Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270199013578/ja1007sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270199013578/ja1007Isup2.hkl |
CCDC reference: 140968
11-Methylpyrido[2,3-b]acridine-5,12-dione was prepared by a published route and yielded spectroscopic data identical in all respects with that previously reported (Bracher, 1989). Recrystallization from a methanol–dichloromethane solution yielded yellow–brown needles [m.p. 520–525 K, literature 513–521 K (Bracher, 1989)] suitable for X-ray analysis. Full assignment of 1H and 13C NMR data were made by use of standard two-dimensional NMR techniques. 1H NMR (200 MHz, CDCl3): δ 9.16 (1H, dd, J = 4.6, 1.8 Hz, H-2), 8.73 (1H, dd, J = 8.0, 1.8 Hz, H-4), 8.45 (1H, dd, J = 8.5, 0.9 Hz, H-10), 8.38 (dd, J = 8.5, 0.9 Hz, H-7), 7.93 (1H, ddd, J = 8.3, 6.9, 1.4 Hz, H-8), 7.79 (1H, ddd, J = 8.3, 6.9, 1.4 Hz, H-9), 7.77 (1H, dd, J = 7.9, 4.6 Hz, H-3), 3.32 (3H, s, CH3); 13C NMR (100 MHz, CDCl3): δ 183.3 (s), 181.8 (d, J = 4 Hz, C-5), 155.6 (ddd, J = 183, 8, 4 Hz, C-2), 152.7 (dd, J = 6, 3 Hz, C-11), 150.2 (t, J = 5 Hz, C-12a), 148.6 (t, J = 8 Hz, C-6a), 147.5 (s, C-5a), 135.7 (dd, J = 170 Hz, 6, C-4), 132.7 (dd, J = 163 Hz, 9, C-8), 132.3 (dd, J = 165 Hz, 7, C-7), 130.0 (d, J = 7 Hz, C-4a), 125.5 (dd, J = 161 Hz, 8, C-10), 129.8 (dd, J = 163 Hz, 9, C-9), 129.8 (m, C-10a), 127.9 (dd, J = 167 Hz, 9, C-3), 125.5 (m, C-11a), 16.7 (q, J = 130 Hz, CH3).
Data collection: SMART (Siemens, 1994); cell refinement: SAINT (Siemens, 1994); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997a); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997b); molecular graphics: SHELXTL (Siemens, 1994); software used to prepare material for publication: SHELXL97.
C17H10N2O2 | Dx = 1.479 Mg m−3 |
Mr = 274.27 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, Pca21 | Cell parameters from 5243 reflections |
a = 25.7526 (17) Å | θ = 1.5–25.0° |
b = 4.2348 (3) Å | µ = 0.10 mm−1 |
c = 11.2966 (7) Å | T = 293 K |
V = 1231.97 (14) Å3 | Needle, brown |
Z = 4 | 0.94 × 0.18 × 0.18 mm |
F(000) = 568 |
Siemens SMART CCD diffractometer | 2040 independent reflections |
Radiation source: fine-focus sealed tube | 1845 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.057 |
Area–detector ω scans | θmax = 25°, θmin = 1.6° |
Absorption correction: multi-scan (Blessing, 1995; Sheldrick, 1998) | h = −25→30 |
Tmin = 0.912, Tmax = 0.982 | k = −5→5 |
6391 measured reflections | l = −14→12 |
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)] = 0.054 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.141 | H-atom parameters constrained |
S = 1.02 | Calculated w = 1/[σ2(Fo2) + (0.0608P)2 + 0.3024P] where P = (Fo2 + 2Fc2)/3 |
2040 reflections | (Δ/σ)max = 0.032 |
190 parameters | Δρmax = 0.16 e Å−3 |
1 restraint | Δρmin = −0.18 e Å−3 |
C17H10N2O2 | V = 1231.97 (14) Å3 |
Mr = 274.27 | Z = 4 |
Orthorhombic, Pca21 | Mo Kα radiation |
a = 25.7526 (17) Å | µ = 0.10 mm−1 |
b = 4.2348 (3) Å | T = 293 K |
c = 11.2966 (7) Å | 0.94 × 0.18 × 0.18 mm |
Siemens SMART CCD diffractometer | 2040 independent reflections |
Absorption correction: multi-scan (Blessing, 1995; Sheldrick, 1998) | 1845 reflections with I > 2σ(I) |
Tmin = 0.912, Tmax = 0.982 | Rint = 0.057 |
6391 measured reflections |
