organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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

aDepartment of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA
*Correspondence e-mail: dhobart@vt.edu

(Received 27 June 2012; accepted 11 July 2012; online 18 July 2012)

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[Gottlieb, A. A., Fujita, Y., Udenfriend, S. & Witkop, B. (1965). Biochemistry, 4, 2507-2513.]); Azad et al. (2012[Azad, B. B., Ashique, R., Labiris, N. R. & Chirakal, R. (2012). J. Labelled Compd. Radiopharm. 55, 23-28.]). For its applications and properties with respect to synthetic collagens, see: Hodges & Raines (2003[Hodges, J. A. & Raines, R. T. (2003). J. Am. Chem. Soc. 125, 9262-9263.], 2005[Hodges, J. A. & Raines, R. T. (2005). J. Am. Chem. Soc. 127, 15923-15932.]); Holmgren et al. (1999[Holmgren, S. K., Bretscher, L. E., Taylor, K. M. & Raines, R. T. (1999). Chem. Biol. 6, 63-70.]); Kim et al. (2005[Kim, W., McMillan, R. A., Snyder, J. P. & Conticello, V. P. (2005). J. Am. Chem. Soc. 127, 18121-18132.]); Mooney et al. (2002[Mooney, S. D., Kollman, P. A. & Klein, T. E. (2002). Biopolymers, 64, 63-71. ]); Persikov et al. (2003[Persikov, A. V., Ramshaw, J. A. M., Kirkpatrick, A. & Brodsky, B. (2003). J. Am. Chem. Soc. 125, 11500-11501. ]); Raines (2005[Raines, R. T. (2005). Polym. Prepr. (Am. Chem. Soc. Div. Polym. Chem.), 46, 181-182. ]); Shoulders & Raines (2009[Shoulders, M. D. & Raines, R. T. (2009). Adv. Exp. Med. Biol. 611, 251-252.]); Shoulders et al. (2006[Shoulders, M. D., Hodges, J. A. & Raines, R. T. (2006). J. Am. Chem. Soc. 128, 8112-8113. ]); Takeuchi & Prockop (1969[Takeuchi, T. & Prockop, D. J. (1969). Biochim. Biophys. Acta Protein Struct. 175, 142-155. ]).

[Scheme 1]

Experimental

Crystal data
  • C5H8FNO2

  • Mr = 133.12

  • Orthorhombic, P 21 21 21

  • 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[Agilent (2011). CrysAlis PRO. Agilent Technologies UK Ltd, Yarnton, Oxfordshire, England.]) Tmin = 0.977, Tmax = 0.996

  • 10227 measured reflections

  • 959 independent reflections

  • 832 reflections with I > 2σ(I)

  • Rint = 0.082

Refinement
  • R[F2 > 2σ(F2)] = 0.038

  • wR(F2) = 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

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA 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)
Symmetry codes: (i) [-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]; (ii) [x-{\script{1\over 2}}, -y+{\script{3\over 2}}, -z].

Data collection: CrysAlis PRO (Agilent, 2011[Agilent (2011). CrysAlis PRO. Agilent Technologies UK Ltd, Yarnton, Oxfordshire, England.]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]); software used to prepare material for publication: OLEX2.

Supporting information


Comment top

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.

Related literature top

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).

Experimental top

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 top

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.

Structure description top

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.

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).

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); 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 (Dolomanov et al., 2009).

