Primary Catalyst Research Articles

Promoting Oxidative Stress in Cancer Starvation Therapy by Site-Specific Startup of Hyaluronic Acid-Enveloped Dual-Catalytic Nanoreactors.

Cutting off the glucose supply by glucose oxidase (GOx) has been regarded as an emerging strategy in cancer starvation therapy. However, the standalone GOx delivery suffered suboptimal potency for tumor elimination and potential risks of damaging vasculatures and normal organs during transportation. To enhance therapeutic efficacy and tumor specificity, a site-specific activated dual-catalytic nanoreactor was herein constructed by embedding GOx and ferrocene in hyaluronic acid (HA)-enveloped dendritic mesoporous silica nanoparticles to promote intratumoral oxidative stress in cancer starvation. In this nanoreactor, the encapsulated GOx served as the primary catalyst that accelerated oxidation of glucose and generation of H2O2, while the covalently linked ferrocene worked as the secondary catalyst for converting the upstream H2O2 to more toxic hydroxyl radicals (•OH) via a classic Fenton reaction. The outmost HA shell not only offered a shielding layer for preventing blood glucose from oxidation during nanoreactor transportation, thus minimizing the probable oxidative damage to normal tissues, but also imparted the nanoreactor with targeting ability for facilitating its internalization into CD44-overexpressing tumor cells. After the nanoreactor was endocytosed by target cells, the HA shell underwent hyaluronidase-triggered degradation in lysosomes and switched on the cascade catalytic reaction mediated by GOx and ferrocene. The resulting glucose exhaustion and •OH accumulation would effectively kill cancer cells and suppress tumor growth via combination of starvation and oxidative stress enhancement. Both in vitro and in vivo results indicated the significantly amplified therapeutic effects of this synergistic therapeutic strategy based on the dual-catalytic nanoreactor. Our study provides a new avenue for engineering therapeutic nanoreactors that take effect in a tumor-specific and orchestrated fashion for cancer starvation therapy.

(Invited) Fundamental Studies of PEM Fuel Cell Catalyst Layer Architectures

Although fuel cells are being deployed in cars in limited commercialization, they still fall short of the DOE targets for this technology, which are required for widespread consumer acceptance. The FC-PAD (Fuel Cell Performance and Durability) consortium was formed to advance the performance and durability of polymer electrolyte membrane fuel cells (PEMFCs) at a pre-competitive level to further enable their commercialization. The primary component that FC-PAD works to understand and improve is the catalyst layer. The primary catalyst layer architecture in use is a porous dispersed Pt-supported carbon catalyst with recast solid ionomer component forming a continuous (percolating) network through the electrode for proton transport; the carbon facilitating the electrical conduction; the active electrochemical reactions conducted on the metallic Pt sites. These thin-layer-electrode films were pioneered at Los Alamos National Labs in the late 1980’s under the direction of Dr. Shimshon Gottesfeld [1,2] As ubiquitous as the thin layer electrode structure has been used, it is still an active field of research to properly understand the structure and improve the reactant transport, water removal and catalyst utilization. The fuel cell catalyst layer is a complex structure that facilitates the electrochemical conversion of hydrogen and oxygen; it provides pathways for reactant transport, and provides both electrical and proton conducting pathways. This has been traditionally referred to as the 3-phase boundary of an electrolyte, an electrode, and a gaseous fuel. In addition to the gas-reactant transport to the active site, the product water must also be managed both in terms of product removal and optimal hydration of the membrane/ionomer providing the proton conductivity. Recent FC-PAD results have examined the structure of the electrode layer. Because performance is largely influenced by the ionomer/catalyst interface within the catalyst layers of a MEA, the “ideal” interface should contain platinum particles with 100% available proton and electrical pathways to maximize catalyst utilization. In addition, the thickness of ionomer film over the catalyst nanoparticles should be optimal to facilitate gas diffusion and water balance without sacrificing its protonic conductivity. LANL’s recent FC-PAD examinations have included using neutron reflectometry to examine the interaction of ionomer (with and without cations such as cerium present as a radical scavenger) with platinum and carbon simulating the electrode structure. Other fundamental properties of the electrode layer being examined includes, the structure and size of catalyst agglomerates, the porosity and relative hydrophobicity of electrode layer pores, and relative distribution of ionomer. A combination of AFM (atomic force microscopy) BET, MIP (mercury intrusion porosimetry), IGC (inverse gas chromatograph) have been employed to help better define these catalyst layer fundamental properties. These types of measurements suggest an inhomogeneous distribution in the electrode layer. Such an inhomogeneous distribution indicates that catalyst utilization is not fully optimized. This talk will discuss many of the factors affecting catalyst layer performance and provide strategies for catalyst layer optimization. Acknowledgments This work was funded through the DOE FC-PAD Consortium with thanks to DOE EERE FCTO, Fuel Cell Team Leader: Dimitrios Papageoropoulos and Technical Development Manager: Greg Kleen. References Wilson, M. S.; Gottesfeld, S., Thin- film catalyst layers for polymer electrolyte fuel cell electrodes, Journal of Applied Electrochemistry (1992), 22(1), 1-7. Wilson, M. S.; Gottesfeld, S, High Performance Catalyzed Membranes of Ultra‐low Pt Loadings for Polymer Electrolyte Fuel Cells, Journal of the Electrochemical Society, Electrochem. Soc. 1992,

