Ruthenium-and osmium-arene complexes of 2-substituted indolo[3,2- c ]quinolines: Synthesis, structure, spectroscopic properties, and antiproliferative activity

Article abstract of DOI:10.1021/om101004z

The synthesis of new modified indolo[3,2-c]quinoline ligands L ¹-L⁸ with metal-binding sites is reported. By coordination to ruthenium-and osmium-arene moieties 16 complexes of the type [(η⁶-p-cymene)M(L)Cl]Cl (1a,b-8a,b), where M is Ru^II or Os^II and L is L¹-L⁸, have been prepared. All compounds were comprehensively characterized by elemental analysis, electrospray ionization mass spectrometry, IR, UV-vis, and NMR spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction (2a, 4a, 4b, 5a, 7a, and 7b). The complexes were tested for antiproliferative activity in vitro in three human cancer cell lines, namely, CH1 (ovarian carcinoma), SW480 (colon adenocarcinoma), and A549 (non-small-cell lung cancer), yielding IC ₅₀ values in the submicromolar or low micromolar range.

Full text of DOI:10.1021/om101004z

Organometallics 2011, 30, 273–283 273
DOI: 10.1021/om101004z
Ruthenium- and Osmium-Arene Complexes of 2-Substituted
Indolo[3,2-c]quinolines: Synthesis, Structure, Spectroscopic Properties,
and Antiproliferative Activity
€
Lukas K. Filak, Gerhard Muhlgassner, Felix Bacher, Alexander Roller, Markus Galanski,
Michael A. Jakupec, Bernhard K. Keppler, and Vladimir B. Arion*
€
Institute of Inorganic Chemistry, University of Vienna, Wahringer Strasse 42, A-1090 Vienna, Austria
Received October 22, 2010
The synthesis of new modified indolo[3,2-c]quinoline ligands L1-L8 with metal-binding sites
is reported. By coordination to ruthenium- and osmium-arene moieties 16 complexes of the type
[(η6-p-cymene)M(L)Cl]Cl (1a,b-8a,b), where M is RuII or OsII and L is L1-L8, have been prepared.
All compounds were comprehensively characterized by elemental analysis, electrospray ionization
mass spectrometry, IR, UV-vis, and NMR spectroscopy, thermogravimetric analysis, and single-
crystal X-ray diffraction (2a, 4a, 4b, 5a, 7a, and 7b). The complexes were tested for antiproliferative
activity in vitro in three human cancer cell lines, namely, CH1 (ovarian carcinoma), SW480 (colon
adenocarcinoma), and A549 (non-small-cell lung cancer), yielding IC50 values in the submicromolar
or low micromolar range.
Introduction
Screen Database.12 Experiments with enzyme assays con-
firmed the assumption, and a larger series of paullones was
evaluated for their biological activity.13-15
Triggered by the success of flavopiridol, the first cyclin-
dependent kinase (cdk) inhibitor under clinical investiga-
tion,1 efforts have been focused on the development of
targeted ruthenium complexes,2-9 among them some with
kinase-inhibitory properties.10,11 Indolo[3,2-d ]benzaze-
pines, also referred to as paullones, were identified as puta-
tive cdk inhibitors by analysis of the National Cancer
Institute (NCI) Human Tumor Cell Line Anti-Cancer Drug
In order to overcome limitations of confined water solu-
bility and bioavailability of these organic compounds, they
were complexed with metal ions. As the paullone backbone
itself is not suitable for coordination to metals, except for
binding via lactam (or thiolactam) groups yielding thermo-
dynamically nonstable four-membered metallocycles, metal-
binding sites had to be created at the periphery of the molecule
scaffold. By complexation of paullones with gallium(III),16,17
ruthenium(II),18-20 osmium(II),19,20 and copper(II),21 their
physicochemical and biological properties could be altered
markedly. Structure-activity relationship studies have shown
*To whom correspondence should be addressed. E-mail: vladimir.
arion@univie.ac.at. Tel: þ43 1 4277 52615. Fax: þ43 1 4277 52630
(V.B.A.).
(1) Christian, B. A.; Grever, M. A.; Byrd, J. C.; Lin, T. S. Clin.
Lymphoma Myeloma 2009, 9 (Suppl. 3), 179.
(2) Ang, W. H.; Dyson, P. J. Eur. J. Inorg. Chem. 2006, 4003.
(12) Zaharevitz, D. W.; Gussio, R.; Leost, M.; Senderowicz, A. M.;
Lahusen, T.; Kunick, C.; Sausville, E. A. Cancer Res. 1999, 59, 2566.
(13) Schultz, C.; Link, A.; Leost, M.; Zaharevitz, D. W.; Gussio, R.;
Sausville, E. A.; Meijer, L.; Kunick, C. J. Med. Chem. 1999, 42, 2909.
(14) Kunick, C.; Zeng, Z.; Gussio, R.; Zaharevitz, D.; Leost, M.;
€
(3) Meggers, E.; Atilla-Gokcumen, G. E.; Grundler, K.; Corazon
Frias, C.; Prokop, A. Dalton Trans. 2009, 10882.
(4) Ratanaphan, A.; Temboot, P.; Dyson, P. J. Chem. Biodiversity
2010, 7, 1290.
(5) Grguric-Sipka, S.; Stepanenko, I. N.; Lazic, J. M.; Bartel, C.;
Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Dalton Trans. 2009, 3334.
ꢀꢁ
(6) Casini, A.; Karotki, A.; Gabbiani, C.; Rugi, F.; Vasak, M.;
€
Totzke, F.; Schachtele, C.; Kubbutat, M. H. G.; Meijer, L.; Lemcke, T.
ChemBioChem 2005, 6, 541.
(15) Becker, A.; Kohfeld, S.; Lader, A.; Preu, L.; Pies, T.; Wieking,
K.; Ferandin, Y.; Knockaert, M.; Meijer, L.; Kunick, C. Eur. J. Med.
Chem. 2010, 45, 335.
Messori, L.; Dyson, P. J. Metallomics 2009, 1, 434.
(7) Renfrew, A. K.; Phillips, A. D.; Egger, A. E.; Hartinger, C. G.;
Bosquain, S. S.; Nazarov, A. A.; Keppler, B. K.; Gonsalvi, L.; Peruzzini,
M.; Dyson, P. J. Organometallics 2009, 28, 1165.
(16) Dobrov, A.; Arion, V. B.; Kandler, N.; Ginzinger, W.; Jakupec,
ꢁ
M. A.; Rufinska, A.; G. v. Keyserlingk, N.; Galanski, M.; Kowol, C.;
(8) Mendoza-Ferri, M. G.; Hartinger, C. G.; Mendoza, M. A.;
Groessl, M.; Egger, A. E.; Eichinger, R. E.; Mangrum, J. B.; Farrell,
N. P.; Maruszak, M.; Bednarski, P. J.; Klein, F.; Jakupec, M. A.;
Nazarov, A. A.; Severin, K.; Keppler, B. K. J. Med. Chem. 2009, 52, 916.
(9) Kandioller, W.; Hartinger, C. G.; Nazarov, A. A.; Bartel, C.;
Skocic, M.; Jakupec, M. A.; Arion, V. B.; Keppler, B. K. Chem.;Eur. J.
2009, 15, 12283.
(10) Anand, R.; Maksimoska, J.; Pagano, N.; Wong, E. Y.; Gimotty,
P. A.; Diamond, S. L.; Meggers, E.; Marmorstein, R. J. Med. Chem.
2009, 52, 1602.
Keppler, B. K. Inorg. Chem. 2006, 45, 1945.
(17) Ginzinger, W.; Arion, V. B.; Giester, G.; Galanski, M.; Keppler,
B. K. Cent. Eur. J. Chem. 2008, 6, 340.
(18) Schmid, W. F.; Zorbas-Seifried, S.; John, R. O.; Arion, V. B.;
Jakupec, M. A.; Roller, A.; Galanski, M.; Chiorescu, I.; Zorbas, H.;
Keppler, B. K. Inorg. Chem. 2007, 46, 3645.
(19) Schmid, W. F.; John, R. O.; Arion, V. B.; Jakupec, M. A.;
Keppler, B. K. Organometallics 2007, 26, 6643.
€
(20) Schmid, W. F.; John, R. O.; Muhlgassner, G.; Heffeter, P.;
Jakupec, M. A.; Galanski, M.; Berger, W.; Arion, V. B.; Keppler,
€
(11) Filak, L. K.; Muhlgassner, G.; Jakupec, M. A.; Heffeter, P.;
B. K. J. Med. Chem. 2007, 50, 6343.
(21) Primik, M. F.; Muhlgassner, G.; Jakupec, M. A.; Zava, O.;
€
Berger, W.; Arion, V. B.; Keppler, B. K. J. Biol. Inorg. Chem. 2010, 15,
903.
Dyson, P. J.; Arion, V. B.; Keppler, B. K. Inorg. Chem. 2010, 49, 302.
r
2010 American Chemical Society
Published on Web 12/27/2010
pubs.acs.org/Organometallics

274 Organometallics, Vol. 30, No. 2, 2011
Filak et al.
Chart 1. Indolo[3,2-d]benzazepine (left) and Indolo[3,2-
c]quinoline (right) Backbones with Atom-Numbering Schemes
indolo[3,2-c]quinolines 1a,b-8a,b (Scheme 1, Chart 2), of
which six were characterized by X-ray diffraction, their spec-
troscopic properties (NMR, UV-vis, FT-IR), thermal beha-
vior, and ESI mass spectra. The cytotoxic activity of these
metal complexes assayed in vitro in three human cancer cell
lines, CH1 (ovarian carcinoma), SW480 (colon adeno-
carcinoma), and A549 (non-small-cell lung carcinoma), is also
reported.
that an intact lactam unit is favorable for cdk inhibition.13,22,23
In vitro cytotoxicity of ruthenium and osmium complexes was,
however, found to be higher if complexation occurred via the
modified lactam group and not through a chelator group at
position 9 of the paullone backbone.20
Experimental Section
Characterization of the Compounds. One-dimensional 1H and
13C NMR and two-dimensional 1H-1H COSY, 1H-1H
TOCSY, 1H-1H ROESY or 1H-1H NOESY, 1H-13C HSQC,
and 1H-13C HMBC NMR spectra were recorded on two
Bruker Avance III spectrometers at 500.32 or 500.10 (1H), and
125.82 or 125.76 (13C) MHz, respectively, by using as a solvent
DMSO-d6 or MeOD-d4 at room temperature and standard
Paullones contain a seven-membered folded azepine ring,
which makes the whole molecule nonplanar (Chart 1). Re-
cently, efforts by us were extended to indolo[3,2-c]quinolines
(Chart 1) that have a framework similar to that of paullones
but comprise a flat six-membered ring instead of the folded
seven-membered azepine ring, making the whole heteroaro-
matic system planar. The antiproliferative properties of this
class of organic molecules have been reported recently,24-28
along with convenient synthetic routes.29 A few ruthenium and
osmium complexes showed a significantly higher in vitro
cytotoxicity compared to that of the related paullone com-
plexes. In addition, the indoloquinolines revealed a high poten-
tial for intercalation into DNA and caused concentration-
dependent cell cycle perturbations. However, the reported
metal complexes of indolo[3,2-c]quinolines showed a much
lower stability in both organic and aqueous media, in some
cases leading to rapid dissociation of the ligands from the
metal-arene scaffold.11
With the intention to increase the hydrolytic stability of
metal complexes by involvement of sp2-hybridized nitrogen
donors, we suggested performing condensation reactions of
the indoloquinoline hydrazine with 2-formyl- and/or 2-acet-
ylpyridine and to bind the resulting Schiff base ligands to
ruthenium(II)-arene and osmium(II)-arene moieties, tak-
ing into account the different kinetics of ligand exchange
reactions at ruthenium(II) and osmium(II).30 Looking for
structure-activity relationships to be elucidated in this class
of complexes, we intended to study the effect of substitution
in position 2 of the parent indoloquinoline on the antipro-
liferative activity.
pulse programs. H and 13C shifts are quoted relative to the
1
solvent residual signals. The atom numbering used for assign-
ments is depicted in Chart S1. IR spectra were measured on a
Bruker Vertex 70 FT-IR spectrometer by means of attenuated
total reflection (ATR) technique, and UV-vis spectra were
recorded with a Perkin-Elmer Lambda 650 spectrophotometer
equipped with a six-cell changer and a Peltier element for
temperature control. Electrospray ionization mass spectrome-
try (ESI-MS) was carried out with a Bruker Esquire 3000
instrument; the samples were dissolved in methanol. Thermo-
gravimetric analysis (TGA) and differential thermal analysis
(DTA) were carried out on a Mettler Toledo TGA/SDTA 851e
instrument. All elemental analyses were performed at the
Microanalytical Laboratory of the University of Vienna with a
Perkin-Elmer 2400 CHN elemental analyzer.
Synthesis of the Ligands. Ethanol was dried using standard
procedures. 2-Aminobenzylamine and substituted indole-2,3-
diones were purchased from Aldrich and used as received.
