dl-Histidine dl-tartrate

Johnson, M.N.; Feeder, N.

doi:10.1107/S1600536804015296

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 60| Part 7| July 2004| Pages o1273-o1274

https://doi.org/10.1107/S1600536804015296

DL-Histidine DL-tartrate

M. N. Johnson ^a ^* and N. Feeder ^b

^aUniversity of Greenwich, Medway Campus, Anson, Chatham Maritime, Kent ME4 4TB, England, and ^bPfizer Ltd, IPC 049, Ramsgate Road, Sandwich, Kent CT13 9NJ, England
^*Correspondence e-mail: matthew_johnson@sandwich.pfizer.com

(Received 11 June 2004; accepted 23 June 2004; online 30 June 2004)

The crystal structure of DL-histidine DL-tartrate, C₆H₁₀N₃O₂⁺·C₄H₅O₆⁻, has been determined as part of an ongoing study of the fundamental effects of chirality on salt formation and hydrates. Discrete single-enantiomer chains of histidine are linked in two dimensions by hydrogen bonds to a racemic pair of tartrate molecules.

Comment

This study was undertaken to identify the effects of chirality on the formation of salts, specifically the way chirality may affect hydration, as a result of interactions between a chiral drug and a chiral counter-ion. DL-Histidine and DL-tartrate samples were purchased from Fluka and used in the crystallization. The asymmetric unit of the title compound, (I), contains one molecule of histidine as a monocation (protonated at the amine and imidazole N atoms and deprotonated at the carboxylic acid) and the tartrate as a monoanion (Fig. 1).

The histidines form chains of single enantiomers (Fig. 2) linked along the b axis by hydrogen bonds from the NH group of the imidazole ring to a carboxyl O atom of the next histidine, similar to those described by Suresh & Vijayan (1987 ). The tartrate anions form dimers containing one D- and one L-tartrate ion in each pair (Fig. 2). The dimers are formed by means of a carboxylic acid O atom bonding to a neighbouring tartrate utilizing a side OH group [2.817 (2) Å]. Each histidine molecule in a chain is linked to the next chain below (viewed down the a axis in Fig. 2) by a single hydrogen bond from a carboxyl O atom to an NH group of the ammonium group [2.749 (2) Å]. The tartrates link the chains of histidine in two dimensions to create a three-dimensional hydrogen-bond network.

Figure 1
ORTEP-3 (Farrugia, 1997

) plot of the asymmetric unit of (I

) (Z = 4), with displacement ellipsoids drawn at the 50% probability level.

Figure 2
Hydrogen-bonding motifs for D-tartrate (green), L-histidine (yellow), D-histidine (blue) and L-tartrate (pink).

Experimental

A 5 ml saturated aqueous solution of DL-histidine was mixed with a 5 ml saturated aqueous solution of DL-tartaric acid and the vial was covered with a pierced film. This was placed in a larger glass vial containing 25 ml of methanol, sealed, and allowed to stand for three weeks at room temperature.

Crystal data

C₆H₁₀N₃O₂⁺·C₄H₅O₆⁻
M_r = 305.25
Monoclinic, P2₁/c
a = 4.9695 (5) Å
b = 13.4392 (12) Å
c = 19.2749 (18) Å
β = 90.253 (2)°
V = 1287.3 (2) Å³
Z = 4
D_x = 1.575 Mg m⁻³
Mo Kα radiation
Cell parameters from 2967 reflections
θ = 1.9–28.0°
μ = 0.14 mm⁻¹
T = 295 (2) K
Needle, colourless
0.50 × 0.10 × 0.10 mm

Data collection

Bruker SMART APEX CCD diffractometer
Thin-slice ω scans
Absorption correction: multi-scan (SADABS; Sheldrick, 1997 ; Blessing, 1995 ) T_min = 0.843, T_max = 0.990
7512 measured reflections
2967 independent reflections
2207 reflections with I > 2σ(I)
R_int = 0.023
θ_max = 28.0°
h = −6 → 6
k = −17 → 17
l = −25 → 25

