Krag Andreasen (syriabun3)

Hydroamination of alkenes catalyzed by transition-metal complexes is an atom-economical method for the synthesis of amines, but reactions of unactivated alkenes remain inefficient. Additions of N-H bonds to such alkenes catalyzed by iridium, gold, and lanthanide catalysts are known, but they have required a large excess of the alkene. New mechanisms for such processes involving metals rarely used previously for hydroamination could enable these reactions to occur with greater efficiency. We report ruthenium-catalyzed intermolecular hydroaminations of a variety of unactivated terminal alkenes without the need for an excess of alkene and with 2-aminopyridine as an ammonia surrogate to give the Markovnikov addition product. Ruthenium complexes have rarely been used for hydroaminations and have not previously catalyzed such reactions with unactivated alkenes. Identification of the catalyst resting state, kinetic measurements, deuterium labeling studies, and DFT computations were conducted and, together, strongly suggest that this process occurs by a new mechanism for hydroamination occurring by oxidative amination in concert with reduction of the resulting imine.Diclofenac sodium (DFS), a nonsteroidal anti-inflammatory drug, is frequently used in ophthalmology, but it causes negative effects on corneas. The mechanisms underlying the toxicities to corneas remains unclear. The present study was designed to assess the cytotoxicity of DFS to human corneal epithelial (HCEP) cells in vitro and further investigate its related mechanisms. The HCEP cells were treated with DFS at different concentrations ranging from 0.003 125% to 0.1%. DFS showed a dose- and time-dependent cytotoxicity to HCEP cells including abnormal morphology and declined viability. HDAC inhibitor mechanism The 0.05% DFS-treated HCEP cells presented cell cycle arrest at S phase, reactive oxygen species (ROS) overproduction, and positive staining of phosphorylated H2AX, suggesting that DFS caused ROS-mediated DNA damage. The upregulation of p53 expression, formation of apoptotic body, phosphatidylserine externalization, and DNA ladder demonstrated that the p53-dependent apoptosis pathway was involved in the cytotoxicity of DFS. Furthermore, DFS activated caspase-8, caspase-9, and caspase-3 altered the expression levels of Bcl-2 family proteins including tBid, Bax, and Bcl-2, as well as increased poly(ADP-ribose) polymerase (PARP) cleavage. DFS also induced ΔΨm disruption, resulting in the release of cytochrome c and apoptosis-inducing factor into the cytoplasm. Additionally, the DFS-induced apoptosis was alleviated by p53 inhibitor. Taken together, DFS triggered p53-dependent apoptosis in HCEP cells via ROS-mediated crosstalk between the extrinsic and intrinsic pathways.Paddlewheel-type complexes are prominent among experimentally known binuclear cobalt complexes and incorporate substituted formamidinate, guanidinate, and carboxylate ligands in digonal, trigonal, and tetragonal arrays around the bimetallic core. Such complexes are modeled here by density functional theory using unsubstituted ligands, extending the whole set to incorporate a variety of metal oxidation states and spin multiplicities. The DFT results for ground state cobalt-cobalt bond lengths and ground state spin multiplicity of the model complexes are often quite close to the experimental results for the corresponding substituted complexes. The three series of complexes often exhibit parallel trends with regard to effects of change in the metal oxidation state and spin multiplicity. The formamidinate and guanidinate series show marked resemblances. The lowered symmetry in many model trigonal complexes implies that such deviations in the experimentally known congeners arise from the inherent electronic structure. For ground state species, the DFT results provide Co-Co bond orders (BOs) from MO occupancy considerations. Further, using a revised electron bookkeeping method, Co-Co formal bond order (fBO)