Photochemical reactions of a diamidocarbene: cyclopropanation of bromonaphthalene, addition to pyridine, and activation of sp3 C-H bonds.

We report unprecedented photochemistry for the diamidocarbene 1. Described within are the double cyclopropanation of 1-bromonaphthalene, the double addition to pyridine, and remarkably, the insertion into the unactivated sp3 C-H bonds of cyclohexane, tetramethylsilane, and n-pentane to give compounds 2-6, respectively. All compounds have been fully characterized, and the solid state structure of 4 was obtained using single crystal electron diffraction.

Photo-Uncaging of a Microtubule-Targeted Rigidin Analogue in Hypoxic Cancer Cells and in a Xenograft Mouse Model.

Marine alkaloid rigidins are cytotoxic compounds known to kill cancer cells at nanomolar concentrations by targeting the microtubule network. Here, a rigidin analogue containing a thioether group was "caged" by coordination of its thioether group to a photosensitive ruthenium complex. In the dark, the coordinated ruthenium fragment prevented the rigidin analogue from inhibiting tubulin polymerization and reduced its toxicity in 2D cancer cell line monolayers, 3D lung cancer tumor spheroids (A549), and a lung cancer tumor xenograft (A549) in nude mice. Photochemical activation of the prodrug upon green light irradiation led to the photosubstitution of the thioether ligand by water, thereby releasing the free rigidin analogue capable of inhibiting the polymerization of tubulin. In cancer cells, such photorelease was accompanied by a drastic reduction of cell growth, not only when the cells were grown in normoxia (21% O2) but also remarkably in hypoxic conditions (1% O2). In vivo, low toxicity was observed at a dose of 1 mg·kg-1 when the compound was injected intraperitoneally, and light activation of the compound in the tumor led to 30% tumor volume reduction, which represents the first demonstration of the safety and efficacy of ruthenium-based photoactivated chemotherapy compounds in a tumor xenograft.

Cyclic (aryl)(amido)carbenes: pushing the π-acidity of amidocarbenes through benzannulation.

Cyclic(aryl)(amido)carbenes were synthesized, and studied via a combination of experimental and computational approaches. These carbenes undergo dimerization when isolation is attempted, however, are trapped with sulfur, selenium, and [Ir(cod)Cl]. The π-acidity, measured using 77Se NMR, revealed that these are the most electrophilic singlet carbenes reported to date whereas the TEP measured demonstrated that these carbenes are poor σ donors.

Synthesis, Spectroscopic Characterization, and Redox Reactivity of a Cyclic (Alkyl) Amino Carbene-Derived Arsamethine Cyanine Dye.

In our efforts to prepare a diarsenic allotrope supported by two cyclic alkyl amino carbene (CAAC) ligands we stumbled upon the synthesis of the first carbene-supported chloroarsinidene 3, which has been fully characterized by a combination of NMR spectroscopic and XRD methods. Although further reduction of 3 was not possible, we found that addition of a second equivalent of CAAC in refluxing toluene afforded the first example of a crystallographically characterized arsamethine cyanine dye (4). The arsenic(I) dye is structurally similar to phosphorus analogues, and contains an arsenide anion with two stereochemically active lone pairs supported by two iminium ligands. The UV/Visible spectrum and redox chemistry of 4 were also explored. Upon reduction with one equivalent of KC8 , 3 is reduced to the originally targeted CAAC2 As2 allotrope 6, whereas oxidation provides access to the first example of an arsenic(II) radical dication (5).