3138
L. Gude et al. / Bioorg. Med. Chem. Lett. 12 (2002) 3135–3139
American Chemical Society Petroleum Research Fund for
a Type G Grant (32897-G3; K.B.G.). L.G. thanks the
Consejerıa de Educacion de la Comunidad de Madrid
and Fondo Social Europeo for a postgraduate fellowship.
27. Perrin, L. C.; Prenzler, P. D.; Culliname, C.; Phillips,
D. R.; Denny, W. A.; McFayden, W. D. J. Inorg. Biochem.
2000, 81, 111.
28. Temple, M. D.; McFayden, W. D.; Holmes, R. J.; Denny,
W. A.; Murray, V. Biochemistry 2000, 39, 5593.
29. Holmes, R. J.; McKeage, M. J.; Murray, V.; Denny,
W. A.; McFayden, W. D. J. Inorg. Biochem. 2001, 85, 209.
30. Lorente, A.; Fernandez-Saiz, M.; Herraiz, F.; Lehn, J.-M.;
Vigneron, J.-P. Tetrahedron Lett. 1999, 40, 5901.
References and Notes
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Lee, H. H.; Denny, W. A.; McFayden, W. D. J. Biol. Chem.
1992, 267, 18805.
32. Characterization of compounds: Mono-acridine ligand: mp
48–51 ꢁC; IR (KBr) u 3048, 2942, 2852, 1735, 1698, 1638, 1595,
1456, 752 cmÀ1; EI–MS m/z: 475 (M+, 33), 283 (67), 235 (69),
192 (100); Z isomer/E isomer=59/41; 1H NMR (CDCl3,
300 MHz) d: 8.66 (d, J=4.9 Hz, H-6 Z), 8.55 (d, J=4.9 Hz,
H-60 Z), 8.51 (d, J=4.9 Hz, H-6 E), 8.51 (d, J=8.8 Hz, H-1,8
Acr Z), 8.42 (d, J=4.9 Hz, H-60 E), 8.38 (d, J=8.8 Hz, H-1,8
Acr E), 8.33 (br s, H-3), 8.24 (two overlapped d, H-4,5 Acr),
8.23(s, H-3 0 Z), 8.16 (s, H-30 E), 7.76 (m, H-3,6 Acr), 7.58 (m,
H-2,7 Acr), 7.16 (d, J=4.9 Hz, H-50 Z), 7.10 (d, J=4.9 Hz,
H-50 E), 6.98 (dd, J=4.9, 1.6 Hz, H-5 E), 6.93(dd, J=4.9,
1.6 Hz, H-5 Z), 4.55 (s, CH2–Acr Z), 4.43(s, CH 2–Acr E), 3.67
(t, J=6.2 Hz, CH2a Z), 3.32 (t, J=6.2 Hz, CH2a E), 2.82 (t,
J=6.2 Hz, CH2b Z), 2.67 (t, J=6.2 Hz, CH2b E), 2.80 (s,
CH3NCO E), 2.60 (s, CH3NCO Z), 2.47 and 2.46 (two s,
CH3–Ar), 2.41 (s, CH3N Z), 1.99 (s, CH3N E); 13C NMR
(CDCl3, 75 MHz) d: 169.43and 168.92 (C ¼O), 156.66 and
156.42 (C-2), 155.11 and 154.92 (C-20), 149.35 (C-6), 148.98
(C-60), 148.57 (C4ꢁ Acr), 148.16 and 148.02 (C-40), 145.01
(C-4), 141.24 (C4ꢁ Acr), 140.52 (C4ꢁ Acr), 130.15 (C-4,5 Acr),
129.84 and 129.76 (C-3,6 Acr), 126.05 and 125.91 (C-2,7 Acr),
125.01 and 124.93(C-5 0), 124.80 and 124.53(C-1,8 Acr),
121.97 and 121.79 (C-30), 121.01 and 120.91 (C-5), 118.55 and
118.39 (C-3), 55.04 (CH2b E), 54.50 (CH2b Z), 53.85 (CH2–
Acr), 48.95 (CH2a E), 44.67 (CH2a Z), 42.19 (CH3N Z), 41.92
(CH3N E), 37.43 (CH3NCO Z), 32.78 (CH3NCO E), 21.15
and 21.10 (CH3–Ar).
8. Bowler, B. E.; Hollis, L. S.; Lippard, S. E. J. Am. Chem.
Soc. 1984, 106, 6102.
9. Bowler, B. E.; Lippard, S. E. Biochemistry 1986, 25, 3031.
10. Pasini, A. Gazz. Chim. Ital. 1987, 117, 763.
11. Bowler, B. E.; Ahmed, K. J.; Sundquist, W. I.; Hollis,
L. S.; Whang, E. E.; Lippard, S. J. J. Am. Chem. Soc. 1989,
111, 1299.
12. Sundquist, W. I.; Bancroft, D. P.; Lippard, S. J. J. Am.
Chem. Soc. 1990, 112, 1590.
