trans-S,S'-(But-2-ene-1,4-diyl)­bis(L-cysteine) dihydrate

In the title compound, C₁₀H₁₈N₂O₄S₂·2H₂O, the two cysteine moieties (zwitterions), separated by the rigid butene-1,4-diyl chain, adopt different conformations. These are characterized by the fact that the first S atom is anti to the carboxyl group in one moiety while the second S atom is gauche to both the carboxyl and protonated amino groups in the other moiety. The cysteine moieties and water mol­ecules are linked by hydrogen bonds, forming a 14-membered ring within the ac plane and layer connections along the b axis, which bind the structure together in three dimensions.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.006 Å
• R factor = 0.041
• wR factor = 0.089
• Data-to-parameter ratio = 11.9

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           25.02
         From the CIF: _reflns_number_total               2338
         Count of symmetry unique reflns         1491
         Completeness (_total/calc)            156.81%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured       847
         Fraction of Friedel pairs measured     0.568
         Are heavy atom types Z>Si present          yes
          Please check that the estimate of the number of Friedel pairs is
          correct. If it is not, please give the correct count in the
          _publ_section_exptl_refinement section of the submitted CIF.

---

S1. Comment

L-Cysteine is one of the essential amino acids in nature. Some of its derivatives present remarkable bioactivities, and they can be used as antioxidants, antibacterial agents (Rabinkov et al., 1998) and chemical precursors of antitumor medicines (Hakimelahi et al., 2002). Although the crystal structure of both L-cysteine (Kerr & Ashmore, 1973, 1975; Görbitz & Dalhus, 1996; Harding et al., 1968) and DL-cysteine (Luger & Weber, 1999) have been reported, structures of bis(L-cysteine) derivatives are rare in the literature (Bigoli et al., 1982).

In this paper, the structure of the title compound, trans-s,s'-(but-2-ene-1,4-diyl)bis(L-cysteine) dihydrate, (I), is reported. The molecular structure of (I) is illustrated in Fig. 1.

The molecule of (I) has a trans configuration. The distance between atoms C5 and C6 is 1.299 (5) Å, which is shorter than the distance of 1.34 (1) Å for a normal C═C bond (Lide, 1992–1993) and the distance of 1.326 Å in trans-2,5-dimethyl-3-hexene-2,5-diol. The angles C4—C5—C6 and C5—C6—C7 are 125.6 (3) and 123.5 (3)°, respectively, which are slightly smaller than those of 127.4 and 124.9° in trans-2,5-dimethy-3-hexene-2,5-diol (Ruysink & Vos, 1974). The torsion angle C4—C5—C6—C7 is 177.7 (4)°, indicating that the butenediyl group is almost planar. The C—S bond lengths [C3—S2 = 1.794 (4), C4—S2 = 1.812 (4), C7—S1 = 1.820 (4) and C8—S1 = 1.80 (4) Å] are in the same magnitude compared with the value of 1.811 (3) Å in L-cysteine (Kerr & Ashmore, 1973). The bond angles C3—S2—C4 and C8—S1—C7 are 102.1 (2) and 100.4 (2)°, respectively, slightly larger than the value of 99.05° in dimethyl sulfide (Lide, 1992–1993).

The difference in the C—O bond lengths of the two carboxyl groups is obviously influenced by hydrogen-bond environment (Table 2). Atoms O1 and O4 are involved in more than one hydrogen bond (O6—H3···O1, O5—H2···O1 and O5—H1···O1; N2—H2b···O4 and O6—H4···O4), while atoms O2 and O3 only take part one hydrogen-bond interaction, which may explain why the C1—O1 [1.252 (5) Å] and C10—O4 [1.263 (4) Å] bond lengths are longer than those of C1—O2 [1.218 (6) Å] and C10—O3 [1.231 (5) Å].

