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Acta Crystallographica Section E: Structure Reports Online logoLink to Acta Crystallographica Section E: Structure Reports Online
. 2012 Jul 18;68(Pt 8):o2490. doi: 10.1107/S1600536812031741

(2S,4R)-4-Fluoro­pyrrolidinium-2-carboxyl­ate

David B Hobart Jr a,*, Joseph S Merola a
PMCID: PMC3414945  PMID: 22904932

Abstract

The crystal structure of the title compound, C5H8FNO2, at 100 K, displays inter­molecular N—H⋯O hydrogen bonding between the ammonium and carboxyl­ate groups as a result of its zwitterionic nature in the solid state. The five-membered ring adopts an envelope conformation with the C atom at the 3-position as the flap. The compound is of inter­est with respect to the synthesis and structural properties of synthetic collagens. The absolute structure was determined by comparison with the commercially available material.

Related literature  

For the synthesis of the title compound, see: Gottlieb et al. (1965 ▶); Azad et al. (2012 ▶). For its applications and properties with respect to synthetic collagens, see: Hodges & Raines (2003 ▶, 2005 ▶); Holmgren et al. (1999 ▶); Kim et al. (2005 ▶); Mooney et al. (2002 ▶); Persikov et al. (2003 ▶); Raines (2005 ▶); Shoulders & Raines (2009 ▶); Shoulders et al. (2006 ▶); Takeuchi & Prockop (1969 ▶). graphic file with name e-68-o2490-scheme1.jpg

Experimental  

Crystal data  

  • C5H8FNO2

  • M r = 133.12

  • Orthorhombic, Inline graphic

  • a = 7.6530 (6) Å

  • b = 8.4128 (6) Å

  • c = 8.6286 (6) Å

  • V = 555.54 (7) Å3

  • Z = 4

  • Mo Kα radiation

  • μ = 0.14 mm−1

  • T = 100 K

  • 0.26 × 0.05 × 0.03 mm

Data collection  

  • Oxford Diffraction Gemini Ultra diffractometer

  • Absorption correction: Gaussian (CrysAlis PRO; Agilent, 2011 ▶) T min = 0.977, T max = 0.996

  • 10227 measured reflections

  • 959 independent reflections

  • 832 reflections with I > 2σ(I)

  • R int = 0.082

Refinement  

  • R[F 2 > 2σ(F 2)] = 0.038

  • wR(F 2) = 0.073

  • S = 1.07

  • 959 reflections

  • 114 parameters

  • All H-atom parameters refined

  • Δρmax = 0.32 e Å−3

  • Δρmin = −0.23 e Å−3

Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: OLEX2.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812031741/im2392sup1.cif

e-68-o2490-sup1.cif (16.2KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812031741/im2392Isup2.hkl

e-68-o2490-Isup2.hkl (47.6KB, hkl)

Supplementary material file. DOI: 10.1107/S1600536812031741/im2392Isup3.cdx

Supplementary material file. DOI: 10.1107/S1600536812031741/im2392Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Enhanced figure: interactive version of Fig. 1

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N6—H6B⋯O2i 0.92 (3) 1.90 (3) 2.744 (2) 152 (2)
N6—H6A⋯O2ii 0.91 (3) 2.01 (3) 2.899 (2) 164 (2)
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Symmetry codes: (i) Inline graphic; (ii) Inline graphic.

Acknowledgments

The authors would like to thank the Virginia Tech Department of Chemistry and the Virginia Tech Crystallography Laboratory for their support.

supplementary crystallographic information

Comment

The title compound is a useful building block in the synthesis of synthetic collagens. Collagen is the most abundant protein found in animals and exists as a triple helix comprised of three strands. The amino acid encoding of the strands follows the X—Y-Gly pattern. Trans-4-fluoroproline has been shown to induce hyperstability of the triple helix when substituted for the Y codon.

Experimental

The title compound was purchased commercially from Bachem Americas, Inc., 3132 Kashiwa Street, Torrance, CA 90505 USA. Single crystals suitable for diffraction were grown via slow evaporation from a 50/50 (v/v) solution of acetone and water.

Refinement

No Flack parameter is reported as Friedel pairs were merged via MERG3 instruction due to the absence of anomalous dispersion effects. Data collection was with Mo radiation and no heavy atoms are present. Chirality at each stereocenter was confirmed by comparison to the known stereochemistry of the commercially available material.

Hydrogen atoms were located from Fourier maps (Q-peaks) and all hydrogen atom parameters were refined.

Figures

Fig. 1.

