organic compounds
4-Nitro-N-phthalyl-L-tryptophan
aDepartment of Chemistry, University of Namur, 61, Rue de Bruxelles, B-5000 Namur, Belgium, and bLouvain Drug Research Institute (LDRI), UCL, 50, Avenue Mounier, B-1200 Woluwe-Saint-Lambert, Belgium
*Correspondence e-mail: johan.wouters@fundp.ac.be
The R)-3-(1H-indol-3-yl)-2-(4-nitro-1,3-dioxoisoindolin-2-yl)propanoic acid], C19H13N3O6, an analogue of epigenetic modulator RG108, is constrained by strong hydrogen bonds between the indole N—H group and a carbonyl O atom of the phthalimide ring of a symmetry-related molecule, and between the protonated O atom of the carboxyl group and a carbonyl O atom of the phthalimide ring. π–π stacking interactions with centroid–centroid distances of 3.638 (1) and 3.610 (1) Å are also observed between indole and phthalimide rings.
of the title compound [systematic name: (2Related literature
For crystallographic information and details of the RG108 analogue, see: Braun et al. (2010) and for details of the biological evaluation, see: Brueckner et al. (2005).
Experimental
Crystal data
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Data collection: CrysAlis PRO (Oxford Diffraction, 2009); cell CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97.
Supporting information
10.1107/S1600536811029138/vm2109sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536811029138/vm2109Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536811029138/vm2109Isup3.cml
Synthesis of the compound was accomplished by micro-wave heating of L-tryptophan (1 mmol, 204 mg) and 4-nitro phthalic anhydride (1 mmol, 193 mg) in 5 ml of DMF. The mixture was then poured in cold aqueous buffer solution (pH = 2) and extracted with ethyl acetate. After drying with Na2SO4, the organic phase is evaporated and the residue is purified by flash
(dichloromethane and methanol: 9/1; yield = 60%, 230 mg).H1 and H2, bound to O4 and N2 respectively and involved in hydrogen bonds, were located from ΔF Fourier difference maps and their position refined freely. All other remaining H-atoms were placed at idealized positions and allowed to ride on their parent atoms, with C—H distances of 0.93 – 0.98 Å and with Uiso(H) = 1.2Ueq(C).
Data collection: CrysAlis PRO (Oxford Diffraction, 2009); cell
CrysAlis PRO (Oxford Diffraction, 2009); data reduction: CrysAlis PRO (Oxford Diffraction, 2009); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and PLATON (Spek, 2009); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).Fig. 1. ORTEP view and atom numbering of the title compound. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level. |