R[F2 > 2σ(F2)] = 0.054 | 1 restraint |
wR(F2) = 0.141 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.16 e Å−3 |
2040 reflections | Δρmin = −0.18 e Å−3 |
190 parameters |
Refinement. The structure was determined by direct methods and refined by full-matrix least squares on F2. Hydrogen atoms were placed geometrically and refined with a riding model (including free rotation about C—C bonds for the methyl group), and with Uiso constrained to be 1.2 (1.5 for the methyl group) times Ueq of the carrier atom. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.28702 (9) | 0.3026 (9) | 0.5575 (3) | 0.0962 (11) | |
O2 | 0.48874 (8) | 0.5722 (8) | 0.5260 (3) | 0.0817 (9) | |
N1 | 0.34850 (11) | 0.0947 (7) | 0.7290 (2) | 0.0599 (8) | |
N6 | 0.42610 (9) | 0.8471 (6) | 0.3681 (2) | 0.0462 (6) | |
C1' | 0.25969 (11) | 0.6673 (9) | 0.3689 (3) | 0.0618 (9) | |
H1'A | 0.2474 | 0.6526 | 0.4499 | 0.093* | |
H1'B | 0.2515 | 0.4735 | 0.3271 | 0.093* | |
H1'C | 0.2429 | 0.8438 | 0.3298 | 0.093* | |
C2 | 0.38132 (16) | −0.0077 (10) | 0.8124 (3) | 0.0675 (10) | |
H2A | 0.3678 | −0.1344 | 0.8733 | 0.081* | |
C3 | 0.43368 (16) | 0.0600 (10) | 0.8150 (3) | 0.0646 (10) | |
H3A | 0.4546 | −0.0145 | 0.8772 | 0.077* | |
C4a | 0.42160 (11) | 0.3458 (8) | 0.6366 (3) | 0.0475 (8) | |
C4 | 0.45459 (13) | 0.2366 (8) | 0.7262 (3) | 0.0566 (9) | |
H4A | 0.4903 | 0.2838 | 0.7251 | 0.068* | |
C5a | 0.40490 (10) | 0.6646 (8) | 0.4488 (3) | 0.0440 (7) | |
C5 | 0.44264 (11) | 0.5311 (8) | 0.5361 (3) | 0.0506 (8) | |
C6a | 0.39462 (11) | 0.9673 (8) | 0.2828 (3) | 0.0434 (7) | |
C7 | 0.41800 (12) | 1.1609 (8) | 0.1966 (3) | 0.0515 (8) | |
H7A | 0.4538 | 1.2038 | 0.2009 | 0.062* | |
C8 | 0.38911 (13) | 1.2867 (9) | 0.1070 (3) | 0.0580 (9) | |
H8A | 0.4049 | 1.4165 | 0.0499 | 0.070* | |
C9 | 0.33586 (13) | 1.2215 (8) | 0.1005 (3) | 0.0594 (9) | |
H9A | 0.3163 | 1.3056 | 0.0377 | 0.071* | |
C10a | 0.34025 (11) | 0.9066 (8) | 0.2783 (3) | 0.0453 (7) | |
C10 | 0.31194 (12) | 1.0397 (8) | 0.1830 (3) | 0.0537 (8) | |
H10A | 0.2761 | 1.0014 | 0.1768 | 0.064* | |
C11a | 0.35069 (11) | 0.5933 (8) | 0.4544 (3) | 0.0434 (7) | |
C11 | 0.31773 (10) | 0.7174 (7) | 0.3687 (3) | 0.0451 (7) | |
C12a | 0.36933 (11) | 0.2704 (8) | 0.6431 (3) | 0.0477 (7) | |
C12 | 0.33125 (11) | 0.3865 (8) | 0.5514 (3) | 0.0501 (8) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0360 (12) | 0.156 (3) | 0.097 (2) | −0.0227 (15) | −0.0073 (13) | 0.051 (2) |
O2 | 0.0325 (11) | 0.131 (3) | 0.0818 (18) | −0.0131 (13) | −0.0113 (12) | 0.0239 (19) |
N1 | 0.0532 (16) | 0.077 (2) | 0.0491 (16) | −0.0020 (14) | 0.0040 (14) | −0.0017 (15) |
N6 | 0.0319 (11) | 0.0553 (15) | 0.0515 (15) | −0.0049 (11) | −0.0003 (11) | −0.0093 (14) |
C1' | 0.0362 (16) | 0.082 (2) | 0.068 (2) | −0.0032 (15) | −0.0036 (15) | 0.002 (2) |
C2 | 0.068 (2) | 0.082 (3) | 0.052 (2) | 0.005 (2) | 0.0014 (18) | −0.002 (2) |
C3 | 0.067 (2) | 0.076 (3) | 0.050 (2) | 0.0108 (19) | −0.0119 (17) | −0.002 (2) |
C4a | 0.0381 (14) | 0.0543 (19) | 0.0500 (17) | 0.0039 (12) | −0.0026 (13) | −0.0148 (16) |
C4 | 0.0472 (16) | 0.063 (2) | 0.059 (2) | 0.0013 (16) | −0.0111 (16) | −0.0047 (18) |
C5a | 0.0319 (13) | 0.0503 (18) | 0.0498 (17) | −0.0008 (12) | −0.0007 (13) | −0.0121 (15) |
C5 | 0.0336 (15) | 0.062 (2) | 0.057 (2) | −0.0043 (14) | −0.0048 (14) | −0.0100 (17) |
