Examination of Property-Reactivity Relationships of Early Transition Metal Carbides and Nitrides as Catalysts and Catalytic Supports

The search for fuel sources that provide alternatives to crude oil has been a continuing priority. The research described investigates material property-reactivity relationships that influence the catalytic performance of early transition-metal carbides and nitrides for reactions involved in the conversion of biomass to liquid transportation fuels, namely selective hydrogenation of oxygenates, water-gas shift, and Fischer-Tropsch synthesis. In particular, this work focuses on understanding the role of three main physical properties on catalyst chemistry, composition, structure, and catalytic reactivity: hydrogen adsorption sites; surface redox chemistry; and strong metal-catalytic support interactions. Experimental and computational results indicate that molybdenum nitride contains hydrogen adsorption sites both on the surface (NH) and in the subsurface layers (MoH). The relative density of surface versus subsurface hydrogen was found to have a direct effect on the hydrogenation of crotonaldehyde, with materials consisting of 95% subsurface hydrogen yielding ~93% selectivity to crotyl alcohol (C=O hydrogenation). Another study compared the synthesis, structural and compositional properties, and water gas shift activities of catalysts produced by depositing platinum onto unpassivated and passivated molybdenum carbide. Passivation (controlled surface oxidation) had a profound effect on the character of interactions between the Pt and support resulting in deleterious effects on Pt loadings, structures, and water gas shift rates. In particular, the unpassivated support adsorbed 3 times as much Pt and exhibited water-gas shift turnover frequencies nearly 4 times higher than those for the passivated support. These differences were determined to result from redox chemistry occurring between molybdenum carbide and the depositing Pt. Lastly, the presence of strong interactions, facilitated at high temperatures, between a molybdenum carbide support and deposited early transition metals was probed using Fischer-Tropsch synthesis. Ruthenium and cobalt were found to be inactive when supported on molybdenum carbide but not on silica, a typical Fischer-Tropsch support. By avoiding high temperature treatments, addition of ruthenium to molybdenum carbide resulted in turnover frequencies 18 times higher than those of bare molybdenum carbide alone and 4 times that of ruthenium on silicon dioxide. These relationships between material properties and reactivity will help inform the design and synthesis for specific applications of these catalysts.PHDChemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135765/1/wyvrattb_1.pd

Characterization of Structural and Electronic Transitions During Reduction and Oxidation of Ru(acac)3 Flow Battery Electrolytes by using X‐ray 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 in situ X‐ray 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 −1.1 V versus Ag/Ag+. In situ XAS and DFT indicate the formation of [Ru(acac)3]− with Ru−O 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 0.7 V. The initial product is likely [Ru(acac)3]+; however, this species is short‐lived, converting to a product with a couple at −0.2 V, a structure that is nearly identical to that of Ru(acac)3 within 3 Å of Ru, and approximately 70 % of the charge extracted from Ru (balance from acetylacetone). This non‐innocence 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 in situ X‐ray 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

Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4)

PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger, cyclic 3′5′ adenosine monophosphate (cAMP). PDE4 inhibitors are known to have anti-inflammatory properties, but their use in the clinic has been hampered by mechanism-associated side effects that limit maximally tolerated doses. In an attempt to initiate the development of better-tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4-inhibitory activity. With this objective, we utilised a high-throughput computational approach that identified moexipril, a well tolerated and safe angiotensin-converting enzyme (ACE) inhibitor, as a PDE4 inhibitor. Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity. Employing a FRET-based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP, EPAC1, we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels. Finally, we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the Hsp20 by cAMP dependent protein kinase A. Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window

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

Automated Optimization under Dynamic Flow Conditions

Automated optimization in flow reactors is a technology that continues to gain interest in academic and industrial research. For drug substance applications, where limited material is available for extensive studies, it is imperative that the automated optimization procedure identify ideal conditions for manufacturing in a resource sparing manner. It is equally as important that these investigations provide data-rich results so that the information can be used for process understanding. Achieving these two objectives in parallel is challenging with traditional automated optimization systems that rely on steady-state data. Dynamic flow systems, which adjust process inputs in a controlled manner to collect transient reaction results, maximize reaction information content. In this work, the gains in reaction knowledge by performing the automated optimization in a dynamic flow system are demonstrated using a nucleophilic aromatic substitution as a case study. A gradient-based search algorithm is used to optimize a multi-faceted objective function that accounts for yield, material input, and productivity. The immense dataset from the automated dynamic optimization was used to establish a reaction model to provide greater insight to the reaction kinetics and selectivity