Electrifying Hydroformylation Catalysts Exposes Voltage-Driven C-C Bond Formation.

Electrochemical reactions can access a significant range of driving forces under operationally mild conditions and are thus envisioned to play a key role in decarbonizing chemical manufacturing. However, many reactions with well-established thermochemical precedents remain difficult to achieve electrochemically. For example, hydroformylation (thermo-HFN) is an industrially important reaction that couples olefins and carbon monoxide (CO) to make aldehydes. However, the electrochemical analogue of hydroformylation (electro-HFN), which uses protons and electrons instead of hydrogen gas, represents a complex C-C bond-forming reaction that is difficult to achieve at heterogeneous electrocatalysts. In this work, we import Rh-based thermo-HFN catalysts onto electrode surfaces to unlock electro-HFN reactivity. At mild conditions of room temperature and 5 bar CO, we achieve Faradaic efficiencies of up to 15% and turnover frequencies of up to 0.7 h-1. This electro-HFN rate is an order of magnitude greater than the corresponding thermo-HFN rate at the same catalyst, temperature, and pressure. Reaction kinetics and operando X-ray absorption spectroscopy provide evidence for an electro-HFN mechanism that involves distinct elementary steps relative to thermo-HFN. This work demonstrates a step-by-step experimental strategy for electrifying a well-studied thermochemical reaction to unveil a new electrocatalyst for a complex and underexplored electrochemical reaction.

Influence of solvent structure and hydrogen bonding on catalysis at solid-liquid interfaces.

Solvent molecules interact with reactive species and alter the rates and selectivities of catalytic reactions by orders of magnitude. Specifically, solvent molecules can modify the free energies of liquid phase and surface species via solvation, participating directly as a reactant or co-catalyst, or competitively binding to active sites. These effects carry consequences for reactions relevant for the conversion of renewable or recyclable feedstocks, the development of distributed chemical manufacturing, and the utilization of renewable energy to drive chemical reactions. First, we describe the quantitative impact of these effects on steady-state catalytic turnover rates through a rate expression derived for a generic catalytic reaction (A → B), which illustrates the functional dependence of rates on each category of solvent interaction. Second, we connect these concepts to recent investigations of the effects of solvents on catalysis to show how interactions between solvent and reactant molecules at solid-liquid interfaces influence catalytic reactions. This discussion demonstrates that the design of effective liquid phase catalytic processes benefits from a clear understanding of these intermolecular interactions and their implications for rates and selectivities.

Unifying Concepts in Electro- and Thermocatalysis toward Hydrogen Peroxide Production.

We examine relationships between H2O2 and H2O formation on metal nanoparticles by the electrochemical oxygen reduction reaction (ORR) and the thermochemical direct synthesis of H2O2. The similar mechanisms of such reactions suggest that these catalysts should exhibit similar reaction rates and selectivities at equivalent electrochemical potentials (µÌ…i), determined by reactant activities, electrode potential, and temperature. We quantitatively compare the kinetic parameters for 12 nanoparticle catalysts obtained in a thermocatalytic fixed-bed reactor and a ring-disk electrode cell. Koutecky-Levich and Butler-Volmer analyses yield electrochemical rate constants and transfer coefficients, which informed mixed-potential models that treat each nanoparticle as a short-circuited electrochemical cell. These models require that the hydrogen oxidation reaction (HOR) and ORR occur at equal rates to conserve the charge on nanoparticles. These kinetic relationships predict that nanoparticle catalysts operate at potentials that depend on reactant activities (H2, O2), H2O2 selectivity, and rate constants for the HOR and ORR, as confirmed by measurements of the operating potential during the direct synthesis of H2O2. The selectivities and rates of H2O2 formation during thermocatalysis and electrocatalysis correlate across all catalysts when operating at equivalent µÌ…i values. This analysis provides quantitative relationships that guide the optimization of H2O2 formation rates and selectivities. Catalysts achieve the greatest H2O2 selectivities when they operate at high H atom coverages, low temperatures, and potentials that maximize electron transfer toward stable OOH* and H2O2* while preventing excessive occupation of O-O antibonding states that lead to H2O formation. These findings guide the design and operation of catalysts that maximize H2O2 formation, and these concepts may inform other liquid-phase chemistries.