C6a | 0.0317 (15) | 0.0507 (18) | 0.0476 (16) | 0.0016 (13) | 0.0008 (13) | −0.0105 (14) |
C7 | 0.0381 (15) | 0.0595 (19) | 0.0569 (19) | −0.0021 (14) | 0.0054 (14) | −0.0062 (17) |
C8 | 0.0520 (17) | 0.067 (2) | 0.055 (2) | 0.0029 (16) | 0.0081 (16) | −0.0009 (18) |
C9 | 0.0526 (18) | 0.071 (2) | 0.055 (2) | 0.0076 (17) | −0.0030 (16) | −0.0008 (19) |
C10a | 0.0340 (15) | 0.0523 (19) | 0.0497 (17) | 0.0007 (13) | 0.0007 (14) | −0.0164 (15) |
C10 | 0.0370 (15) | 0.067 (2) | 0.057 (2) | 0.0044 (14) | −0.0054 (14) | −0.0084 (17) |
C11a | 0.0308 (12) | 0.0510 (18) | 0.0485 (17) | −0.0009 (12) | 0.0008 (13) | −0.0145 (14) |
C11 | 0.0295 (13) | 0.0542 (18) | 0.0517 (18) | −0.0001 (12) | 0.0012 (12) | −0.0128 (15) |
C12a | 0.0416 (16) | 0.0538 (18) | 0.0478 (17) | −0.0012 (13) | 0.0020 (14) | −0.0105 (14) |
C12 | 0.0332 (15) | 0.067 (2) | 0.0496 (18) | −0.0028 (13) | 0.0019 (13) | −0.0021 (17) |
O1—C12 | 1.195 (4) | C5a—C11a | 1.430 (4) |
O2—C5 | 1.205 (4) | C5a—C5 | 1.496 (4) |
N1—C12a | 1.335 (4) | C6a—C7 | 1.408 (4) |
N1—C2 | 1.338 (5) | C6a—C10a | 1.424 (4) |
N6—C5a | 1.313 (4) | C7—C8 | 1.364 (5) |
N6—C6a | 1.358 (4) | C8—C9 | 1.401 (5) |
C1'—C11 | 1.510 (4) | C9—C10 | 1.357 (5) |
C2—C3 | 1.379 (5) | C10a—C10 | 1.417 (4) |
C3—C4 | 1.363 (5) | C10a—C11 | 1.422 (5) |
C4a—C12a | 1.385 (4) | C11a—C11 | 1.391 (4) |
C4a—C4 | 1.400 (5) | C11a—C12 | 1.489 (4) |
C4a—C5 | 1.483 (5) | C12a—C12 | 1.509 (4) |
C12a—N1—C2 | 116.0 (3) | C7—C8—C9 | 119.7 (3) |
C5a—N6—C6a | 117.7 (2) | C10—C9—C8 | 121.3 (3) |
N1—C2—C3 | 124.4 (4) | C10—C10a—C11 | 124.0 (3) |
C4—C3—C2 | 119.0 (3) | C10—C10a—C6a | 117.5 (3) |
C12a—C4a—C4 | 118.4 (3) | C11—C10a—C6a | 118.5 (3) |
C12a—C4a—C5 | 121.2 (3) | C9—C10—C10a | 120.9 (3) |
C4—C4a—C5 | 120.4 (3) | C11—C11a—C5a | 119.0 (3) |
C3—C4—C4a | 118.3 (3) | C11—C11a—C12 | 121.9 (2) |
N6—C5a—C11a | 124.1 (3) | C5a—C11a—C12 | 119.0 (3) |
N6—C5a—C5 | 114.2 (2) | C11a—C11—C10a | 117.6 (2) |
C11a—C5a—C5 | 121.7 (3) | C11a—C11—C1' | 123.4 (3) |
O2—C5—C4a | 120.6 (3) | C10a—C11—C1' | 119.0 (3) |
O2—C5—C5a | 121.6 (3) | N1—C12a—C4a | 123.9 (3) |
C4a—C5—C5a | 117.9 (2) | N1—C12a—C12 | 114.8 (3) |
N6—C6a—C7 | 117.0 (2) | C4a—C12a—C12 | 121.3 (3) |
N6—C6a—C10a | 123.0 (3) | O1—C12—C11a | 122.6 (3) |
C7—C6a—C10a | 120.0 (3) | O1—C12—C12a | 118.8 (3) |
C8—C7—C6a | 120.5 (3) | C11a—C12—C12a | 118.6 (2) |
Experimental details
Crystal data | |
Chemical formula | C17H10N2O2 |
Mr | 274.27 |
Crystal system, space group | Orthorhombic, Pca21 |
Temperature (K) | 293 |
a, b, c (Å) | 25.7526 (17), 4.2348 (3), 11.2966 (7) |
V (Å3) | 1231.97 (14) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.94 × 0.18 × 0.18 |
Data collection | |
Diffractometer | Siemens SMART CCD diffractometer |
Absorption correction | Multi-scan (Blessing, 1995; Sheldrick, 1998) |
Tmin, Tmax | 0.912, 0.982 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 6391, 2040, 1845 |
Rint | 0.057 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.054, 0.141, 1.02 |
No. of reflections | 2040 |
No. of parameters | 190 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.16, −0.18 |
Computer programs: SMART (Siemens, 1994), SAINT (Siemens, 1994), SAINT, SHELXS97 (Sheldrick, 1997a), SHELXL97 (Sheldrick, 1997b), SHELXTL (Siemens, 1994), SHELXL97.
