(R) Histidinium (2R,3R) tartrate

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organic papers

o1476

Johnson and Feeder C₆H₁₀N₃O₂+C₄H₅O₆ÿ DOI: 10.1107/S160053680401863X Acta Cryst.(2004). E60, o1476±o1477

Acta Crystallographica Section E

Structure Reports Online

ISSN 1600-5368

(

R

)-Histidinium (2

R

,3

R

)-tartrate

M. N. Johnson* and N. Feeder

Pfizer Ltd, IPC 049, Ramsgate Road, Sandwich, Kent CT13 9NJ, England

Correspondence e-mail:

matthew johnson@sandwich.pfizer.com

Key indicators

Single-crystal X-ray study

T= 291 K

Mean(C±C) = 0.003 AÊ

Rfactor = 0.030

wRfactor = 0.076 Data-to-parameter ratio = 7.3

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

The crystal structure of (R)-histidinium (2R,3R)-tartrate, C6H10N3O2+C4H5O6ÿ, has been determined as part of an

ongoing study into the fundamental effects of chirality on salt formation and hydration. Repeating layers of (R)-histidinium and (2R,3R)-tartrate interlink to form a three-dimensional network through simple translational symmetry of the unit cell.

Comment

This study was undertaken to identify the effects of chirality on the formation of salts, speci®cally the way chirality may affect hydration, as a result of interactions between a chiral drug and a chiral counterion. The absolute con®guration can be considered determined as the chiral properties of the starting materials are well characterized. (R)-Histidine and (2R,3R)-tartaric acid samples were purchased from Fluka and used in the crystallization. The asymmetric unit and unit cell contain one histidine as a monocation (protonated at the amine and imidazole ring N atoms and deprotonated at the carboxylic acid group), and one tartrate as a monoanion (see scheme below and Fig. 1).

The (R)-histidinium layer is formed by chains of linked histidinium cations hydrogen bonded from the imidazole ring (N2) to carboxyl oxygen (O1). The two-dimensional layer is created by a hydrogen bond from N3 (ammonium group) to the adjacent (R)-histidinium carboxyl group (O2). The (2R,3R)-tartrate anions also form chains, with each link created by hydrogen bonding between the carboxyl OH (O3) group to an oxygen (O8) of the carboxylate group (Fig. 2). The (2R,3R)-tartrate two-dimensional layer is maintained by a single hydrogen bond from a hydroxyl group (O6) to a neighbouring carboxyl oxygen (O7). The three-dimensional crystal structure is formed of repeating layers of (R )-histidinium and (2R,3R)-tartrate ions, as shown in Fig. 2. The (R)-histidinium layer is linked to one (2R,3R)-tartrate layer through two hydrogen bonds from the ammonium group (N3) to O7 (carboxylate). The next layer of tartrates is hydrogen bonded to the imidazole ring (N1ÐH1 O5) and the carboxylate atom O1. Atom O1 is bifurcated, maintaining both the histidine chains and the tartrate/histidine interaction with O5.

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Experimental

A saturated aqueous solution (5 ml) of (R)-histidine was mixed with a saturated aqueous solution (5 ml) of (2R,3R)-tartartic acid and the vial was covered with a pierced ®lm. This was placed in a larger glass vial containing methanol (25 ml), sealed and allowed to stand for three weeks at room temperature. Crystals of a suitable size for use for single-crystal X-ray diffraction analysis were removed and mounted on glass ®bres.

Crystal data

C6H10N3O2+C4H5O6ÿ

Mr= 305.25 Triclinic,P1

a= 5.3712 (18) AÊ

b= 7.637 (3) AÊ

c= 8.460 (3) AÊ

= 72.025 (5)

= 73.872 (5)

= 81.144 (5)

V= 316.2 (2) AÊ3

Z= 1

Dx= 1.602 Mg mÿ3 MoKradiation Cell parameters from 1902

re¯ections

= 2.6±28.1

= 0.14 mmÿ1

T= 291 (2) K Tablet, colourless 0.50.30.1 mm

Data collection

Bruker SMART APEX CCD diffractometer

Thin-slice!scans

Absorption correction: multi-scan (Blessing, 1995)

Tmin= 0.802,Tmax= 0.990 2658 measured re¯ections

1407 independent re¯ections 1382 re¯ections withI> 2(I)