Effect of Pd Coordination and Isolation on the Catalytic Reduction of O2 to H2O2 over PdAu Bimetallic Nanoparticles.

The direct synthesis of hydrogen peroxide (H2 + O2 → H2O2) may enable low-cost H2O2 production and reduce environmental impacts of chemical oxidations. Here, we synthesize a series of Pd1Aux nanoparticles (where 0 ≤ x ≤ 220, ∼10 nm) and show that, in pure water solvent, H2O2 selectivity increases with the Au to Pd ratio and approaches 100% for Pd1Au220. Analysis of in situ XAS and ex situ FTIR of adsorbed 12CO and 13CO show that materials with Au to Pd ratios of ∼40 and greater expose only monomeric Pd species during catalysis and that the average distance between Pd monomers increases with further dilution. Ab initio quantum chemical simulations and experimental rate measurements indicate that both H2O2 and H2O form by reduction of a common OOH* intermediate by proton-electron transfer steps mediated by water molecules over Pd and Pd1Aux nanoparticles. Measured apparent activation enthalpies and calculated activation barriers for H2O2 and H2O formation both increase as Pd is diluted by Au, even beyond the complete loss of Pd-Pd coordination. These effects impact H2O formation more significantly, indicating preferential destabilization of transition states that cleave O-O bonds reflected by increasing H2O2 selectivities (19% on Pd; 95% on PdAu220) but with only a 3-fold reduction in H2O2 formation rates. The data imply that the transition states for H2O2 and H2O formation pathways differ in their coordination to the metal surface, and such differences in site requirements require that we consider second coordination shells during the design of bimetallic catalysts.

Pax3 isoforms in sensory neurogenesis: expression and function in the ophthalmic trigeminal placode.

BACKGROUND: In the trigeminal placode, Pax3 is classified as necessary but not sufficient for sensory neuron differentiation. One hypothesis is that different Pax3 isoforms regulate cellular differentiation uniquely. Pax3 is known to sometimes activate and sometimes repress gene transcription, and its activity can be dependent on the isoforms present. Pax3 isoforms had not previously been characterized in chick sensory neurogenesis. RESULTS: Reverse transcriptase-polymerase chain reaction (PCR) analysis revealed three well-expressed Pax3 splice variants: full-length (flPax3), Pax3V1, and Pax3V2. Each was characterized for its effect on neurogenesis by misexpression in placodal ectoderm. The differences observed were more apparent under conditions of enhanced neurogenesis (by means of Notch inhibition), where flPax3 and Pax3V1 caused failed differentiation, while Pax3V2 misexpression resembled the neuronal differentiation seen in controls. Quantitative PCR analysis revealed a progressive increase in Pax3 expression, but no significant change in relative isoform expression. Of interest, Notch inhibition led to a significant increase in Pax3 expression. CONCLUSIONS: We can conclude that: (1) flPax3 and Pax3V1 inhibit neuronal differentiation; (2) Pax3V2 is permissive for neuronal differentiation; (3) while absolute levels change over time, relative splice form expression levels are largely maintained in the trigeminal placode domain; and (4) Pax3 expression generally increases in response to Notch inhibition.

Direct propylene epoxidation via water activation over Pd-Pt electrocatalysts.

Direct electrochemical propylene epoxidation by means of water-oxidation intermediates presents a sustainable alternative to existing routes that involve hazardous chlorine or peroxide reagents. We report an oxidized palladium-platinum alloy catalyst (PdPtOx/C), which reaches a Faradaic efficiency of 66 ± 5% toward propylene epoxidation at 50 milliamperes per square centimeter at ambient temperature and pressure. Embedding platinum into the palladium oxide crystal structure stabilized oxidized platinum species, resulting in improved catalyst performance. The reaction kinetics suggest that epoxidation on PdPtOx/C proceeds through electrophilic attack by metal-bound peroxo intermediates. This work demonstrates an effective strategy for selective electrochemical oxygen-atom transfer from water, without mediators, for diverse oxygenation reactions.

Distinct Site Motifs Activate O2 and H2 on Supported Au Nanoparticles in Liquid Water.