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.044
wR(F²) = 0.118
S = 1.02
2967 reflections
194 parameters
H-atom parameters constrained
w = 1/[σ²(F_o²) + (0.0666P)²] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max = 0.001
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bonding geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯O8	0.86	1.93	2.7689 (19)	166
N1—H1⋯O2ⁱ	0.86	1.84	2.6871 (19)	169
N3—H3A⋯O2ⁱⁱ	0.89	1.87	2.7532 (18)	173
N3—H3B⋯O7ⁱⁱⁱ	0.89	2.09	2.7937 (18)	135
N3—H3B⋯O6ⁱⁱⁱ	0.89	2.35	3.1374 (18)	147
N3—H3C⋯O7ⁱⁱ	0.89	1.85	2.7178 (18)	164
O3—H3D⋯O1^iv	0.82	1.77	2.5856 (17)	173
O5—H5A⋯O4^v	0.82	2.11	2.8174 (19)	145
O5—H5A⋯O4	0.82	2.30	2.7015 (19)	111
O6—H6⋯O8^vi	0.82	1.92	2.7152 (18)	162
Symmetry codes: (i) $[1-x,{\script{1\over 2}}+y,{\script{3\over 2}}-z]$ ; (ii) x-1,y,z; (iii) 1-x,1-y,1-z; (iv) $[1+x,{\script{3\over 2}}-y,z-{\script{1\over 2}}]$ ; (v) 2-x,2-y,1-z; (vi) 1+x,y,z.

The unit-cell dimensions and angles were compared to those reported for the parent histidine enantiomers by Edington & Harding (1974 ) and Madden et al. (1972 ). All H atoms were placed geometrically [C—H = 0.93–0.98, N—H = 0.86–0.89 and O—H = 0.82 Å; U_iso(H) = 1.2 or 1.5 times U_eq(parent atom)] and refined using a riding model.

Data collection: SMART (Siemens, 1994 ); cell refinement: SAINT (Siemens, 1994); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997 ) and Materials Studio (Accelrys, 2001 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S1600536804015296/dn6150sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536804015296/dn6150Isup2.hkl

Computing details top

Data collection: SMART (Siemens, 1994); cell refinement: SAINT (Siemens, 1994); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997) and Materials Studio (Accelrys, 2001); software used to prepare material for publication: SHELXL97.

(I) top

Crystal data top

C₆H₁₀N₃O₂⁺·C₄H₅O₆⁻	F(000) = 640
M_r = 305.25	D_x = 1.575 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P2ybc	Cell parameters from 2967 reflections
a = 4.9695 (5) Å	θ = 1.9–28.0°
b = 13.4392 (12) Å	µ = 0.14 mm⁻¹
c = 19.2749 (18) Å	T = 295 K
β = 90.253 (2)°	Needle, colourless
V = 1287.3 (2) Å³	0.50 × 0.10 × 0.10 mm
Z = 4

