Three osmium analogues 3a–3c of hydroxytamoxifen were prepared. The antiproliferative effects of these complexes were measured against two breast cancer cell lines (MCF-7 and MDA-MB-231) and compared with those of their homologues of ferrocene (1a–1c) and ruthenocene (2a–2c). The tamoxifen-like complexes 2c and 3c derived from osmium and ruthenium show good cytotoxicities against the two cell lines (IC₅₀ values between 2 and 3 μM), albeit lower than those of ferrocifen 1c (IC₅₀ between 0.5 and 0.8 μM). These complexes induce senescence of the cells at low concentration (0.5 μM). The mono- and diphenol complexes of osmium and ruthenium show little cytotoxicity against the two cell lines (2a, 2b, 3a, 3b; IC₅₀ ≈ 30 μM), whereas the iron analogues show high cytotoxicity (1a and 1b; IC₅₀ = 0.6–1.1 μM against MDA-MB-231). Further studies show that the cytotoxicity of the tamoxifen-like complexes of ruthenium and osmium is multifactorial and is partly due to the presence of the amino chain. Added to this is an effect of the metal center that could be due to a difference in the rate of formation, solubility, and stability of the corresponding quinone methides or to a difference in the acidity of the phenol protons. This work reveals the differences in the mechanisms of action that exist among the complexes of these three metallocenes. The uniqueness of the ferrocene complexes is underlined, but the cytotoxicity of the tamoxifen-like complexes of osmium and ruthenium is also demonstrated.

The reaction of Na[HRu₃(CO)₁₁] (2) with SbPh₂Cl in dry tetrahydrofuran (THF) afforded the cluster Ru₃(CO)₁₀(μ-H)(μ-SbPh₂) (3); in dry dichloromethane (DCM), the six-membered ring Ru₆(CO)₂₀(μ-H)₂(μ-SbPh₂)₂ (4) was obtained instead. The trimethylamine N-oxide (TMNO) activated reaction of Ru₃(CO)₁₂ (1) with distibine Sb₂Ph₄ produced Ru₃(CO)₁₀(μ-SbPh₂)₂ (6) through an Sb–Sb bond oxidative addition. Cluster 6 is fluxional through Ru–Ru bond isomerization. In contrast, its group 15 monosubstituted derivatives Ru₃(CO)₉(μ-SbPh₂)₂(L) (7, L = phosphane, arsine or stibine) or the disubstituted derivatives Ru₃(CO)₈(μ-SbPh₂)₂(L)₂ (8) did not exhibit such fluxionality. Instead, isomerization through a turnstile mechanism involving the group 15 ligand occurred. The treatment of 6 with SbPh₂Cl afforded the fused-ring clusters Ru₃(CO)₉(μ-SbPh₂)₃(Cl) (9) and Ru₃(CO)₈(μ-SbPh₂)₃(Cl)(SbPh₂CH₂Cl) (10).

A structure–activity relationship (SAR) study of the triosmium carbonyl cluster Os₃(CO)₁₀(NCCH₃)₂ was carried out with a series of clusters of the general formula Os₃(CO)_12−nL_n, cationic osmium clusters and a hemi-labile maltolato-Os cluster. The SAR results showed that good solubility in DMSO and at least one vacant site are required for cytotoxicity. In vitro evaluation of these new compounds showed that some are selectively active against estrogen receptor (ER)-independent MDA-MB-231 breast cancer cell lines relative to ER-dependent MCF-7 breast cancer cells, suggesting that the compounds have a different biological target specific to MDA-MB-231 cells. In particular, the maltolato cluster exhibits strong antiproliferative activity, with an IC₅₀ value of 3 μM after only 24 h incubation. Additionally, biochemical assays conducted with the cationic cluster show that it induces apoptosis, although a biological target has not yet been identified. Further research to establish the molecular targets of these compounds and to develop improved organometallic clusters as potential breast cancer therapeutics is underway.

Zidovudine (azidothymidine, AZT) was the first drug approved for human immunodeficiency virus (HIV) treatment. Unfortunately, AZT is known to lead to severe side effects, many of which are generally thought to result from increased reactive oxygen species (ROS) production. In this work, the pro-oxidative properties of AZT and other thymidine analogues were investigated electrochemically at microelectrodes. Macrophages pre-incubated with AZT were found to release significant amounts of reactive species, including H₂O₂, ONOO⁻, NO^. and NO₂⁻. Interestingly, the total amounts of released species were the greatest when cells were incubated with azido-containing analogues. The pro-oxidative effect of these compounds decreased significantly when the free azide terminal group was modified by reaction with a triosmium cluster. As expected, thymidine incubation did not lead to any increase in overall ROS levels. This work implicates the azido moiety in AZT-induced oxidative stress.

Single-source organometallic precursors based on a number of homometallic clusters as well as heterometallic cluster RuOs₃(CO)₁₃(µ-H)₂ have been used for the chemical vapor deposition of osmium films and osmium–ruthenium alloy films, respectively. Copyright © 2009 John Wiley & Sons, Ltd.