
N1—C2—H2	106.6 (10)	C2—N1—H2n	110.6 (14)
C3—C2—H2	111.6 (10)	H1n—N1—H2n	110 (2)
C1—C2—H2	105.9 (10)	C2—N1—H3n	111.4 (13)
C2—C3—S1	112.34 (10)	H1n—N1—H3n	100.8 (19)
C2—C3—H32	108.4 (12)	H2n—N1—H3n	110.8 (18)
S1—C3—H32	106.6 (12)	C1—O1—H1o	114.6 (13)
C2—C3—H31	113.5 (13)	C3—S1—H1s	102.0 (10)
O2—C1—C2—N1	145.39 (13)	O1—C1—C2—C3	−160.94 (12)
O1—C1—C2—N1	−37.42 (14)	N1—C2—C3—S1	60.27 (13)
O2—C1—C2—C3	21.87 (18)	C1—C2—C3—S1	−176.64 (9)

Symmetry code: (i) −x+2, −y+1, −z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H2n···O4^ii	0.89 (2)	2.10 (2)	2.9715 (15)	170 (2)
N1—H3n···O4^iii	0.92 (2)	2.29 (2)	3.0106 (14)	135 (2)
N1—H1n···O3	0.85 (2)	2.12 (2)	2.8797 (15)	148 (2)
N1—H1n···O1^iv	0.85 (2)	2.61 (2)	3.0726 (16)	115 (2)
N1—H1n···O4^i	0.85 (2)	2.32 (2)	2.9677 (15)	133 (2)
O1—H1o···O3^v	0.93 (2)	1.57 (2)	2.4982 (13)	175 (2)
S1—H1s···O2^vi	1.135 (19)	2.51 (2)	3.6200 (15)	164 (1)
C2—H2···O2^vii	0.976 (17)	2.421 (17)	3.1431 (16)	130 (1)
C3—H32···O2^viii	0.99 (2)	2.51 (2)	3.453 (2)	161 (2)

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