Data collection top

Bruker SMART APEX CCD diffractometer	2967 independent reflections
Radiation source: fine-focus sealed tube	2207 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.023
Detector resolution: 67 pixels mm^-1	θ_max = 28.0°, θ_min = 1.9°
Thin–slice ω scans	h = −6→6
Absorption correction: multi-scan (SADABS; Sheldrick, 1997; Blessing, 1995)	k = −17→17
T_min = 0.843, T_max = 0.990	l = −25→25
7512 measured reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.118	H-atom parameters constrained
S = 1.02	w = 1/[σ²(F_o²) + (0.0666P)²] where P = (F_o² + 2F_c²)/3
2967 reflections	(Δ/σ)_max = 0.001
194 parameters	Δρ_max = 0.44 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.1685 (3)	0.73187 (12)	0.66501 (9)	0.0318 (4)
C2	0.2198 (4)	0.77519 (13)	0.72645 (10)	0.0386 (4)
H2	0.1342	0.7610	0.7681	0.046*
C3	0.4909 (4)	0.84349 (13)	0.65168 (10)	0.0372 (4)
H3	0.6224	0.8836	0.6319	0.045*
C4	−0.0369 (4)	0.65675 (12)	0.64434 (10)	0.0358 (4)
H4A	−0.1390	0.6824	0.6052	0.043*
H4B	−0.1609	0.6473	0.6825	0.043*
C5	0.0819 (3)	0.55634 (11)	0.62459 (9)	0.0298 (4)
H5	0.2238	0.5664	0.5901	0.036*
C6	0.1981 (3)	0.49876 (11)	0.68674 (8)	0.0286 (4)
C7	0.8407 (4)	0.92923 (12)	0.38923 (9)	0.0392 (4)
C8	0.6893 (4)	0.85823 (12)	0.43616 (9)	0.0376 (4)
H8	0.4990	0.8773	0.4372	0.045*
C9	0.7135 (3)	0.75243 (11)	0.40876 (8)	0.0281 (4)
H9	0.6004	0.7473	0.3671	0.034*
C10	0.6010 (3)	0.67992 (12)	0.46299 (8)	0.0273 (3)
N1	0.4190 (3)	0.84348 (11)	0.71715 (8)	0.0377 (4)
H1	0.4868	0.8807	0.7491	0.045*
N2	0.3426 (3)	0.77602 (10)	0.61863 (8)	0.0364 (4)
H2A	0.3533	0.7621	0.5752	0.044*
N3	−0.1363 (3)	0.49502 (9)	0.59342 (7)	0.0282 (3)
H3A	−0.2652	0.4854	0.6246	0.042*
H3B	−0.0698	0.4365	0.5803	0.042*
H3C	−0.2046	0.5264	0.5567	0.042*
O1	0.0532 (3)	0.48152 (10)	0.73684 (7)	0.0461 (4)
O2	0.4328 (3)	0.46847 (11)	0.68080 (7)	0.0495 (4)
O3	0.7603 (3)	0.92187 (10)	0.32456 (7)	0.0481 (4)
H3D	0.8607	0.9543	0.2996	0.072*
O4	1.0095 (3)	0.98561 (11)	0.41035 (7)	0.0591 (4)
O5	0.7946 (4)	0.85996 (10)	0.50444 (7)	0.0601 (5)
H5A	0.8650	0.9141	0.5119	0.090*
O6	0.9796 (2)	0.72979 (9)	0.38935 (6)	0.0358 (3)
H6	1.0753	0.7274	0.4241	0.054*
O7	0.7460 (3)	0.60922 (9)	0.48094 (6)	0.0404 (3)
O8	0.3696 (2)	0.69787 (9)	0.48593 (6)	0.0373 (3)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0383 (9)	0.0256 (8)	0.0315 (9)	0.0024 (7)	−0.0027 (7)	0.0006 (7)
C2	0.0436 (10)	0.0401 (10)	0.0320 (9)	−0.0066 (8)	0.0008 (8)	−0.0019 (7)
C3	0.0361 (9)	0.0333 (9)	0.0423 (11)	−0.0002 (7)	0.0060 (8)	−0.0009 (8)
C4	0.0367 (10)	0.0292 (8)	0.0412 (10)	0.0039 (7)	−0.0063 (8)	−0.0017 (7)
C5	0.0297 (8)	0.0269 (8)	0.0327 (9)	−0.0001 (6)	−0.0035 (7)	0.0009 (7)
C6	0.0304 (9)	0.0273 (8)	0.0279 (8)	0.0006 (7)	−0.0017 (7)	−0.0003 (6)
C7	0.0551 (11)	0.0276 (9)	0.0348 (10)	0.0012 (8)	0.0075 (9)	0.0001 (7)
C8	0.0510 (11)	0.0294 (9)	0.0326 (9)	0.0001 (8)	0.0089 (8)	0.0012 (7)
C9	0.0297 (8)	0.0304 (8)	0.0241 (8)	0.0012 (6)	0.0000 (6)	−0.0001 (6)
C10	0.0312 (9)	0.0283 (8)	0.0224 (8)	−0.0025 (7)	−0.0038 (6)	−0.0038 (6)
N1	0.0421 (9)	0.0369 (8)	0.0343 (8)	−0.0071 (6)	−0.0015 (7)	−0.0104 (6)
N2	0.0470 (9)	0.0360 (8)	0.0263 (7)	0.0054 (6)	0.0017 (6)	−0.0049 (6)
N3	0.0316 (7)	0.0257 (7)	0.0272 (7)	0.0007 (5)	−0.0008 (6)	0.0008 (5)
O1	0.0492 (8)	0.0501 (8)	0.0392 (8)	0.0112 (6)	0.0127 (6)	0.0072 (6)
O2	0.0344 (7)	0.0703 (9)	0.0438 (8)	0.0153 (6)	0.0063 (6)	0.0235 (7)
O3	0.0602 (9)	0.0482 (8)	0.0358 (8)	−0.0120 (7)	0.0006 (6)	0.0124 (6)
O4	0.0872 (12)	0.0490 (8)	0.0411 (8)	−0.0283 (8)	0.0049 (8)	−0.0044 (7)
O5	0.1103 (13)	0.0425 (8)	0.0275 (7)	−0.0259 (8)	0.0044 (8)	−0.0045 (6)
O6	0.0343 (7)	0.0434 (7)	0.0297 (6)	0.0033 (5)	0.0052 (5)	0.0001 (5)
O7	0.0489 (7)	0.0368 (7)	0.0354 (7)	0.0086 (6)	0.0026 (6)	0.0093 (5)
O8	0.0314 (7)	0.0471 (7)	0.0335 (7)	−0.0024 (5)	0.0036 (5)	−0.0007 (5)

