RSS-Feed abonnieren
DOI: 10.1055/s-0034-1378838
Iridium-Stabilized π-Selenocyclohexadienyls: Synthesis, Molecular Structure, and Cytotoxicity
Publikationsverlauf
Received: 18. März 2015
Accepted after revision: 29. Mai 2015
Publikationsdatum:
15. Juni 2015 (online)
![](https://www.thieme-connect.de/media/synlett/201511/lookinside/thumbnails/st-2015-b0191-l_10-1055_s-0034-1378838-1.jpg)
Dedicated to Professor K. Peter C. Vollhardt on the occasion of his 69th birthday
Abstract
A series of iridium-stabilized selenocyclohexadienyls of general formula [Cp*Ir(η5-C6H5–nMenSe)][BF4] {Cp* = η5-C5Me5, n = 0, n = 1, and n = 3} is described, with the selenocyclohexadienyl unit being isolated for the first time by π-coordination to a Cp*Ir moiety. The solid-state structure of one of [Cp*Ir(η5-C6H2Me3Se)][BF4] was determined by single-crystal X-ray diffraction analysis. These compounds are obtained in good yields as orange-red microcrystalline solids by halogen displacement from the related π-bonded arene-chlorinated starting materials using Na2Se as the selenium source. Furthermore, these new compounds display relevant cytotoxic properties towards human ovarian cancer cells.
Key words
selenocyclohexadienyls - iridium-stabilized intermediates - π-complexes - X-ray crystal structureSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1378838.
- Supporting Information
-
References and Notes
-
1a Le Bras J, Vaissermann J, Amouri H. Organometallics 1996; 15: 5706
-
1b Le Bras J, Vaissermann J, Amouri H. Organometallics 1998; 17: 1116
- 1c Le Bras J, Vaissermann J, Amouri H. Inorg. Chem. 1998; 37: 5056
- 1d Le Bras J, Vaissermann J, Amouri H. Organometallics 1998; 17: 5850
-
1e Le Bras J, Rager MN, Besace Y, Vaisserman J, Amouri H. Organometallics 1997; 16: 1765
- 1f Le Bras J, Vaissermann J, Amouri H. J. Organomet. Chem. 1998; 567: 57
- 1g Moussa J, Guyard-Duhayon C, Herson P, Amouri H, Rager MN, Jutand A. Organometallics 2004; 23: 6231
- 1h Wallasch M, Wolmershauser G, Sitzmann H. Angew. Chem. Int. Ed. 2005; 44: 2597
- 2a Ireland BJ, McDonald R, Fogg DE. Organometallics 2013; 32: 4723
- 2b Kechaou-Perrot M, Vendier L, Bastin S, Sotiropoulos J.-M, Miqueu K, Menendez-Rodriguez L, Crochet P, Cadierno V, Igau A. Organometallics 2014; 33: 6294
- 3a Yuki M, Miyake Y, Nishibayashi Y. Organometallics 2010; 29: 4148
- 3b Komuro T, Matsuo T, Kawaguchi H, Tatsumi K. J. Am. Chem. Soc. 2003; 125: 2070
- 4a Suzuki R, Matsumoto K, Kurata H, Oda M. Chem. Commun. 2000; 1357
- 4b Hachiya M, Ito M, Matsuo T, Hashizume D, Fueno H, Tanaka K, Tamao K. Org. Lett. 2011; 13: 2666
- 5 Organoselenium Chemistry: Modern Developments in Organic Synthesis. In Topics in Current Chemistry. Vol. 208. Wirth T. Springer; Berlin: 2000
- 6a Murai T, Kato S. Top. Curr. Chem. 2000; 208: 177
- 6b Li GM, Zingaro RA, Segi M, Reibenspies J, Nakajima HT. Organometallics 1997; 16: 756
- 6c Beer L, Reed RW, Robertson CM, Oakley RT, Tham FS, Haddon RC. Org. Lett. 2008; 10: 3121
- 7a Amouri H. Synlett 2011; 1357
- 7b Amouri H, Le Bras J. Acc. Chem. Res. 2002; 35: 501
- 7c Amouri H, Vaissermann J, Besace Y, Vollhardt KP. C, Ball GE. Organometallics 1993; 12: 605
- 8a Amouri H, Besace Y, Le Bras J, Vaissermann J. J. Am. Chem. Soc. 1998; 120: 6171