C19H13N3O6 | F(000) = 392 |
Mr = 379.33 | Dx = 1.501 Mg m−3 |
Monoclinic, P21 | Cu Kα radiation, λ = 1.54184 Å |
Hall symbol: P 2yb | Cell parameters from 4268 reflections |
a = 7.0569 (3) Å | θ = 2.8–67.9° |
b = 15.5302 (8) Å | µ = 0.97 mm−1 |
c = 7.6947 (4) Å | T = 293 K |
β = 95.415 (4)° | Prism, yellow |
V = 839.54 (7) Å3 | 0.22 × 0.10 × 0.03 mm |
Z = 2 |
Oxford Diffraction Xcalibur Ruby Gemini ultra diffractometer | 2966 independent reflections |
Radiation source: fine-focus sealed tube | 2735 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.029 |
Detector resolution: 10.3712 pixels mm-1 | θmax = 68.0°, θmin = 5.7° |
ω scans | h = −8→8 |
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009) | k = −18→17 |
Tmin = 0.815, Tmax = 0.972 | l = −9→8 |
9007 measured reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.031 | w = 1/[σ2(Fo2) + (0.0492P)2 + 0.1477P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.091 | (Δ/σ)max < 0.001 |
S = 1.06 | Δρmax = 0.15 e Å−3 |
2966 reflections | Δρmin = −0.13 e Å−3 |
262 parameters | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
1 restraint | Extinction coefficient: 0.0080 (8) |
0 constraints | Absolute structure: Flack (1983), 1371 Friedel pairs |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: −0.1 (2) |
Secondary atom site location: difference Fourier map |
C19H13N3O6 | V = 839.54 (7) Å3 |
Mr = 379.33 | Z = 2 |
Monoclinic, P21 | Cu Kα radiation |
a = 7.0569 (3) Å | µ = 0.97 mm−1 |
b = 15.5302 (8) Å | T = 293 K |
c = 7.6947 (4) Å | 0.22 × 0.10 × 0.03 mm |
β = 95.415 (4)° |
Oxford Diffraction Xcalibur Ruby Gemini ultra diffractometer | 2966 independent reflections |
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009) | 2735 reflections with I > 2σ(I) |
Tmin = 0.815, Tmax = 0.972 | Rint = 0.029 |
9007 measured reflections |
R[F2 > 2σ(F2)] = 0.031 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.091 | Δρmax = 0.15 e Å−3 |
S = 1.06 | Δρmin = −0.13 e Å−3 |
2966 reflections | Absolute structure: Flack (1983), 1371 Friedel pairs |
262 parameters | Absolute structure parameter: −0.1 (2) |
1 restraint |
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 | ||
C1 | 0.7937 (3) | 0.58969 (13) | 0.3293 (3) | 0.0401 (4) | |
C2 | 0.8237 (3) | 0.64858 (13) | 0.4829 (3) | 0.0385 (4) | |
C3 | 0.7949 (3) | 0.73572 (14) | 0.5072 (3) | 0.0427 (5) | |
C4 | 0.8157 (3) | 0.77052 (15) | 0.6745 (3) | 0.0481 (5) | |
H4 | 0.7881 | 0.8283 | 0.6913 | 0.058* | |
C5 | 0.8772 (3) | 0.71950 (17) | 0.8159 (3) | 0.0533 (6) | |
H5 | 0.8943 | 0.7437 | 0.9269 | 0.064* | |
C6 | 0.9135 (3) | 0.63265 (16) | 0.7939 (3) | 0.0497 (5) | |
