Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270100011975/qd0040sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270100011975/qd0040Isup2.hkl |
CCDC reference: 152675
The title compound was purchased from Research Biochemicals International (lot ZXY-296 C) as a crystalline sample.
The H atom on N1 was located by difference synthesis (N—H = 0.86 Å). All H atoms were treated as riding atoms (C—H = 0.93 Å).
Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1989); cell refinement: CAD-4 EXPRESS; data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1990).
C7H5N3O2 | Z = 4 |
Mr = 163.14 | F(000) = 336 |
Monoclinic-, P21/n | Dx = 1.560 Mg m−3 |
a = 5.020 (1) Å | Cu Kα radiation, λ = 1.5418 Å |
b = 9.636 (1) Å | Cell parameters from 25 reflections |
c = 14.506 (1) Å | θ = 40–45° |
α = 90° | µ = 1.01 mm−1 |
β = 98.232 (4)° | T = 293 K |
γ = 90° | Needle, orange–yellow |
V = 694.46 (16) Å3 | 0.70 × 0.25 × 0.18 mm |
Enraf-Nonius diffractometer | 1223 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.010 |
Graphite monochromator | θmax = 71.9°, θmin = 5.5° |
θ/2θ scans | h = 0→6 |
Absorption correction: analytical (Spek, 1997) | k = −8→11 |
Tmin = 0.537, Tmax = 0.839 | l = −17→17 |
1877 measured reflections | 3 standard reflections every 60 min |
1355 independent reflections | intensity decay: 2% |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.037 | H-atom parameters constrained |
wR(F2) = 0.109 | Calculated w = 1/[σ2(Fo2) + (0.0544P)2 + 0.1541P] where P = (Fo2 + 2Fc2)/3 |
S = 1.10 | (Δ/σ)max = 0.001 |
1355 reflections | Δρmax = 0.20 e Å−3 |
110 parameters | Δρmin = −0.15 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0079 (12) |
C7H5N3O2 | γ = 90° |
Mr = 163.14 | V = 694.46 (16) Å3 |
Monoclinic-, P21/n | Z = 4 |
a = 5.020 (1) Å | Cu Kα radiation |
b = 9.636 (1) Å | µ = 1.01 mm−1 |
c = 14.506 (1) Å | T = 293 K |
α = 90° | 0.70 × 0.25 × 0.18 mm |
β = 98.232 (4)° |
Enraf-Nonius diffractometer | 1223 reflections with I > 2σ(I) |
Absorption correction: analytical (Spek, 1997) | Rint = 0.010 |
Tmin = 0.537, Tmax = 0.839 | 3 standard reflections every 60 min |
1877 measured reflections | intensity decay: 2% |
1355 independent reflections |
R[F2 > 2σ(F2)] = 0.037 | 0 restraints |
wR(F2) = 0.109 | H-atom parameters constrained |
S = 1.10 | Δρmax = 0.20 e Å−3 |
1355 reflections | Δρmin = −0.15 e Å−3 |
110 parameters |
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 | Uiso*/Ueq | ||
C7 | 0.4179 (3) | 0.28020 (14) | 0.04060 (9) | 0.0407 (3) | |
C6 | 0.2458 (3) | 0.33636 (16) | 0.09695 (11) | 0.0474 (4) | |
H6 | 0.1338 | 0.4098 | 0.0753 | 0.057* | |
C5 | 0.2390 (3) | 0.28378 (17) | 0.18587 (11) | 0.0503 (4) | |
H5 | 0.1229 | 0.3232 | 0.2230 | 0.060* | |
C4 | 0.4001 (3) | 0.17484 (16) | 0.22000 (10) | 0.0470 (4) | |
H4 | 0.3930 | 0.1403 | 0.2795 | 0.056* | |
C3A | 0.5750 (3) | 0.11678 (15) | 0.16378 (10) | 0.0418 (3) | |
C3 | 0.7637 (3) | 0.00659 (17) | 0.17263 (11) | 0.0499 (4) | |
H3 | 0.8028 | −0.0486 | 0.2254 | 0.060* | |
N2 | 0.8762 (2) | −0.00789 (13) | 0.09720 (9) | 0.0511 (4) | |
N1 | 0.7668 (2) | 0.09196 (12) | 0.03689 (8) | 0.0447 (3) | |
H1 | 0.8091 | 0.1041 | −0.0179 | 0.054* | |
C1A | 0.5843 (3) | 0.16938 (14) | 0.07349 (9) | 0.0384 (3) | |
N8 | 0.4260 (3) | 0.33609 (13) | −0.05120 (9) | 0.0500 (3) | |
O9 | 0.5911 (3) | 0.28690 (14) | −0.09639 (8) | 0.0706 (4) | |
O10 | 0.2714 (3) | 0.43003 (14) | −0.08015 (9) | 0.0680 (4) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C7 | 0.0403 (7) | 0.0418 (7) | 0.0409 (7) | −0.0041 (5) | 0.0088 (5) | −0.0035 (5) |
C6 | 0.0426 (7) | 0.0463 (8) | 0.0543 (8) | 0.0037 (6) | 0.0109 (6) | −0.0070 (6) |