13. Palmer, B. D.; Lee, H. H.; Johnson, P.; Baguley, B. C.;
Wickham, G.; Wakelin, L. P. G.; McFayden, W. D.; Denny,
W. A. J. Med. Chem. 1990, 33, 3008.
14. Gibson, D.; Gean, K. F.; Ben-Shoshan, R.; Ramu, A.;
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15. Lee, H. H.; Palmer, B. D.; Baguley, B. C.; Chin, M.;
McFayden, W. D.; Wickham, G.; Thorsbourne-Palmer, D.;
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2983.
16. Murray, V.; Motyka, H.; England, P. R.; Wickham, G.;
Lee, H. H.; Denny, W. A.; McFayden, W. D. J. Biol. Chem.
1992, 267, 18805.
17. Kech, M. V.; Lippard, S. J. J. Am. Chem. Soc. 1992, 114,
3386.
18. Murray, V.; Motyka, H.; England, P. R.; Wickham, G.;
Lee, H. H.; Denny, W. A.; McFayden, W. D. Biochemistry
1992, 31, 11812.
Complex 1: mp 255 ꢁC dec.; IR (KBr) u 3060, 2931, 1627,
1546, 1522, 1438, 1417, 756 cmÀ1
, (Nujol, CsI) u 336,
324 cmÀ1; 1H NMR (DMSO-d6, 300 MHz) d: 9.52–9.24 (m, H-
6,60), 8.62–8.45 (m, H-1,8 Acr), 8.30–8.07 (m, H-3,30, H-4,5
Acr), 7.88–7.75 (m, H-3,6 Acr), 7.70–7.56 (m, H-2,7 Acr, H-
50), 7.48 (d, J=5.9 Hz, H-5), 7.16 (d, J=5.9 Hz, H-5), 4.56 (s,
CH2–Acr), 4.47 (s, CH2–Acr), 3.59 (t, J=6 Hz, CH2a), 3.35
(br, CH2a), 2.80–2.60 (m, CH3NCO, CH2b), 2.35 (s, CH3–Ar,
CH3N), 1.99 (s, CH3N); 195Pt NMR (DMF-d7, 64.2 MHz) d
À2325 (195Pt NMR chemical shifts are referenced externally to
K2PtCl4 in D2O at À1624 ppm); FAB-MS (m-NBA) m/z
742.00 (M++2), calcd for C30H29Cl2N5OPt (740.1397).
19. McKeage, M. J.; Kelland, L. R., In Molecular Aspects of
Anticancer Drug-DNA Interactions; Neidle, S., Waring, M.,
eds.; CRC: Boca Raton, FL, 1993; Vol. 1, p 169.
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21, 393.
Bis-acridine ligand: mp 79–82 ꢁC; IR (KBr) u 3055, 2941,
2850, 1734, 1636, 1547, 1519, 1458, 1403, 752 cmÀ1; FAB-MS
(m-NBA) m/z 767.25 (M++1), calcd for C48H46N8O2
(766.3744); Z,Z isomer/ZE isomer/EE isomer=30/44/26%;
1H NMR (CDCl3, 300 MHz) d: 8.67 (d, J=4.8 Hz, H-6 ZZ),
8.52–8.48 (m, H-1,8 Acr ZZ+ZE, H-6 EE, H-6 ZE), 8.39–
8.31 (m, H-1,8 Acr EE+ZE, H-3 ZZ+EE+ZE, H-6 ZE),
8.27–8.21 (m, H-3 ZE, H-4,5 Acr), 7.79–7.70 (m, H-3,6 Acr),
7.61–7.52 (m, H-2,7 Acr), 6.99 (dd, J=4.8, 1.6 Hz, H-5 EE),
6.93(dd, J=4.8, 1.6 Hz, H-5 ZE+ZZ), 6.84 (dd, J=4.8,
1.6 Hz, H-5 ZE), 4.54, 4.53, 4.44 and 4.39 (s, CH2–Acr), 3.67
and 3.64 (two t, J=5.9 Hz CH2a ZZ+ZE), 3.30 (t, J=5.9 Hz,
CH2a EE), 3.24 (t, J=5.9 Hz, CH2a ZE), 2.82 (t, J=5.9 Hz,
CH2b ZZ+ZE), 2.80 (s, CH3NCO EE), 2.76 (s, CH3NCO
ZE), 2.67 (t, J=5.9 Hz, CH2b EE+ZE), 2.59 (s, CH3NCO
ZZ), 2.54 (s, CH3NCO ZE), 2.48 (s, CH3N ZZ), 2.46 (s,
CH3N ZE), 1.97 (s, CH3N EE), 1.90 (s, CH3N ZE); 13C NMR
(CDCl3, 75 MHz) d: 169.38 and 168.83 (C¼O), 155.77, 155.58,
155.52 and 155.34 (C-2), 149.51 and 149.44 (C-6), 148.59 (C4ꢁ
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