Geometric parameters (Å, º) top

C1—C2	1.343 (3)	C7—C8	1.517 (2)
C1—N2	1.381 (2)	C8—O5	1.414 (2)
C1—C4	1.489 (2)	C8—C9	1.522 (2)
C2—N1	1.362 (2)	C8—H8	0.9800
C2—H2	0.9300	C9—O6	1.4092 (19)
C3—N1	1.313 (2)	C9—C10	1.536 (2)
C3—N2	1.329 (2)	C9—H9	0.9800
C3—H3	0.9300	C10—O7	1.2407 (19)
C4—C5	1.522 (2)	C10—O8	1.2574 (19)
C4—H4A	0.9700	N1—H1	0.8600
C4—H4B	0.9700	N2—H2A	0.8600
C5—N3	1.487 (2)	N3—H3A	0.8900
C5—C6	1.537 (2)	N3—H3B	0.8900
C5—H5	0.9800	N3—H3C	0.8900
C6—O1	1.229 (2)	O3—H3D	0.8200
C6—O2	1.241 (2)	O5—H5A	0.8200
C7—O4	1.200 (2)	O6—H6	0.8200
C7—O3	1.311 (2)

C2—C1—N2	105.53 (15)	C7—C8—C9	109.92 (14)
C2—C1—C4	131.08 (17)	O5—C8—H8	109.2
N2—C1—C4	123.29 (15)	C7—C8—H8	109.2
C1—C2—N1	108.13 (16)	C9—C8—H8	109.2
C1—C2—H2	125.9	O6—C9—C8	111.69 (14)
N1—C2—H2	125.9	O6—C9—C10	112.87 (13)
N1—C3—N2	107.93 (15)	C8—C9—C10	109.09 (13)
N1—C3—H3	126.0	O6—C9—H9	107.7
N2—C3—H3	126.0	C8—C9—H9	107.7
C1—C4—C5	113.69 (14)	C10—C9—H9	107.7
C1—C4—H4A	108.8	O7—C10—O8	125.43 (15)
C5—C4—H4A	108.8	O7—C10—C9	117.58 (14)
C1—C4—H4B	108.8	O8—C10—C9	116.99 (14)
C5—C4—H4B	108.8	C3—N1—C2	109.12 (15)
H4A—C4—H4B	107.7	C3—N1—H1	125.4
N3—C5—C4	108.02 (13)	C2—N1—H1	125.4
N3—C5—C6	107.87 (12)	C3—N2—C1	109.29 (14)
C4—C5—C6	113.34 (14)	C3—N2—H2A	125.4
N3—C5—H5	109.2	C1—N2—H2A	125.4
C4—C5—H5	109.2	C5—N3—H3A	109.5
C6—C5—H5	109.2	C5—N3—H3B	109.5
O1—C6—O2	124.38 (16)	H3A—N3—H3B	109.5
O1—C6—C5	119.22 (15)	C5—N3—H3C	109.5
O2—C6—C5	116.30 (14)	H3A—N3—H3C	109.5
O4—C7—O3	125.44 (16)	H3B—N3—H3C	109.5
O4—C7—C8	122.86 (17)	C7—O3—H3D	109.5
O3—C7—C8	111.69 (16)	C8—O5—H5A	109.5
O5—C8—C7	111.23 (15)	C9—O6—H6	109.5
O5—C8—C9	107.99 (14)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O8	0.86	1.93	2.7689 (19)	166
N1—H1···O2ⁱ	0.86	1.84	2.6871 (19)	169
N3—H3A···O2ⁱⁱ	0.89	1.87	2.7532 (18)	173
N3—H3B···O7ⁱⁱⁱ	0.89	2.09	2.7937 (18)	135
N3—H3B···O6ⁱⁱⁱ	0.89	2.35	3.1374 (18)	147
N3—H3C···O7ⁱⁱ	0.89	1.85	2.7178 (18)	164
O3—H3D···O1^iv	0.82	1.77	2.5856 (17)	173
O5—H5A···O4^v	0.82	2.11	2.8174 (19)	145
O5—H5A···O4	0.82	2.30	2.7015 (19)	111
O6—H6···O8^vi	0.82	1.92	2.7152 (18)	162

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

References

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