The two cysteine moieties (zwitterions), separated by the rigid butene-1,4-diyl skeleton, adopt different conformations. Atom S1 is anti to the C10/O3/O4 carboxyl group, with a S1—C8—C9—C10 torsion angle of 178.4°. However, atom S2 is gauche with respect to both the C1/O1/O2 carboxyl and protonated amino groups; the corresponding torsion angles, S2—C3—C2—C1 and S2—C3—C2—N1, are 61.8 (4) and 57.8 (4)°, respectively. The difference is clearly illustrated by the Newman projection shown in Fig. 4.

The molecules are arranged in the crystal lattice parallel to the ac plane, in which two N—H groups of the protonated amino group and two C—O groups of the carboxyl group, as well as two water molecules, form a 14-membered ring via hydrogen bonds. Interestingly, these molecules are linked together through hydrogen bonds along the b axis to form a three-dimensional network with an infinite tunnel.

Besides overwhelming intermolecular hydrogen bonding, there exists one intramolecular hydrogen-bond interaction (N2—H2b···O4) in the S1/C8/C9/C10/N2 moiety. No such interaction is found in the other moiety, which may explain the conformational differences of the two zwitterion moieties.

S2. Experimental

Compound (I) was synthesized by a modified literature method (Kalopissis & Manousses, 1975). A solution of 5.35 g (0.0025 mol) of trans-1,4-dibromo-2-butene in 5 ml e thanol was added dropwise to a mixture of 0.88 g (0.005 mol) of L-cysteine hydrochloride monohydrate, 1 ml of 10 mol l⁻¹ sodium hydroxide, 5 ml of water and 7.5 ml of ethanol. After that, the reaction mixture was stirred for 10 h at room temperature. The precipitate was filtered off and recrystallized from water. Needle-like colorless crystal were obtained (yield 68%; m.p. 513–515 K (decomposition)]; IR (KBr): 3479 (b), 3024 (b), 2924 (s), 1687 (w), 1613 (versus, b), 1483 (s), 1419 (s), 1393 (s), 1342 (s), 1303 (s), 1069 (w), 1045 (w), 966 (versus) cm⁻¹; 1H NMR (D₂O): δ 5.65 (2H, bs), 4.17 (2H, t), 3.23 (4H, bs), 3.14 (2H, d), 3.00 (2H, dd) p.p.m. 10 mg of (I) was dissolved in 10 ml hot distilled water and, after filtration, the solution was kept at room temperature for 10 d yielding colorless single crystals of (I) suitable for X-ray analysis.

S3. Refinement

The water atoms H1–H4 were located on a difference Fourier map and refined using constraints.

Computing details

Data collection: SMART (Bruker, 1997); cell refinement: SMART); data reduction: SAINT (Bruker, 1997) and SHELXTL (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. View of the molecular structure of (I), with 30% probability ellipsoids, H atoms are shown as small spheres of arbitrary radii.
	Fig. 2. The crystal cell structure of (I), with a 14-membered hydrogen bond.
	Fig. 3. A packing diagram for (I), viewed along the b axis.
	Fig. 4. The Newman projection of (I).

Trans-s,s'-2-butene-1,4-diylbis(L-cysteine) dihydrate

Crystal data

C10H22N2O6S2	F(000) = 352
Mr = 330.42	Dx = 1.453 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 11.672 (4) Å	Cell parameters from 1870 reflections
b = 5.3982 (19) Å	θ = 2.7–23.1°
c = 12.413 (4) Å	µ = 0.38 mm^−1
β = 105.020 (5)°	T = 293 K
V = 755.4 (4) Å^3	Prism, colourless
Z = 2	0.30 × 0.15 × 0.10 mm

Data collection

Bruker CCD area-detector diffractometer	2338 independent reflections
Radiation source: fine-focus sealed tube	1894 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.032
ϕ and ω scans	θmax = 25.0°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Bruker, 1997)	h = −13→8
Tmin = 0.895, Tmax = 0.963	k = −5→6
3157 measured reflections	l = −13→14