Figures top
[Figure 1] Fig. 1. View of the title compound showing displacement ellipsoids at the 50% probability level.
[Figure 2] Fig. 2. 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].
(2S,4R)-4-Fluoropyrrolidinium-2-carboxylate top
Crystal data top
C5H8FNO2Dx = 1.592 Mg m3
Mr = 133.12Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 1887 reflections
a = 7.6530 (6) Åθ = 3.6–30.0°
b = 8.4128 (6) ŵ = 0.14 mm1
c = 8.6286 (6) ÅT = 100 K
V = 555.54 (7) Å3Prism, clear light colourless
Z = 40.26 × 0.05 × 0.03 mm
F(000) = 280
Data collection top
Oxford Diffraction Gemini Ultra
diffractometer
959 independent reflections
Radiation source: fine-focus sealed tube, fine-focus sealed tube832 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.082
Detector resolution: 16.0122 pixels mm-1θmax = 30.1°, θmin = 3.6°
phi and ω scansh = 1010
Absorption correction: gaussian
(CrysAlis PRO; Agilent, 2011)
k = 1111
Tmin = 0.977, Tmax = 0.996l = 1212
10227 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.038Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.073All 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 parametersΔρmax = 0.32 e Å3
0 restraintsΔρmin = 0.23 e Å3
Crystal data top
C5H8FNO2V = 555.54 (7) Å3
Mr = 133.12Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.6530 (6) ŵ = 0.14 mm1
b = 8.4128 (6) ÅT = 100 K
c = 8.6286 (6) Å0.26 × 0.05 × 0.03 mm
Data collection top
Oxford Diffraction Gemini Ultra
diffractometer
959 independent reflections
Absorption correction: gaussian
(CrysAlis PRO; Agilent, 2011)
832 reflections with I > 2σ(I)
Tmin = 0.977, Tmax = 0.996Rint = 0.082
10227 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0380 restraints
wR(F2) = 0.073All H-atom parameters refined
S = 1.07Δρmax = 0.32 e Å3
959 reflectionsΔρmin = 0.23 e Å3
114 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
F10.24111 (16)0.73474 (16)0.53792 (14)0.0194 (3)
O20.58809 (19)0.59578 (17)0.07960 (17)0.0143 (3)
O30.4982 (2)0.82996 (18)0.01402 (17)0.0177 (3)
N60.2662 (2)0.8837 (2)0.2162 (2)0.0109 (3)
C40.3974 (3)0.7510 (2)0.2345 (2)0.0104 (4)
C50.5019 (3)0.7239 (2)0.0854 (2)0.0104 (4)
C70.1571 (3)0.6913 (3)0.3970 (2)0.0130 (4)
C80.1078 (3)0.8427 (3)0.3133 (2)0.0124 (4)
C90.2903 (3)0.6117 (3)0.2947 (2)0.0137 (4)
H40.480 (3)0.787 (3)0.317 (3)0.010 (6)*
H8A0.011 (3)0.822 (3)0.247 (3)0.013 (6)*
H70.056 (3)0.629 (3)0.424 (3)0.011 (6)*
H8B0.084 (3)0.927 (3)0.387 (3)0.008 (6)*
H9A0.233 (3)0.560 (3)0.208 (3)0.020 (7)*
H9B0.358 (3)0.540 (3)0.353 (3)0.022 (7)*
H6A0.231 (3)0.895 (3)0.115 (3)0.026 (7)*
H6B0.314 (3)0.975 (3)0.256 (3)0.020 (7)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0170 (6)0.0320 (8)0.0092 (6)0.0011 (6)0.0006 (5)0.0004 (5)
O20.0151 (7)0.0142 (7)0.0136 (7)0.0048 (6)0.0027 (6)0.0023 (6)
O30.0248 (8)0.0158 (7)0.0124 (7)0.0051 (7)0.0053 (7)0.0031 (6)
N60.0115 (8)0.0101 (8)0.0112 (8)0.0008 (7)0.0000 (7)0.0014 (7)
C40.0110 (8)0.0110 (9)0.0091 (8)0.0004 (8)0.0003 (7)0.0002 (8)
C50.0094 (8)0.0113 (9)0.0106 (8)0.0034 (8)0.0000 (7)0.0015 (8)
C70.0119 (9)0.0158 (10)0.0114 (9)0.0018 (8)0.0018 (8)0.0003 (8)
C80.0106 (9)0.0153 (9)0.0112 (9)0.0017 (8)0.0007 (8)0.0022 (8)
C90.0149 (10)0.0118 (9)0.0144 (10)0.0009 (8)0.0013 (8)0.0035 (9)
Geometric parameters (Å, º) top
F1—C71.423 (2)C4—H41.00 (2)
O2—C51.265 (2)C7—C81.512 (3)
O3—C51.238 (2)C7—C91.505 (3)
N6—C41.509 (3)C7—H70.96 (2)
N6—C81.513 (3)C8—H8A0.95 (3)
N6—H6A0.91 (3)C8—H8B0.97 (2)
N6—H6B0.92 (3)C9—H9A0.97 (3)
C4—C51.532 (3)C9—H9B0.94 (3)
C4—C91.521 (3)
C4—N6—C8107.85 (15)F1—C7—H7107.3 (14)
C4—N6—H6A111.6 (17)C8—C7—H7111.6 (13)
C4—N6—H6B108.2 (15)C9—C7—C8105.27 (17)
C8—N6—H6A108.5 (17)C9—C7—H7116.6 (14)
C8—N6—H6B107.5 (15)N6—C8—H8A109.4 (15)
H6A—N6—H6B113 (2)N6—C8—H8B110.1 (13)
N6—C4—C5111.70 (16)C7—C8—N6104.86 (16)
N6—C4—C9104.28 (16)C7—C8—H8A109.3 (15)
N6—C4—H4105.8 (13)C7—C8—H8B110.5 (13)
C5—C4—H4108.2 (13)H8A—C8—H8B112.4 (19)
C9—C4—C5116.93 (17)C4—C9—H9A108.9 (15)
C9—C4—H4109.3 (13)C4—C9—H9B112.4 (15)
O2—C5—C4115.64 (17)C7—C9—C4102.86 (17)
O3—C5—O2126.79 (19)C7—C9—H9A110.3 (15)
O3—C5—C4117.53 (18)C7—C9—H9B110.2 (15)
F1—C7—C8107.72 (17)H9A—C9—H9B112 (2)
F1—C7—C9108.03 (17)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N6—H6B···O2i0.92 (3)1.90 (3)2.744 (2)152 (2)
N6—H6A···O2ii0.91 (3)2.01 (3)2.899 (2)164 (2)
Symmetry codes: (i) x+1, y+1/2, z+1/2; (ii) x1/2, y+3/2, z.