H6 | 0.9581 | 0.5984 | 0.8881 | 0.060* | |
C7 | 0.8815 (3) | 0.59866 (14) | 0.6286 (3) | 0.0410 (4) | |
C8 | 0.8976 (3) | 0.50848 (14) | 0.5709 (2) | 0.0402 (4) | |
C9 | 0.8329 (3) | 0.42945 (12) | 0.2879 (3) | 0.0391 (4) | |
H9 | 0.9070 | 0.3854 | 0.3557 | 0.047* | |
C10 | 0.6282 (3) | 0.39570 (14) | 0.2619 (3) | 0.0479 (5) | |
H10A | 0.5655 | 0.4077 | 0.3661 | 0.057* | |
H10B | 0.5601 | 0.4265 | 0.1656 | 0.057* | |
C11 | 0.6167 (3) | 0.30101 (14) | 0.2249 (3) | 0.0437 (5) | |
C12 | 0.5649 (3) | 0.26268 (17) | 0.0691 (3) | 0.0532 (6) | |
H12 | 0.5355 | 0.2917 | −0.0357 | 0.064* | |
C13 | 0.6095 (3) | 0.15405 (15) | 0.2600 (3) | 0.0488 (5) | |
C14 | 0.6192 (3) | 0.07499 (16) | 0.3441 (4) | 0.0607 (7) | |
H14 | 0.5920 | 0.0241 | 0.2830 | 0.073* | |
C15 | 0.6705 (3) | 0.07453 (17) | 0.5213 (4) | 0.0650 (7) | |
H15 | 0.6779 | 0.0224 | 0.5810 | 0.078* | |
C16 | 0.7115 (3) | 0.15063 (19) | 0.6124 (4) | 0.0590 (6) | |
H16 | 0.7468 | 0.1482 | 0.7318 | 0.071* | |
C17 | 0.7012 (3) | 0.22977 (16) | 0.5303 (3) | 0.0479 (5) | |
H17 | 0.7294 | 0.2801 | 0.5928 | 0.058* | |
C18 | 0.6472 (3) | 0.23231 (14) | 0.3505 (3) | 0.0413 (4) | |
C19 | 0.9328 (3) | 0.44380 (13) | 0.1227 (3) | 0.0433 (5) | |
N1 | 0.8488 (2) | 0.50773 (11) | 0.3922 (2) | 0.0397 (4) | |
N2 | 0.5622 (3) | 0.17470 (15) | 0.0885 (3) | 0.0591 (6) | |
N3 | 0.7496 (3) | 0.79406 (12) | 0.3599 (3) | 0.0518 (5) | |
O1 | 0.7311 (2) | 0.60263 (10) | 0.18047 (19) | 0.0526 (4) | |
O2 | 0.9409 (2) | 0.44385 (10) | 0.65541 (19) | 0.0518 (4) | |
O3 | 1.0857 (3) | 0.47711 (14) | 0.1246 (2) | 0.0659 (5) | |
O4 | 0.8377 (3) | 0.41420 (14) | −0.0186 (2) | 0.0709 (6) | |
O5 | 0.8221 (3) | 0.77922 (12) | 0.2254 (2) | 0.0683 (5) | |
O6 | 0.6475 (3) | 0.85593 (12) | 0.3807 (3) | 0.0768 (6) | |
H1 | 0.913 (5) | 0.425 (2) | −0.120 (5) | 0.093 (11)* | |
H2 | 0.525 (6) | 0.138 (3) | 0.008 (5) | 0.095 (12)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0449 (10) | 0.0354 (11) | 0.0400 (11) | 0.0023 (8) | 0.0046 (8) | 0.0025 (8) |
C2 | 0.0382 (9) | 0.0391 (11) | 0.0391 (10) | −0.0004 (8) | 0.0080 (8) | −0.0029 (8) |
C3 | 0.0408 (10) | 0.0409 (11) | 0.0475 (11) | −0.0011 (8) | 0.0092 (8) | −0.0035 (9) |
C4 | 0.0440 (11) | 0.0449 (12) | 0.0576 (13) | −0.0067 (9) | 0.0161 (9) | −0.0150 (10) |
C5 | 0.0539 (12) | 0.0625 (14) | 0.0451 (12) | −0.0119 (11) | 0.0133 (10) | −0.0138 (11) |
C6 | 0.0527 (12) | 0.0579 (15) | 0.0397 (11) | −0.0068 (10) | 0.0100 (9) | −0.0027 (10) |
C7 | 0.0434 (10) | 0.0442 (11) | 0.0363 (10) | −0.0038 (8) | 0.0083 (8) | −0.0055 (8) |
C8 | 0.0414 (10) | 0.0436 (11) | 0.0362 (10) | 0.0003 (8) | 0.0078 (8) | 0.0037 (9) |