Refinement

Refinement on F^2	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ^2(Fo^2) + (0.04P)^2] where P = (Fo^2 + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.041	(Δ/σ)max = 0.026
wR(F^2) = 0.089	Δρmax = 0.22 e Å^−3
S = 1.03	Δρmin = −0.29 e Å^−3
2338 reflections	Absolute structure: (Flack, 1983)
197 parameters	Absolute structure parameter: 0.06 (10)
5 restraints

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 > 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
S1	0.98558 (8)	0.4300 (2)	1.10310 (7)	0.0328 (3)
S2	0.45673 (9)	0.1031 (2)	0.85490 (8)	0.0422 (3)
O1	0.6590 (3)	0.2498 (7)	0.6583 (2)	0.0616 (10)
O2	0.5305 (3)	−0.0490 (7)	0.5978 (3)	0.0590 (9)
O3	0.8327 (3)	−0.1955 (6)	1.2887 (2)	0.0494 (8)
O4	1.0023 (2)	−0.1342 (5)	1.4161 (2)	0.0431 (8)
N1	0.3428 (3)	0.2090 (7)	0.5987 (2)	0.0440 (9)
H1A	0.2838	0.3031	0.6086	0.066*
H1B	0.3398	0.0613	0.6298	0.066*
H1C	0.3359	0.1902	0.5261	0.066*
N2	1.0210 (3)	0.3356 (6)	1.3602 (2)	0.0344 (8)
H2B	1.0007	0.3545	1.4240	0.052*
H2C	1.0254	0.4834	1.3298	0.052*
H2D	1.0913	0.2608	1.3735	0.052*
C1	0.5569 (4)	0.1601 (10)	0.6329 (3)	0.0414 (12)
C2	0.4582 (3)	0.3297 (8)	0.6518 (3)	0.0326 (9)
H2A	0.4622	0.4892	0.6153	0.039*
C3	0.4690 (3)	0.3735 (8)	0.7745 (3)	0.0369 (11)
H3A	0.4079	0.4901	0.7811	0.044*
H3B	0.5451	0.4508	0.8071	0.044*
C4	0.6099 (3)	0.0045 (8)	0.9034 (3)	0.0387 (11)
H4A	0.6131	−0.1543	0.9406	0.046*
H4B	0.6430	−0.0166	0.8399	0.046*
C5	0.6824 (3)	0.1883 (8)	0.9819 (3)	0.0348 (10)
H5A	0.6677	0.2036	1.0517	0.042*
C6	0.7645 (3)	0.3291 (8)	0.9611 (3)	0.0332 (10)
H6A	0.7823	0.3120	0.8926	0.040*
C7	0.8319 (3)	0.5170 (8)	1.0413 (3)	0.0357 (10)
H7A	0.7925	0.5408	1.1004	0.043*
H7B	0.8302	0.6738	1.0028	0.043*
C8	0.9649 (3)	0.1480 (7)	1.1733 (3)	0.0282 (9)
H8A	0.9037	0.0508	1.1233	0.034*
H8B	1.0379	0.0531	1.1881	0.034*