Indoloquinolines A were synthesized by reaction of 2-amino-
benzylamine with indole-2,3-diones in acetic acid and further
chlorinated with phosphorus oxychloride to derivatives B by
following the procedures reported previously (Scheme 1).24,25,29
Compounds B were heated in neat hydrazine hydrate under an
Ar atmosphere for 24-29 h, and after cooling, compounds C
were filtered off, washed with water and diethyl ether, dried
in vacuo, and used without further purification. Acetylpyridine
hydrazone was prepared as described elsewhere.31
General Procedure A. To the corresponding 11H-indolo[3,2-c]-
quinolin-6-yl)hydrazine (1 equiv) in a 25 mL Schlenk tube was
added a solution of 2-formylpyridine (1.1 equiv) or 2-acetylpyri-
dine (1.1 equiv) in ethanol, and the resulting mixture was stirred
under an argon atmosphere for 24 h. The mixture was allowed to
cool to room temperature; the precipitate formed was filtered
off, washed with small amounts of ethanol (2 ꢀ 1 mL) and
diethyl ether (2 ꢀ 2 mL), and dried in vacuo at 50 °C.
Herein we report on the synthesis of 16 novel ruthe-
nium(II)-arene and osmium(II)-arene complexes with modified
(22) Leost, M.;Schultz, C.;Link, A.;Wu, Y. Z.;Biernat, J.;Mandelkow,
E.-M.;Bibb, J. A.;Snyder, G. L.;Greengard, P.;Zaharevitz, D. W.;Gussio,
R.; Senderowicz, A. M.; Sausville, E. A.; Kunick, C.; Meijer, L. Eur. J.
Biochem. 2000, 267, 5983.
(23) Kunick, C.; Lauenroth, K.; Wieking, K.; Xie, X.; Schultz, C.;
Gussio, R.; Zaharevitz, D.; Leost, M.; Meijer, L.; Weber, A.; Jørgensen,
F. S.; Lemcke, T. J. Med. Chem. 2004, 47, 22.
N-(5,11-Dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-
2-yl-methylidene)azine (L1). General procedure A: (11H-Indolo-
[3,2-c]quinolin-6-yl)hydrazine (500 mg, 2.01 mmol), ethanol
(10 mL), 2-formylpyridine (212 μL, 2.22 mmol). Yield: 607 mg,
89%. Anal. Calcd for C21H15N5 0.15H2O (Mr 340.08): C, 74.17;
3
(24) Chen, Y. L.; Chung, C. H.; Chen, I. L.; Chen, P. H.; Jeng, H. W.
Bioorg. Med. Chem. 2002, 10, 2705.
H, 4.53; N, 20.59. Found: C, 74.09; H, 4.46; N, 20.72. ESI-MS
(methanol), positive: m/z 338 [M þ H]þ, 360 [M þ Na]þ. IR
(ATR, selected bands, νmax): 3337, 2935, 2830, 1631, 1569,
(25) Hu, X. W.; Chien, C. M.; Yang, S. H.; Lin, Y. H.; Lu, C. M.;
Chen, Y. L.; Lin, S. R. Cell Biol. Toxicol. 2006, 22, 417.
(26) Yang, S. H.; Chien, C. M.; Lu, C. M.; Chen, Y. L.; Chang, L. S.;
Lin, S. R. Leuk. Res. 2007, 31, 1413.
(27) Chien, C. M.; Sheng-Huei Yang, S. H.; Lin, K. L.; Chen, Y. L.;
Chang, L. S.; Lin, S. R. Chem.-Biol. Interact. 2008, 176, 40.
(28) Tzeng, C. C.; Chen, Y. L.; Lin, J. J.; Lu, C. M. U.S. Pat. Appl.
US2009/0298846 A1, Dec. 3, 2009.
1528, 1456, 1367, 1216, 1029, 1002, 745, 717, 680, 637 cm-1
.
N-(5,11-Dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-
2-yl-ethylidene)azine (L2). General procedure A: (11H-Indolo-
[3,2-c]quinolin-6-yl)hydrazine (500 mg, 2.01 mmol), ethanol
(10 mL), 2-acetylpyridine (248 μL, 2.22 mmol). Yield: 561 mg, 76%.
(29) Bergman, J.; Engqvist, R.; Stalhandske, C.; Wallberg, H. Tetra-
hedron 2003, 59, 1033.
(30) Peacock, A. F. A.; Melchart, M.; Habtemariam, A.; Parsons, S.;
Sadler, P. J. Chem.;Eur. J. 2007, 13, 2601.
(31) Kowol, C. R.; Reisner, E.; Chiorescu, I.; Arion, V. B.; Galanski,
M.; Deubel, D. V.; Keppler, B. K. Inorg. Chem. 2008, 47, 11032.

Article
Organometallics, Vol. 30, No. 2, 2011 275
Scheme 1. Synthesis of the Modified Indoloquinoline Ligandsa
a Reagents and conditions: (i) HOAc, Ar, 140 °C, 4 h; (ii) POCl3, Ar, 140 °C, 24-27 h; (iii) N2H4 H2O, Ar, 120 °C, 24-29 h; (iv) EtOH, Ar, 65 °C, 24 h;
3
(v) 1-butanol, Ar, 130 °C, 27 h.
N-(2-Chloro-5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-
Chart 2. Ruthenium(II)- and Osmium(II)-Arene Complexes
pyridin-2-yl-methylidene)azine (L4). General procedure A:
(2-Chloro-11H-indolo[3,2-c]quinolin-6-yl)hydrazine (700 mg, 2.48
mmol), ethanol (10 mL), 2-formylpyridine (260 μL, 2.72 mmol).
with Modified Indoloquinoline Ligandsa
Yield: 599 mg, 65%. Anal. Calcd for C21H14N5Cl 0.25H2O (Mr
3
376.33): C, 67.12; H, 3.88; N, 18.61. Found: C, 67.16; H, 3.81; N,
18.44. ESI-MS (methanol), positive: m/z 372 [M þ H]þ. IR (ATR,
selected bands, νmax): 3339, 3060, 2752, 1631, 1567, 1529, 1217,
1152, 1046, 999, 930, 809, 741, 676, 620 cm-1
.
N-(2-Chloro-5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-
pyridin-2-yl-ethylidene)azine (L5). General procedure A: (2-Chloro-
11H-indolo[3,2-c]quinolin-6-yl)hydrazine (700 mg, 2.48 mmol),
ethanol (10 mL), 2-acetylpyridine (303 μL, 2.72 mmol). Yield:
640 mg, 67%. Anal. Calcd for C22H16N5Cl (Mr 385.85): C, 68.48;
H, 4.18; N, 18.15. Found: C, 68.21; H, 4.10; N, 18.08. ESI-MS
(methanol), positive: m/z 386 [M þ H]þ, 408 [M þ Na]þ. IR (ATR,
selected bands, νmax): 3335, 3104, 2955, 1629, 1542, 1453, 1429,
1406, 1363, 1277, 1217, 1154, 1015, 809, 747 cm-1
.
N-(2-Bromo-5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-
pyridin-2-yl-ethylidene)azine (L6). General procedure A: (2-Bromo-
11H-indolo[3,2-c]quinolin-6-yl)hydrazine (800 mg, 2.45 mmol),
ethanol (10 mL), 2-acetylpyridine (300 μL, 2.72 mmol). Yield:
890 mg, 84%. Anal. Calcd for C22H16N5Br 0.1H2O (Mr 432.10):
3
C, 61.15; H, 3.78; N, 16.21. Found: C, 61.01; H, 3.59; N, 16.29. ESI-
MS (methanol), positive: m/z 432 [M þ H]þ. IR (ATR, selected
bands, νmax): 3331, 3076, 2954, 1628, 1538, 1452, 1428, 1405, 1275,
1215, 1152, 1014, 994, 807, 777, 745, 717, 678 cm-1
.
N-(2-Methyl-5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-
pyridin-2-yl-ethylidene)azine (L7). General procedure A: (2-Meth-
yl-11H-indolo[3,2-c]quinolin-6-yl)hydrazine (800 mg, 3.05 mmol),
ethanol (8 mL), 2-acetylpyridine (376 μL, 3.36 mmol). Anal. Calcd
a Underlined compounds have been characterized by X-ray crystal-
lography.
for C23H19N5 0.2H2O (Mr 369.03): C, 74.86; H, 5.30; N, 18.98.
3
Found: C, 74.86; H, 4.95; N, 18.71. Yield: 1016 mg, 91%. ESI-MS
(methanol), positive: m/z366 [M þ H]þ, 388 [M þ Na]þ. IR(ATR,
selected bands, νmax): 3352, 3037, 2964, 2870, 1630, 1598, 1530,
Anal. Calcd for C22H17N5 0.15H2O (Mr 354.11): C, 74.62;
3
H, 4.92; N, 19.78. Found: C, 74.44; H, 4.58; N, 19.89. ESI-MS
(methanol), positive: m/z 352 [M þ H]þ, 374 [M þ Na]þ. IR
(ATR, selected bands, νmax): 3353, 3085, 2955, 1627, 1534, 1456,
1459, 1332, 1277, 1218, 1017, 994, 806, 778, 747, 670, 635 cm-1
.
N-(2-Nitro-5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-
pyridin-2-yl-ethylidene)azine (L8). A mixture of 6-chloro-2-nitro-
11H-indolo[3,2-c]quinoline (1000 mg, 3.36 mmol), 2-acetylpyri-
dine hydrazone (730 mg, 5.40 mmol), and 1-butanol (10 mL) in a
Schlenk tube under argon atmosphere was heated at 130 °C for
27 h. After cooling to room temperature, the solid formed was
filtered off, washed with water (4 ꢀ 5 mL) and ethanol (2 ꢀ 2 mL),
and dried in vacuo. Further purification was performed by dissolu-
tion of the product in ethyl acetate (1.5 L/g) and washing the
organic phase with half saturated aqueous NaHCO3 solution
(5 ꢀ 300 mL) and brine (2 ꢀ 300 mL). The solvent was removed
under reduced pressure, and the product was dried in vacuo.
1372, 1278, 1218, 1032, 1006, 964, 781, 717, 679, 630 cm-1
.
N-(2-Fluoro-5,11-dihydroindolo[3,2-c]quinolin-6-yl)-N0-(1-pyri-
din-2-yl-ethylidene)azine (L3). General procedure A: (2-Fluoro-
11H-indolo[3,2-c]quinolin-6-yl)hydrazine (800 mg, 3.01 mmol),
ethanol (10 mL), 2-acetylpyridine (371 μL, 3.31 mmol). Yield:
1040 mg, 94%. Anal. Calcd for C22H16N5F (Mr 369.39): C, 71.53;
H, 4.37; N, 18.96. Found: C, 71.37; H, 4.13; N, 18.72. ESI-MS
(methanol), positive: m/z 370 [M þ H]þ, 392 [M þ Na]þ. IR
(ATR, selected bands, νmax): 3349, 3083, 2956, 2919, 2876, 1162,
1589, 1540, 1453, 1277, 1218, 1200, 1015, 873, 856, 807, 748, 679,
613 cm-1
.

276 Organometallics, Vol. 30, No. 2, 2011
Filak et al.
Yield: 1194 mg, 90%. Anal. Calcd for C22H16N6O2 0.25H2O (Mr
(methanol), positive: m/z 698 [M - Cl]þ, 662 [M - Cl - HCl]þ.
IR (ATR, selected bands, νmax): 3656, 3398, 2963, 2869, 1628,
1591, 1522, 1465, 1398, 1339, 1227, 1033, 1006, 777, 751, 704,
647 cm-1. 1H NMR (500 MHz, CD3OD): δ 9.38 (d, 1H, 3J = 5.7
Hz, H18), 9.13 (s, 1H, H14), 8.39 (d, 1H, 3J = 8.0 Hz, H7),
8.21-8.12 (m, 3H, H1þH20þH21), 7.72-7.66 (m, 3H,
H4þH10þH19), 7.62-7.57 (m, 1H, H3), 7.51-7.47 (m, 1H, H9),
3
400.91): C, 65.91; H, 4.15; N, 20.96. Found: C, 65.95; H, 4.43; N, 20.88.
ESI-MS (methanol), positive: m/z 397 [M þ H]þ, 419 [M þ Na]þ. IR
(ATR, selected bands, νmax): 3316, 2920, 1614, 1541, 1509, 1457, 1408,
1319, 1270, 1146, 1095, 1014, 791, 734, 676, 609, 589 cm-1
.
32
Synthesis of the Complexes. [RuIICl(μ-Cl)(η6-p-cymene)]2
33
and its osmium analogue [OsIICl(μ-Cl)(η6-p-cymene)]2 were
prepared according to the literature.
7.46-7.42 (m, 1H, H2), 7.40-7.35 (m, 1H, H8), 6.16 (d, 1H, 3J =
0
5.8 Hz, Hcy20), 5.92-5.88 (m, 2H, Hcy1þHcy2 ), 5.35 (d, 1H, 3J =
General Procedure B. To a mixture of the corresponding
ligand (1 equiv) and [MCl2(p-cymene)2]2 (0.5 equiv), where M
is Ru or Os, in a 25 mL Schlenk tube was added dry ethanol
under Ar at room temperature. The resulting solution was
protected from light and stirred for 24 h. The precipitate formed
was collected under suction, washed with a small amount of
ethanol (1-2 mL) and diethyl ether (2 ꢀ 5-10 mL), and dried
in vacuo at 47-50 °C under light protection.
General Procedure C. To a mixture of the corresponding
ligand (1 equiv) [MCl2(p-cymene)2]2 (0.5 equiv), where M is
Ru or Os, in a 25 mL Schlenk tube was added dry ethanol under
Ar. The resulting solution was protected from light and stirred
at room temperature for 24 h. The precipitate formed was
collected under suction, washed with a small amount of ethanol
(1-2 mL) and diethyl ether (2 ꢀ 5-10 mL), and dried in vacuo at
47 °C under light protection. To the mother liquor was added
diethyl ether (15-20 mL), whereupon a second crop of product
was precipitated. This solid was also collected under suction and
dried in vacuo at 47-50 °C under light protection. In all cases the
NMR spectra of both crops were identical.