C9 | 0.0482 (10) | 0.0314 (10) | 0.0381 (10) | 0.0020 (8) | 0.0068 (8) | 0.0011 (8) |
C10 | 0.0477 (12) | 0.0417 (12) | 0.0549 (13) | 0.0001 (9) | 0.0085 (9) | 0.0007 (10) |
C11 | 0.0409 (10) | 0.0400 (11) | 0.0511 (12) | −0.0037 (8) | 0.0087 (9) | −0.0006 (9) |
C12 | 0.0575 (13) | 0.0598 (15) | 0.0422 (11) | −0.0117 (11) | 0.0034 (10) | −0.0017 (10) |
C13 | 0.0442 (11) | 0.0413 (11) | 0.0618 (14) | −0.0044 (9) | 0.0104 (10) | −0.0042 (10) |
C14 | 0.0490 (12) | 0.0396 (12) | 0.095 (2) | −0.0061 (9) | 0.0157 (13) | −0.0023 (12) |
C15 | 0.0497 (12) | 0.0517 (15) | 0.095 (2) | 0.0012 (11) | 0.0143 (13) | 0.0218 (14) |
C16 | 0.0486 (12) | 0.0678 (16) | 0.0610 (15) | 0.0017 (11) | 0.0068 (10) | 0.0146 (12) |
C17 | 0.0430 (10) | 0.0505 (12) | 0.0506 (12) | 0.0002 (9) | 0.0060 (9) | 0.0034 (10) |
C18 | 0.0371 (9) | 0.0404 (11) | 0.0474 (11) | −0.0035 (8) | 0.0088 (8) | −0.0003 (9) |
C19 | 0.0553 (12) | 0.0359 (10) | 0.0388 (10) | −0.0026 (9) | 0.0053 (9) | −0.0012 (8) |
N1 | 0.0527 (10) | 0.0349 (9) | 0.0315 (8) | 0.0015 (7) | 0.0053 (7) | −0.0001 (7) |
N2 | 0.0653 (13) | 0.0558 (14) | 0.0568 (13) | −0.0161 (10) | 0.0081 (10) | −0.0152 (10) |
N3 | 0.0536 (10) | 0.0382 (10) | 0.0639 (13) | −0.0008 (8) | 0.0069 (9) | −0.0001 (8) |
O1 | 0.0717 (10) | 0.0440 (8) | 0.0401 (8) | 0.0082 (7) | −0.0046 (7) | −0.0003 (7) |
O2 | 0.0694 (10) | 0.0456 (9) | 0.0406 (8) | 0.0043 (7) | 0.0057 (7) | 0.0065 (7) |
O3 | 0.0628 (11) | 0.0857 (13) | 0.0511 (9) | −0.0194 (9) | 0.0148 (8) | −0.0044 (8) |
O4 | 0.0945 (13) | 0.0828 (13) | 0.0363 (8) | −0.0362 (11) | 0.0113 (9) | −0.0052 (8) |
O5 | 0.1017 (14) | 0.0533 (10) | 0.0511 (10) | 0.0083 (9) | 0.0135 (9) | 0.0002 (8) |
O6 | 0.0812 (12) | 0.0447 (10) | 0.1084 (16) | 0.0170 (9) | 0.0289 (11) | 0.0126 (10) |
C1—O1 | 1.205 (3) | C10—H10B | 0.9700 |
C1—N1 | 1.403 (3) | C11—C12 | 1.358 (3) |
C1—C2 | 1.493 (3) | C11—C18 | 1.442 (3) |
C2—C3 | 1.384 (3) | C12—N2 | 1.375 (3) |
C2—C7 | 1.392 (3) | C12—H12 | 0.9300 |
C3—C4 | 1.391 (3) | C13—N2 | 1.369 (3) |
C3—N3 | 1.463 (3) | C13—C14 | 1.386 (4) |
C4—C5 | 1.382 (4) | C13—C18 | 1.413 (3) |
C4—H4 | 0.9300 | C14—C15 | 1.377 (4) |
C5—C6 | 1.386 (4) | C14—H14 | 0.9300 |
C5—H5 | 0.9300 | C15—C16 | 1.391 (4) |
C6—C7 | 1.376 (3) | C15—H15 | 0.9300 |
C6—H6 | 0.9300 | C16—C17 | 1.381 (4) |
C7—C8 | 1.477 (3) | C16—H16 | 0.9300 |
C8—O2 | 1.219 (2) | C17—C18 | 1.401 (3) |
C8—N1 | 1.386 (3) | C17—H17 | 0.9300 |
C9—N1 | 1.455 (2) | C19—O3 | 1.195 (3) |
C9—C19 | 1.527 (3) | C19—O4 | 1.306 (3) |
C9—C10 | 1.532 (3) | N2—H2 | 0.86 (4) |
C9—H9 | 0.9800 | N3—O5 | 1.219 (3) |
C10—C11 | 1.499 (3) | N3—O6 | 1.221 (3) |