- 8b Amouri H, Vaissermann J, Grotjahn DB, Rager MN. Organometallics 2000; 19: 1740
- 8c Amouri H, Rager MN, Vaissermann J, Grotjahn DB. Organometallics 2000; 19: 5143
- 8d Amouri H, Thouvenot R, Gruselle M. C. R. Chimie 2002; 5: 257
- 8e Lev DA, Grotjahn DB, Amouri H. Organometallics 2005; 24: 4232
- 9a Moussa J, Lev DA, Boubekeur K, Rager MN, Amouri H. Angew. Chem. Int. Ed. 2006; 45: 3854
- 9b Moussa J, Rager MN, Boubekeur K, Amouri H. Eur. J. Inorg. Chem. 2007; 2648
- 9c Moussa J, Amouri H. Angew. Chem. Int. Ed. 2008; 47: 1372
- 10a Amouri H, Moussa J, Renfrew AK, Dyson PJ, Rager MN, Chamoreau LM. Angew. Chem. Int. Ed. 2010; 49: 7530
- 10b Dubarle-Offner J, Clavel CM, Gontard G, Dyson PJ, Amouri H. Chem. Eur J. 2014; 20: 5795
- 11a Hartinger CG, Dyson PJ. Chem. Soc. Rev. 2009; 38: 391
- 11b Hartinger CG, Metzler-Nolte N, Dyson PJ. Organometallics 2012; 31: 5677
- 12 Typical Procedure for the Synthesis of Complexes 1–3 In a Schlenk tube kept under argon, AgOTf (387 mg, 1.51 mmol) in acetone (15 mL) was added to a solution of [Cp*Ir(μ-Cl)(Cl)]2 (300 mg, 0.38 mmol) in acetone (15 mL). The mixture becomes instantly yellow orange with the formation of a white precipitate AgCl. The solution was then filtered, and the precipitate was washed by small portion of acetone (5 mL) to give the solvated iridium complex. In a second step, the halogenated arene (0.45 mL, 3.8 mmol) was then added and after stirring 10 min, the solvent was removed under vacuum, BF3·2H2O (1 mL) was added, and the mixture was stirred at r.t. The expected π-halogenated arene complex was obtained by adding Et2O (30 mL). After removing the solvent, the solid was washed by Et2O (4 × 10 mL) and dried under vacuum to give a white microcrystalline solid.[Cp*Ir(η6-C6H5Cl)][BF4]2 (1) Yield 90%. 1H NMR (300 MHz, CD3NO2): δ = 2.45 (s, 15 H, Cp*), 7.51 (m, 3 H), 7.69 (m, 2 H). 13C NMR (100 MHz, CD3NO2): δ = 7.76 (Cp*), 97.39, 98.37, 103.10, 106.75, 114.88. Anal. Calcd for C16H20ClIrB2F8·0.5CH2Cl2: C, 30.21; H, 3.23. Found: C, 30.35; H, 3.26. [Cp*Ir(η6-C6H4CH3Cl)][BF4]2 (2) Yield 80%. 1H NMR (300 MHz, CD3CN): δ = 2.22 (s, 15 H, Cp*), 2.55 (s, 3 H), 7.24–7.34 (m, 3 H), 7.25 (d, J = 6 Hz, 1 H), 7.52 (d, J = 6 Hz, 1 H). 13C NMR (100 MHz, CD3CN): δ = 8.57 (CH3, Cp*), 16.08 (CH3), 97.29 (CH), 98.21 (CH), 98.59 (CH), 106.02 (CH), 114.97 (C, Cp*), 115.29 (C), 118.18 (C). Anal. Calcd for C17H22ClIrB2F8·CH2Cl2: C, 30.34; H, 3.40. Found: C, 30.50; H, 3.39. {Cp*Ir[η6-C6H2(CH3)3Cl]}[BF4]2 (3) Yield 78%. 1H NMR (300 MHz, CD3NO2): δ = 2.24 (s, 15 H, Cp*), 2.66 (s, 3 H), 2.69 (s, 6 H), 7.31 (s, 2 H). 13C NMR (100 MHz, CD3NO2): δ = 8.31, 17.28, 17.41, 98.70, 105.63, 114.77, 114.94. Anal. Calcd for C19H26ClIrB2F8·2CH2Cl2: C, 30.55; H, 3.66. Found: C, 30.62; H, 3.59 Typical Procedure for the Synthesis of 4–6 In a Schlenk tube kept under argon, a solution of the halogenated iridium complex (0.16 mmol) in MeCN (15 mL) was transferred to Na2Se (80 mg, 0.64 mmol) kept under argon in another Schlenk tube. After stirring 20 min, the solvent was evaporated under vacuum, then the residue was extracted by CH2Cl2 (20 mL) and filtered through Celite. The solution was evaporated to give the target compounds as orange red solids. [Cp*Ir(η5-C6H5Se)][BF4] (4) Yield 90%. 