Metabolic activation of CaMKII by coenzyme A

Active metabolism regulates oocyte cell death via calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated phosphorylation of caspase-2, but the link between metabolic activity and CaMKII is poorly understood. Here we identify coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte apoptosis by directly activating CaMKII. We found that CoA directly binds to the CaMKII regulatory domain in the absence of Ca(2+) to activate CaMKII in a calmodulin-dependent manner. Furthermore, we show that CoA inhibits apoptosis not only in X. laevis oocytes but also in Murine oocytes. These findings uncover a direct mechanism of CaMKII regulation by metabolism and further highlight the importance of metabolism in preserving oocyte viability

Synthesis of a Tris(phosphaalkene)phosphine Ligand and Fundamental Organometallic Reactions on Its Sterically Shielded Metal Complexes

A new tris­(phosphaalkene)­phosphine ligand (<b>1</b>) was synthesized via phospha-Wittig methodology. Metalation of <b>1</b> with [RhCl­(C₂H₄)₂]₂ and [IrCl­(COE)₂]₂ (COE = cyclooctene) produced trigonal bipyramidal metal chlorides <b>2a</b> (M = Rh) and <b>2b</b> (M = Ir) in which the ligand coordinates in a tetradentate fashion. X-ray crystallographic studies on <b>1</b>·1.5THF, <b>2a</b>·5CHCl₃, and <b>2b</b>·2.5CHCl₃ combined with DFT calculations revealed a pronounced change in hybridization of the phosphaalkene phosphorus atoms upon coordination to the Rh/Ir centers, resulting in highly sterically congested metal complexes. Nucleophilic substitution on <b>2a</b> with NaN₃ afforded Rh–N₃ complex <b>3</b>; computational analysis, IR spectroscopy, and ¹⁵N­{¹H} NMR spectroscopy on isotopologue ^<b>15</b><b>N-3</b> provided additional structural insights. Halide abstraction of the chloride in <b>2b</b> with AgOTf in the presence of acetonitrile afforded cationic Ir–NCMe complex <b>4</b>. Evidence of the bound acetonitrile unit was obtained by 2D NMR spectroscopy and deuterium labeling studies