Literature DB >> 21588926

2-Fluoro-l-histidine.

Kiran K Andra¹, John C Bullinger, James G Bann, David M Eichhorn.

Abstract

The title compound, C(6)H(8)FN(3)O(2), an analog of histidine, shows a reduced side-chain pK(a) (ca 1). The title structure exhibits a shortening of the bond between the proximal ring N atom and the F-substituted ring C atom, indicating an increase in π-bond character due to an inductive effect of fluorine.

Entities: Chemical Disease Gene

Year: 2010 PMID： 21588926 PMCID： PMC3009228 DOI： 10.1107/S1600536810038663

Source DB: PubMed Journal: Acta Crystallogr Sect E Struct Rep Online ISSN： 1600-5368

Related literature

For the structure of l-histidine, see Madden, et al. (1972 ▶). For the use of 2-fluoro-l-histidine in biochemistry, see Eichler et al. (2005 ▶); Wimalasena et al. (2007 ▶). For a related synthetic procedure, see DeClerq et al. (1978 ▶).

Experimental

Crystal data

C6H8FN3O2 M = 173.15 Orthorhombic, a = 5.1880 (3) Å b = 7.3480 (5) Å c = 18.7169 (12) Å V = 713.51 (8) Å3 Z = 4 Mo Kα radiation μ = 0.14 mm−1 T = 150 K 0.16 × 0.14 × 0.13 mm

Data collection

Bruker APEXII CCD area-detector diffractometer Absorption correction: numerical (SADABS; Sheldrick, 2000 ▶) T min = 0.978, T max = 0.983 3663 measured reflections 1352 independent reflections 1257 reflections with I > 2σ(I) R int = 0.022

Refinement

R[F 2 > 2σ(F 2)] = 0.043 wR(F 2) = 0.125 S = 1.06 1352 reflections 109 parameters H-atom parameters constrained Δρmax = 0.42 e Å−3 Δρmin = −0.47 e Å−3 Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 1996 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Version 2.3; CCDC, 2009 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶). Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810038663/im2231sup1.cif Structure factors: contains datablocks I. DOI: 10.1107/S1600536810038663/im2231Isup2.hkl Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C₆H₈FN₃O₂	F(000) = 360
M_r = 173.15	D_x = 1.612 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 4008 reflections
a = 5.1880 (3) Å	θ = 3.7–20.4°
b = 7.3480 (5) Å	µ = 0.14 mm⁻¹
c = 18.7169 (12) Å	T = 150 K
V = 713.51 (8) Å³	Plate, colorless
Z = 4	0.16 × 0.14 × 0.13 mm

Bruker APEXII CCD area-detector diffractometer	1352 independent reflections
Radiation source: fine-focus sealed tube	1257 reflections with I > 2σ(I)
graphite	R_int = 0.022
phi and ω scans	θ_max = 26.0°, θ_min = 3.0°
Absorption correction: numerical (SADABS; Sheldrick, 2000)	h = −6→6
T_min = 0.978, T_max = 0.983	k = −9→9
3663 measured reflections	l = −22→17

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)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.125	H-atom parameters constrained
S = 1.06	w = 1/[σ²(F_o²) + (0.0739P)² + 0.5836P] where P = (F_o² + 2F_c²)/3
1352 reflections	(Δ/σ)_max = 0.035
109 parameters	Δρ_max = 0.42 e Å⁻³
0 restraints	Δρ_min = −0.47 e Å⁻³

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.

	x	y	z	U_iso*/U_eq
C1	0.9310 (5)	0.5230 (3)	0.24487 (13)	0.0145 (5)
C2	0.8280 (5)	0.5747 (3)	0.31908 (13)	0.0136 (5)
H2A	0.9601	0.6496	0.3445	0.016*
C3	0.7728 (6)	0.4010 (4)	0.36301 (13)	0.0173 (6)
H3A	0.6410	0.3273	0.3380	0.021*
H3B	0.9322	0.3275	0.3663	0.021*
C4	0.6798 (5)	0.4441 (3)	0.43659 (14)	0.0162 (5)
C5	0.7962 (5)	0.4134 (4)	0.50022 (13)	0.0168 (6)
H5	0.9572	0.3548	0.5077	0.020*
C6	0.4353 (5)	0.5534 (4)	0.51566 (14)	0.0175 (6)
F1	0.2479 (3)	0.6321 (2)	0.55168 (9)	0.0310 (5)
N1	0.5862 (4)	0.6829 (3)	0.31144 (11)	0.0141 (5)
H1A	0.5249	0.7074	0.2687	0.017*
H1B	0.5049	0.7222	0.3497	0.017*
N2	0.6359 (4)	0.4835 (3)	0.55190 (12)	0.0176 (5)
H2B	0.6594	0.4828	0.5985	0.021*
N3	0.4443 (4)	0.5346 (3)	0.44706 (12)	0.0175 (5)
O1	1.1696 (3)	0.4958 (3)	0.24076 (10)	0.0183 (4)
H1	1.2086	0.4683	0.1986	0.027*
O2	0.7692 (4)	0.5062 (3)	0.19595 (9)	0.0210 (4)

