An ex vivo perfused ventilated murine lung model suggests lack of acute pulmonary toxicity of the potential novel anticancer agent (-)-englerin A.

(-)-Englerin A (EA), a potential novel anti-cancer drug, is a potent selective activator of classical transient receptor potential 4 and 5 (TRPC4, TRPC5) channels. As TRPC4 channels are expressed and functional in the lung endothelium, possible side effects such as lung edema formation may arise during its administration. Well-established in vivo rodent models for toxicological testing, however, rapidly degrade this compound to its inactive derivative, englerin B.

Ca Signaling by TRPV4 Channels in Respiratory Function and Disease.

Members of the transient receptor potential (TRP) superfamily are broadly expressed in our body and contribute to multiple cellular functions. Most interestingly, the fourth member of the vanilloid family of TRP channels (TRPV4) serves different partially antagonistic functions in the respiratory system. This review highlights the role of TRPV4 channels in lung fibroblasts, the lung endothelium, as well as the alveolar and bronchial epithelium, during physiological and pathophysiological mechanisms.

TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema.

Ischemia/reperfusion-induced edema (IRE), one of the most significant causes of mortality after lung transplantation, can be mimicked ex vivo in isolated perfused mouse lungs (IPL). Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel studied in endothelium; however, its role in the lung epithelium remains elusive. Here, we show enhanced IRE in TRPV4-deficient (TRPV4-/-) IPL compared with that of WT controls, indicating a protective role of TRPV4 in maintenance of the alveolar epithelial barrier.

Disproportionation Equilibrium of a μ-Oxodiiron(III) Complex Giving Rise to C-H Activation Reactivity: Structural Snapshot of a Unique Oxoiron(IV) Adduct.

μ-Oxodiiron(III) species are air-stable and unreactive products of autoxidation processes of monomeric heme and non-heme iron(II) complexes. Now, the organometallic [(L )Fe -(μ-O)-Fe (L )] complex 1 (L is a macrocyclic tetracarbene) is shown to be reactive in C-H activation without addition of further oxidants. Studying the oxidation of dihydroanthracene, it was found that 1 thermally disproportionates in MeCN solution into its oxoiron(IV) (2) and iron(II) components; the former is the active species in the observed oxidation processes.

Spin-State Variations of Iron(III) Complexes with Tetracarbene Macrocycles.

Starting from their six-coordinate iron(II) precursor complexes [L Fe(MeCN)] , a series of iron(III) complexes of the known macrocyclic tetracarbene ligand L and its new octamethylated derivative L , both providing four imidazol-2-yliden donors, were synthesized. Several five- and six-coordinate iron(III) complexes with different axial ligands (Cl , OTf , MeCN) were structurally characterized by X-ray diffraction and analyzed in detail with respect to their spin state variations, using a bouquet of spectroscopic methods (NMR, UV/Vis, EPR, and Fe Mößbauer). Depending on the axial ligands, either low-spin (S=1/2) or intermediate-spin (S=3/2) states were observed, whereas high-spin (S=5/2) states were inaccessible because of the extremely strong in-plane σ-donor character of the macrocyclic tetracarbene ligands.