Orange-glowing iron at room temperature: Many photoactive coordination compounds contain precious metals. Replacing ruthenium with more–earth-abundant iron has been a long-sought goal, but iron compounds generally relax too rapidly after light absorption to channel the energy productively. Kjær et al. prepared an iron compound with an excited state stable enough to emit light for nanoseconds, or that could engage in bimolecular electron transfer (see the Perspective by Young and Oldacre). Targeting a ligand-to-metal rather than metal-to-ligand charge-transfer state was key to the achievement, as was the octahedral coordination environment rigidly enforced by two tridentate carbene ligands. Science , this issue p. 249 ; see also p. 225

The photofunctionality of the cobalt–hexacarbene complex [Co(III)(PhB(MeIm)₃)₂]⁺ (PhB(MeIm)₃ = tris(3-methylimidazolin-2-ylidene)(phenyl)borate) has been investigated by time-resolved optical spectroscopy. The complex displays a weak (Φ ∼ 10^–4) but remarkably long-lived (τ ∼ 1 μs) orange photoluminescence at 690 nm in solution at room temperature following excitation with wavelengths shorter than 350 nm. The strongly red-shifted emission is assigned from the spectroscopic evidence and quantum chemical calculations as a rare case of luminescence from a metal-centered state in a 3d⁶ complex. Singlet oxygen quenching supports the assignment of the emitting state as a triplet metal-centered state and underlines its capability of driving excitation energy transfer processes.

Salinomycin has found renewed interest as an agent for prevention of cancer recurrence through selectively targeting cancer stem cells. Strategies for generation of improved salinomycin analogs by individual modification of its hydroxyl groups are presented. An evaluation of the dose–response effects of the resulting library on breast cancer cell lines shows that acylation of the C20 hydroxyl can be used to improve IC₅₀ values down to one fifth that of salinomycin.

Tumors are phenotypically heterogeneous and include subpopulations of cancer cells with stemlike properties. The natural product salinomycin, a K⁺-selective ionophore, was recently found to exert selectivity against such cancer stem cells. This selective effect is thought to be due to inhibition of the Wnt signaling pathway, but the mechanistic basis remains unclear. Here, we develop a functionally competent fluorescent conjugate of salinomycin to investigate the molecular mechanism of this compound. By subcellular imaging, we demonstrate a rapid cellular uptake of the conjugate and accumulation in the endoplasmic reticulum (ER). This localization is connected to induction of Ca²⁺ release from the ER into the cytosol. Depletion of Ca²⁺ from the ER induces the unfolded protein response as shown by global mRNA analysis and Western blot analysis of proteins in the pathway. In particular, salinomycin-induced ER Ca²⁺ depletion up-regulates C/EBP homologous protein (CHOP), which inhibits Wnt signaling by down-regulating β-catenin. The increased cytosolic Ca²⁺ also activates protein kinase C, which has been shown to inhibit Wnt signaling. These results reveal that salinomycin acts in the ER membrane of breast cancer cells to cause enhanced Ca²⁺ release into the cytosol, presumably by mediating a counter-flux of K⁺ ions. The clarified mechanistic picture highlights the importance of ion fluxes in the ER as an entry to inducing phenotypic effects and should facilitate rational development of cancer treatments.

Fe(III) complexes with N-heterocyclic carbene (NHC) ligands belong to the rare examples of Earth-abundant transition metal complexes with long-lived luminescent charge-transfer excited states that enable applications as photosensitizers for charge separation reactions. We report three new hexa-NHC complexes of this class: [Fe(brphtmeimb)₂]PF₆ (brphtmeimb = [(4-bromophenyl)tris(3-methylimidazol-2-ylidene)borate]^-, [Fe(meophtmeimb)₂]PF₆ (meophtmeimb = [(4-methoxyphenyl)tris(3-methylimidazol-2-ylidene)borate]^-, and [Fe(coohphtmeimb)₂]PF₆ (coohphtmeimb = [(4-carboxyphenyl)tris(3-methylimidazol-2-ylidene)borate]^-. These were derived from the parent complex [Fe(phtmeimb)₂]PF₆ (phtmeimb = [phenyltris(3-methylimidazol-2-ylidene)borate]^- by modification with electron-withdrawing and electron-donating substituents, respectively, at the 4-phenyl position of the ligand framework. All three Fe(III) hexa-NHC complexes were characterized by NMR spectroscopy, high-resolution mass spectroscopy, elemental analysis, single crystal X-ray diffraction analysis, electrochemistry, Mößbauer spectroscopy, electronic spectroscopy, magnetic susceptibility measurements, and quantum chemical calculations. Their ligand-to-metal charge-transfer (²LMCT) excited states feature nanosecond lifetimes (1.6-1.7 ns) and sizable emission quantum yields (1.7-1.9%) through spin-allowed transition to the doublet ground state (²GS), completely in line with the parent complex [Fe(phtmeimb)₂]PF₆ (2.0 ns and 2.1%). The integrity of the favorable excited state characteristics upon substitution of the ligand framework demonstrates the robustness of the scorpionate motif that tolerates modifications in the 4-phenyl position for applications such as the attachment in molecular or hybrid assemblies.