Fig. 1.

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View of the title compound showing displacement ellipsoids at the 50% probability level.

Fig. 2.

Fig. 2.

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A view of a section of the crystal packing of the title compound along [101] showing N6–H6B···O2i and N6–H6A···O2ii hydrogen bonds [Symmetry code (i) 3/2 - x, 1 - y, 1/2 + z; (ii) +x, +y, 1 + z].

Crystal data

C5H8FNO2 Dx = 1.592 Mg m−3
Mr = 133.12 Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121 Cell parameters from 1887 reflections
a = 7.6530 (6) Å θ = 3.6–30.0°
b = 8.4128 (6) Å µ = 0.14 mm−1
c = 8.6286 (6) Å T = 100 K
V = 555.54 (7) Å3 Prism, clear light colourless
Z = 4 0.26 × 0.05 × 0.03 mm
F(000) = 280
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Data collection

Oxford Diffraction Gemini Ultra diffractometer 959 independent reflections
Radiation source: fine-focus sealed tube, fine-focus sealed tube 832 reflections with I > 2σ(I)
Graphite monochromator Rint = 0.082
Detector resolution: 16.0122 pixels mm-1 θmax = 30.1°, θmin = 3.6°
phi and ω scans h = −10→10
Absorption correction: gaussian (CrysAlis PRO; Agilent, 2011) k = −11→11
Tmin = 0.977, Tmax = 0.996 l = −12→12
10227 measured reflections
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Refinement

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)] = 0.038 Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.073 All H-atom parameters refined
S = 1.07 w = 1/[σ2(Fo2) + (0.0203P)2 + 0.2288P] where P = (Fo2 + 2Fc2)/3
959 reflections (Δ/σ)max < 0.001
114 parameters Δρmax = 0.32 e Å−3
0 restraints Δρmin = −0.23 e Å−3
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Special details

Experimental. Recrystallized from 50/50 acetone/water.Absorption correction: CrysAlisPro, Agilent Technologies, Version 1.171.34.49 (release 20-01-2011 CrysAlis171 .NET) (compiled Jan 20 2011,15:58:25) Numerical absorption correction based on gaussian integration over a multifaceted crystal model
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.
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Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

x y z Uiso*/Ueq
F1 0.24111 (16) 0.73474 (16) 0.53792 (14) 0.0194 (3)
O2 0.58809 (19) 0.59578 (17) 0.07960 (17) 0.0143 (3)
O3 0.4982 (2) 0.82996 (18) −0.01402 (17) 0.0177 (3)
N6 0.2662 (2) 0.8837 (2) 0.2162 (2) 0.0109 (3)
C4 0.3974 (3) 0.7510 (2) 0.2345 (2) 0.0104 (4)
C5 0.5019 (3) 0.7239 (2) 0.0854 (2) 0.0104 (4)
C7 0.1571 (3) 0.6913 (3) 0.3970 (2) 0.0130 (4)
C8 0.1078 (3) 0.8427 (3) 0.3133 (2) 0.0124 (4)
C9 0.2903 (3) 0.6117 (3) 0.2947 (2) 0.0137 (4)
H4 0.480 (3) 0.787 (3) 0.317 (3) 0.010 (6)*
H8A 0.011 (3) 0.822 (3) 0.247 (3) 0.013 (6)*
H7 0.056 (3) 0.629 (3) 0.424 (3) 0.011 (6)*
H8B 0.084 (3) 0.927 (3) 0.387 (3) 0.008 (6)*
H9A 0.233 (3) 0.560 (3) 0.208 (3) 0.020 (7)*
H9B 0.358 (3) 0.540 (3) 0.353 (3) 0.022 (7)*
H6A 0.231 (3) 0.895 (3) 0.115 (3) 0.026 (7)*
H6B 0.314 (3) 0.975 (3) 0.256 (3) 0.020 (7)*
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Atomic displacement parameters (Å2)