5.7 Hz, Hcy1 ), 2.75-2.606 (m, 1H, Hcy3), 2.29 (s, 3H, Hcy5), 1.12 (d,
3
3
3H, J = 6.9 Hz, Hcy4 ), 1.08 (d, 3H, J = 6.9 Hz, Hcy4) ppm,
H5þH11 not obsd. 13C NMR (125 MHz, CD3OD): δ 157.6 (CH,
C14), 156.1 (Cq, C16), 155.1 (CH, C18), 149.1 (Cq, C6), 139.7 (CH,
C20), 139.5 (Cq, C11a), 138.9 (Cq, C10a), 136.2 (Cq, C4a), 129.6 (CH,
C3), 127.1 (CH, C19), 126.0 (CH, C21), 124.8 (CH, C9), 123.5 (Cq,
C6b), 123.3 (CH, C2), 121.9 (CH, C1), 121.9 (CH, C7), 121.4 (CH,
C8), 116.9 (CH, C4), 113.2 (Cq, C11b), 111.5 (CH, C10), 103.8 (Cq,
0
C6a), 97.1 (Cq, Ccy1a), 96.3 (Cq, Ccy2a), 79.0 (CH, Ccy2 ), 77.6 (CH,
0
Ccy2), 76.4 (CH, Ccy1), 74.5 (CH, Ccy1 ), 31.3 (CH, Ccy3), 21.2
0
(CH3, Ccy4), 20.9 (CH3, Ccy4 ), 17.6 (CH3, Ccy5) ppm.
(η6-p-Cymene)[N-(5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-
KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoruthenium(II)
Chloride (2a). General procedure B: N-(5,11-Dihydroindolo-
[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-ethylidene)azine
(200 mg, 0.57 mmol), [RuCl2(p-cymene)2]2 (175 mg, 0.29
mmol), ethanol (5 mL). Yield: 282 mg, 75% (orange solid).
Anal. Calcd for C32H31N5Cl2Ru 1.5H2O (Mr 684.62): C,
3
56.14; H, 5.01; N, 10.23. Found: C, 56.22; H, 4.98; N, 10.22.
ESI-MS (methanol), positive: m/z 622 [M - Cl]þ. IR (ATR,
selected bands, νmax): 3650, 3345, 3149, 2965, 1630, 1587, 1528,
1462, 1397, 1340, 1223, 745, 702, 702, 638 cm-1. 1H NMR (500
MHz, CD3OD): δ 10.59 (br s, 1H, H5), 9.50 (d, 1H, 3J = 5.4
(η6-p-Cymene)[N-(5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-
KN0-(1-KN-pyridin-2-yl-methylidene)]azinechloridoruthenium(II)
Chloride (1a). General procedure B: N-(5,11-Dihydroindolo-
[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-methylidene)azine
(200 mg, 0.59 mmol), [RuCl2(p-cymene)2]2 (182 mg, 0.30 mmol),
ethanol (5 mL). Yield: 337 mg, 88% (yellow solid). Anal. Calcd
3
Hz, H18), 8.50 (d, 1H, J = 8.0 Hz, H7), 8.26-8.22 (m, 1H,
H
H
H
20), 8.20 (d, 1H, 3J = 7.9 Hz, H1), 8.13 (d, 1H, 3J = 7.9 Hz,
3
21), 7.77-7.73 (m, 2H, H4þH19), 7.71 (d, 1H, J = 8.2 Hz,
for C31H29N5Cl2Ru 1.5H2O (Mr 670.59): C, 55.52; H, 4.81; N,
3
10), 7.60-7.55 (m, 1H, H3), 7.52-7.47 (m, 1H, H9),
10.44. Found: C, 55.54; H, 4.69; N, 10.37. ESI-MS (methanol),
positive: m/z 608 [M - Cl]þ. IR (ATR, selected bands, νmax):
3655, 3412, 2967, 2868, 1628, 1590, 1527, 1466, 1400, 1228, 1008,
3
7.44-7.38 (m, 2H, H2þH8), 5.89 (d, 1H, J = 6.2 Hz, Hcy20),
5.66 (d, 1H, 3J = 6.2 Hz, Hcy1), 5.64 (d, 1H, 3J = 6.2 Hz, Hcy2 ),
0
777, 751, 718, 704 cm-1
.
1H NMR (500 MHz, CD3OD):
5.18 (d, 1H, 3J = 6.2 Hz, Hcy1 ), 2.86-2.76 (s, 3H, H15þm, 1H,
0
δ 9.44 (d, 1H, 3J = 5.6 Hz, H18), 8.72 (s, 1H, H14), 8.40 (d, 1H,
3J = 8.0 Hz, H7), 8.20-8.15 (m, 2H, H1þH20), 7.97 (d, 1H, 3J =
7.9 Hz, H21), 7.81 (d, 1H, 3J = 8.4 Hz, H4), 7.73-7.67 (m, 2H,
H10þH19), 7.63-7.58 (m, 1H, H3), 7.51-7.47 (m, 1H, H9),
7.45-7.41 (m, 1H, H2), 7.39-7.35 (m, 1H, H8), 5.87 (d, 1H,
3J = 6.1 Hz, Hcy2), 5.65 (d, 1H, 3J = 6.1 Hz, Hcy1), 5.62 (d, 1H,
H
cy3), 2.22 (s, 3H, Hcy5), 1.15 (d, 3H, 3J = 6.9 Hz, Hcy4 ), 1.11
(d, 3H, 3J = 6.9 Hz, Hcy4) ppm, H11 not obsd. 13C NMR (125
MHz, CD3OD): δ 165.5 (Cq, C14). 155.6 (Cq, C16), 155.4 (Cq,
C
18), 147.9 (Cq, C6), 139.5 (CH, C20), 139.2 (Cq, C11a), 138.8
(Cq, C10a), 136.5 (Cq, C4a), 129.5 (CH, C3), 126.5 (CH, C19),
125.7 (CH, C21), 124.7 (CH, C9), 123.7 (Cq, C6b), 123.0 (CH,
C2), 121.9 (CH, C1), 121.8 (CH, C7), 121.4 (CH, C8), 116.9
0
0
3J = 6.2 Hz, Hcy2 ), 5.21 (d, 1H, 3J = 6.2 Hz, Hcy1 ), 2.86-2.76
0
(m, 1H, Hcy3), 2.23 (s, 3H, Hcy5), 1.16 (d, 3H, 3J = 6.9 Hz, Hcy4 ),
(CH, C4), 113.2 (Cq, C11b), 111.5 (CH, C10), 104.5 (Cq, Ccy2a),
0
1.12 (d, 3H, J = 6.9 Hz, Hcy4) ppm, H5þH11 not obsd. 13C
3
104.2 (Cq, C6a), 103.8 (Cq, Ccy1a), 87.6 (CH, Ccy2 ), 86.0 (CH,
0
NMR (125 MHz, CD3OD): δ 156.4 (CH, C14), 155.5 (CH, C18),
154.9 (Cq, C16), 149.0 (Cq, C6), 139.5 (CH, C20), 138.9 (Cq, C10a),
136.3 (Cq, C4a), 129.6 (CH, C3), 126.3 (CH, C19), 126.3 (CH,
C21), 124.8 (CH, C9), 123.5 (Cq, C6b), 123.3 (CH, C2), 121.9 (2
C
cy2), 85.6 (CH, Ccy1), 84.0 (CH, Ccy1 ), 31.0 (CH, Ccy3), 21.0
0
(CH3, Ccy4), 20.7 (CH3, Ccy4 ), 17.8 (CH3, Ccy5), 14.5 (CH3,
C
15) ppm.
(η6-p-Cymene)[N-(5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-
CH, C1 þ C7), 121.4 (CH, C8), 117.0 (CH, C4), 113.3 (Cq, C11b),
KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoosmium(II) Chlo-
ride (2b). General procedure C: N-(5,11-Dihydroindolo[3,2-c]-
quinolin-6-ylidene)-N0-(1-pyridin-2-yl-ethylidene)azine (188 mg,
0.57 mmol), [OsCl2(p-cymene)2]2 (212 mg, 0.27 mmol, ethanol
(4.8 mL). Yield: 269 mg þ66 mg, 84% (orange solid). Anal. Calcd
111.5 (CH, C10), 105.1 (Cq, Ccy2a), 104.1 (Cq, C6a), 103.7 (Cq,
0
Ccy1a), 87.0 (CH, Ccy2 ), 85.9 (CH, Ccy2), 85.7 (CH, Ccy1), 840.0
0
(CH, Ccy1 ), 31.1 (CH, Ccy3), 21.0 (CH3, Ccy4), 20.7 (CH3, Ccy4 ),
17.7 (CH3, Ccy5) ppm, C11a not observed.
(η6-p-Cymene)[N-(5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-
KN0-(1-KN-pyridin-2-yl-methylidene)]azinechloridoosmium(II)
Chloride (1b). General procedure B: N-(5,11-Dihydroindolo-
[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-methylidene)azine
(170 mg, 0.50 mmol), [OsCl2(p-cymene)2]2 (199 mg, 0.25 mmol),
ethanol (4.5 mL). Yield: 298 mg, 81% (yellow solid). Anal.
for C32H31N5Cl2Os 2H2O (Mr 782.79): C, 49.10; H, 4.51; N, 8.95.
3
Found: C, 49.19; H, 4.44; N, 8.78. ESI-MS (methanol), positive:
m/z 712 [M - Cl]þ, 676 [M - Cl - HCl]þ. IR (ATR, selected
bands, νmax): 3642, 3338, 3069, 2965, 2875, 1630, 1587, 1525, 1463,
1400, 1223, 1035, 1011, 745, 698, 637 cm-1. 1H NMR (500 MHz,
CD3OD): δ 9.43 (d, 1H, 3J = 5.4 Hz, H18), 8.46 (d, 1H, 3J = 7.9
Hz, H7), 8.26-8.21 (m, 2H, H20þH21), 8.19 (dd, 1H, 3J = 8.1 Hz,
4J = 0.9 Hz, H1), 7.76-7.72 (m, 1H, H19), 7.71 (d, 1H, 3J = 8.2
Hz, H10), 7.62 (d, 1H, 3J = 8.3 Hz, H4), 7.59-7.54 (m, 1H, H3),
7.51-7.47 (m, 1H, H9), 7.44-7.37 (m, 2H, H2þH80), 6.17 (d, 1H,
3J = 5.8 Hz, Hcy2), 5.92 (d, 1H, 3J = 5.8 Hz, Hcy2 ), 5.87 (d, 1H,
Calcd for C31H29N5Cl2Os 1.5H2O (Mr 759.75): C, 49.01; H,
4.25; N, 9.22. Found: C, 49.05; H, 4.07; N, 9.06. ESI-MS
3
(32) Bennett, M. A.; Smith, A. K. J. Chem. Soc., Dalton Trans. 1974,
233.
(33) Kiel, W. A.; Ball, R. G.; Graham, W. A. G. J. Organomet. Chem.
1990, 383, 481.
0
3
3J = 5.8 Hz, Hcy1), 5.32 (d, 1H, J = 5.8 Hz, Hcy1 ), 2.86 (s,
3H, H15) 2.75-2.66 (m, 1H, Hcy3), 2.28 (s, 3H, Hcy5), 1.11 (d, 3H,

Article
Organometallics, Vol. 30, No. 2, 2011 277
0
0
3J = 7.0 Hz, Hcy4 ), 1.07 (d, 3H, 3J = 7.0 Hz, Hcy4) ppm, H5þH11
not obsd. 13C NMR (125 MHz, CD3OD): δ 166.5 (Cq, C14).
156.6 (Cq, C16), 155.3 (CH, C18), 148.0 (Cq, C6), 139.5 (CH, C20),
139.2 (Cq, C11a), 138.8 (Cq, C10a), 136.3 (Cq, C4a), 129.5 (CH, C3),
127.3 (CH, C19), 125.8 (CH, C21), 124.7 (CH, C9), 123.7 (Cq, C6b),
123.0 (CH, C2), 121.9 (CH, C1), 121.7 (CH, C7), 121.4 (CH, C8),
96.9 (Cq, Ccy1a), 95.7 (Cq, Ccy2a), 79.3 (CH, Ccy2 ), 77.7 (CH,
0
Ccy2), 76.2 (CH, Ccy1), 74.5 (CH, Ccy1 ), 31.2 (CH, Ccy3),
0
21.3 (CH3, Ccy4), 20.9 (CH3, Ccy4 ), 17.7 (CH3, Ccy5), 14.2
(CH3, C15) ppm.
(η6-p-Cymene)[N-(2-chloro-5,11-dihydroindolo[3,2-c]quinolin-
6-ylidene)-KN0-(1-KN-pyridin-2-yl-methylidene)]azinechlorido-
ruthenium(II) Chloride (4a). General procedure B: N-(2-Chloro-
5,11-dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-
methylidene)azine (200 mg, 0.54 mmol), [RuCl2(p-cymene)2]2
(188 mg, 0.27 mmol), ethanol (4.5 mL). Yield: 344 mg, 94%
116.8 (CH, C4), 113.2 (Cq, C11b), 111.5 (CH, C10), 103.9 (Cq, C6a),
0
97.0 (Cq, Ccy1a), 95.6 (Cq, Ccy2a), 79.3 (CH, Ccy2 ), 77.7 (CH, Ccy2),
0
76.1 (CH, Ccy1), 74.40 (CH, Ccy1 ), 31.2 (CH, Ccy3), 21.3 (CH3,
Ccy4), 20.9 (CH3, Ccy4 ), 17.7 (CH3, Ccy5), 14.2 (CH3, C15) ppm.