Rint= 0.011

max= 28.4

h=ÿ6!7

k=ÿ10!10

l=ÿ11!11

Re®nement

Re®nement onF2

R[F2_{> 2}₍_F2_{)] = 0.030}

wR(F2_{) = 0.076}

S= 1.07 1407 re¯ections 194 parameters

H-atom parameters constrained

w= 1/[2₍_F

o2) + (0.0511P)2 + 0.0492P]

whereP= (Fo2+ 2Fc2)/3 (/)max= 0.001

max= 0.20 e AÊÿ3 min=ÿ0.23 e AÊÿ3

Table 1

Hydrogen-bonding geometry (AÊ,_).

DÐH A DÐH H A D A DÐH A

N1ÐH1 O8i _0.86 _1.90 _{2.760 (2)} ₁₇₃ N1ÐH1 O5i _0.86 _2.55 _{2.993 (3)} ₁₁₃ N2ÐH2A O1ii _0.86 _2.09 _{2.810 (3)} ₁₄₂ N2ÐH2A O6ii _0.86 _2.47 _{2.961 (3)} ₁₁₇ N3ÐH3A O7iii _0.89 _1.91 _{2.799 (2)} ₁₇₆ N3ÐH3C O2iv _0.89 _1.96 _{2.822 (3)} ₁₆₂ O5ÐH500 O1v _0.82 _1.95 _{2.741 (3)} ₁₆₃ O6ÐH600 O7iv _0.82 _2.08 _{2.744 (2)} ₁₃₈ O3ÐH300 O8ii _0.82 _1.72 _{2.533 (2)} ₁₇₂ Symmetry codes: (i)xÿ1;1y;1z; (ii)x;1y;z; (iii) 1x;1y;z; (iv) 1x;y;z; (v)x;y;zÿ1.

All H atoms were positioned geometrically (NÐH = 0.86±0.89, OÐH = 0.82 and CÐH = 0.93±0.98 AÊ) and re®ned using a riding model, with Uiso(H) = 1.2 or 1.5 times Ueq(N), 1.5Ueq(O) and

1.2Ueq(C). In the absence of signi®cant anomalous dispersion effects

Friedel pairs were merged prior to re®nement.

Data collection:SMART(Bruker, 2002); cell re®nement:SAINT

(Bruker, 2002); data reduction:SAINT; program(s) used to solve structure:SHELXS97 (Sheldrick, 1997); program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP

(Sheldrick, 1996) and Materials Studio (Accelrys, 2001); software used to prepare material for publication:SHELXL97.

References

Accelrys (2001).Materials Studio. Accelrys Ltd, 334 Cambridge Science Park, Cambridge CB4 0WN, England.

Blessing, R. H. (1995).Acta Cryst.A51, 33±38.

Bruker (2002).SAINT(Version 6.02) andSMART(Version 5.622). Bruker AXS Inc., Madison, Wisconsin, USA.

Sheldrick, G. M. (1997).XP. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA.

Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of GoÈttingen, Germany.

Figure 2

Hydrogen-bonding (dashed lines) motifs in the (R)-histidinium (blue) and (2R,3R)-tartrate (green) ions of (I).

Figure 1

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supporting information

sup-1

Acta Cryst. (2004). E60, o1476–o1477

supporting information

Acta Cryst. (2004). E60, o1476–o1477 [https://doi.org/10.1107/S160053680401863X]

(

R

)-Histidinium (2

R

,3

R

)-tartrate

M. N. Johnson and N. Feeder

(I)

Crystal data C6H10N3O2+·C4H5O6−

Mr = 305.25

Triclinic, P1 Hall symbol: P 1 a = 5.3712 (18) Å b = 7.637 (3) Å c = 8.460 (3) Å α = 72.025 (5)° β = 73.872 (5)° γ = 81.144 (5)° V = 316.2 (2) Å3

Z = 1 F(000) = 160 Dx = 1.602 Mg m−3

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 1902 reflections θ = 2.6–28.1°

µ = 0.14 mm−1

T = 291 K

Tabular, colourless 0.5 × 0.3 × 0.1 mm

Data collection

Bruker SMART APEX CCD diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

Thin–slice ω scans

Absorption correction: multi-scan (Blessing, 1995)