Esophageal IgE, IgG4, and mucosal eosinophilia in individuals with dysphagia.

Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with EoE manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (IgE) is directed, if any, have not yet been characterized. Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of EoE. Specific IgE (sIgE) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal IgE response and IgG4 to food allergens, were measured. There was no difference in total IgE harvested between the 2 biopsy methods (p > 0.05) or between the EoE-positive (N = 12) and EoE-negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum IgE to any of the airborne or food proteins tested, but low levels of IgE specific to Candida and Staphylococcus enterotoxins were detected. Low levels of IgG4 specific to wheat, soy, peanut, and egg were also detected. Both MBB and STB are able to harvest measureable levels of IgE and IgG4 from the esophageal mucosa. Low levels of serum-specific IgE suggest that other inflammatory mechanisms, besides type I, IgE-mediated, allergen-specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both IgE-mediated and non-IgE-mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia.

The Role of ABS CDOs in the Financial Crisis

We examine the role of asset-backed security collateralized debt obligations (ABS CDOs) as a primary catalyst for the financial crisis. We show how ABS CDOs became the main investment vehicle for the riskiest investment-grade securities in the private-label mortgage market. We estimate a final tally of writedowns on ABS CDOs, $410 billion in total, with $325 billion assumed by AAA and “super-senior” securities, which had minimal capital, margin, or liquidity requirements. Pre-crisis regulations allowed excessive leverage at some firms investing in these securities, imperiling their solvency and placing them at the center of the financial crisis.

Expanding the Scope of Protein Synthesis Using Modified Ribosomes.

The ribosome produces all of the proteins and many of the peptides present in cells. As a macromolecular complex composed of both RNAs and proteins, it employs a constituent RNA to catalyze the formation of peptide bonds rapidly and with high fidelity. Thus, the ribosome can be argued to represent the key link between the RNA World, in which RNAs were the primary catalysts, and present biological systems in which protein catalysts predominate. In spite of the well-known phylogenetic conservation of rRNAs through evolutionary history, rRNAs can be altered readily when placed under suitable pressure, e.g. in the presence of antibiotics which bind to functionally critical regions of rRNAs. While the structures of rRNAs have been altered intentionally for decades to enable the study of their role(s) in the mechanism of peptide bond formation, it is remarkable that the purposeful alteration of rRNA structure to enable the elaboration of proteins and peptides containing noncanonical amino acids has occurred only recently. In this Perspective, we summarize the history of rRNA modifications, and demonstrate how the intentional modification of 23S rRNA in regions critical for peptide bond formation now enables the direct ribosomal incorporation of d-amino acids, β-amino acids, dipeptides and dipeptidomimetic analogues of the normal proteinogenic l-α-amino acids. While proteins containing metabolically important functional groups such as carbohydrates and phosphate groups are normally elaborated by the post-translational modification of nascent polypeptides, the use of modified ribosomes to produce such polymers directly is also discussed. Finally, we describe the elaboration of such modified proteins both in vitro and in bacterial cells, and suggest how such novel biomaterials may be exploited in future studies.

Preparation of Butadiene-Isoprene Copolymer with High Vinyl Contents by Al(OPhCH₃)(i-Bu)₂/MoO₂Cl₂∙TNPP.