Au nanoparticles catalyze the activation and conversion of small molecules with rates and kinetic barriers that depend on the dimensions of the nanoparticle, composition of the support, and presence of catalytically culpable water molecules that solvate these interfaces. Here, molecular interpretations of steady-state rate measurements, kinetic isotope effects, and structural characterizations reveal how the interface of Au nanoparticles, liquid water, and metal oxide supports mediate the kinetically relevant activation of H2 and sequential reduction of O2-derived intermediates during the formation of H2O2 and H2O. Rates of H2 consumption are 10-100 fold greater on Au nanoparticles supported on metal oxides (e.g., titania) compared to more inert and hydrophobic materials (carbon, boron nitride). Similarly, Au nanoparticles on reducible and Lewis acidic supports (e.g., lanthana) bind dioxygen intermediates more strongly and present lower barriers (<22 kJ mol-1) for O-O bond dissociation than inert interfaces formed with silica (>70 kJ mol-1). Selectivities for H2O2 formation increase significantly as the diameters of the Au nanoparticles increase because differences in nanoparticle size change the relative fractions of exposed sites that exist at Au-support interfaces. In contrast, site-normalized rates and barriers for H2 activation depend weakly on the size of Au nanoparticles and the associated differences in active site motifs. These findings suggest that H2O aids the activation of H2 at sites present across all surface Au atoms when nanoparticles are solvated by water. However, molecular O2 preferentially binds and dissociates at Au-support interfaces, leading to greater structure sensitivity for barriers of O-O dissociation across different support identities and sizes of Au nanoparticles. These insights differ from prior knowledge from studies of gas-phase reactions of H2 and O2 upon Au nanoparticle catalysts within dilute vapor pressures of water (10-4 to 0.1 kPa H2O), in which catalysis occurs at the perimeter of the Au-support interface. In contrast, contacting Au catalysts with liquid water (55.5 M H2O) expands catalysis to all surface Au atoms and enables appreciable H2O2 formation.

Sensory neuron differentiation is regulated by notch signaling in the trigeminal placode.

Trigeminal sensory neurons develop from the neural crest and neurogenic placodes, and have been studied as a principal model of sensory neuron formation. While the Notch pathway has been extensively characterized in central nervous system development and other developmental processes, it has not been well characterized in sensory neurogenesis. Here we studied the functional role of Notch signaling in the trigeminal ophthalmic (opV) placode, a prime model of sensory neurogenesis. To establish a good spatiotemporal description of Notch pathway genes in the chick trigeminal placode, a stage-specific expression analysis was conducted, showing that expression of most Notch pathway genes and effectors are expressed in the placode, with expression primarily being confined to ectodermal cells. Expression was highest at stages of peak neuronal differentiation. To test the function of Notch signaling in opV placode cell differentiation, Notch receptor cleavage was blocked using the gamma-secretase inhibitor, DAPT, or signaling was activated by misexpression of the Notch intracellular domain (NICD). Notch activation resulted in a significant reduction in sensory neurogenesis. Cells remained in the ectoderm and did not differentiate. Expression of the opV specification marker Pax3 was also lost in targeted cells. DAPT exposure resulted in a dramatic increase in neurogenesis without increasing proliferation, where many differentiated cells were found in the mesenchyme and, surprisingly, within the ectoderm. This is the first result clearly showing prolific neuronal differentiation in the ectoderm of the trigeminal placodes after experimental manipulation of a molecular signaling pathway, thus identifying Notch signaling as a primary regulator of the sensory neuron fate in the opV placode.

Solvent molecules form surface redox mediators in situ and cocatalyze O2 reduction on Pd.

Solvent molecules influence the reactions of molecular hydrogen and oxygen on palladium nanoparticles. Organic solvents activate to form reactive surface intermediates that mediate oxygen reduction through pathways distinct from reactions in pure water. Kinetic measurements and ab initio quantum chemical calculations indicate that methanol and water cocatalyze oxygen reduction by facilitating proton-electron transfer reactions. Methanol generates hydroxymethyl intermediates on palladium surfaces that efficiently transfer protons and electrons to oxygen to form hydrogen peroxide and formaldehyde. Formaldehyde subsequently oxidizes hydrogen to regenerate hydroxymethyl. Water, on the other hand, heterolytically oxidizes hydrogen to produce hydronium ions and electrons that reduce oxygen. These findings suggest that reactions of solvent molecules at solid-liquid interfaces can generate redox mediators in situ and provide opportunities to substantially increase rates and selectivities for catalytic reactions.