(η6-p-Cymene)[N-(2-fluoro-5,11-dihydroindolo[3,2-c]quinolin-
6-ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoruthe-
nium(II) Chloride (3a). General procedure B: N-(2-Fluoro-5,11-
dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-eth-
ylidene)azine (180mg, 0.49mmol), [RuCl2(p-cymene)2]2 (149 mg,
0.24 mmol), ethanol (4 mL). Yield: 287 mg, 87% (orange solid).
(orange-yellow solid). Anal. Calcd for C31H28N5Cl3Ru 0.5H2O
3
(Mr 687.02): C, 54.19; H, 4.25; N, 10.19. Found: C, 54.17; H, 4.28;
N, 9.96. ESI-MS (methanol), positive: m/z 642 [M - Cl]þ. IR
(ATR, selected bands, νmax): 3665, 3382, 3025, 2963, 2867, 2648,
1629, 1589, 1530, 1458, 1403, 1331, 1295, 1228, 1085, 1011, 938,
825, 772, 748, 695 cm-1. 1H NMR (500 MHz, CD3OD): δ 9.44 (d,
1H, 3J = 5.6 Hz, H18), 8.72 (s, 1H, H14), 8.33 (d, 1H, 3J = 7.8 Hz,
H7), 8.17-8.12 (m, 1H, H20), 8.11 (d, 1H, 4J = 2.3 Hz, H1), 7.92
(d, 1H, 3J = 7.6 Hz, H21), 7.75 (d, 1H, 3J = 8.8 Hz, H4), 7.73-
7.67 (m, 2H, H10þH19), 7.54 (dd, 1H, 3J = 8.8 Hz, 4J = 2.3 Hz,
H3), 7.53-7.49 (m, 1H, H9), 7.37-7.33 (m, 1H, H8), 5.87 (d, 1H,
3J = 6.2 Hz, Hcy2), 5.65 (d, 1H, 3J = 6.2 Hz, Hcy1), 5.61 (d, 1H,
Anal. Calcd for C32H30N5FCl2Ru 1.25H2O (Mr 698.11): C,
3
55.05; H, 4.69; N, 10.03. Found: C, 55.04; H, 4.38; N, 9.94.
ESI-MS (methanol), positive: m/z 640 [M - Cl]þ. IR (ATR,
selected bands, νmax): 3656, 3350, 3069, 2967, 1638, 1596, 1532,
1461, 1395, 1339, 1226, 1202, 1016, 873, 811, 779, 742, 707, 644
cm-1. 1H NMR (500 MHz, CD3OD): δ 9.51 (d, 1H, 3J = 5.7 Hz,
H18), 8.51 (d, 1H, 3J = 7.8 Hz, H7), 8.27-8.22 (m, 1H, H20), 8.14
(d, 1H, 3J = 8.0 Hz, H21), 7.93 (dd, 1H, J = 8.9, 2.1 Hz, H1),
0
0
3J = 6.2 Hz, Hcy2 ), 5.22 (d, 1H, 3J = 6.2 Hz, Hcy1 ), 2.83-2.74
0
(m, 1H, Hcy3), 2.22 (s, 3H, Hcy5), 1.15 (d, 3H, 3J = 7.0 Hz, Hcy4 ),
7.78-7.73 (m, 2H, H4þH19), 7.71 (d, 1H, J = 8.2 Hz, H10),
3
1.11 (d, 3H, 3J = 7.0 Hz, Hcy4) ppm, H5 and H11 not obsd. 13
C
7.54-7.50 (m, 1H, H9), 7.44-7.40 (m, 1H, H8), 7.39-7.34 (m,
NMR (125 MHz, CD3OD): δ 157.0 (CH, C14). 155.5 (CH, C18),
154.7 (Cq, C16), 148.6 (Cq, C6), 139.7 (CH, C20), 138.9 (Cq, C10a),
138.1 (Cq, C11a), 134.8 (Cq, C4a), 129.4 (CH, C3), 128.6 (Cq, C2),
126.5 (2Cq, C19þC21), 125.1 (CH, C9), 123.2 (Cq, C6b), 122.0 (CH,
C7), 121.6 (CH, C8), 121.4 (CH, C1), 118.4 (CH, C4), 114.5 (Cq,
1H, H3), 5.90 (d, 1H, 3J = 6.2 Hz, Hcy2), 5.67 (d, 1H, 3J = 6.2 Hz,
0
H
H
H
H
cy10), 5.65 (d, 1H, 3J = 6.2 Hz, Hcy2 ), 5.22 (d, 1H, 3J = 6.2 Hz,
cy1 ), 2.87-2.79 (m, 1H, Hcy3), 2.708 (s, 3H, H15), 2.22 (s, 3H,
cy5), 1.15 (d, 3H, 3J = 6.9 Hz, Hcy4 ), 1.11 (d, 3H, 3J = 6.9 Hz,
cy4) ppm, H5 and H11 not obsd. 13C NMR (125 MHz, CD3OD):
C
11b), 111.6 (CH, C10), 105.3 (Cq, Ccy2a), 104.7 (Cq, C6a), 103.7
0
δ 165.8 (Cq, C14). 158.7 (d, Cq, 1J = 240 Hz, C2), 155.5 (Cq, C16),
155.4 (CH, C18), 147.6 (Cq, C6), 139.5 (CH, C20), 138.9 (Cq, C10a),
138.3 (d, Cq, 4J = 2.5 Hz, C11a), 133.1 (d, Cq, 4J = 1.5 Hz, C4a),
126.6 (CH, C19), 125.7 (CH, C21), 125.0 (CH, C9), 123.5 (Cq, C6b),
121.9 (CH, C7), 121.6 (CH, C8), 118.7 (d, CH, 3J = 8 Hz, C4),
117.1 (d, CH, 2J = 25 Hz, C3), 114.2 (d, Cq, 3J = 9 Hz, C11b),
(Cq, Ccy1a), 86.9 (CH, Ccy2 ), 85.8 (2CH, Ccy1þCcy2), 84.1 (CH,
0
0
C
cy1 ), 31.1 (CH, Ccy3), 21.0 (CH3, Ccy4), 20.7 (CH3, Ccy4 ), 17.7
(CH3, Ccy5) ppm.
(η6-p-Cymene)[N-(2-chloro-5,11-dihydroindolo[3,2-c]quinolin-6-
ylidene)-KN0-(1-KN-pyridin-2-yl-methylidene)]azinechloridoosmium-
(II) Chloride (4b). General procedure B: N-(2-Chloro-5,11-
dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-meth-
ylidene)azine (200 mg, 0.54 mmol), [OsCl2(p-cymene)2]2 (213 mg,
0.27 mmol), ethanol (4.5 mL). Yield: 347 mg, 84% (orange-red
111.6 (CH, C10), 107.3 (d, CH, 2J = 25 Hz, C1), 104.8 (Cq, C6a),
0
104.6 (Cq, Ccy2a), 103.7 (Cq, Ccy1a), 87.60 (CH, Ccy2 ), 86.0
(CH, Ccy2), 85.7 (CH, Ccy1), 84.1 (CH, Ccy1 ), 31.0 (CH, Ccy3),
0
21.0 (CH3, Ccy4), 20.7 (CH3, Ccy4 ), 17.8 (CH3, Ccy5), 14.4 (CH3,
C15) ppm.
solid). Anal. Calcd for C31H28N5Cl3Os H2O (Mr 785.19): C,
3
47.42; H, 3.85; N, 8.92. Found: C, 47.31; H, 3.81; N, 8.67. ESI-
MS (methanol), positive: m/z 732 [M - Cl]þ, 696 [M - Cl -
HCl]þ. IR (ATR, selected bands, νmax): 3654, 2965, 2872, 1630,
1588, 1518, 1454, 1397, 1371, 1333, 1224, 1011, 773, 745, 693, 651
cm-1. 1H NMR (500 MHz, CD3OD): δ 9.38 (d, 1H, 3J = 5.7 Hz,
H18), 9.12 (s, 1H, H14), 8.36 (d, 1H, 3J = 7.9 Hz, H7), 8.18-8.11
(m, 3H, H1þH20þH21), 7.72-7.67 (m, 2H, H10þH19), 7.63 (d,
1H, 3J = 8.8 Hz, H4), 7.54 (dd, 1H, 3J = 8.8 Hz, 4J = 2.3 Hz, H3),
(η6-p-Cymene)[N-(2-fluoro-5,11-dihydroindolo[3,2-c]quinolin-6-
ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoosmium-
(II) Chloride (3b). General procedure B: N-(2-Fluoro-5,11-
dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-eth-
ylidene)azine (180 mg, 0.49 mmol), [OsCl2(p-cymene)2]2 (193 mg,
0.24 mmol), ethanol (4 mL). Yield: 333 mg, 90% (orange solid).
Anal. Calcd for C32H30N5FCl2Os 1.5H2O (Mr 791.77): C, 48.54;
3
H, 4.20; N, 8.85. Found: C, 48.62; H, 3.99; N, 8.66. ESI-MS
(methanol), positive: m/z 730 [M - Cl]þ, 694 [M - Cl - HCl]þ.
IR (ATR, selected bands, νmax): 3648, 3350, 3163, 3067, 2966,
1638, 1598, 1528, 1461, 1396, 1225, 1202, 810, 778, 742, 694, 643
cm-1. 1H NMR (500 MHz, CD3OD): δ 9.44 (d, 1H, 3J = 5.6 Hz,
H18), 8.47 (d, 1H, 3J =7.9Hz, H7), 8.26-8.20 (m, 2H, H20þH21),
7.92 (dd, 1H, J = 8.9, 2.8 Hz, H1), 7.77-7.73 (m, 1H, H19), 7.71
(d, 1H, 3J = 8.2 Hz, H10), 7.61 (dd, 1H, J = 8.2 þ 4.6 Hz, H4),
7.53-7.49 (m, 1H, H9), 7.42-7.38 (m, 1H, H8), 7.37-7.32 (m,
7.53-7.49 (m, 1H, H9), 7.40-7.36 (m, 1H, H8), 6.17 (d, 1H, 3J =
0
5.9 Hz, Hcy20), 5.92-5.88 (m, 2H, Hcy1þHcy2 ), 5.38 (d, 1H, 3J =
5.9 Hz, Hcy1 ), 2.74-2.065 (m, 1H, Hcy3), 2.29 (s, 3H, Hcy5), 1.12 (d,
3H, 3J = 6.9 Hz, Hcy4 ), 1.07 (d, 3H, 3J = 6.9 Hz, Hcy4) ppm, H5
and H11 not obsd. 13C NMR (125 MHz, CD3OD): δ 158.2 (CH,
C14), 156.0 (Cq, C16), 155.1 (CH, C18), 148.8 (Cq, C6), 139.7 (CH,
C20), 138.9 (Cq, C10a), 138.1 (Cq, C11a), 134.6 (Cq, C4a), 129.4 (CH,
C3), 128.5 (Cq, C2), 127.2 (CH, C19), 126.1 (CH, C21), 125.1 (CH,
C9), 123.3 (Cq, C6b), 122.0 (CH, C7), 121.6 (CH, C8), 121.4 (CH,
1H, H3), 6.18 (d, 1H, 3J = 5.8Hz, Hcy2), 5.93 (d, 1H, 3J = 5.8 Hz,
C1), 118.3 (CH, C4), 114.4 (Cq, C11b), 111.6 (CH, C10), 104.5 (Cq,
0
0
Hcy20), 5.88 (d, 1H, 3J = 5.8 Hz, Hcy1), 5.34 (d, 1H, 3J = 5.8 Hz,
Hcy1 ), 2.86 (s, 3H, H15), 2.75-2.66 0(m, 1H, Hcy3), 2.28 (s, 3H,
Hcy5), 1.10 (d, 3H, 3J = 7.0 Hz, Hcy4 ), 1.07 (d, 3H, 3J = 7.0 Hz,
Hcy4) ppm, H5 and H11 not obsd. 13C NMR (125 MHz, CD3OD):
δ 166.7 (Cq, C14), 158.7 (d, Cq, 1J = 242 Hz, C2), 156.5 (Cq, C16),
155.3(CH, C18), 147.3(Cq, C6), 139.6 (CH, C20), 138.9 (Cq, C10a),
138.3 (d, Cq, 4J = 2.7 Hz, C11a), 132.9 (d, Cq, 4J = 1.8 Hz, C4a),
127.4(CH, C19), 125.9 (CH, C21), 125.0 (CH, C9), 123.5 (Cq, C6b),
121.9 (CH, C7), 121.6 (CH, C8), 118.6 (d, CH, 3J = 9 Hz, C4),
117.1 (d, CH, 2J = 25 Hz, C3), 114.1 (d, Cq, 3J = 9 Hz, C11b),
111.6 (CH, C10), 107.3 (d, CH, 2J = 25 Hz, C1), 104.5 (Cq, C6a),
C6a), 97.1 (Cq, Ccy1a), 96.6 (Cq, Ccy2a), 79.0 (CH, Ccy2 ), 77.6 (CH,
0
Ccy2), 76.5 (CH, Ccy1), 74.7 (CH, Ccy1 ), 31.3 (CH, Ccy3), 21.2
0
(CH3, Ccy4), 20.9 (CH3, Ccy4 ), 17.6 (CH3, Ccy5) ppm.