In this study, a butadiene-isoprene coordination polymerization was initiated by a binary molybdenum (Mo)-based catalytic system consisting of modified MoO2Cl2 as the primary catalyst, triethyl aluminum substituted by m-cresol as the co-catalyst and tris(nonyl phenyl) phosphate (TNPP) as the ligand. The effects of the amount of catalyst and type of co-catalyst were investigated in detail. Experimental results indicated that when the butadiene-isoprene coordination polymerization was initiated by the binary Mo-based catalytic system, the monomer conversion could reach 90%. The resulting butadiene units were primarily based on 1,2-structures, and the reactivity ratios of butadiene and isoprene were 1.13 and 0.31, respectively. The reaction in the catalytic system was attributed to the non-ideal and non-constant ratio copolymerization. When the addition of isoprene monomers was relatively low, the isoprene units on the butadiene-isoprene copolymers were primarily based on the 1,2- and 3,4-structures. Moreover, the orientation of active centers to 1,2- and 3,4-structures gradually decreased with an increase in the addition of isoprene monomers, which resulted in the generation of high vinyl butadiene-isoprene copolymers.

Asymmetric 1,3‐Dipolar Cycloaddition Reactions of Enones by Primary Amine Catalysis

AbstractWe report herein a 1,3‐dipolar cycloaddition between enones and nitrones with good to excellent distereo‐ and enantioselectivities by a chiral primary amine catalyst, which furnishes an operationally simple synthetic protocol for the fused bicyclic isoxazolidine derivatives with multiple stereogenic centers.

Fundamental Implications for Location Accuracy in Ultra-Dense 5G Cellular Networks

At the threshold of 5G, much is promised based on the predicate of hyper-accurate location-aware communications. Although the unique spectral real estate associated with 5G implies the possibility of such a persistent localization scheme, we submit that precision range based localization is not a generational inevitability but rather achievable only under the correct architectural philosophy. To show this, we consider a fundamental component that limits or enables any positioning system: the underlying infrastructure geometry. The significance of this research follows from several significant results. First, cell ultra densification, although the primary catalyst of Long Term Evolution (LTE)/LTE-Advanced capacity improvement and a major disruptive technology in 5G networks, will not alone provide for more accurate user positioning. To show this, we derive a closed-form solution to the Cramér-Rao lower bound specific to 5G networks given that infrastructure is distributed via the Poisson point process (PPP). This result is used to justify a positioning services architecture that fundamentally embraces a variable number of supporting access points. In fact, we show that without this architecture, a foundational decline in positioning performance may inadvertently be realized. Finally, by numerically comparing our results with other point processes common in cellular network modeling, we present justification for the PPP as an appropriate model for analyzing positioning performance in ultra dense 5G infrastructures.

Catalytic gasification of pine-sawdust: Effect of primary and secondary catalysts

Pine sawdust steam gasification in a fixed double bed reactor and continuous flow was investigated. K2CO3 as primary catalyst and cobalt supported on γ-Al2O3 and SiO2-Al2O3 as secondary catalyst was investigated. Thermal and catalytic steam gasification was compared. The effect of the support in tar yield and the H2/CO ratio was pursued. It is noteworthy to observe that the primary catalyst increases the biomass gasification. It is also marked the total consumption of CH4 species by the primary catalyst. The catalysts (K2CO3 and K2CO3-Co/γ-Al2O3) reduced tar formation from 11% in the thermal gasification to a value of 2.0% and 0.5% respectively. This tar yield reduction could be explained due to the action of potassium actives species of the primary catalyst combined with the lower acid strength of the support; high metal dispersion of cobalt species and the higher fraction of metallic cobalt species in Co/γ-Al2O3 catalyst. The catalysts decrease the formation of CO2 from 21% in the thermal gasification to values on the order of 3%. The highest H2/CO ratio with a value of 1.6 was obtained by K2CO3-γ-Al2O3 catalytic system. The presence of cobalt supported catalysts favored hydrogen consumption reactions such as reverse water gas shift reaction.

Ruthenium complexes with N-functionalized secondary amino ligands: a new class of catalysts toward efficient hydrogenation of esters.