C5 | 0.0459 (8) | 0.0571 (9) | 0.0519 (8) | 0.0004 (7) | 0.0205 (6) | −0.0123 (7) |
C4 | 0.0475 (8) | 0.0561 (9) | 0.0402 (7) | −0.0043 (6) | 0.0157 (6) | −0.0047 (6) |
C3A | 0.0384 (7) | 0.0456 (7) | 0.0426 (7) | −0.0033 (6) | 0.0100 (5) | −0.0038 (6) |
C3 | 0.0453 (8) | 0.0523 (8) | 0.0532 (8) | 0.0037 (6) | 0.0101 (6) | 0.0029 (7) |
N2 | 0.0438 (7) | 0.0503 (7) | 0.0608 (8) | 0.0064 (5) | 0.0128 (5) | −0.0042 (6) |
N1 | 0.0421 (6) | 0.0480 (7) | 0.0470 (6) | 0.0008 (5) | 0.0169 (5) | −0.0066 (5) |
C1A | 0.0340 (6) | 0.0417 (7) | 0.0415 (7) | −0.0054 (5) | 0.0120 (5) | −0.0085 (5) |
N8 | 0.0553 (7) | 0.0507 (7) | 0.0449 (7) | −0.0056 (6) | 0.0102 (5) | −0.0012 (5) |
O9 | 0.0865 (9) | 0.0781 (9) | 0.0549 (7) | 0.0056 (7) | 0.0357 (6) | 0.0059 (6) |
O10 | 0.0755 (8) | 0.0666 (8) | 0.0594 (7) | 0.0098 (6) | 0.0011 (6) | 0.0119 (6) |
C7—C6 | 1.3818 (19) | C3A—C1A | 1.4115 (19) |
C7—C1A | 1.3970 (19) | C3A—C3 | 1.417 (2) |
C7—N8 | 1.4425 (18) | C3—N2 | 1.309 (2) |
C6—C5 | 1.391 (2) | C3—H3 | 0.9300 |
C6—H6 | 0.9300 | N2—N1 | 1.3620 (18) |
C5—C4 | 1.374 (2) | N1—C1A | 1.3480 (17) |
C5—H5 | 0.9300 | N1—H1 | 0.8600 |
C4—C3A | 1.3975 (19) | N8—O9 | 1.2234 (17) |
C4—H4 | 0.9300 | N8—O10 | 1.2265 (18) |
C6—C7—C1A | 119.42 (13) | C1A—C3A—C3 | 104.04 (12) |
C6—C7—N8 | 120.17 (13) | N2—C3—C3A | 111.54 (14) |
C1A—C7—N8 | 120.41 (12) | N2—C3—H3 | 124.2 |
C7—C6—C5 | 120.42 (14) | C3A—C3—H3 | 124.2 |
C7—C6—H6 | 119.8 | C3—N2—N1 | 106.21 (12) |
C5—C6—H6 | 119.8 | C1A—N1—N2 | 111.85 (11) |
C4—C5—C6 | 121.42 (13) | C1A—N1—H1 | 124.1 |
C4—C5—H5 | 119.3 | N2—N1—H1 | 124.1 |
C6—C5—H5 | 119.3 | N1—C1A—C7 | 134.06 (13) |
C5—C4—C3A | 118.83 (13) | N1—C1A—C3A | 106.35 (12) |
C5—C4—H4 | 120.6 | C7—C1A—C3A | 119.58 (12) |
C3A—C4—H4 | 120.6 | O9—N8—O10 | 123.12 (14) |
C4—C3A—C1A | 120.32 (13) | O9—N8—C7 | 117.43 (13) |
C4—C3A—C3 | 135.63 (14) | O10—N8—C7 | 119.45 (13) |
C1A—C7—C6—C5 | 0.4 (2) | C6—C7—C1A—N1 | 178.93 (14) |
N8—C7—C6—C5 | −179.38 (13) | N8—C7—C1A—N1 | −1.3 (2) |
C7—C6—C5—C4 | −0.4 (2) | C6—C7—C1A—C3A | −0.2 (2) |
C6—C5—C4—C3A | 0.3 (2) | N8—C7—C1A—C3A | 179.54 (12) |
C5—C4—C3A—C1A | −0.2 (2) | C4—C3A—C1A—N1 | −179.25 (12) |
C5—C4—C3A—C3 | −179.04 (16) | C3—C3A—C1A—N1 | −0.06 (15) |
C4—C3A—C3—N2 | 178.86 (16) | C4—C3A—C1A—C7 | 0.1 (2) |
C1A—C3A—C3—N2 | −0.13 (17) | C3—C3A—C1A—C7 | 179.31 (12) |
C3A—C3—N2—N1 | 0.27 (17) | C6—C7—N8—O9 | 176.57 (14) |
C3—N2—N1—C1A | −0.31 (16) | C1A—C7—N8—O9 | −3.2 (2) |
N2—N1—C1A—C7 | −179.01 (14) | C6—C7—N8—O10 | −2.9 (2) |
N2—N1—C1A—C3A | 0.23 (15) | C1A—C7—N8—O10 | 177.36 (12) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···N2i | 0.86 | 2.28 | 2.941 (2) | 134 |
N1—H1···O9 | 0.86 | 2.29 | 2.749 (2) | 114 |
Symmetry code: (i) −x+2, −y, −z. |
Experimental details
Crystal data | |
Chemical formula | C7H5N3O2 |
Mr | 163.14 |
Crystal system, space group | Monoclinic-, P21/n |
Temperature (K) | 293 |
a, b, c (Å) | 5.020 (1), 9.636 (1), 14.506 (1) |
α, β, γ (°) | 90, 98.232 (4), 90 |
V (Å3) | 694.46 (16) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 1.01 |
Crystal size (mm) | 0.70 × 0.25 × 0.18 |
Data collection | |
Diffractometer | Enraf-Nonius diffractometer |
Absorption correction | Analytical (Spek, 1997) |
Tmin, Tmax | 0.537, 0.839 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 1877, 1355, 1223 |
Rint | 0.010 |
(sin θ/λ)max (Å−1) | 0.616 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.037, 0.109, 1.10 |
No. of reflections | 1355 |
No. of parameters | 110 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.20, −0.15 |
Computer programs: CAD-4 EXPRESS (Enraf-Nonius, 1989), CAD-4 EXPRESS, HELENA (Spek, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 1990).