Tmin = 0.802, Tmax = 0.990

2658 measured reflections 1407 independent reflections 1382 reflections with I > 2σ(I) Rint = 0.011

θmax = 28.4°, θmin = 2.6°

h = −6→7 k = −10→10 l = −11→11

Refinement Refinement on F2

Least-squares matrix: full R[F2_{> 2}_σ₍_F2_{)] = 0.030}

wR(F2_{) = 0.076}

S = 1.07 1407 reflections 194 parameters 3 restraints

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H atoms treated by a mixture of independent and constrained refinement

w = 1/[σ2₍_F

o2) + (0.0511P)2 + 0.0492P]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max = 0.001

Δρmax = 0.20 e Å−3

Δρmin = −0.23 e Å−3

Absolute structure: Flack (1983), 999 friedel pairs

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Special details

Experimental. The data was collected at room temperature using a Bruker SMART– APEX CCD area-detector (Mo Kα radiation). Intensities were intergrated from a series of exposures. Each exposure covered 0.3° in ω, with an exposure time of 60 s and the total data set was more than a sphere. The SAINT software containing SADABS was used to intergrate and correct the data.

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₎

x y z Uiso*/Ueq

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supporting information

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Acta Cryst. (2004). E60, o1476–o1477

H600 0.7422 −0.1128 0.5170 0.047* O3 0.3409 (3) 0.3313 (2) 0.4069 (2) 0.0346 (4) H300 0.3991 0.4321 0.3822 0.052* O4 0.7451 (3) 0.2238 (2) 0.4303 (2) 0.0368 (4)

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

C1 0.0303 (10) 0.0253 (9) 0.0254 (9) −0.0044 (8) −0.0058 (8) −0.0086 (7) C2 0.0305 (11) 0.0274 (11) 0.0330 (10) −0.0071 (8) −0.0041 (9) −0.0088 (8) C3 0.0353 (11) 0.0256 (10) 0.0388 (11) −0.0048 (9) −0.0002 (9) −0.0101 (9) C4 0.0256 (9) 0.0298 (10) 0.0319 (10) −0.0049 (8) −0.0057 (8) −0.0128 (8) C5 0.0215 (9) 0.0208 (9) 0.0257 (9) −0.0019 (7) −0.0047 (7) −0.0055 (7) C6 0.0264 (10) 0.0258 (10) 0.0230 (8) −0.0095 (7) −0.0046 (7) −0.0046 (7) C10 0.0286 (10) 0.0177 (9) 0.0300 (10) −0.0047 (7) −0.0064 (8) −0.0071 (7) C9 0.0275 (9) 0.0159 (8) 0.0280 (9) −0.0043 (7) −0.0036 (8) −0.0058 (7) C8 0.0220 (9) 0.0194 (9) 0.0261 (9) −0.0037 (7) 0.0005 (7) −0.0070 (7) C7 0.0283 (9) 0.0213 (9) 0.0234 (9) −0.0051 (7) −0.0011 (7) −0.0098 (7) N1 0.0284 (9) 0.0318 (9) 0.0311 (9) −0.0069 (7) 0.0020 (7) −0.0102 (7) N2 0.0315 (9) 0.0265 (9) 0.0307 (8) −0.0084 (7) 0.0018 (7) −0.0068 (7) N3 0.0248 (8) 0.0240 (8) 0.0291 (9) −0.0078 (6) −0.0001 (7) −0.0078 (7) O1 0.0322 (8) 0.0230 (7) 0.0456 (9) −0.0066 (6) −0.0066 (7) −0.0012 (6) O2 0.0268 (9) 0.0372 (9) 0.0622 (12) −0.0109 (7) −0.0113 (8) −0.0035 (8) O7 0.0277 (8) 0.0237 (8) 0.0544 (10) −0.0079 (6) 0.0058 (7) −0.0114 (7) O8 0.0335 (8) 0.0197 (7) 0.0435 (9) −0.0076 (6) 0.0041 (7) −0.0133 (6) O5 0.0410 (9) 0.0289 (8) 0.0242 (7) −0.0127 (7) 0.0021 (6) −0.0068 (6) O6 0.0315 (8) 0.0260 (7) 0.0302 (7) −0.0017 (6) −0.0049 (6) −0.0018 (6) O3 0.0304 (8) 0.0177 (7) 0.0535 (10) −0.0056 (5) −0.0057 (7) −0.0091 (6) O4 0.0297 (8) 0.0351 (8) 0.0491 (9) −0.0086 (6) −0.0085 (7) −0.0150 (7)