C9	0.9306 (3)	0.1825 (7)	1.2825 (3)	0.0266 (8)
H9A	0.8539	0.2673	1.2674	0.032*
C10	0.9195 (3)	−0.0686 (9)	1.3333 (3)	0.0317 (9)
O5	0.2479 (3)	0.2084 (8)	0.3453 (3)	0.0740 (11)
O6	0.7661 (3)	0.2056 (7)	0.4830 (3)	0.0572 (9)
H4	0.8416 (16)	0.266 (7)	0.512 (3)	0.038 (11)*
H3	0.728 (4)	0.178 (12)	0.539 (3)	0.099*
H2	0.297 (3)	0.345 (5)	0.351 (4)	0.063*
H1	0.277 (4)	0.051 (4)	0.340 (4)	0.066*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0318 (6)	0.0388 (6)	0.0288 (5)	−0.0032 (5)	0.0096 (4)	0.0045 (5)
S2	0.0360 (6)	0.0594 (8)	0.0322 (6)	−0.0110 (6)	0.0109 (4)	0.0029 (6)
O1	0.0337 (18)	0.099 (3)	0.058 (2)	0.0064 (17)	0.0206 (14)	0.0044 (19)
O2	0.067 (2)	0.052 (2)	0.063 (2)	0.0183 (19)	0.0257 (16)	−0.009 (2)
O3	0.060 (2)	0.045 (2)	0.0472 (18)	−0.0201 (16)	0.0211 (15)	−0.0082 (16)
O4	0.0511 (18)	0.040 (2)	0.0407 (16)	0.0058 (14)	0.0159 (14)	0.0122 (14)
N1	0.040 (2)	0.059 (3)	0.0305 (17)	0.0137 (18)	0.0058 (15)	−0.0003 (18)
N2	0.052 (2)	0.026 (2)	0.0259 (17)	−0.0014 (16)	0.0129 (15)	−0.0032 (15)
C1	0.042 (3)	0.061 (4)	0.026 (2)	0.020 (3)	0.0178 (19)	0.013 (2)
C2	0.029 (2)	0.037 (3)	0.033 (2)	0.0042 (18)	0.0106 (17)	0.0027 (19)
C3	0.035 (2)	0.040 (3)	0.035 (2)	0.0093 (19)	0.0090 (17)	−0.008 (2)
C4	0.048 (3)	0.040 (3)	0.028 (2)	−0.003 (2)	0.0088 (18)	0.001 (2)
C5	0.038 (2)	0.043 (3)	0.0222 (19)	0.001 (2)	0.0049 (16)	−0.001 (2)
C6	0.038 (2)	0.038 (3)	0.024 (2)	0.006 (2)	0.0082 (17)	0.0041 (19)
C7	0.037 (2)	0.034 (3)	0.035 (2)	−0.0011 (18)	0.0061 (17)	0.0037 (19)
C8	0.034 (2)	0.031 (3)	0.0194 (18)	0.0010 (18)	0.0053 (15)	0.0005 (18)
C9	0.027 (2)	0.025 (2)	0.0286 (19)	0.0030 (16)	0.0087 (15)	0.0012 (17)
C10	0.040 (2)	0.030 (2)	0.033 (2)	0.004 (2)	0.0224 (18)	−0.002 (2)
O5	0.056 (2)	0.064 (3)	0.110 (3)	−0.0246 (19)	0.037 (2)	−0.011 (3)
O6	0.043 (2)	0.076 (3)	0.0567 (19)	−0.0064 (18)	0.0217 (15)	−0.0144 (19)