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···N2i | 0.86 | 2.280 | 2.941 (2) | 133.74 |
N1—H1···O9 | 0.86 | 2.289 | 2.749 (2) | 113.65 |
Symmetry code: (i) −x+2, −y, −z. |
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7-Nitroindazole, (I), is an inhibitor of nitric oxide synthase (NOS), the enzyme responsible for the generation of the ubiquitous neurotransmitter nitric oxide (Moore et al., 1993). In the early 1990 s, it was discovered that (I) exhibited selectivity for neuronal NOS (nNOS) (Babbedge et al., 1993; MacKenzie et al., 1994) and it soon became the standard investigative tool for the study of effects related to nNOS (Rivier, 1998). Shortly after these findings, it became clear that (I) may have utility as a neuroprotecting agent when it was found that it protected against MPTP-induced neurotoxicity in the mouse (Schulz et al., 1995; Przedborski et al., 1996) and baboon (Hantraye et al., 1996). Although initial arguments suggested that nNOS may mediate, in part, MPTP-induced neurotoxicity (Przedborski et al., 1996), more recent studies in the mouse (Castagnoli et al., 1997) and rat (Desvignes et al., 1999) provided evidence that (I) also is an inhibitor of monoamine oxidase B (MAO-B), which may contribute to the protective effect of this compound against MPTP neurotoxicity (Di Monte et al., 1997). It has now been suggested and that this action on MAO-B, rather than NOS inhibition, is the mechanism by which (I) prevents MPTP-induced ATP depletion (Royland et al., 1999).
The conformation of (I) is of interest because of its unique ability to inhibit both MAO-B and nNOS, two biologically important enzyme systems. Furthermore, its general use as an investigative drug to study the inhibition of nNOS makes a structural study of this molecule important. Several reversible inhibitors of MAO have planar structures, including the endogenous indole derivative isatin, (Medvedev et al., 1995) an MAO-B selective inhibitor, and the commercially available (in Europe) phenyloxazolidinone toloxatone, an MAO-A selective inhibitor (Moureau et al., 1992, 1995).
Von Auwers, in 1891, was the first to report that indazoles exist in a tautomeric equilibrium. Evidence obtained from molecular refractivity measurements in Von Auwers' laboratory later suggested the predominance of the tautomer possessing the benzenoid structure (Von Auwers et al., 1937). It was also shown by UV spectroscopy (Rousseau & Linwall, 1950) as well as by proton (Elguero et al., 1966) and 14N NMR (Witanowski et al., 1972) that the data from indazole more closely resemble those obtained from 1-methylindazole than those from 2-methylindazole, further supporting evidence for the predominance of the benzenoid structure. The crystal structure of indazoles (Escande et al., 1974; Escande & Lapasset, 1974) also supported these conclusions. Ab initio studies by the group of Elguero (Catalan & Elguero, 1994; Catalan et al., 1996) suggested that indazole occurs in the N1H tautomeric form in the gas phase and in solution both in the ground and excited states and that the N1H tautomer is more stable than its N2H congener by 4 kcal mol−1.
Compound (I) adopts, in the solid state, a planar conformation assisted by intramolecular hydrogen bonding between the 7-nitro group and a H atom on N1 of the indazole structure. An H atom was unambigously detected from the Fourier difference map on N1 but not on N2. This H atom is further engaged in an intermolecular hydrogen bond leading to the formation of stable dimers in the crystal packing (Table 1). A planar conformation would have been less likely if the N2H tautomer had formed.