1H NMR (300 MHz, CD2Cl2): δ = 2.19 (s, 15 H, Cp*), 6.70 (t, J = 6 Hz, 2 H), 6.80 (d, J = 6 Hz, 2 H), 7.25 (t, J = 6 Hz, 1 H). 13C NMR (100 MHz, CD3NO2): δ = 8.73, 89.06, 92.37, 99.87, 100.61. Anal. Calcd for C16H20IrSeBF4·H2O: C, 32.66; H, 3.77. Found: C, 32.61; H, 3.88. ESI-HRMS: m/z = 485.0341 [M+]. [Cp*Ir(η5-C6H4CH3Se)][BF4] (5) Yield 95%. 1H NMR (300 MHz, CD2Cl2): δ = 2.08 (s, 15 H, Cp*), 2.09 (s, 3 H), 6.79 (t, J = 6 Hz, 1 H), 6.93 (d, J = 6 Hz, 1 H), 7.14 (d, J = 6 Hz, 1 H), 7.44 (t, J = 6 Hz, 1 H). 13C NMR (100 MHz, CD2Cl2): δ = 7.58, 21.32, 89.27, 91.21, 92.58, 98.81, 100.24, 111.86, 131.66. Anal. Calcd for C17H22IrSeBF4·1.5CH2Cl2: C, 31.79; H, 3.51. Found: C, 31.11; H, 3.59. {Cp*Ir[η5-C6H2(CH3)3Se]}[BF4] (6) Yield 75%. 1H NMR (300 MHz, CD2Cl2): δ = 1.90 (s, 15 H, Cp*), 2.20 (s, 6 H), 2.46 (s, 3 H), 6.69 (s, 2 H). 13C NMR (100 MHz, CD3NO2): δ = 7.48, 13.94, 15.06, 93.44, 95.56, 97.56, 98.90.
- 13 Iwaoka M, Tomoda S. J. Am. Chem. Soc. 1994; 116: 4463
- 14 Garud DR, Tanahashi N, Ninomiya M, Koketsu M. Tetrahedron 2009; 65: 4775
- 15 Fischer H, Tiriliomis A, Gerbing U, Huber B, Muller G. J. Chem. Soc., Chem. Commun. 1987; 559
- 16 Okuma K, Kojima K, Kaneko I, Tsujimoto Y, Ohta H, Yokomori Y. J. Chem. Soc., Perkin Trans. 1 1994; 2151
- 17 Cell Culture and Cell Viability Assay Human A2780 and A2780cisR ovarian carcinoma cells were obtained from the European Centre of Cell Cultures (ECACC, UK) and were routinely grown in RPMI 1640 medium supplemented with GlutaMAX (Gibco) containing heat-inactivated fetal calf serum (FCS, Sigma, USA) (10%) and antibiotics (penicillin/streptomycin, 1%) at 37 °C and CO2 (5%). Cytotoxicity was determined using the MTT assay [MTT = 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. Cells were seeded in 96-well plates as monolayers with 100 μL of cell solution per well and pre-incubated for 24 h in the cell medium. Compounds were prepared as DMSO solution that were rapidly dissolved in the culture medium and serially diluted to the appropriate concentration to give a final DMSO concentration of 0.5%. 100 μL of the drug solution was added to each well, and the plates were incubated for another 72 h. Subsequently, MTT (5 mg/mL solution) was added to the cells, and the plates were incubated for further 4 h. The culture medium was aspirated, and the purple formazan crystals formed by the mitochondrial dehydrogenase activity of vital cells were dissolved in DMSO. The optical density, directly proportional to the number of surviving cells, was quantified at 540 nm using a multiwell plate reader, and the fraction of surviving cells was calculated from the absorbance of untreated control cells. Evaluation is based on means from two independent experiments, each comprising three microcultures per concentration level.
- 18 Murray BS, Menin L, Scopelliti R, Dyson PJ. Chem. Sci. 2014; 5: 2536
- 19a Erlandsson M, Landaeta VR, Gonsalvi L, Peruzzini M, Phillips AD, Dyson PJ, Laurenczy G. Eur. J. Inorg. Chem. 2008; 620
- 19b Gras M, Therrien B, Süss-Fink G, Casini A, Edafe F, Dyson PJ. J. Organomet. Chem. 2010; 695: 1119
- 19c Wirth S, Rohborgner CJ, Cieslak M, Kazmierczak-Baranska J, Donevski S, Nawrot B, Lorenz IP. J. Biol. Inorg. Chem. 2015; 15: 429
- 19d Medici S, Peana M, Nurchi VM, Lachowicz J, Crisponi G, Zoroddu MA. Coord. Chem. Rev. 2015; 284: 329