Geometric parameters (Å, º)

S1—C8	1.801 (4)	C3—H3B	0.9700
S1—C7	1.821 (4)	C4—C5	1.491 (5)
S2—C3	1.794 (4)	C4—H4A	0.9700
S2—C4	1.812 (4)	C4—H4B	0.9700
O1—C1	1.249 (5)	C5—C6	1.301 (5)
O2—C1	1.220 (6)	C5—H5A	0.9300
O3—C10	1.229 (5)	C6—C7	1.494 (5)
O4—C10	1.265 (4)	C6—H6A	0.9300
N1—C2	1.487 (5)	C7—H7A	0.9700
N1—H1A	0.8900	C7—H7B	0.9700
N1—H1B	0.8900	C8—C9	1.522 (4)
N1—H1C	0.8900	C8—H8A	0.9700
N2—C9	1.483 (5)	C8—H8B	0.9700
N2—H2B	0.8900	C9—C10	1.514 (6)
N2—H2C	0.8900	C9—H9A	0.9800
N2—H2D	0.8900	O5—H2	0.93 (3)
C1—C2	1.536 (6)	O5—H1	0.92 (3)
C2—C3	1.514 (5)	O6—H4	0.92 (3)
C2—H2A	0.9800	O6—H3	0.93 (4)
C3—H3A	0.9700
C8—S1—C7	100.41 (18)	C5—C4—H4B	109.3
C3—S2—C4	102.09 (18)	S2—C4—H4B	109.3
C2—N1—H1A	109.5	H4A—C4—H4B	108.0
C2—N1—H1B	109.5	C6—C5—C4	125.6 (3)
H1A—N1—H1B	109.5	C6—C5—H5A	117.2
C2—N1—H1C	109.5	C4—C5—H5A	117.2
H1A—N1—H1C	109.5	C5—C6—C7	123.5 (3)
H1B—N1—H1C	109.5	C5—C6—H6A	118.3
C9—N2—H2B	109.5	C7—C6—H6A	118.3
C9—N2—H2C	109.5	C6—C7—S1	113.4 (3)
H2B—N2—H2C	109.5	C6—C7—H7A	108.9
C9—N2—H2D	109.5	S1—C7—H7A	108.9
H2B—N2—H2D	109.5	C6—C7—H7B	108.9
H2C—N2—H2D	109.5	S1—C7—H7B	108.9
O2—C1—O1	125.8 (4)	H7A—C7—H7B	107.7
O2—C1—C2	118.4 (4)	C9—C8—S1	115.3 (3)
O1—C1—C2	115.7 (5)	C9—C8—H8A	108.5
N1—C2—C3	110.1 (3)	S1—C8—H8A	108.5
N1—C2—C1	107.4 (4)	C9—C8—H8B	108.5
C3—C2—C1	112.1 (3)	S1—C8—H8B	108.5
N1—C2—H2A	109.0	H8A—C8—H8B	107.5
C3—C2—H2A	109.0	N2—C9—C10	110.6 (3)
C1—C2—H2A	109.0	N2—C9—C8	109.9 (3)
C2—C3—S2	115.8 (3)	C10—C9—C8	109.4 (3)
C2—C3—H3A	108.3	N2—C9—H9A	109.0
S2—C3—H3A	108.3	C10—C9—H9A	109.0
C2—C3—H3B	108.3	C8—C9—H9A	109.0
S2—C3—H3B	108.3	O3—C10—O4	125.2 (4)
H3A—C3—H3B	107.4	O3—C10—C9	117.4 (3)
C5—C4—S2	111.4 (3)	O4—C10—C9	117.3 (4)
C5—C4—H4A	109.3	H2—O5—H1	121 (4)
S2—C4—H4A	109.3	H4—O6—H3	111 (4)
O2—C1—C2—N1	−11.6 (5)	C5—C6—C7—S1	108.5 (4)
O1—C1—C2—N1	170.3 (3)	C8—S1—C7—C6	−61.1 (3)
O2—C1—C2—C3	109.5 (4)	C7—S1—C8—C9	−77.6 (3)
O1—C1—C2—C3	−68.6 (5)	S1—C8—C9—N2	−56.9 (3)
N1—C2—C3—S2	57.6 (4)	S1—C8—C9—C10	−178.5 (3)
C1—C2—C3—S2	−61.9 (4)	N2—C9—C10—O3	165.9 (3)
C4—S2—C3—C2	91.0 (3)	C8—C9—C10—O3	−72.9 (4)
C3—S2—C4—C5	66.2 (3)	N2—C9—C10—O4	−16.4 (4)
S2—C4—C5—C6	−110.4 (4)	C8—C9—C10—O4	104.9 (4)
C4—C5—C6—C7	177.8 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1C···O5	0.89	2.22	3.053 (5)	157
O6—H3···O1	0.93 (4)	1.90 (3)	2.787 (4)	159 (6)
N2—H2D···O5^i	0.89	1.97	2.788 (5)	152
N2—H2B···O4^ii	0.89	1.99	2.864 (4)	165
O6—H4···O4^iii	0.92 (3)	1.89 (3)	2.805 (4)	174 (4)
O5—H2···O2^iv	0.93 (3)	2.03 (3)	2.821 (5)	142 (4)
O5—H2···O1^iv	0.93 (3)	2.26 (2)	3.122 (5)	156 (4)
O5—H1···O1^v	0.92 (3)	1.80 (2)	2.709 (5)	175 (5)

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