A series of ruthenium complexes (o-PPh2C6H4NHR)2RuCl2 (R = Me, 3; Et, 4; CH2Ph, 5) and (o-PPh2C6H4NH2)[(CH2NHR)2]RuCl2 (R = Me, 7; Et, 8; iPr, 9) modulated with mono-N-functionalized secondary amino ligands were synthesized and demonstrated as efficient catalysts in the hydrogenation of esters into alcohols. The catalytic performances of these new complexes are much better than their corresponding primary amino ligand-constituted complexes (o-PPh2C6H4NH2)2RuCl2 (2) and (o-PPh2C6H4NH2)[(CH2NH2)2]RuCl2 (6). The significant improvement is attributed to the increased electron density of the secondary amino ligand in comparison with that of the primary amino ligand.

Primary amine catalyzed diastereo- and enantioselective Michael reaction of thiazolones and α,β-unsaturated ketones.

The chiral primary amine catalyzed asymmetric Michael reaction of thiazolones and α,β-unsaturated ketones was reported. Two different optimal catalytic systems were obtained corresponding to cyclic and linear α,β-unsaturated ketones. By employing chiral primary amines as the catalysts and amino-acid derivatives as the additives, a variety of Michael adducts containing the scaffold of the thiazole ring were prepared in moderate to good yields and with excellent diastereo- and enantioselectivities (up to 95% yield, all up to >19/1 dr, up to 96% ee). The reaction was scaled up to obtain 1.73 grams of the Michael adduct with the maintenance of yield and stereoselectivity.

Oxidative cleavage of β-O-4 bonds in lignin model compounds with a single-atom Co catalyst

Single-atom catalysts are emerging as primary catalysts for many reactions due to their 100% utilization of active metal centers leading to high catalytic efficiencies.

Steric Effect of Protonated Tertiary Amine in Primary-Tertiary Diamine Catalysis: A Double-Layered Sterimol Model.

Steric shielding effects are seldom adopted in the stereocontrol with chiral primary amine catalysts. An unexpected steric shielding effect of protonated tertiary amine, a typical hydrogen-bonding moiety, was disclosed. A linear free energy relationship between structure and enantioselectivity was established in three reactions when a double-layered Sterimol model was introduced.

Dichotomy in redundant enhancers points to presence of initiators of gene regulation

BackgroundThe regulatory landscape of a gene locus often consists of several functionally redundant enhancers establishing phenotypic robustness and evolutionary stability of its regulatory program. However, it is unclear what mechanisms are employed by redundant enhancers to cooperatively orchestrate gene expression.ResultsBy comparing redundant enhancers to single enhancers (enhancers present in a single copy in a gene locus), we observed that the DNA sequence encryption differs between these two classes of enhancers, suggesting a difference in their regulatory mechanisms. Initiator enhancers, which are a subset of redundant enhancers and show similar sequence encryption to single enhancers, differ from the rest of redundant enhancers in their sequence encryption, evolutionary conservation and proximity to target genes. Genes hosting initiator enhancers in their loci feature elevated levels of expression. Initiator enhancers show a high level of 3D chromatin contacts with both transcription start sites and regular enhancers, suggesting their roles as primary activators and intermediate catalysts of gene expression, through which the regulatory signals of redundant enhancers are propagated to the target genes. In addition, GWAS and eQTLs variants are significantly enriched in initiator enhancers compared to redundant enhancers, suggesting a key functional role these sequences play in gene regulation.ConclusionsThe specific characteristics and widespread abundance of initiator enhancers advocate for a possible universal hierarchical mechanism of tissue-specific gene regulation involving multiple redundant enhancers acting through initiator enhancers.

Organocatalytic [6+4] Cycloadditions via Zwitterionic Intermediates: Chemo-, Regio-, and Stereoselectivities.

The mechanisms and origins of chemo- and stereoselectivities of the organocatalytic [6+4] cycloaddition between 2-cyclopentenone and tropone have been investigated by a combined computational and experimental study. In the presence of a cinchona alkaloid primary amine catalyst and an acid additive, 2-cyclopentenone forms a cross-dienamine intermediate that subsequently undergoes a stepwise [6+4] cycloaddition reaction via a zwitterionic intermediate. The rate-determining transition state features a strong hydrogen-bonding interaction between the tropone oxygen atom and the protonated quinuclidine directing the reaction course leading to a highly periselective [6+4] cycloaddition. The importance of the strong hydrogen-bonding interaction is also demonstrated by the influence of the concentration of the acid additive on the yields and enantioselectivities of the reaction. The corresponding [4+2] cycloaddition reaction has a much higher energy barrier. The enantioselectivity of the [6+4] cycloaddition originates from different repulsive hydrogen-hydrogen interactions that distinguish the diastereomeric transition states.