U11 U22 U33 U12 U13 U23
F1 0.0170 (6) 0.0320 (8) 0.0092 (6) 0.0011 (6) 0.0006 (5) 0.0004 (5)
O2 0.0151 (7) 0.0142 (7) 0.0136 (7) 0.0048 (6) 0.0027 (6) 0.0023 (6)
O3 0.0248 (8) 0.0158 (7) 0.0124 (7) 0.0051 (7) 0.0053 (7) 0.0031 (6)
N6 0.0115 (8) 0.0101 (8) 0.0112 (8) 0.0008 (7) 0.0000 (7) −0.0014 (7)
C4 0.0110 (8) 0.0110 (9) 0.0091 (8) 0.0004 (8) −0.0003 (7) −0.0002 (8)
C5 0.0094 (8) 0.0113 (9) 0.0106 (8) −0.0034 (8) 0.0000 (7) −0.0015 (8)
C7 0.0119 (9) 0.0158 (10) 0.0114 (9) −0.0018 (8) 0.0018 (8) −0.0003 (8)
C8 0.0106 (9) 0.0153 (9) 0.0112 (9) 0.0017 (8) 0.0007 (8) −0.0022 (8)
C9 0.0149 (10) 0.0118 (9) 0.0144 (10) 0.0009 (8) 0.0013 (8) 0.0035 (9)
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Geometric parameters (Å, º)

F1—C7 1.423 (2) C4—H4 1.00 (2)
O2—C5 1.265 (2) C7—C8 1.512 (3)
O3—C5 1.238 (2) C7—C9 1.505 (3)
N6—C4 1.509 (3) C7—H7 0.96 (2)
N6—C8 1.513 (3) C8—H8A 0.95 (3)
N6—H6A 0.91 (3) C8—H8B 0.97 (2)
N6—H6B 0.92 (3) C9—H9A 0.97 (3)
C4—C5 1.532 (3) C9—H9B 0.94 (3)
C4—C9 1.521 (3)
C4—N6—C8 107.85 (15) F1—C7—H7 107.3 (14)
C4—N6—H6A 111.6 (17) C8—C7—H7 111.6 (13)
C4—N6—H6B 108.2 (15) C9—C7—C8 105.27 (17)
C8—N6—H6A 108.5 (17) C9—C7—H7 116.6 (14)
C8—N6—H6B 107.5 (15) N6—C8—H8A 109.4 (15)
H6A—N6—H6B 113 (2) N6—C8—H8B 110.1 (13)
N6—C4—C5 111.70 (16) C7—C8—N6 104.86 (16)
N6—C4—C9 104.28 (16) C7—C8—H8A 109.3 (15)
N6—C4—H4 105.8 (13) C7—C8—H8B 110.5 (13)
C5—C4—H4 108.2 (13) H8A—C8—H8B 112.4 (19)
C9—C4—C5 116.93 (17) C4—C9—H9A 108.9 (15)
C9—C4—H4 109.3 (13) C4—C9—H9B 112.4 (15)
O2—C5—C4 115.64 (17) C7—C9—C4 102.86 (17)
O3—C5—O2 126.79 (19) C7—C9—H9A 110.3 (15)
O3—C5—C4 117.53 (18) C7—C9—H9B 110.2 (15)
F1—C7—C8 107.72 (17) H9A—C9—H9B 112 (2)
F1—C7—C9 108.03 (17)
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Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A
N6—H6B···O2i 0.92 (3) 1.90 (3) 2.744 (2) 152 (2)
N6—H6A···O2ii 0.91 (3) 2.01 (3) 2.899 (2) 164 (2)
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Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) x−1/2, −y+3/2, −z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IM2392).

References

  1. Agilent (2011). CrysAlis PRO. Agilent Technologies UK Ltd, Yarnton, Oxfordshire, England.
  2. Azad, B. B., Ashique, R., Labiris, N. R. & Chirakal, R. (2012). J. Labelled Compd. Radiopharm. 55, 23–28.
  3. Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.
  4. Gottlieb, A. A., Fujita, Y., Udenfriend, S. & Witkop, B. (1965). Biochemistry, 4, 2507–2513.
  5. Hodges, J. A. & Raines, R. T. (2003). J. Am. Chem. Soc. 125, 9262–9263. [DOI] [PubMed]
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  7. Holmgren, S. K., Bretscher, L. E., Taylor, K. M. & Raines, R. T. (1999). Chem. Biol. 6, 63–70. [DOI] [PubMed]
  8. Kim, W., McMillan, R. A., Snyder, J. P. & Conticello, V. P. (2005). J. Am. Chem. Soc. 127, 18121–18132. [DOI] [PubMed]
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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812031741/im2392sup1.cif

e-68-o2490-sup1.cif (16.2KB, cif)

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812031741/im2392Isup2.hkl

e-68-o2490-Isup2.hkl (47.6KB, hkl)

Supplementary material file. DOI: 10.1107/S1600536812031741/im2392Isup3.cdx

Supplementary material file. DOI: 10.1107/S1600536812031741/im2392Isup4.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Enhanced figure: interactive version of Fig. 1

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography

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