(η6-p-Cymene)[N-(2-chloro-5,11-dihydroindolo[3,2-c]quinolin-6-
ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoruthenium-
(II) Chloride (5a). General procedure B: N-(2-Chloro-5,11-dihy-
droindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-ethylidene)-
hydrazine (200 mg, 0.52 mmol), [RuCl2(p-cymene)2]2 (174 mg,
0.28 mmol), ethanol (4.7 mL). Yield: 262 mg, 73% (yellow solid).
Anal. Calcd for C32H30N5Cl3Ru 1.5H2O (Mr 719.07): C, 53.45;
3
H, 4.63; N, 9.74. Found: C, 53.28; H, 4.51; N, 9.65. ESI-MS

278 Organometallics, Vol. 30, No. 2, 2011
Filak et al.
(methanol), positive: m/z 656 [M - Cl]þ. IR (ATR, selected
bands, νmax): 3656, 3357, 3146, 3063, 2966, 1628, 1589, 1536,
1457, 1434, 1395, 1332, 1224, 1016, 813, 784, 744, 713, 696, 640
cm-1. 1H NMR (500 MHz, CD3OD): δ 9.50 (d, 1H, 3J = 5.6 Hz,
H18), 8.50 (d, 1H, 3J = 7.9 Hz, H7), 8.26-8.19 (d, 1H, 4J = 2.1
Hz, H1þm, 1H, H20), 8.13 (d, 1H, 3J = 8.0 Hz, H21), 7.78-7.74
(m, 1H, H19), 7.71(d, 1H, 3J = 8.4 Hz, H10), 7.68(d, 1H, 3J = 8.8
Hz, H4), 7.53-7.49 (m, 2H, H3þH9), 7.43-7.39 (m, 1H, H8),
5.90 (d, 1H, 3J = 6.2 Hz, Hcy20), 5.67 (d, 1H, 3J = 6.2 Hz, Hcy10),
5.65 (d, 1H, 3J = 6.2 Hz, Hcy2 ), 5.22 (d, 1H, 3J = 6.2 Hz, Hcy1 ),
2.86-2.76 (m, 1H, Hc0y3þs, 3H, H15), 2.21 (s, 3H, Hcy5), 1.15 (d,
3H, 3J = 6.9 Hz, Hcy4 ), 1.11 (d, 3H, 3J = 6.9 Hz, Hcy4) ppm, H5
and H11 not obsd. 13C NMR (125 MHz, CD3OD): δ 166.0 (Cq,
C14), 155.5 (CH, C18), 155.4 (Cq, C16), 147.5 (Cq, C6), 139.5 (CH,
C20), 138.9 (Cq, C10a), 137.8 (Cq, C11a), 135.0 (Cq, C4a), 129.3
(CH, C3), 128.2 (Cq, C2), 126.6 (CH, C19), 125.8 (CH, C21), 125.0
(CH, C9), 123.5 (Cq, C6b), 121.9 (CH, C7), 121.6 (CH, C8), 121.3
(CH, C1), 118.4 (CH, C4), 114.5 (Cq, C11b), 111.6 (CH, C10),
104.8 (Cq, C6a), 104.6 (Cq, Ccy2a), 103.7 (Cq, Ccy1a), 87.5 (CH,
2.86-2.76 (s, 3H, H15 þ0 m, 1H, Hcy3), 2.22 (s, 3H, Hcy5), 1.15
(d, 3H, 3J = 7.0 Hz, Hcy4 ), 1.11 (d, 3H, 3J = 6.9 Hz, Hcy4) ppm,
H5 and H11 not obsd. 13C NMR (125 MHz, CD3OD): δ 166.1 (Cq,
C14), 155.5 (CH, C18), 155.4 (Cq, C16), 147.5 (Cq, C6), 139.5 (CH,
C20), 138.9 (Cq, C10a), 137.7 (Cq, C11a), 135.4 (Cq, C4a), 132.1 (CH,
C3), 126.6 (CH, C19), 125.8 (CH, C21), 125.1 (CH, C9), 124.4 (CH,
C1), 123.5 (Cq, C6b), 121.9 (CH, C7), 121.6 (CH, C8), 118.6 (CH,
C4), 115.4 (Cq, C2), 114.9 (Cq, C11b), 111.6 (CH, C10), 104.8 (Cq,
0
C6a), 104.6 (Cq, Ccy2a), 103.7 (Cq, Ccy1a), 87.5 (CH, Ccy2 ), 86.0
0
(CH, Ccy2), 85.7 (CH, Ccy1), 84.2 (CH, Ccy1 ), 31.1 (CH, Ccy3),
0
21.0 (CH3, Ccy4), 20.7 (CH3, Ccy4 ), 17.8 (CH3, Ccy5), 14.5 (CH3,
C15) ppm.
(η6-p-Cymene)[(N-(2-bromo-5,11-dihydroindolo[3,2-c]quinolin-
6-ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoosmium-
(II) Chloride (6b). General procedure C: N-(2-Bromo-5,11-dihy-
droindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-ethylidene)-
azine (200 mg, 0.47 mmol), [OsCl2(p-cymene)2]2 (184 mg, 0.23
mmol), ethanol (4 mL). Yield: 231 þ 106 mg, 88% (red solid).
Elemental analysis of pure product was obtained by dissolution of
the first crop in methanol and filtration through a GF3-filter,
followed by evaporation of the solvent under reduced pressure and
drying in vacuo at 45 °C. Anal. Calcd for C32H30N5BrCl2Os (Mr
825.65): C, 46.55; H, 3.66; N, 8.48. Found: C, 46.40; H, 3.62; N,
8.41. ESI-MS (methanol), positive: m/z 790 [M - Cl]þ, 754 [M -
Cl - HCl]þ. IR (ATR, selected bands, νmax): 3615, 3232, 2965,
2748, 1625, 1585, 1454, 1402, 1332, 1222, 1155, 1023, 811, 784, 749,
695, 641, 617, 576 cm-1. 1H NMR (500 MHz, CD3OD): δ 9.43 (d,
1H, 3J = 5.5 Hz, H18), 8.45 (d, 1H, 3J = 7.9 Hz, H7), 8.36 (d, 1H,
4J = 1.9 Hz, H1), 8.26-8.19 (m, 2H, H20þH21), 7.77-7.72 (m, 1H,
H19), 7.70 (d, 1H, 3J = 8.0 Hz, H10), 7.64 (dd, 1H, 3J = 8.7 Hz,
4J = 1.9 Hz, H3), 7.53-7.47 (m, 2H, H4þH9), 7.42-7.37 (m, 1H,
H8),0 6.18 (d, 1H, 3J = 5.6 Hz, Hcy2), 5.92 (d, 1H, 3J = 5.7 Hz,
0
0
Ccy2 ), 86.0 (CH, Ccy2), 85.7 (CH, Ccy1), 84.1 (CH, Ccy1 ), 31.0
0
(CH, Ccy3), 21.0 (CH3, Ccy4), 20.7 (CH3, Ccy4 ), 17.7 (CH3, Ccy5),
14.5 (CH3, C15) ppm.
(η6-p-Cymene)[N-(2-chloro-5,11dihydroindolo[3,2-c]quinolin-6-
ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoosmium-
(II) Chloride (5b). General procedure B: N-(2-Chloro-5,11-
dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-eth-
ylidene)azine (200 mg, 0.52 mmol), [OsCl2(p-cymene)2]2 (205 mg,
0.27 mmol), ethanol (4.5 mL). Yield: 320 mg, 79% (orange-
yellow solid). Anal. Calcd for C32H30N5Cl3Os 2H2O (Mr 817.23):
3
C, 47.03; H, 4.19; N, 8.57. Found: C, 46.81; H, 4.06; N, 8.39. ESI-
MS (methanol), positive: m/z 746 [M - Cl]þ, 710 [M - Cl -
HCl]þ. IR (ATR, selected bands, νmax): 3656, 3360, 3161, 2965,
1629, 1590, 1532, 1457, 1395, 1331, 1256, 1016, 812, 783, 743, 694,
640 cm-1. 1H NMR (500 MHz, CD3OD): δ 9.43 (d, 1H, 3J = 5.6
H
H
H
H
cy20), 5.87 (d, 1H, 3J = 5.6 Hz, Hcy1), 5.34 (d, 1H, 3J = 5.7 Hz,
cy1 ), 2.86 (s, 3H, H15), 2.74-2.65 0(m, 1H, Hcy3), 2.27 (s, 3H,
cy5), 1.10 (d, 3H, 3J = 6.8 Hz, Hcy4 ), 1.06 (d, 3H, 3J = 6.9 Hz,
cy4) ppm, H5 and H11 not obsd. 13C NMR (125 MHz, CD3OD):
3
Hz, H18), 8.46 (d, 1H, J = 7.9 Hz, H7), 8.27-8.20 (m, 3H,
H1þH20þH21), 7.77-7.73 (m, 1H, H19), 7.71 (d, 1H, 3J = 8.2 Hz,
H10), 7.58 (d, 1H, 3J = 8.8 Hz, H4), 7.55-7.49 (m, 2H, H3þH9),
δ 166.9 (Cq, C14), 156.4 (Cq, C16), 155.4 (CH, C18), 147.6 (Cq, C6),
139.6 (CH, C20), 138.9 (Cq, C10a), 137.6 (Cq, C11a), 135.2(Cq, C4a),
132.1 (CH, C3), 127.5 (CH, C19), 125.9 (CH, C21), 125.0 (CH, C9),
124.4 (CH, C1), 123.5 (Cq, C6b), 121.8 (CH, C7), 121.6 (CH, C8),
7.42-7.38 (m, 1H, H8), 6.19 (d, 1H, 3J = 5.8 Hz, Hcy2), 5.94 (d,
0
1H, 3J = 5.7 Hz, Hcy2 ), 5.88 (d, 1H, 3J = 5.8 Hz, Hcy1), 5.36 (d,
0
3
1H, J = 5.7 Hz, Hcy1 ), 2.86 (s, 3H, H15), 2.75-2.66 (m, 1H,
0
cy3), 2.28 (s, 3H, Hcy5), 1.11 (d, 3H, 3J = 6.9 Hz, Hcy4 ), 1.07 (d,
118.5 (CH, C4), 115.4 (Cq, C2), 114.9 (Cq, C11b), 111.6 (CH, C10),
H
0
3H, 3J = 6.9 Hz, Hcy4) ppm, H5 and H11 not obsd. 13C NMR (125
MHz, CD3OD): δ 166.9 (Cq, C14), 156.4 (Cq, C16), 155.3 (CH,
C18), 147.7 (Cq, C6), 139.6 (CH, C20), 138.9 (Cq, C10a), 137.8 (Cq,
104.5 (Cq, C6a), 96.9 (Cq, Ccy1a), 95.8 (Cq, Ccy2a), 79.2 (CH, Ccy2 ),
0
77.8 (CH, Ccy2), 76.2 (CH, Ccy1), 74.5(CH, Ccy1 ), 31.2 (CH, Ccy3),
0
21.3 (CH3, Ccy4), 20.8 (CH3, Ccy4 ), 17.7 (CH3, Ccy5), 14.3 (CH3,
C15) ppm.
C
11a), 134.8 (Cq, C4a), 129.3 (CH, C3), 128.2 (Cq, C2), 127.5 (CH,
C19), 125.9 (CH, C21), 125.0 (CH, C9), 123.5 (Cq, C6b), 121.8 (CH,
C7), 121.6 (CH, C8), 121.3 (CH, C1), 118.3 (CH, C4), 114.4 (Cq,
(η6-p-Cymene)[N-(2-methyl-5,11-dihydroindolo[3,2-c]quinolin-
6-ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoruthenium-
(II) Chloride (7a). General procedure C: N-(2-Methyl-5,11-dihy-
droindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-ethylidene)-
azine (180 mg, 0.49 mmol), [RuCl2(p-cymene)2]2 (151 mg, 0.25
mmol), ethanol (4 mL). Yield: 173 þ 133 mg, 92% (bright orange
C
C
11b), 111.6 (CH, C10), 104.5 (Cq, C6a), 96.9 (Cq, Ccy1a), 95.8 (Cq,
0
cy2a), 79.2 (CH, Ccy2 ), 77.7 (CH, Ccy2), 76.2 (CH, Ccy1), 74.5
0
0
(CH, Ccy1 ), 31.2 (CH, Ccy3), 21.3 (CH3, Ccy4), 20.8 (CH3, Ccy4 ),
17.7 (CH3, Ccy5), 14.2 (CH3, C15) ppm.