O1—C12 | 1.195 (4) | C4a—C12a | 1.385 (4) |
O2—C5 | 1.205 (4) | C4a—C5 | 1.483 (5) |
N1—C12a | 1.335 (4) | C5a—C11a | 1.430 (4) |
N1—C2 | 1.338 (5) | C5a—C5 | 1.496 (4) |
N6—C5a | 1.313 (4) | C11a—C12 | 1.489 (4) |
N6—C6a | 1.358 (4) | C12a—C12 | 1.509 (4) |
C1'—C11 | 1.510 (4) | ||
O2—C5—C4a | 120.6 (3) | C10a—C11—C1' | 119.0 (3) |
O2—C5—C5a | 121.6 (3) | O1—C12—C11a | 122.6 (3) |
C4a—C5—C5a | 117.9 (2) | O1—C12—C12a | 118.8 (3) |
C11a—C11—C10a | 117.6 (2) | C11a—C12—C12a | 118.6 (2) |
C11a—C11—C1' | 123.4 (3) |
The search for new human anticancer agents from the marine environment has resulted in the isolation of a large range of polycyclic alkaloids based upon the pyridoacridine framework (Molinski, 1993). Two such examples are the cytotoxic pentacyclic alkaloids ascididemin and its analogue 2-bromoleptoclinidinone (Kobayashi et al., 1988; Bloor & Schmitz, 1987; deGuzman & Schmitz, 1989; Bracher, 1997; Lindsay et al., 1998). Both molecules associate with DNA, probably via base-pair intercalation. In direct contrast to this, previous studies have noted that the tetracyclic synthetic precursor to ascididemin, 11-methylpyrido[2,3-b]acridine-5,12-dione, (I) (NSC 659780), exhibits only modest cytotoxicity (Bracher, 1997), and moderate antibacterial and antifungal properties (Lindsay et al., 1995). As part of our studies directed towards understanding the chemistry (Lindsay et al., 1997, 1998; Copp et al., 1999) and biological activities (Lindsay et al., 1995; Copp et al., 1999) of ascididemin and related marine alkaloids, we now report on the crystal structure of (I).
The title molecule was found to be highly planar, with the greatest deviations from the mean molecular plane being for the quinone atoms O1 [0.125 (4) Å] and O2 [0.195 (4) Å], thus making it a good DNA intercalating chromophore. There are few reported X-ray studies of the quinoline–quinone substructure present in rings AB of (I) although this fragment is present in many biologically active agents, including the antibiotic streptonigrin (Chiu & Lipscomb, 1975) and aza-analogues of the antitumour agent mitoxantrone (Krapcho et al., 1994). Bond lengths observed for rings A and B of (I) are comparable to those reported for other quinoline–quinone-bearing compounds (Chiu & Lipscomb, 1975; Kita et al., 1991; Gieren & Schanda, 1977). However, steric congestion between the quinone O1 and methyl C1' atoms is apparent in (I), as evidenced by bond angles of 118.8 (3) (O1—C12—C12a) and 122.6 (3)° (O1—C12—C11a). This interaction is presumably also responsible for the quinone O atoms bending out of the plane of the rings. Extensive π-π stacking was evident in the crystal of (I), with rings BCD of one molecule overlapping rings ABC of an adjacent molecule. The perpendicular separation between individual chromophores is 3.4 Å.