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0173 (12)	0.0116 (11)	0.0145 (12)	−0.0012 (11)	0.0038 (11)	−0.0003 (9)
C2	0.0127 (11)	0.0145 (12)	0.0137 (12)	0.0002 (10)	0.0000 (10)	−0.0010 (10)
C3	0.0233 (13)	0.0161 (11)	0.0125 (12)	0.0045 (12)	0.0032 (11)	0.0016 (9)
C4	0.0180 (12)	0.0154 (11)	0.0153 (13)	−0.0001 (10)	0.0029 (10)	0.0027 (10)
C5	0.0173 (13)	0.0156 (12)	0.0176 (13)	−0.0024 (11)	0.0023 (11)	0.0032 (10)
C6	0.0188 (13)	0.0190 (13)	0.0148 (13)	−0.0012 (11)	0.0060 (11)	−0.0003 (10)
F1	0.0305 (9)	0.0356 (10)	0.0269 (9)	0.0061 (8)	0.0057 (8)	−0.0049 (7)
N1	0.0164 (10)	0.0175 (10)	0.0084 (10)	0.0038 (9)	0.0000 (9)	0.0002 (8)
N2	0.0218 (11)	0.0206 (11)	0.0105 (10)	−0.0026 (9)	−0.0013 (8)	0.0004 (9)
N3	0.0186 (10)	0.0185 (10)	0.0156 (11)	0.0032 (10)	0.0011 (9)	0.0009 (9)
O1	0.0167 (9)	0.0227 (9)	0.0155 (9)	−0.0002 (8)	0.0033 (7)	−0.0057 (8)
O2	0.0175 (9)	0.0352 (10)	0.0101 (9)	−0.0026 (9)	−0.0006 (7)	−0.0028 (8)

C1—O2	1.248 (3)	C4—N3	1.405 (3)
C1—O1	1.256 (3)	C5—N2	1.376 (3)
C1—C2	1.536 (4)	C5—H5	0.9500
C2—N1	1.492 (3)	C6—N3	1.292 (3)
C2—C3	1.545 (4)	C6—F1	1.317 (3)
C2—H2A	1.0000	C6—N2	1.344 (4)
C3—C4	1.493 (4)	N1—H1A	0.8800
C3—H3A	0.9900	N1—H1B	0.8800
C3—H3B	0.9900	N2—H2B	0.8800
C4—C5	1.354 (4)	O1—H1	0.8400

O2—C1—O1	127.0 (2)	C5—C4—C3	129.2 (2)
O2—C1—C2	117.0 (2)	N3—C4—C3	120.7 (2)
O1—C1—C2	116.0 (2)	C4—C5—N2	106.6 (2)
N1—C2—C1	109.7 (2)	C4—C5—H5	126.7
N1—C2—C3	109.6 (2)	N2—C5—H5	126.7
C1—C2—C3	110.0 (2)	N3—C6—F1	125.6 (2)
N1—C2—H2A	109.2	N3—C6—N2	115.7 (2)
C1—C2—H2A	109.2	F1—C6—N2	118.7 (2)
C3—C2—H2A	109.2	C2—N1—H1A	120.0
C4—C3—C2	112.1 (2)	C2—N1—H1B	120.0
C4—C3—H3A	109.2	H1A—N1—H1B	120.0
C2—C3—H3A	109.2	C6—N2—C5	104.9 (2)
C4—C3—H3B	109.2	C6—N2—H2B	127.6
C2—C3—H3B	109.2	C5—N2—H2B	127.6
H3A—C3—H3B	107.9	C6—N3—C4	102.7 (2)
C5—C4—N3	110.1 (2)	C1—O1—H1	109.5

4 in total

1. Antimetabolic activities of 2-fluoro-L-histidine.

Authors: E De Clercq; A Billiau; V G Edy; K L Kirk; L A Cohen
Journal: Biochem Biophys Res Commun Date: 1978-06-14 Impact factor: 3.575

2. Biosynthetic incorporation of fluorohistidine into proteins in E. coli: a new probe of macromolecular structure.

Authors: Jack F Eichler; John C Cramer; Kenneth L Kirk; James G Bann
Journal: Chembiochem Date: 2005-12 Impact factor: 3.164

3. A short history of SHELX.

Authors: George M Sheldrick
Journal: Acta Crystallogr A Date: 2007-12-21 Impact factor: 2.290

4. Effect of 2-fluorohistidine labeling of the anthrax protective antigen on stability, pore formation, and translocation.

Authors: D Shyamali Wimalasena; John C Cramer; Blythe E Janowiak; Stephen J Juris; Roman A Melnyk; D Eric Anderson; Kenneth L Kirk; R John Collier; James G Bann
Journal: Biochemistry Date: 2007-11-29 Impact factor: 3.162