C10—H10A | 0.9700 | O4—H1 | 1.00 (4) |
O1—C1—N1 | 122.92 (18) | C12—C11—C10 | 127.1 (2) |
O1—C1—C2 | 131.44 (18) | C18—C11—C10 | 126.7 (2) |
N1—C1—C2 | 105.61 (16) | C11—C12—N2 | 110.2 (2) |
C3—C2—C7 | 118.11 (19) | C11—C12—H12 | 124.9 |
C3—C2—C1 | 133.98 (19) | N2—C12—H12 | 124.9 |
C7—C2—C1 | 107.76 (18) | N2—C13—C14 | 130.9 (2) |
C2—C3—C4 | 120.1 (2) | N2—C13—C18 | 106.9 (2) |
C2—C3—N3 | 121.67 (19) | C14—C13—C18 | 122.2 (2) |
C4—C3—N3 | 118.2 (2) | C15—C14—C13 | 117.6 (2) |
C5—C4—C3 | 120.2 (2) | C15—C14—H14 | 121.2 |
C5—C4—H4 | 119.9 | C13—C14—H14 | 121.2 |
C3—C4—H4 | 119.9 | C14—C15—C16 | 121.2 (2) |
C4—C5—C6 | 120.6 (2) | C14—C15—H15 | 119.4 |
C4—C5—H5 | 119.7 | C16—C15—H15 | 119.4 |
C6—C5—H5 | 119.7 | C17—C16—C15 | 121.8 (2) |
C7—C6—C5 | 118.1 (2) | C17—C16—H16 | 119.1 |
C7—C6—H6 | 121.0 | C15—C16—H16 | 119.1 |
C5—C6—H6 | 121.0 | C16—C17—C18 | 118.3 (2) |
C6—C7—C2 | 122.7 (2) | C16—C17—H17 | 120.8 |
C6—C7—C8 | 129.2 (2) | C18—C17—H17 | 120.8 |
C2—C7—C8 | 108.11 (17) | C17—C18—C13 | 118.9 (2) |
O2—C8—N1 | 123.29 (19) | C17—C18—C11 | 133.8 (2) |
O2—C8—C7 | 129.99 (18) | C13—C18—C11 | 107.29 (19) |
N1—C8—C7 | 106.71 (17) | O3—C19—O4 | 123.7 (2) |
N1—C9—C19 | 108.63 (16) | O3—C19—C9 | 122.70 (19) |
N1—C9—C10 | 112.37 (17) | O4—C19—C9 | 113.59 (18) |
C19—C9—C10 | 116.40 (17) | C8—N1—C1 | 111.65 (16) |
N1—C9—H9 | 106.3 | C8—N1—C9 | 123.58 (16) |
C19—C9—H9 | 106.3 | C1—N1—C9 | 124.30 (16) |
C10—C9—H9 | 106.3 | C13—N2—C12 | 109.5 (2) |
C11—C10—C9 | 113.22 (18) | C13—N2—H2 | 125 (3) |
C11—C10—H10A | 108.9 | C12—N2—H2 | 125 (3) |
C9—C10—H10A | 108.9 | O5—N3—O6 | 124.1 (2) |
C11—C10—H10B | 108.9 | O5—N3—C3 | 117.55 (18) |
C9—C10—H10B | 108.9 | O6—N3—C3 | 118.3 (2) |
H10A—C10—H10B | 107.7 | C19—O4—H1 | 109 (2) |
C12—C11—C18 | 106.1 (2) | ||
O1—C1—C2—C3 | −1.5 (4) | C16—C17—C18—C13 | −1.3 (3) |
N1—C1—C2—C3 | −179.2 (2) | C16—C17—C18—C11 | 178.1 (2) |
O1—C1—C2—C7 | 173.8 (2) | N2—C13—C18—C17 | −179.45 (18) |
N1—C1—C2—C7 | −3.9 (2) | C14—C13—C18—C17 | 1.8 (3) |
C7—C2—C3—C4 | −2.8 (3) | N2—C13—C18—C11 | 1.0 (2) |
C1—C2—C3—C4 | 172.1 (2) | C14—C13—C18—C11 | −177.7 (2) |
C7—C2—C3—N3 | 174.80 (18) | C12—C11—C18—C17 | −179.8 (2) |
C1—C2—C3—N3 | −10.3 (3) | C10—C11—C18—C17 | −3.3 (4) |
C2—C3—C4—C5 | 4.2 (3) | C12—C11—C18—C13 | −0.4 (2) |
N3—C3—C4—C5 | −173.46 (19) | C10—C11—C18—C13 | 176.2 (2) |
C3—C4—C5—C6 | −1.9 (3) | N1—C9—C19—O3 | 45.1 (3) |
C4—C5—C6—C7 | −1.7 (3) | C10—C9—C19—O3 | 173.1 (2) |
C5—C6—C7—C2 | 3.2 (3) | N1—C9—C19—O4 | −136.7 (2) |
C5—C6—C7—C8 | −176.1 (2) | C10—C9—C19—O4 | −8.7 (3) |
C3—C2—C7—C6 | −0.9 (3) | O2—C8—N1—C1 | 176.27 (19) |