Enantioselective Oxidative Coupling of Carboxylic Acids to α-Branched Aldehydes.

A new reactivity in organocatalysis is proposed to account for the coupling of carboxylic acids to α-branched aldehydes by combining primary amine catalysis and an oxidant. The developed methodology is an enantioselective α-coupling of aromatic and aliphatic carboxylic acids to α-branched aldehydes and proceeds in high yields (up to 97%) and for most examples good enantioselectivities (up to 92% ee). On the basis of experimental and mechanistic observations, the role of the primary amine catalyst is discussed.

MgCl2‐supported Ziegler‐Natta catalysts: A DFT‐D ‘flexible‐cluster’ approach. TiCl4 and probe donor adducts

AbstractIn this paper we introduce a DFT‐D ‘flexible‐cluster’ approach to the computational modeling of MgCl2‐supported Ziegler‐Natta catalysts. The adsorption of TiCl4 and probe donor molecules on plain and defective lateral terminations of monolayered MgCl2 clusters was studied allowing for full structure relaxation by means of modern DFT methods including dispersion corrections. The approach offers a good compromise between speed and accuracy, and has great potential for realistic simulations of the catalytic species in industrially relevant formulations. In particular, compared with periodic DFT‐D descriptions, it is better able to capture the features of real nano‐sized and highly disordered primary catalyst particles with complex adsorbate compositions.

Role of temperature on gasification performance and tar composition in a fountain enhanced conical spouted bed reactor

The steam gasification of sawdust was carried out in a bench scale plant fitted with a fountain confined conical spouted bed reactor and a nonporous draft tube, and using olivine as primary catalyst. The effect temperature (in the 800–900 °C range) had on product distribution (gas, tar and char) and composition was studied. Not only did temperature have a positive effect on the gas yield and carbon conversion, but it also played a crucial role in tar removal, as its concentration fell from 49.2 g Nm−3 (on a dry basis) at 800 °C to 6.7 g Nm−3 operating at 900 °C. Moreover, temperature also enhanced the hydrogen yield of the gas, recording a value of 7.28 wt% at 900 °C. Regarding tar formation and its evolution pathway, as gasification temperature was increased the tar composition (analyzed by GC/MS, FTIR and simulated distillation techniques) evolved to more stable aromatic compounds (of higher molecular weight), such as naphthalene or fluoranthene, with heterocyclic or light aromatic compounds being almost absent at 900 °C.

M-Cresol-substituted triethyl aluminum/MoCl5/TBP catalytic system for coordination polymerization of butadiene

Coordination polymerization of butadiene was initiated by a catalyst system consisting of tributyl phosphate (TBP) as ligand, molybdenum pentachloride as primary catalyst and triethyl aluminum substituted by m-cresol as co-catalyst. The effects of the substitution of m-cresol on the activity of the catalyst system, molecular weight and molecular weight distribution, intrinsic viscosity and microstructures of the resulting polymers were investigated in details. The molecular weight and molecular weight distribution of the polymerization products were determined by GPC. The microstructure of the polymerization products was characterized by FTIR, 13C NMR and DSC techniques. The experimental results indicated that the polymerization activity of the reaction system and the molecular weight of the polymerization products gradually increased with the increase of the substitution content of m-cresol, namely, Al(OPhCH3)2Et > Al(OPhCH3)Et2 > Al(OPhCH3)0.5Et2.5>AlEt3. The 1,2-structure contents of the polymerization products could be adjusted between 89 and 91% through the control of the substitution of m-cresol, and there was minute quantities of crystalline structures in the resulting polymers due to the increasing content of the syndiotactic 1,2-polybutadiene. In a word, the existence and increase of steric hindrance of m-cresol made it easier for polymerization products to form interdisciplinary 1,2-structure.

Asymmetric α‐Alkylation of β‐Ketocarbonyls via Direct Phenacyl Bromide Photolysis by Chiral Primary Amine

AbstractEnantioselective α‐photoalkylation of β‐ketocarbonyls without any external photosensitizer was described in this work. The photoalkylation reactions, enabled solely by a chiral primary amine catalyst, provided convenient constructions of all‐carbon quaternary stereocenters with good activity and high enantioselectivity. Mechanism studies revealed a direct photolytic radical chain process under visible light irradiation.