Experimental details

Crystal data
Chemical formulaC5H8FNO2
Mr133.12
Crystal system, space groupOrthorhombic, P212121
Temperature (K)100
a, b, c (Å)7.6530 (6), 8.4128 (6), 8.6286 (6)
V3)555.54 (7)
Z4
Radiation typeMo Kα
µ (mm1)0.14
Crystal size (mm)0.26 × 0.05 × 0.03
Data collection
DiffractometerOxford Diffraction Gemini Ultra
Absorption correctionGaussian
(CrysAlis PRO; Agilent, 2011)
Tmin, Tmax0.977, 0.996
No. of measured, independent and
observed [I > 2σ(I)] reflections
10227, 959, 832
Rint0.082
(sin θ/λ)max1)0.705
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.073, 1.07
No. of reflections959
No. of parameters114
H-atom treatmentAll H-atom parameters refined
Δρmax, Δρmin (e Å3)0.32, 0.23

Computer programs: CrysAlis PRO (Agilent, 2011), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), OLEX2 (Dolomanov et al., 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N6—H6B···O2i0.92 (3)1.90 (3)2.744 (2)152 (2)
N6—H6A···O2ii0.91 (3)2.01 (3)2.899 (2)164 (2)
Symmetry codes: (i) x+1, y+1/2, z+1/2; (ii) x1/2, y+3/2, z.
 

Acknowledgements

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

References

First citationAgilent (2011). CrysAlis PRO. Agilent Technologies UK Ltd, Yarnton, Oxfordshire, England.  Google Scholar
First citationAzad, B. B., Ashique, R., Labiris, N. R. & Chirakal, R. (2012). J. Labelled Compd. Radiopharm. 55, 23–28.  CAS Google Scholar
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First citationHodges, J. A. & Raines, R. T. (2003). J. Am. Chem. Soc. 125, 9262–9263.  Web of Science CrossRef PubMed CAS Google Scholar
First citationHodges, J. A. & Raines, R. T. (2005). J. Am. Chem. Soc. 127, 15923–15932.  Web of Science CrossRef PubMed CAS Google Scholar
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First citationKim, W., McMillan, R. A., Snyder, J. P. & Conticello, V. P. (2005). J. Am. Chem. Soc. 127, 18121–18132.  Web of Science CrossRef PubMed CAS Google Scholar
First citationMooney, S. D., Kollman, P. A. & Klein, T. E. (2002). Biopolymers, 64, 63–71.   Web of Science CrossRef PubMed CAS Google Scholar
First citationPersikov, A. V., Ramshaw, J. A. M., Kirkpatrick, A. & Brodsky, B. (2003). J. Am. Chem. Soc. 125, 11500–11501.   Web of Science CrossRef PubMed CAS Google Scholar
First citationRaines, R. T. (2005). Polym. Prepr. (Am. Chem. Soc. Div. Polym. Chem.), 46, 181–182.   CAS Google Scholar
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
First citationShoulders, M. D., Hodges, J. A. & Raines, R. T. (2006). J. Am. Chem. Soc. 128, 8112–8113.   Web of Science CrossRef PubMed CAS Google Scholar
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First citationTakeuchi, T. & Prockop, D. J. (1969). Biochim. Biophys. Acta Protein Struct. 175, 142–155.   CrossRef CAS Web of Science Google Scholar

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