C1—C2—C7—C6 | −177.10 (18) | C7—C8—N1—C1 | −2.7 (2) |
C3—C2—C7—C8 | 178.52 (17) | O2—C8—N1—C9 | 3.8 (3) |
C1—C2—C7—C8 | 2.4 (2) | C7—C8—N1—C9 | −175.13 (18) |
C6—C7—C8—O2 | 0.6 (4) | O1—C1—N1—C8 | −173.90 (19) |
C2—C7—C8—O2 | −178.8 (2) | C2—C1—N1—C8 | 4.1 (2) |
C6—C7—C8—N1 | 179.5 (2) | O1—C1—N1—C9 | −1.5 (3) |
C2—C7—C8—N1 | 0.1 (2) | C2—C1—N1—C9 | 176.45 (17) |
N1—C9—C10—C11 | −155.69 (18) | C19—C9—N1—C8 | −134.89 (18) |
C19—C9—C10—C11 | 78.1 (2) | C10—C9—N1—C8 | 94.9 (2) |
C9—C10—C11—C12 | −105.8 (3) | C19—C9—N1—C1 | 53.6 (2) |
C9—C10—C11—C18 | 78.3 (3) | C10—C9—N1—C1 | −76.7 (2) |
C18—C11—C12—N2 | −0.4 (3) | C14—C13—N2—C12 | 177.3 (2) |
C10—C11—C12—N2 | −176.9 (2) | C18—C13—N2—C12 | −1.3 (3) |
N2—C13—C14—C15 | −179.5 (2) | C11—C12—N2—C13 | 1.1 (3) |
C18—C13—C14—C15 | −1.1 (3) | C2—C3—N3—O5 | −34.6 (3) |
C13—C14—C15—C16 | −0.1 (4) | C4—C3—N3—O5 | 143.1 (2) |
C14—C15—C16—C17 | 0.5 (4) | C2—C3—N3—O6 | 147.9 (2) |
C15—C16—C17—C18 | 0.2 (3) | C4—C3—N3—O6 | −34.5 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O1i | 0.86 (4) | 2.28 (4) | 3.002 (3) | 142 (4) |
O4—H1···O2ii | 1.00 (4) | 1.78 (4) | 2.716 (2) | 154 (3) |
Symmetry codes: (i) −x+1, y−1/2, −z; (ii) x, y, z−1. |
Experimental details
Crystal data | |
Chemical formula | C19H13N3O6 |
Mr | 379.33 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 293 |
a, b, c (Å) | 7.0569 (3), 15.5302 (8), 7.6947 (4) |
β (°) | 95.415 (4) |
V (Å3) | 839.54 (7) |
Z | 2 |
Radiation type | Cu Kα |
µ (mm−1) | 0.97 |
Crystal size (mm) | 0.22 × 0.10 × 0.03 |
Data collection | |
Diffractometer | Oxford Diffraction Xcalibur Ruby Gemini ultra diffractometer |
Absorption correction | Multi-scan (CrysAlis PRO; Oxford Diffraction, 2009) |
Tmin, Tmax | 0.815, 0.972 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9007, 2966, 2735 |
Rint | 0.029 |
(sin θ/λ)max (Å−1) | 0.601 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.031, 0.091, 1.06 |
No. of reflections | 2966 |
No. of parameters | 262 |
No. of restraints | 1 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.15, −0.13 |
Absolute structure | Flack (1983), 1371 Friedel pairs |
Absolute structure parameter | −0.1 (2) |
Computer programs: CrysAlis PRO (Oxford Diffraction, 2009), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 2008), ORTEPIII (Burnett & Johnson, 1996) and PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
N2—H2···O1i | 0.86 (4) | 2.28 (4) | 3.002 (3) | 142 (4) |
O4—H1···O2ii | 1.00 (4) | 1.78 (4) | 2.716 (2) | 154 (3) |
Symmetry codes: (i) −x+1, y−1/2, −z; (ii) x, y, z−1. |
