Highly Active and Selective Zr/MCF Catalyst for Production of 1,3-Butadiene from Ethanol in a Dual Fixed Bed Reactor System

Copper and zirconium oxide clusters were highly dispersed on mesocellular siliceous foam (MCF), a mesoporous silica support with ultra large, interconnected nanopores. These catalysts (denoted as Cu/MCF and Zr/MCF) were separately loaded into two fixed bed reactors as catalysts for the conversion of ethanol (EtOH) to 1,3-butadiene (BD). Under optimal conditions, high BD selectivity (up to 73%) and ethanol conversion (up to 96%) were achieved at weight hourly space velocities of 1.5 and 3.7 h^–1. This translates to an unprecedented productivity of 1.4 g_BD/g_catalyst h^–1 (208 g_BD/l_catalyst h^–1). The high catalytic performance is attributed to the highly selective and active catalysts. The EtOH dehydrogenation activity of Cu/MCF could be accurately controlled in the first reactor, which delivers a fixed ratio of the acetaldehyde/EtOH mixture to Zr/MCF in the second reactor. The optimal ratio minimizes EtOH dehydration to ethylene by Zr/MCF, while maximizing the selectivity to BD. MCF was found to be superior over commercial porous silica in terms of EtOH conversion, BD selectivity, and tolerance to coking. High BD selectivity was maintained with a slight decrease in EtOH conversion over 42 h, which was readily restored upon regeneration by thermal treatment in air

Iterative in Situ Click Chemistry Assembles a Branched Capture Agent and Allosteric Inhibitor for Akt1

We describe the use of iterative in situ click chemistry to design an Akt-specific branched peptide triligand that is a drop-in replacement for monoclonal antibodies in multiple biochemical assays. Each peptide module in the branched structure makes unique contributions to affinity and/or specificity resulting in a 200 nM affinity ligand that efficiently immunoprecipitates Akt from cancer cell lysates and labels Akt in fixed cells. Our use of a small molecule to preinhibit Akt prior to screening resulted in low micromolar inhibitory potency and an allosteric mode of inhibition, which is evidenced through a series of competitive enzyme kinetic assays. To demonstrate the efficiency and selectivity of the protein-templated in situ click reaction, we developed a novel QPCR-based methodology that enabled a quantitative assessment of its yield. These results point to the potential for iterative in situ click chemistry to generate potent, synthetically accessible antibody replacements with novel inhibitory properties