Iridium-Stabilized π-Selenocyclohexadienyls: Synthesis, Molecular Structure, and Cytotoxicity

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-C₆H_5–nMe_nSe)][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 structure

• References and Notes

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• 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.
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