Cg-Cg : distance (Å) between ring centroids; α : dihedral angle(°) between ring planes 1 and 2 ; β : angle (°) between Cg(1)-->Cg(2) vector and normal to ring plane 1 ; γ : angle (°) between Cg(1)-->Cg(2) vector and normal to ring plane 2 ; Cg1_Perp : perpendicular distance (Å) of Cg(1) on ring plane 2 ; Cg2_Perp : perpendicular distance (Å) of Cg(2) on ring plane 1. |
Cg(I)-Cg(J) | sym (J) | Cg-Cg | α | β | γ | Cg1_Perp | Cg2_Perp |
Cg(1)-Cg(2) | (i) | 3.638 (1) | 7.24 | 18.69 | 20.72 | -3.403 (1) | 3.446 (1) |
Cg(1)-Cg(2) | (ii) | 3.610 (1) | 7.24 | 19.41 | 12.26 | 3.528 (1) | 3.405 (1) |
Symmetry codes : (i) 1 - x, 1/2 + y, 1 - z, (ii) 2 - x, 1/2 + y, 1 - z |
Acknowledgements
This work was supported in part by the Fonds National de la Recherche Scientifique (FRS – FNRS, Belgium) by a Télévie grant (IB). AT acknowledges the FRIA (Fonds pour la formation à la Recherche dans l'Industrie et dans l'Agriculture) for financial support.
References
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4-Nitro-N-phthalyl-L-tryptophan is an analog of RG108, a DNA methyltransferase (DNMT) inhibitor discovered by virtual screening (Brueckner et al. (2005)). Introduction of a nitro functional group on the phtalimide moiety is excepted to improve inhibition ability (unpublished results).
Isomer S (C9) of 4-nitro-N-phthalyl-tryptophan is obtained from L-tryptophan and nitrophthalic anhydride in DMF.
Two main types of H-bonding interactions are observed in the structure: one between N—H of the indole ring (N2) and O1 of the phtalimide ring, and the other between the protonated oxygen (O4) from the carboxylic moiety and O2 from the phtalimide ring (see Table 1).
In addition to H-bonds, crystal packing organization is further stabilized by π–π-stacking interactions involving symmetry-related molecules, in particularly between the 6-membered coupled rings of nitrophthalimide and indole moiety (see Table 2). No interactions of this type are present in the packing of the dicyclohexylamine salt of RG108 (Braun et al. (2010), because of the presence of the ammonium counter-cation and water molecules included in the crystalline network.
In contrast to the structure of the dicyclohexylamine salt of RG108 (Braun et al. (2010)), where the compound conformation is constrained by strong (charge-assisted) H-bonds with the dicyclohexylammonium ion and extra water molecules, the angle between the two fused rings is 14.23 (4)° in the present structure compared to 58.35 (4)° in the case of the RG108 salt. The torsion angle of the chain between the two aromatic moieties (N1—C9—C10—C11) is also distinct: -155.66 (17)° and -61.93 (17) ° for the title and RG108 salt structures, respectively.