(η6-p-Cymene)[N-(2-bromo-5,11-dihydroindolo[3,2-c]quinolin-
6-ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoruthenium-
(II) Chloride (6a). General procedure B: N-(2-Bromo-5,11-
dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-eth-
ylidene)azine (200 mg, 0.47 mmol), [RuCl2(p-cymene)2]2 (142 mg,
0.23 mmol), ethanol (4.2 mL). Yield: 234 mg, 68% (yellow solid).
solid). Anal. Calcd for C33H33N5Cl2Ru H2O(Mr 689.64): C, 57.47;
3
H, 5.12; N, 10.16. Found: C, 57.45; H, 4.89; N, 10.16. ESI-MS
(methanol), positive: m/z 636 [M - Cl]þ. IR (ATR, selected bands,
ν
max): 3655, 3336, 3155, 3064, 2964, 1638, 1586, 1528, 1460, 1427,
1
1392, 1335, 1223, 812, 780, 744, 706, 643 cm-1. H NMR (500
MHz, CD3OD): δ 10.54 (br s, 1H, H5), 9.49 (d, 1H, 3J = 5.5 Hz,
H18), 8.49 (d, 1H, 3J = 7.9 Hz, H7), 8.24-8.20 (m, 1H, H20), 8.11
(d, 1H, 3J = 7.9 Hz, H21), 8.00 (s, 1H, H1), 7.75-7.71 (m, 1H, H19),
Anal. Calcd for C32H30N5Cl2BrRu 1.5H2O (Mr 763.52): C,
3
50.34; H, 4.36; N, 9.17. Found: C, 50.16; H, 4.18; N, 9.08. ESI-
MS (methanol), positive: m/z 702 [M - Cl]þ. IR (ATR, selected
bands, νmax): 3652, 3359, 3217, 3142, 2966, 1626, 1586, 1534, 1455,
7.70 (d, 1H, J = 8.2 Hz, H10), 7.63 (d, 1H, J = 8.4 Hz, H4),
3
3
7.50-7.46 (m, 1H, H9), 7.41-7.37 (m, 2H, H3þH8), 5.87 (d, 1H,
1
1393, 1331, 1222, 1014, 812, 744, 712, 693, 642, 577 cm-1. H
3J = 6.0 Hz, Hcy20 ), 5.63 (d, 1H, 3J = 6.0 Hz, Hcy1), 5.60 (d, 1H,
0
NMR (500 MHz, CD3OD): δ 9.50 (d, 1H, 3J = 5.6 Hz, H18), 8.50
(d, 1H, 3J = 7.8 Hz, H7), 8.37 (d, 1H, 4J = 1.9 Hz, H1), 8.24 (ddd,
3J = 7.9, 7.8Hz, 4J = 1.4 Hz, H20), 8.13 (d, 1H, 3J = 7.9Hz, H21),
7.76 (ddd, 1H, 3J = 7.9, 5.6 Hz, 4J = 1.3 Hz, H19), 7.71 (d, 1H,
3J = 8.2 Hz, H10), 7.66-7.62 (m, 2H, H3þH4), 7.51 (ddd, 1H,
3J = 8.2, 7.1 Hz, 4J = 1.2 Hz, H9), 7.43-7.39 (m, 1H, H8), 5.90 (d,
1H, 3J = 6.2 Hz, Hcy2), 5.67 (d, 1H, 3J = 6.2 Hz, Hcy1), 5.65 (d,
3J = 6.0 Hz, Hcy2 ), 5.13 (d, 1H, 3J = 06.0 Hz, Hcy1 ), 2.85-2.75 (s,
3H, H15þm, 1H, Hcy3), 2.52 (s, 3H, H2 ), 2.20 (s, 3H, Hcy5), 1.14 (d,
cy40
3H, 3J = 6.9 Hz, H ), 1.10 (d, 3H, 3J = 6.9 Hz, Hcy4) ppm, H11
not obsd. 13C NMR (125 MHz, CD3OD): δ 165.1 (Cq, C14). 155.7
(Cq, C16), 155.4 (CH, C18), 147.8 (Cq, C6), 139.4 (CH, C20),
139.2 (Cq, C11a), 138.8 (Cq, C10a), 134.4 (Cq, C4a), 133.1 (Cq, C2),
130.7 (CH, C3), 126.3 (CH, C19), 125.5 (CH, C21), 124.6 (CH, C9),
123.7 (Cq, C6b), 121.8 (CH, C7), 121.5 (CH, C1), 121.3 (CH, C8),
0
0
1H, 3J = 6.1 Hz, Hcy2 ), 5.22 (d, 1H, 3J = 6.1 Hz, Hcy1 ),

Article
Organometallics, Vol. 30, No. 2, 2011 279
116.8 (CH, C4), 113.1 (Cq, C11b), 111.5 (CH, C10), 104.3 (Cq, Ccy2a),
(η6-p-Cymene)[(N-(2-nitro-5,11-dihydroindolo[3,2-c]quinolin-6-
ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoosmium-
(II) Chloride (8b). General procedure C: N-(2-Nitro-5,11-dihy-
droindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-ethylidene)-
azine (152 mg, 0.38 mmol), [OsCl2(p-cymene)2]2 (152 mg, 0.19
mmol), ethanol (3.8 mL). Yield: 234 mg, 77% (brown solid).
Elemental analysis of pure product was obtained by dissolution
of the first crop in methanol (60 mL) and filtration through a GF3-
filter, followed by evaporation of the solvent under reduced
pressure and drying in vacuo at 47 °C. Anal. Calcd for C32H30-
0
104.2 (Cq, C6a), 103.8 (Cq, Ccy1a), 87.6 (CH, Ccy2 ), 86.0 (CH,
0
C
cy2), 85.5 (CH, Ccy1), 84.0 (CH, Ccy1 ), 31.0 (CH, Ccy3), 21.0 (CH3,
0
0
Ccy4), 20.7 (CH3, Ccy4 ), 19.8 (CH3, C2 ), 17.8 (CH3, Ccy5), 14.5
(CH3, C15) ppm.
(η6-p-Cymene)[(N-(2-methyl-5,11-dihydroindolo[3,2-c]quinolin-
6-ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoosmium-
(II) Chloride (7b). General procedure C: N-(2-Methyl-5,11-
dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-eth-
ylidene)azine (180 mg, 0.49 mmol), [OsCl2(p-cymene)2]2 (195 mg,
0.25 mmol), ethanol (4 mL). Yield: 244 þ 82 mg, 87% (red
solid). Elemental analysis of pure product was obtained by
dissolution of the first crop in methanol and filtration through a
GF3-filter, followed by evaporation of the solvent under
reduced pressure and drying in vacuo at 47 °C. Anal. Calcd
N6O2Cl2Os H2O (Mr 809.77): C, 47.46; H, 3.98; N, 10.38. Found:
3
C, 47.41; H, 3.81; N, 10.14. ESI-MS (methanol), positive: m/z 757
[M - Cl]þ, 721 [M - Cl - HCl]þ. IR (ATR, selected bands, νmax):
3337, 3038, 2964, 1627, 1600, 1521, 1459, 1404, 1331, 1282, 1220,
1156, 1140, 1018, 827, 772, 742, 700 cm-1. 1H NMR (500 MHz,
CD3OD): δ 9.46 (d, 1H, 3J = 5.6 Hz, H18), 9.17 (d, 1H, 4J = 2.5
Hz, H1), 8.47 (d, 1H, 3J=7.9Hz,H7), 8.38(dd,1H, 3J=9.1Hz, 4J
= 2.5 Hz, H3), 8.30-8.23 (m, 2H, H20þH21), 7.80-7.76 (m, 1H,
H19), 7.74 (d, 1H, 3J = 8.3 Hz, H10), 7.71 (d, 1H, 3J = 9.1 Hz, H4),
7.56-7.52 (m, 1H, H9), 7.45-7.41 (m, 1H, 0H8), 6.23 (d, 1H, 3J =
5.8 Hz, Hcy2), 6.01 (d, 1H, 3J = 5.7 Hz, Hcy2 ), 5.96 (d, 1H, 3J = 5.8
for C33H33N5Cl2Os 0.75H2O (Mr 774.30): C, 51.19; H, 4.49; N,
3
9.04. Found: C, 51.23; H, 4.51; N, 8.93. ESI-MS (methanol),
positive: m/z 726 [M - Cl]þ, 690 [M - Cl - HCl]þ. IR (ATR,
selected bands, νmax): 3656, 3336, 3173, 3059, 2965, 2869, 1636,
1586, 1460, 1396, 1334, 1222, 1147, 1123, 1023, 812, 784, 744,
700, 639 cm-1. 1H NMR (500 MHz, CD3OD): δ 10.20 (br s, 1H,
H5), 9.42 (d, 1H, 3J = 5.6 Hz, H18), 8.45 (d, 1H, 3J = 7.8 Hz,
H7), 8.24-8.19 (m, 2H, H20þH21), 7.99 (br s, 1H, H1), 7.75-
7.71 (m, 1H, H19), 7.69 (d, 1H, 3J = 8.1 Hz, H10), 7.52-7.46 (m,
2H, H4þ H9), 7.41-7.35 (m, 2H, H3þH80), 6.15 (d, 1H, 3J = 5.8
Hz, Hcy2), 5.89 (d, 1H, 3J = 5.8 Hz, Hcy2 ), 5.85 (d, 1H, 3J = 5.8
0
3
Hz, Hcy1), 5.47 (d, 1H, J = 5.7 Hz, Hcy1 ), 2.87 (s, 3H, H15),
2.78-2.69 (m, 1H, Hcy3), 2.30 (s, 3H, Hcy5), 1.13 (d, 3H, 3J = 7.0
0
Hz, Hcy4 ), 1.09 (d, 3H, 3J = 7.0 Hz, Hcy4) ppm, H5 and H11 not
obsd. 13C NMR (125 MHz, CD3OD): δ 167.9 (Cq, C14). 156.2 (Cq,
C16), 155.4 (CH, C18), 147.3 (Cq, C6), 142.9 (Cq, C2), 140.2 (Cq,
C4a), 139.7 (CH, C20), 139.0 (Cq, C10a), 137.8 (Cq, C11a), 127.8 (CH,
C19), 126.3 (CH, C21), 125.4 (CH, C9), 123.9 (CH, C3), 123.4 (Cq,
C6b), 121.9 (CH, C8), 121.8 (CH, C7), 118.2 (CH, C1), 113.3 (Cq,
0
3
Hz, Hcy1), 5.26 (d, 1H, J = 5.8 Hz, Hcy1 ), 2.86 (s, 3H, H15),
0
2.72-2.65 (m, 1H, Hcy3), 2.52 (s, 3H, H2 ), 2.27 (s, 3H, Hcy5),
0
1.10 (d, 3H, 3J = 7.0 Hz, Hcy4 ), 1.06 (d, 3H, 3J = 7.1 Hz, Hcy4
)
ppm, H11 not obsd. 13C NMR (125 MHz, CD3OD): δ 166.1 (Cq,
C14). 156.6 (Cq, C16), 155.3 (CH, C18), 148.0 (Cq, C6),
139.5 (CH, C20), 139.1 (Cq, C11a), 138.8 (Cq, C10a), 134.2 (Cq,
C4a), 133.1 (Cq, C2), 130.7 (CH, C3), 127.2 (CH, C19), 125.7
(CH, C21), 124.6 (CH, C9), 123.7 (Cq, C6b), 121.7 (CH, C7),
121.5 (CH, C1), 121.3 (CH, C8), 116.7 (CH, C4), 113.0
C
C
C
11b), 111.8 (CH, C10), 104.8 (Cq, C6a), 96.9 (Cq, Ccy1a), 96.2 (Cq,
0
cy2a0 ), 79.2(CH, Ccy2 ), 77.8 (CH, Ccy2), 76.4(CH, Ccy1), 74.7 (CH,
0
cy1 ), 31.3 (CH, Ccy3), 21.3 (CH3, Ccy4), 20.9 (CH3, Ccy4 ), 17.7
(CH3, Ccy5), 14.3 (CH3, C15) ppm.
Crystallographic Structure Determination. X-ray diffraction
measurements were performed on a Bruker X8 APEXII CCD
diffractometer. Single crystals were positioned at 40, 40, 40, 40,
40, and 35 mm from the detector, and 1304, 1131, 1919, 1565,
1936, and 1059 frames were measured, each for 40, 60, 20, 30, 30,
and 90 s over 1°, 1°, 1°, 1°, 1°, and 0.5° scan width for 2a, 4a, 4b,
5a, 7a, and 7b, correspondingly. The data were processed using
SAINT software.34 Crystal data, data collection parameters,
and structure refinement details are given in Table 2. The struc-
tures were solved by direct methods and refined by full-matrix
least-squares techniques. Non-H atoms for 2a, 4a, 4b, 5a, 7a,
and 7b were refined with anisotropic displacement parameters
(except those of cocrystallized disordered solvent molecules). H
atoms were inserted in calculated positions and refined with a
riding model. Refinement of the structure of 2a revealed that the
arene occupies two statistically disordered positions (rotational
disorder around the Ru-arenecentroid). The disorder was re-
solved with constrained isotropic displacement parameters and
restrained bond distances using EADP and SADI instruc-
tions of SHELX97, respectively. The site occupation factors
(sof) were refined to about 0.60:0.40. The Cl2 counterion was
also found disordered over two positions with sof 0.55:
0.45. The following software programs and computer were
used: structure solution and refinement, SHELXS-97 and
SHELXL-97;35 molecular diagrams, ORTEP-3;36 computer,
Intel CoreDuo.
(Cq, C11b), 111.4 (CH, C10), 103.9 (Cq, C6a), 97.1 (Cq, Ccy1a),
0
95.5 (Cq, Ccy2a), 79.3 (CH, Ccy2 ), 77.7 (CH, Ccy2), 75.9 (CH,
0
Ccy1), 74.3 (CH, Ccy1 ), 31.2 (0CH, Ccy3), 21.3 (CH3, Ccy4), 20.8
0
(CH3, Ccy4 ), 19.8 (CH3, C2 ), 17.7 (CH3, Ccy5), 14.2 (CH3,
C15) ppm.
