Alcohol coupling, also known as the Guerbet reaction, is a potentially important process to increase the value of short chain alcohols. Metal oxides, metal phosphates, and supported transition ...metals, such as copper, are important components of heterogeneous catalysts for the reaction. However, the wide variety of catalyst compositions, reaction conditions, and reactor configurations used to study the reaction complicate a direct comparison of various catalysts. In this review, rates over different catalysts will be compared, the influences of the acid and base properties of the catalyst on product selectivity will be presented, and possible reaction paths to accomplish alcohol coupling will be discussed.
Isotopic transient analysis of the ethanol coupling reaction to butanol on MgO at 673K revealed that half of the surface is covered with adsorbed ethanol, identified as ethoxide by DRIFTS, whereas ...the surface coverage of reactive intermediates leading to butanol was an order of magnitude lower than that of ethoxide. The high coverage of ethoxide and hydroxide inhibited CC coupling reactions, such as aldol addition reactions, that occur readily on MgO and lead to deactivation. Display omitted
► Acetaldehyde, butanol, and ethene were produced from ethanol on MgO at 673K. ► Ethanol dissociatively adsorbed on MgO forming surface ethoxide and hydroxide species. ► The coverage of adsorbed ethanol was about 50% of surface MgO pairs. ► The coverage of coupling intermediates was an order of magnitude lower than ethanol. ► High coverage of ethoxide and hydroxide inhibited coupling reactions.
Isotopic transient analysis of ethanol coupling to butanol over MgO in a fixed-bed reactor at 673K revealed a surface coverage of adsorbed ethanol equivalent to about 50% of the exposed MgO atomic pairs. DRIFTS of ethanol reaction at 673K confirmed that the surface was populated primarily with adsorbed ethoxide and hydroxide, presumably from the dissociative adsorption of ethanol. The coverage of reactive intermediates leading to butanol was an order of magnitude lower than that of adsorbed ethanol, and about half the surface base sites counted by adsorption of CO2. The intrinsic turnover frequency for the coupling reaction at 673K determined by isotopic transient analysis was 0.04s−1, which is independent of any assumptions about the nature of the active sites. Although the ethanol coupling reaction appears to involve aldol condensation of an aldehyde intermediate, the high coverage of ethanol under steady-state conditions apparently inhibits unproductive CC coupling reactions that deactivate the catalyst at high temperature.
The purpose of this study was to explore how kindergarten students (aged 5-6 years) engaged with mathematics as they learned programming with robot coding toys. We video-recorded 16 teaching sessions ...of kindergarten students' (N = 36) mathematical and programming activities. Students worked in small groups (4-5 students) with robot coding toys on the floor in their classrooms, solving tasks that involved programming these toys to move to various locations on a grid. Drawing on a semiotic mediation perspective, we analyzed video data to identify the mathematics concepts and skills students demonstrated and the overlapping mathematics-programming knowledge exhibited by the students during these programming tasks. We found that kindergarten children used spatial, measurement, and number knowledge, and the design of the tasks, affordances of the robots, and types of programming knowledge influenced how the students engaged with mathematics. The paper concludes with a discussion about the intersections of mathematics and programming knowledge in early childhood, and how programming robot toys elicited opportunities for students to engage with mathematics in dynamic and interconnected ways, thus creating an entry point to reassert mathematics beyond the traditional school content and curriculum.
Background and Context: There is a need for early childhood assessments of computational thinking (CT). However, there is not consensus on a guiding framework, definition, or set of proxies in which ...to measure CT. We are addressing this problem by using Evidence Centered Design (ECD) to develop an assessment of kindergarten-aged children's CT.
Objective: To present a design case on the development of the assessment, specifically the algorithmic thinking (AT) tasks and to share validity evidence that emerged.
Method: We focus on the AT sub-component of CT and present the principled assessment design process using ECD.
Findings: Our operationalization of CT includes spatial reasoning as a sub-component. Pilot results showed an acceptable internal consistency reliability for the AT items and critical design decisions that contributed to validity evidence.
Implications: An important contribution of this work is the inclusion of spatial reasoning in our definition of early childhood CT.
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Bruton’s tyrosine kinase (BTK) is a Tec family kinase with a well-defined role in the B cell receptor (BCR) pathway. It has become an attractive kinase target for selective B cell ...inhibition, and for the treatment of B cell related diseases. Many BTK inhibitors have been discovered for the treatment of cancer and rheumatoid arthritis, including a series of BTK inhibitors based on 8-amino-imidazo1,5-apyrazine we recently reported. The X-ray crystal structures of BTK with inhibitors were also published, which provided great help for the SAR design. Here we report our SAR work introducing ring constraints for the 3-position piperidine amides on the BTK inhibitors based on 8-amino-imidazo1,5-apyrazine. This modification improved the potency in BTK inhibitions, as well as the PK profile and the off-target selectivity. The dose-dependent efficacy of two BTK inhibitors was observed in the rat collagen induced arthritis (CIA) model.
The selectivity of histone deacetylase inhibitors (HDACis) is greatly impacted by the zinc binding groups. In an effort to search for novel zinc binding groups, we applied a parallel medicinal ...chemistry (PMC) strategy to quickly synthesize substituted benzamide libraries. We discovered a series containing 2-substituted benzamides as the zinc binding group which afforded highly selective and potent HDAC3 inhibitors, exemplified by compound 16 with a 2-methylthiobenzamide. Compound 16 inhibited HDAC3 with an IC50 of 30 nM and with unprecedented selectivity of >300-fold over all other HDAC isoforms. Interestingly, a subtle change of the 2-methylthio to a 2-hydroxy benzamide in 20 retains HDAC3 potency but loses all selectivity over HDAC 1 and 2. This significant difference in selectivity was rationalized by X-ray crystal structures of HDACis 16 and 20 bound to HDAC2, revealing different binding modes to the catalytic zinc ion. This series of HDAC3 selective inhibitors served as tool compounds for investigating the minimal set of HDAC isoforms that must be inhibited for the HIV latency activation in a Jurkat 2C4 cell model and potentially as leads for selective HDAC3 inhibitors for other indications.
We describe the research that led to the discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a “flat” GT1 mutant profile. This NS5A ...inhibitor contains a unique tetracyclic indole core while maintaining the imidazole–proline–valine Moc motifs of our previous NS5A inhibitors. Compound 40 is currently in early clinical trials and is under evaluation as part of an all-oral DAA regimen for the treatment of chronic HCV infection.
HIV persistence in latently infected, resting CD4+ T cells is broadly considered a barrier to eradicate HIV. Activation of the provirus using latency-reversing agents (LRAs) followed by ...immune-mediated clearance to purge reservoirs has been touted as a promising therapeutic approach. Histone deacetylases (HDACs) and histone acetyltransferases (HATs) control the acetylation level of lysine residues in histones to regulate the gene transcription. Several clinical HDAC inhibitors had been examined as LRAs, which induced HIV activation in vitro and in vivo. Here we report the discovery of a series of selective and potent class I HDAC inhibitors based on aryl ketones as a zinc binding group, which reversed HIV latency using a Jurkat model of HIV latency in 2C4 cells. The SAR led to the discovery of a highly selective class I HDAC inhibitor 10 with excellent potency. HDACi 10 induces the HIV gag P24 protein in patient latent CD4+ T cells.
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