49 research outputs found
Characterization of Structural and Electronic Transitions During Reduction and Oxidation of Ru(acac)3 Flow Battery Electrolytes by using Xâray Absorption Spectroscopy
Metal acetylacetonates possess several very attractive electrochemical properties; however, their cyclabilities fall short of targets for use in nonaqueous redox flow batteries. This paper describes structural and compositional changes during the reduction and oxidation of ruthenium(III) acetylacetonate [Ru(acac)3], a representative acetylacetonate. Voltammetry, bulk electrolysis, and inâ
situ Xâray absorption spectroscopy (XAS) results are complemented by those from density functional theory (DFT) calculations. The reduction of Ru(acac)3 in acetonitrile is highly reversible, producing a couple at â1.1â
V versus Ag/Ag+. Inâ
situ XAS and DFT indicate the formation of [Ru(acac)3]â with RuâO bonds lengthened relative to Ru(acac)3, nearly all of the charge localized on Ru, and no ligand shedding. The oxidation of Ru(acac)3 is quasireversible, with a couple at 0.7â
V. The initial product is likely [Ru(acac)3]+; however, this species is shortâlived, converting to a product with a couple at â0.2â
V, a structure that is nearly identical to that of Ru(acac)3 within 3â
Ă
of Ru, and approximately 70â% of the charge extracted from Ru (balance from acetylacetone). This nonâinnocence likely contributes to the instability of [Ru(acac)3]+. Taken together, the results suggest that the stabilities and cyclabilities of acetylacetonates are determined by the degree of charge transfer to/from the metal.Track changes: The structural and electronic changes of Ru(acac)3 during oxidation and reduction are characterized using bulk electrolysis and inâ
situ Xâray absorption spectroscopy. Reduction is found to be reversible with minimal structural changes, and the electrons being stored entirely on the ruthenium. Oxidation results in a rapid side reaction as a result of electrons extracted from the ligand.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134821/1/celc201600360-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134821/2/celc201600360_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134821/3/celc201600360.pd
Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum
The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes
Characterization of a Thermally Induced Irreversible Conformational Transition of Amylose Tris(3,5-dimethylphenylcarbamate) Chiral Stationary Phase in Enantioseparation of Dihydropyrimidinone Acid by Quasi-Equilibrated Liquid Chromatography and Solid-State NMR
The Immunosuppressive and Toxic Effects of FK-506 Are Mechanistically Related: Pharmacology of a Novel Antagonist of FK-506 and Rapamycin
FK-506 inhibits Ca2+-dependent transcription of lymphokine genes in T cells, and thereby acts as a powerful immunosuppressant. However, its potential therapeutic applications may be seriously limited by several side effects, including nephrotoxicity and neurotoxicity. At present, it is unclear whether these immunosuppressive and toxic effects result from interference with rehted biochemical processes. FK-506 is known to interact with FK-binding protein-12 (FKBP-12), an abundant cytosolic protein with cis.trans peptidyl-prolyl isomerase activity (PPlase) activity. Because rapamycin (RAP) similarly binds to FKBP-12, although it acts in a manner different from FK-506, by inhibiting T cell responses to lymphokines, such an interaction with FKBP-12 is not sufcient to mediate immunosuppression. Recently, it was found that the complex of FKBP-12 with FK-506, but not with RAP, inhibits the phosphatase activity of calcineurin. Here, we used b685,818, the C18-hydroxy, C21-ethyl derivative of FK-506, to explore further the role of FKBP-12 in the immunosuppressive and toxic actions of FK-506. Although b685,818 bound with high afnity to FKBP-12 and inhibited its PPlase activity, it did not suppress T cell activation, and, when complexed with FKBP-12, did not affect calcineurin phosphatase activity. However, b685,818 was a potent antagonist of the immunosuppressive activity of both FK-506 and RAP. Moreover, L-685,818 did not induce any toxicity in dogs and rats or in a mouse model of acute FK-506 nephrotoxicity, but it blocked the effect of FK-506 in this model. Therefore, FK-506 toxicity involves the disruption of biochemical mechanisms related to those implicated in T cell activation. Like immunosuppression, this toxicity is not due to the inhibition of the PPlase activity of FKBP-12, but may be linked to the inhibition of the phosphatase activity of calcineurin by the drug FKBP-12 complex