(η6-p-Cymene)[(N-(2-nitro-5,11-dihydroindolo[3,2-c]quinolin-6-
ylidene)-KN0-(1-KN-pyridin-2-yl-ethylidene)]azinechloridoruthe-
nium(II) Chloride (8a). General procedure B: N-(2-Nitro-5,11-
dihydroindolo[3,2-c]quinolin-6-ylidene)-N0-(1-pyridin-2-yl-eth-
ylidene)azine (153 mg, 0.39 mmol), [RuCl2(p-cymene)2]2 (118 mg,
0.19 mmol), ethanol (3.8 mL). Yield: 207 mg, 77% (brown solid).
Anal. Calcd for C32H30N6O2Cl2Ru 0.5H2O (Mr 711.60): C,
3
54.01; H, 4.39; N, 11.81. Found: C, 53.75; H, 4.17; N, 11.61.
ESI-MS (methanol), positive: m/z 667 [M - Cl]þ. IR (ATR,
selected bands, νmax): 3330, 3036, 2964, 1627, 1594, 1520, 1459,
1402, 1331, 1282, 1221, 1156, 1091, 1019, 826, 771, 743, 695 cm-1
.
1H NMR (500 MHz, CD3OD): δ 9.53 (d, 1H, 3J = 5.7 Hz, H18),
9.17 (d, 1H, 4J = 2.3 Hz, H1), 8.51 (d, 1H, 3J = 7.8 Hz, H7), 8.38
(dd, 1H, 3J = 9.1 Hz, 4J = 2.5 Hz, H3), 8.29-8.25 (m, 1H, H20)
3
8.18 (d, 1H, 3J = 8.1 Hz, H21), 7.82 (d, 1H, J = 9.1 Hz, H4),
7.81-7.78 (m, 1H, H19), 7.74 (d, 1H, 3J = 8.2Hz, H10), 7.57-7.52
3
(m, 1H, H9) 7.46-7.42 (m, 1H, H8), 5.95 (d, 1H, J = 6.3 Hz,
0
H
H
H
H
cy2)0 , 5.74-5.70 (m, 2H, Hcy1þHcy2 ), 5.33 (d, 1H, 3J = 6.1 Hz,
cy1 ), 2.89-2.81 (m, 1H, Hcy3), 2.709 (s, 3H, H15), 2.24 (s, 3H,
cy5), 1.17 (d, 3H, 3J = 6.9 Hz, Hcy4 ), 1.13 (d, 3H, 3J = 6.9 Hz,
cy4) ppm, H5 and H11 not obsd. 13C NMR (125 MHz, CD3OD):
Cell Lines and Culture Conditions. CH1 (ovarian carcinoma,
human) cells were donated by Lloyd R. Kelland (CRC Centre
for Cancer Therapeutics, Institute of Cancer Research, Sutton,
U.K.). SW480 (colon adenocarcinoma, human) cells and A549
(non-small-cell lung cancer, human) cells were kindly provided
δ 167.9 (Cq, C14), 156.2 (Cq, C16), 155.4 (CH, C18), 147.3 (Cq, C6),
142.9 (Cq, C2), 140.2 (Cq, C4a), 139.7 (CH, C20), 139.0 (Cq, C10a),
137.8 (Cq, C11a), 127.8 (CH, C19), 126.3 (CH, C21), 125.4 (CH,
C9), 123.9 (CH, C3), 123.4 (Cq, C6b), 121.9 (CH, C8), 121.8 (CH,
C7), 118.2 (CH, C1), 113.3 (Cq, C11b), 111.8 (CH, C10), 104.8 (Cq,
0
C6a), 96.9 (Cq, Ccy1a), 96.2 (Cq, Ccy2a), 79.2 (CH, Ccy2 ), 77.8
(34) SAINT-Plus, version 7.06a, and APEX2; Bruker-Nonius AXS
Inc.: Madison, WI, 2004.
(35) Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.
(36) Johnson, G. K. Report ORNL-5138; OAK Ridge National
Laboratory: Oak Ridge, TN, 1976.
0
(CH, Ccy2), 76.4 (CH, Ccy1), 74.7 (CH, Ccy1 ), 31.3 (CH, Ccy3),
0
21.3 (CH3, Ccy4), 20.9 (CH3, Ccy4 ), 17.7 (CH3, Ccy5), 14.3 (CH3,
C15) ppm.

280 Organometallics, Vol. 30, No. 2, 2011
Table 1. Selected Bond Distances (A) and Angles (deg) for Complexes 2a, 4a, 4b, 5a, 7a, and 7b
Filak et al.
˚
2a
4a
4b
5a
7a
7b
M-Cl
2.4121(9)
2.100(3)
2.073(3)
2.188(5)a
1.390
76.73(12)
88.18(9)
82.82(9)
2.405(2)
2.111(6)
2.101(7)
2.204(16)
1.419(8)
76.9(3)
2.4085(18)
2.108(6)
2.082(5)
2.202(12)
1.425(5)
76.4(2)
2.4149(11)
2.078(4)
2.086(4)
2.201(9)
1.415(5)
76.51(14)
87.06(11)
83.20(11)
2.4137(16)
2.075(5)
2.075(5)
2.202(10)
1.409(6)
76.55(19)
87.41(15)
83.70(14)
2.421(5)
2.092(14)
2.067(14)
2.21(1)
1.43(1)
75.8(5)
M-N4
M-N5
M-Carene av
Carene-Carene av
N4-M-N5
N4-M-Cl
N5-M-Cl
88.0(2)
84.61(19)
86.10(17)
81.53(17)
85.5(4)
81.9(4)
a The mean value was calculated only for the first disordered component.
Table 2. Crystal Data and Details of Data Collection for 2a, 4a, 4b, 5a, 7a, and 7b
2a 1.7H2O
4a
4b 0.25Et2O 1.5H2O
5a EtOH
7a 0.5EtOH 0.2H2O
7b H2O
3
3
3
3
3
3
3
empirical formula C32H34.4Cl2N5O1.7Ru C31H28Cl3N5Ru
678.00
C32H33.5Cl3N5O1.75Os Ru C34H36Cl3N5ORu C34H36.4Cl2N5O0.7Ru C33H35Cl2N5OOs
812.69
C2/c
fw
space group
688.22
P21/n
738.10
P21/n
699.26
P21/n
778.76
C2/c
I4
˚
a [A]
10.4899(3)
11.8881(3)
25.1390(8)
26.5354(10)
26.5354(10)
9.0872(4)
17.2834(5)
14.0348(5)
29.4680(11)
10.7350(4)
12.0515(4)
25.1678(9)
10.6834(11)
12.0598(12)
25.482(3)
11.690(2)
21.276(4)
25.898(4)
˚
b [A]
˚
c [A]
R [deg]
β [deg]
γ [deg]
V [A ]
Z
95.195(2)
106.416(4)
94.293(2)
93.080(7)
102.712(9)
3
˚
3122.08(16)
4
6398.5(4)
8
6856.6(4)
8
3246.9(2)
4
3278.3(6)
4
6283.4(19)
8
˚
λ [A]
F
0.71073
1.464
0.71073
1.408
0.71073
1.575
0.71073
1.510
0.71073
1.417
0.71073
1.646
calcd [g cm-3
]
cryst size [mm3]
T [K]
0.25 ꢀ 0.25 ꢀ 0.15
100
0.710
0.30 ꢀ 0.05 ꢀ 0.05 0.50 ꢀ 0.25 ꢀ 0.03
0.30 ꢀ 0.15 ꢀ 0.10 0.15 ꢀ 0.15 ꢀ 0.03
0.35 ꢀ 0.20 ꢀ 0.10
100
4.264
100
100
100
100
μ [mm-1
]
0.768
0.0593
0.1646
1.034
3.988
0.0546
0.1388
1.084
0.766
0.0542
0.1581
1.092
0.675
0.0637
0.1836
1.041
a
R1
wR2
0.0504
0.1363
1.041
0.0915
0.2343
1.012
b
GOFc
P
P
P
P
P
a R1 =
and p is the total number of parameters refined.
Fo| - |Fc
/
|Fo|. b wR2 = { [w(Fo2 - Fc2)2]/ [w(Fo2)2]}1/2. c GOF = { [w(Fo2 - Fc2)2]/(n - p)}1/2, where n is the number of reflections
by Brigitte Marian (Institute of Cancer Research, Department
of Medicine I, Medical University of Vienna, Austria). All cell
culture media and reagents were purchased from Sigma-Aldrich
Austria. Cells were grown without antibiotics in 75 cm2 culture
flasks (Iwaki/Asahi Technoglass) as adherent monolayer cul-
tures in Minimal Essential Medium (MEM) supplemented with
10% heat-inactivatedfetalbovine serum, 1mMsodiumpyruvate,
and 2 mM L-glutamine. Cultures were maintained at 37 °C in a
humidified atmosphere containing 5% CO2 and 95% air.
formed by viable cells was dissolved in DMSO (150 μL/well).
Optical densities at 550 nm were measured with a microplate
reader (Tecan Spectra Classic), using a reference wavelength of
690 nm to correct for unspecific absorption. The quantity of
viable cells was expressed as percentage of untreated controls,
and 50% inhibitory concentrations (IC50) were calculated from
concentration-effect curves by interpolation. Evaluation is based
on at least three independent experiments, each comprising three
replicates per concentration level.
Cytotoxicity in Cancer Cell Lines. Cytotoxicity in the cell
lines mentioned above was determined by the colorimetric
MTT assay (MTT = 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-
tetrazolium bromide). For this purpose, cells were harvested
from culture flasks by trypsinization and seeded in aliquots of
100 μL/well into 96-well microculture plates (Iwaki/Asahi
Technoglass) in the following densities, in order to ensure
exponential growth of untreated controls throughout the ex-
periment: 1.5 ꢀ 103 (CH1), 2.5 ꢀ 103 (SW480), and 4.0 ꢀ 103
(A549) viable cells per well. Cells were allowed to settle and
resume exponential growth in drug-free MEM supplemented
with 10% heat-inactivated fetal bovine serum, 1 mM sodium
pyruvate, 4 mM L-glutamine, and 1% nonessential amino acids
(100ꢀ stock) for 24 h. DMSO stocks of the test compounds were
serially diluted in the same medium and added to the plates in
aliquots of 100 μL/well such that the maximum DMSO content
did not exceed 0.5%. After continuous exposure for 96 h,
medium was replaced by 100 μL/well RPMI 1640 medium
(supplemented with 10% heat-inactivated fetal bovine serum
and 4 mM L-glutamine) plus 20 μL/well MTT in phosphate-
buffered saline (5 mg/mL). After incubation for 4 h, medium/
MTT mixtures were removed, and the formazan product
Results and Discussion
Synthesis and Characterization of the Ligands and Com-
plexes. The modified indoloquinoline ligands L1-L7 and L8
were prepared in four and three steps, correspondingly, as
shown in Scheme 1. First, by reaction of 2-aminobenzyl-
amine with indole-2,3-diones in acetic acid the indoloquino-
lines A were prepared, which were further chlorinated with
phosphorus oxychloride to derivatives B (Scheme 1).24,25,29
In the third step species B were allowed to react with excess
hydrazine hydrate to yield indoloquinoline-hydrazines C.
Finally the ligands L1-L7 were prepared by condensation
reaction of compounds C with 2-formyl- or 2-acetylpyridine
(Experimental Section, General Procedure A). This reaction
pathway proved to be unsuited for L8, since upon reaction
with hydrazine, both the nitro group and the imidoyl chloride
were reduced. Therefore L8 was prepared by direct coupling
of 2-acetylpyridine hydrazone with the imidoyl chloride spe-
cies B. Complexation was realized following a conventional

Article
Organometallics, Vol. 30, No. 2, 2011 281
Figure 2. ORTEP view of the cation in 4b 0.25(C2H5)2O
3
3
1.5H2O with thermal ellipsoids drawn at the 50% probability
level with an intramolecular hydrogen bonding N2-H Cl2
Figure 1. ORTEP view of the cation in 4a with thermal ellip-
soids drawn at the 50% probability level with an intramolecular
3 3 3
˚
[N2-H 0.88, H Cl2 2.313, N2 Cl2 3.177 A, N2-H Cl2
hydrogen bonding N2-H Cl2 [N2-H 0.88, H Cl2 2.304,
3 3 3 3 3 3
3 3 3 3 3 3 3 3 3
167.3°].
˚
N2 Cl2 3.180 A, N2-H Cl2 174.1°].
3 3 3 3 3 3
1
The H and 13C NMR spectra of the ligands and ruthe-
nium(II)- and osmium(II)-arene complexes indicate their
C1 molecular symmetry in solution. Whereas the NMR shifts
of the indoloquinoline backbone remained almost unaf-
fected by complexation, the resonances of protons and
carbon atoms forming the five-membered chelate ring were
markedly shifted, along with the ones neighboring the bind-
ing site. The signal of C18, for example, was shifted downfield
by about 6-7 ppm (ca. 155 ppm, compared to 149 ppm in the
metal free ligand), and that of its proton H18 was shifted from
8.6 ppm in the ligand to 9.4-9.5 ppm in the complex. As
expected for protons neighboring a stereogenic metal center,
four distinct signals were observed for the aromatic protons
of the p-cymene ligands.
μ-chlorido bridge splitting reaction of the dimeric starting
materials [(η6-p-cymene)MII(μ-Cl)Cl]2, where M = Ru, Os,
with modified indoloquinolines L1-L8 in dry ethanol, afford-
ing compounds 1a,b-8a,b in 68-94% yield. With the excep-
tion of 6b, all complexes were hydrated. Thermogravimetric
analysis showed that hydrated samples lose water upon heat-
ing with a rate of 10 °C/min to 120 °C under nitrogen and take
up water again on cooling and contact with air within 1 h (see
Figure S3 for 5a).