Geometric parameters (Å, º)

C1—C2 1.359 (3) C10—C9 1.538 (3)

C1—N2 1.377 (3) C9—O5 1.411 (3)

C1—C4 1.497 (3) C9—C8 1.539 (3)

C2—N1 1.373 (3) C9—H9 0.9800

C2—H2 0.9300 C8—O6 1.406 (2)

C3—N1 1.319 (3) C8—C7 1.525 (3)

C3—N2 1.328 (3) C8—H8 0.9800

C3—H3 0.9300 C7—O4 1.213 (3)

C4—C5 1.540 (3) C7—O3 1.307 (3)

C4—H4A 0.9700 N1—H1 0.8600

C4—H4B 0.9700 N2—H2A 0.8600

C5—N3 1.490 (3) N3—H3A 0.8900

C5—C6 1.536 (3) N3—H3B 0.8900

C5—H5 0.9800 N3—H3C 0.8900

C6—O2 1.240 (3) O5—H500 0.8200

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C10—O7 1.237 (3) O3—H300 0.8200 C10—O8 1.269 (3)

C2—C1—N2 105.75 (18) C10—C9—C8 107.52 (16) C2—C1—C4 133.0 (2) O5—C9—H9 109.5 N2—C1—C4 121.18 (19) C10—C9—H9 109.5 C1—C2—N1 107.40 (19) C8—C9—H9 109.5 C1—C2—H2 126.3 O6—C8—C7 111.96 (16) N1—C2—H2 126.3 O6—C8—C9 112.15 (15) N1—C3—N2 108.2 (2) C7—C8—C9 108.21 (15)

N1—C3—H3 125.9 O6—C8—H8 108.1

N2—C3—H3 125.9 C7—C8—H8 108.1

C1—C4—C5 114.23 (17) C9—C8—H8 108.1 C1—C4—H4A 108.7 O4—C7—O3 125.39 (19) C5—C4—H4A 108.7 O4—C7—C8 122.49 (19) C1—C4—H4B 108.7 O3—C7—C8 112.12 (17) C5—C4—H4B 108.7 C3—N1—C2 109.1 (2) H4A—C4—H4B 107.6 C3—N1—H1 125.5 N3—C5—C6 109.32 (16) C2—N1—H1 125.5 N3—C5—C4 107.87 (16) C3—N2—C1 109.61 (18) C6—C5—C4 110.70 (17) C3—N2—H2A 125.2

N3—C5—H5 109.6 C1—N2—H2A 125.2

C6—C5—H5 109.6 C5—N3—H3A 109.5

C4—C5—H5 109.6 C5—N3—H3B 109.5

O2—C6—O1 126.2 (2) H3A—N3—H3B 109.5 O2—C6—C5 117.46 (19) C5—N3—H3C 109.5 O1—C6—C5 116.27 (17) H3A—N3—H3C 109.5 O7—C10—O8 125.67 (19) H3B—N3—H3C 109.5 O7—C10—C9 116.51 (18) C9—O5—H500 109.5 O8—C10—C9 117.82 (18) C8—O6—H600 109.5 O5—C9—C10 113.51 (16) C7—O3—H300 109.5 O5—C9—C8 107.33 (16)

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supporting information

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Acta Cryst. (2004). E60, o1476–o1477

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A N1—H1···O8i _0.86 _1.90 _{2.760 (2)} ₁₇₃

N1—H1···O5i _0.86 _2.55 _{2.993 (3)} ₁₁₃

N2—H2A···O1ii _0.86 _2.09 _{2.810 (3)} ₁₄₂

N2—H2A···O6ii _0.86 _2.47 _{2.961 (3)} ₁₁₇

N3—H3A···O7iii _0.89 _1.91 _{2.799 (2)} ₁₇₆

N3—H3C···O2iv _0.89 _1.96 _{2.822 (3)} ₁₆₂

O5—H500···O1v _0.82 _1.95 _{2.741 (3)} ₁₆₃

O6—H600···O7iv _0.82 _2.08 _{2.744 (2)} ₁₃₈

O3—H300···O8ii _0.82 _1.72 _{2.533 (2)} ₁₇₂