Col11a1a Expression Is Required for Zebrafish Development.

The autosomal dominant chondrodystrophies, the Stickler type 2 and Marshall syndromes, are characterized by facial abnormalities, vision deficits, hearing loss, and articular joint issues resulting from mutations in COL11A1. Zebrafish carry two copies of the Col11a1 gene, designated Col11a1a and Col11a1b. Col11a1a is located on zebrafish chromosome 24 and Col11a1b is located on zebrafish chromosome 2. Expression patterns are distinct for Col11a1a and Col11a1b and Col11a1a is most similar to COL11A1 that is responsible for human autosomal chondrodystrophies and the gene responsible for changes in the chondrodystrophic mouse model cho/cho. We investigated the function of Col11a1a in craniofacial and axial skeletal development in zebrafish using a knockdown approach. Knockdown revealed abnormalities in Meckel's cartilage, the otoliths, and overall body length. Similar phenotypes were observed using a CRISPR/Cas9 gene-editing approach, although the CRISPR/Cas9 effect was more severe compared to the transient effect of the antisense morpholino oligonucleotide treatment. The results of this study provide evidence that the zebrafish gene for Col11a1a is required for normal development and has similar functions to the mammalian COL11A1 gene. Due to its transparency, external fertilization, the Col11a1a knockdown, and knockout zebrafish model systems can, therefore, contribute to filling the gap in knowledge about early events during vertebrate skeletal development that are not as tenable in mammalian model systems and help us understand Col11a1-related early developmental events.

FGF and Notch signaling in sensory neuron formation: a multifactorial approach to understanding signaling pathway hierarchy.

The ophthalmic trigeminal (opV) placode exclusively gives rise to sensory neurons, making it a good model to study the molecular regulation of sensory neurogenesis. A number of signaling pathways including Wnt, PDGF, FGF, and Notch have been shown to be involved in the process of opV placode cell development. However, the regulatory relationships between these signaling pathways in placode cells are still unknown and have been difficult to study experimentally. Using a novel multifactorial approach in chick embryos that allows for inhibition of FGF throughout the tissue or in individual cells, with simultaneous inactivation of Notch signaling, we investigated the potential interaction between the FGF and Notch signaling pathways in trigeminal sensory neurogenesis. This study builds on prior research describing the individual role of FGF signaling or Notch signaling in opV placode development, where blocking FGF signaling resulted in neurogenesis failure, while blocking Notch signaling resulted in enhanced neurogenesis. Reported here, blocking both pathways simultaneously resulted in a reduction in the number of cells delaminating from the opV placode and undergoing sensory neuron differentiation. Further, Notch inhibition alone did not lead to an increase in the number of cells expressing FGFR4 or in the FGFR4 expression domain, but did result in a highly fragmented basal lamina, which was reversed when blocking FGF signaling. Cumulatively, the results presented here do not support a model of Notch/FGF interdependence, rather that FGF and Notch act in parallel to promote sensory neurogenesis.

The expression patterns of minor fibrillar collagens during development in zebrafish.

Minor fibrillar collagens are recognized as the organizers and nucleators during collagen fibrillogenesis but likely serve additional functions. The minor fibrillar collagens include collagens type V and XI. Mutations of collagens type V and XI can cause Ehlers-Danlos, Stickler's, and Marshall's syndromes in human. We have characterized the spatiotemporal expression patterns of Col11a1, Col11a2, Col5a1 as well as Col5a3 in zebrafish embryos by in situ hybridization. Col5a1 is expressed in developing somites, neural crest, the head mesenchyme, developing cranial cartilage, pharyngeal arches and vertebrae. Col5a3 is detected in the notochord, mesenchyme cells in the eyes and lens. Both Col11a1 and Col11a2 have similar expression patterns, including notochord, otic vesicle, and developing cranial cartilages. Zebrafish may therefore serve as a valuable vertebrate model system for the study of diseases associated with collagens type V and XI mutations.