The ESI-MS spectra of ligands L1-L8 in methanol showed
the molecular peak ions [M þ H]þ. Additional peaks were
assigned to [M þ Na]þ for L1-L3, L5, L7, and L8. For com-
plexes 1a,b-8a,b, the peak due to [M - Cl]þ (where M=
[(η6-p-cymene)MII(L)Cl]Cl) was observed. Further, osmium
complexes 1b-8b showed a small signal that was assigned
to [M - Cl - HCl]þ. The fact that the [M - Cl]þ peak was the
base peak in all spectra measured indicates the higher
stability of this family of complexes compared to the quite
recently reported metal-arene-based indoloquinolines.11
Further evidence was provided by UV-vis measurements
of 1a,b-8a,b in 1% DMSO/H2O over 24 h (see Figures S4
and S5 for details). The observed changes in the optical
spectra of the ruthenium complexes were significant, but
smaller than those of the complexes reported previously.
DMSO (1%) did not influence the spectra, as could be shown
by a comparative 24 h run of complex 1a in pure water (data
shown in Figure S4). Attempts to suppress the hydrolysis of
the Ru-Cl bond by addition of sodium chloride resulted in
slow precipitation of the complexes. No precipitation occurred
in the presence of media for the MTT assay (MEM supple-
mented with 10% heat-inactivated fetal bovine serum, 1 mM
sodium pyruvate, 4 mM L-glutamine, and 1% nonessential
amino acids (100ꢀ)). The osmium compounds remained
practically intact in solution over 24 h, as depicted in Figure S5.
The higher stability of osmium than ruthenium compounds is,
however, well documented in the literature.30,37-40
Crystal Structures. The results of the X-ray diffraction
studies of [(η6-p-cymene)Ru(L2)Cl]Cl 1.7H2O (2a 1.7H2O),
3
3
[(η6-p-cymene)Ru(L4)Cl]Cl (4a), [(η6-p-cymene)Os(L4)Cl]-
Cl 0.25Et2O 1.5H2O (4b 0.25Et2O 1.5H2O), [(η6-p-cymene)Ru-
3
3
3
3
(L5)Cl]Cl C2H5OH (5a C2H5OH), [(η6-p-cymene)Ru(L7)-
Cl]Cl 0.5C2H5OH 0.2H2O (7a 0.5C2H5OH 0.2H2O), and
3
3
3
3
3
3
[(η6-p-cymene)Os(L7)Cl]Cl H2O (7b H2O) are shown in
3
3
Figures S1, 1-4, and S2, respectively. All complexes have a
typical “three-leg piano-stool” geometry of ruthenium(II) and
osmium(II) arene complexes,41-44 with an η6 π-bound p-cymene
ring forming the seat and three other donor atoms (two nitro-
gens, N4 and N5, of indolo[3,2-c]quinoline and one chlorido
ligand) as the legs of the stool. Selected bond distances and
angles are quoted in Table 1. All complexes with the exception of
4a crystallize as racemates owing to the presence of the stereo-
genic metal center.
Upon binding to ruthenium(II) or osmium(II), the ligands
form a five-membered chelate ring, N4C13C14N5M (M=
Ru, Os). The torsion angle ΘN4-C13-C14-N5, which serves as
a measure of the distortion of the chelate ring from planarity,
is -7.6(5)°, 0.8(11)°, -6.5(10)°, -4.4(6)°, -4.0°, and -6(2)°
for 2a, 4a, 4b, 5a, 7a, and 7b, respectively.
Cytotoxicity in Cancer Cell Lines. Cytotoxicity of the
ruthenium complexes 1a-7a and analogous osmium complexes
(37) Reedijk, J. Platinum Met. Rev. 2008, 52, 2.
€
(41) El-khateeb, M.; Damer, K.; Gorls, H.; Weigand, W. J. Organo-
met. Chem. 2007, 692, 2227.
(42) Kandioller, W.; Hartinger, C. G.; Nazarov, A. A.; Kuznetsov,
M. L.; John, R. O.; Bartel, C.; Jakupec, M. A.; Arion, V. B.; Keppler,
B. K. Organometallics 2009, 28, 4249.
(38) Hanif, M.; Henke, H.; Meier, S. M.; Martic, S.; Labib, M.;
Kandioller, W.; Jakupec, M. A.; Arion, V. B.; Kraatz, H.-B.; Keppler,
B. K.; Hartinger, C. G. Inorg. Chem. 2010, 49, 7953.
(39) van Rijt, S. H.; Hebden, A. J.; Amaresekera, T.; Deeth, R. J.;
Clarkson, G. J.; Parsons, S.; McGowan, P. C.; Sadler, P. J. J. Med.
Chem. 2009, 52, 7753.
(43) Zagermann, J.; Kuchta, M. C.; Merz, K.; Metzler-Nolte, N.
(40) Hanif, M.; Nazarov, A. A.; Hartinger, C. G.; Kandioller, W.;
Jakupec, M. A.; Arion, V. B.; Dyson, P. J.; Keppler, B. K. Dalton Trans.
2009, 39, 7345.
J. Organomet. Chem. 2009, 694, 862.
(44) Albrecht, C.; Gauthier, S.; Wolf, J.; Scopelliti, R.; Severin, K.
Eur. J. Inorg. Chem. 2009, 1003.

282 Organometallics, Vol. 30, No. 2, 2011
Filak et al.
Table 3. Cytotoxicity of Ruthenium and Osmium Arene-Based
Indoloquinoline Complexes in Three Human Cancer Cell Lines
IC50 (μM)a
compound
CH1
SW480
A549
1a
1b
2a
2b
3a
3b
4a
4b
5a
5b
6a
6b
7a
7b
2.2 ( 0.6
0.19 ( 0.06
0.70 ( 0.06
0.24 ( 0.02
2.8 ( 0.9
2.1 ( 0.4
0.26 ( 0.03
1.0 ( 0.2
1.0 ( 0.2
2.3 ( 1.0
2.9 ( 0.6
0.76 ( 0.03
0.51 ( 0.04
5.0 ( 1.0
1.2 ( 0.3
1.5 ( 0.6
6.0 ( 1.5
0.83 ( 0.19
4.6 ( 0.8
1.8 ( 0.3
14 ( 3
1.2 ( 0.5
10 ( 3
0.32 ( 0.13
0.42 ( 0.05
3.8 ( 0.6
0.55 ( 0.14
1.3 ( 0.2
1.0 ( 0.4
5.1 ( 1.8
1.8 ( 0.2
9.3 ( 3.4
3.9 ( 0.5
7.2 ( 1.7
7.8 ( 2.1
2.0 ( 0.4
3.2 ( 0.4
Figure 3. ORTEP view of the cation in 5a C2H5OH with
3
thermal ellipsoids drawn at the 50% probability level with an
intramolecular hydrogen bonding N2-H Cl2 [N2-H 0.88,
2.3 ( 0.4
0.28 ( 0.02
0.57 ( 0.20
3 3 3
0.19 ( 0.02
0.19 ( 0.08
˚
H
Cl2 2.340, N2 Cl2 3.176 A, N2-H Cl2 158.8°].
3 3 3 3 3 3
3 3 3
a 50% inhibitory concentrations (means ( standard derivations), as
obtained by the MTT assay (continuous exposure for 96 h).
values >200 μM), and in the majority of cases they are
at least as cytotoxic (up to 10 times more potent in a few
cases) as [(η6-p-cymene)RuII(en)Cl](PF6) (IC50 values: 4.4,
3.5, and 7.1 μM in CH1, SW480, and A549 cells,
respectively).5
Generally, the impact of most structural modifications
on cytotoxicity is not dramatic, and structure-activity rela-
tionships are blurred by overlapping ranges of variation.
Mostly, the complexes of the formylpyridine series
tend to be at least as cytotoxic as their analogues of the
acetylpyridine series, and most osmium complexes show
cytotoxic potencies either somewhat higher than or at least
similar to those of the corresponding ruthenium complexes.
Variation of the substituent R1 in the complexes of the
acetylpyridine series yields the following pattern, which is
illustrated by the concentration-effect curves depicted in
Figure S6: The presence of a halogen atom in complexes 3a,
3b, 5a, 5b, 6a, and 6b in position 2 results in an up to 5.4-fold
lowered impact on cell viability compared to complexes 2a
and 2b, lacking a substituent in this position. In contrast, the
presence of a methyl substituent results in either comparable
cytotoxicity (osmium complex 7b) or 2- to 4-fold enhanced
cytotoxicity (ruthenium complex 7a) compared to the corre-
sponding unsubstituted analogues and 3-15 times higher
cytotoxicity compared to the corresponding fluoro analo-
gues 3a and 3b, containing the most electronegative substi-
tuent. Even though variation of the halogen group (F, Cl, or
Br) does not yield a uniform pattern, these observations
suggest that electron-withdrawing substituents tend to be
disadvantageous for cytotoxic potency, whereas an electron-
donating methyl substituent is not.
Final Remarks. The reported results establish synthetic
access to a new family of ruthenium(II)- and osmium(II)-
arene complexes with 2-substituted indoloquinolines. The
metal-free modified indoloquinolines could not be tested for
antiproliferative activity because of their insufficient solubi-
lity in biological media. Binding to ruthenium(II)- and
osmium(II)-arene moieties resulted in complexes with
improved solubility, enabling most of them to be tested as
potential antitumor agents. The use of iminopyridines as
chelating moieties instead of ethylenediamine ones afforded
complexes that are markedly more stable in aqueous solution
containing 1% DMSO. As expected, the osmium(II)
Figure 4. ORTEP view of the cation in 7a 0.5C2H5OH
3
3
0.2H2O with thermal ellipsoids drawn at the 40% probability
level with an intramolecular hydrogen bonding N2-H Cl2
3 3 3
˚
[N2-H 0.88, H Cl2 2.363, N2 Cl2 3.207 A, N2-H Cl2
160.9°].
3 3 3 3 3 3 3 3 3
1b-7b was assessed by means of a colorimetric microculture
assay (MTT assay) in three human cancer cell lines, yielding the
IC50 values listed in Table 3. The uncomplexed indoloquinoline
derivatives L1-L8 as well as complexes 8a and 8b could not
be tested because of insufficient solubility. Hence, binding to a
ruthenium-arene or osmium-arene moiety makes this class of
potentially pharmacologically active indoloquinoline deriva-
tives applicable for biological testing in solution, whatever role
the metal may play in the mechanism of action, in particular in
interactions with biological targets.
All compounds tested are potent inhibitors of cancer cell
proliferation in vitro, with IC50 values in the submicromolar
to low micromolar range: 0.19-3.8 μM in the rather chemo-
sensitive ovarian cancer cell line CH1, 0.26-5.0 μM in the
colon carcinoma cell line SW480, and 0.83-14 μM in the
rather chemoresistant non-small-cell lung cancer cell line
A549. 1b is consistently the most active of these compounds,
with IC50 values comparable to those of three related in-
doloquinoline complexes reported previously.11 A compar-
ison with simple cymene complexes of ruthenium(II) with
coordination to one chlorido ligand and two N-donors,
such as NH3 or ethylenediamine (en), shows that the pre-
sence of an indoloquinoline ligand is mostly advantageous.
All of the ruthenium complexes 1a-7a are much more
cytotoxic than [(η6-p-cymene)RuII(NH3)2Cl](PF6) (IC50

Article
Organometallics, Vol. 30, No. 2, 2011 283
complexes were more stable than the ruthenium(II) conge-
ners and practically remained intact over 24 h according to
optical spectra measurements. All complexes show remark-
ably high antiproliferative activities in human cancer cell lines
with IC50 values in the 10-7 to 10-5 M concentration range,
depending on the cell line. Like in the case of paullones, the
electronic properties of substituents in position 2 have no dis-
tinct effect on cytotoxicity,45,46 although electron-withdrawing
substituents tend to be disadvantageous for cytotoxic activity,
whereas an electron-donating methyl group is not. The formyl-
pyridine series was at least as active as the acetylpyridine
analogues. Clear-cut structure-activity relationships were
often hindered by overlapping ranges of variation.
Acknowledgment. The authors thank Dr. P. Unfried
for measuring the TG/DTA curves and A. Dobrov for
collection of the ESI-MS data. Financial Support of the
FWF (Austrian Science Fund, project number P22339)
is kindly acknowledged. Special thanks is given to K. Schiessl
for drawing the magician in the Table of Contents Entry.
Supporting Information Available: The atom-numbering
scheme used for the NMR characterization, NMR data of
the ligands L1-L8, ORTEP views of the cations of 2a and 7b,
concentration-effect curves of substances 1a, 1b, 4a, and 4b,
and CIF files of 2a, 4a, 4b, 5a, 7a, and 7b. This material is
available free of charge via the Internet at http://pubs.acs.org.
(45) Kunick, C.; Schultz, C.; Lemcke, T.; Zaharevitz, D. W.; Gussio,
R.; Jalluri, R. K.; Sausville, E. A.; Leost, M.; Meijer, L. Bioorg. Med.
Chem. Lett. 2000, 10, 567.
(46) Xie, X.; Lemcke, T.; Gussio, R.; Zaharevitz, D. W.; Leost, M.;
Meijer, L.; Kunick, C. Eur. J. Med. Chem. 2005, 40, 655.