Catalysis at gold-ligand interfaces: a frustrated Lewis pair mechanism for selective reduction reaction / Catalise na interface ouro-ligante: pares de Lewis frustrados aplicados em reações de redução seletivas

The interaction of the organic ligands with metal nanoparticle has a very important role for applications in catalysis, as well as other processes involving ligands that can activate or poison the surface of metal nanoparticles. Very little has been studied so far on the role of organic ligands used either in the preparation of nanoparticles for applications in catalysis or addition in the reaction to activate the catalyst. In this thesis, we have studied strategies for the synthesis of metal nanoparticles, their use as components for the preparation of supported catalysts and activation and deactivation processes involving the ligands used as stabilizers or purposely added to the reaction medium or support for stimulate new reactivity and selectivity in reactions of industrial interest, such as hydrogenation. Here, the concept of frustrated Lewis pairs (FLPs) has been expanded to surface-FLP analogous formed by combining gold nanoparticles (NPs) and Lewis bases, such as amines or phosphines, creating a new channel for the heterolytic cleavage of H2, and thereby performing selective hydrogenation reactions with gold. A first approach to improve the catalytic activity of gold nanoparticles was to analyze the effect of nitrogen-containing bases. The starting inactive gold nanoparticles became highly active for the selective hydrogenation of alkyne into cis-alkenes. The hydrogenation proceeded smoothly and fully selective using H2 as the hydrogen source and under relatively mild conditions (80 °C, 6 bar H2). Our studies also have revealed that the presence of capping ligands blocks the adsorption of the amine to the gold surface, avoiding the FLPs interface and thereby leading to low catalytic activity. When the capping ligands were removed from the catalyst surface and an amine ligand was added, the FLPs interface is recovered and an enhanced catalytic activity was observed. Furthermore, we have demonstrated the successful use of simple organophosphorus ligands to boost the catalytic activity of Au NPs for a range of important reduction reactions, namely, epoxides, N-oxides, sulfoxides, and alkynes. Furthermore, the choice of phosphorus-containing ligands resulted in a decrease in the amount necessary to reach high conversion and selectivity in comparison with our previous study with N-containing ligands. The ligand-to-metal ratio decreased from 100 (amine/Au) to 1 (phosphite/Au). The synthesis of gold nanoparticles supported on N-doped carbon supports was used as an alternative method for the synthesis of a heterogeneous active gold catalyst for selective hydrogenations. The main advantage with respect to previous studies was to avoid the addition of external ligands, in large excess, for the activation of gold surfaces via FLP, making the whole process environmentally and economically attractive

A interação dos ligantes orgânicos com nanopartículas de metal certamente tem um papel muito importante para aplicações em catálise, bem como outros processos envolvendo ligantes que podem ativar ou envenenar a superfície de nanopartículas metálicas. Até agora, muito pouco foi estudado sobre o papel dos ligantes orgânicos utilizados na preparação de nanopartículas para aplicações em catálise ou adição na reação para ativar o catalisador. Nesta tese, foram estudadas estratégias para a síntese de nanopartículas metálicas, seu uso como componentes para a preparação de catalisadores suportados e processos de ativação e desativação envolvendo ligantes empregados como estabilizantes ou propositalmente adicionados ao meio de reação ou suporte para estimular novas reatividades e seletividade em reações de interesse industrial, como reações de hidrogenação. Aqui, o conceito de pares de Lewis frustrados (FLPs) foi expandido para o seu análogo de superfície formado pela combinação de nanopartículas (NPs) de ouro e bases de Lewis, como aminas ou fosfinas, criando um novo canal para a clivagem heterolítica de H2 e, assim, realizando reações seletivas de hidrogenação com ouro. Uma primeira abordagem para melhorar a atividade catalítica das nanopartículas de ouro foi analisar o efeito de bases contendo nitrogênio. As nanopartículas de ouro inicialmente inativas tornaram-se altamente ativas para a hidrogenação seletiva de alquino em cis-alquenos. A hidrogenação prosseguiu foi factível e totalmente seletiva usando H2 como fonte de hidrogênio e sob condições relativamente amenas (80 °C, 6 bar de H2). Nossos estudos também revelaram que a presença de estabilizantes pode bloquear a adsorção da base na superfície do ouro, impedindo a formação da interface FLPs e, portanto, levando a baixa atividade catalítica. Quando os estabilizantes foram removidos da superfície do catalisador e um ligante foi adicionado, o FLPs é formado sendo a atividade catalítica aprimorada. Além disso, demonstramos o uso bem-sucedido de ligantes organofosforados atuando como ativadores de Au NPs em uma série de importantes reações de redução, como, epóxidos, N-óxidos, sulfóxidos e alquinos. Além disso, a escolha do ligante fosforado resultou em uma diminuição na quantidade necessária para alcançar alta conversão mantendo a seletividade inalterada. A relação ligante/metal diminuiu de 100/1 (amina/Au) para 1/1 (fosfito/Au). A síntese de nanopartículas de ouro suportadas em carbono dopado com nitrogênio foi utilizada como método alternativo para a síntese de um catalisador heterogêneo de ouro ativo para hidrogenações seletivas. A principal vantagem em relação aos estudos anteriores foi evitar a adição de ligantes externos, em grande excesso, para a ativação de superfícies de ouro via FLP, tornando todo o processo ambiental e economicamente atraente

Decarboxylative alkenylation.

Olefin chemistry, through pericyclic reactions, polymerizations, oxidations, or reductions, has an essential role in the manipulation of organic matter. Despite its importance, olefin synthesis still relies largely on chemistry introduced more than three decades ago, with metathesis being the most recent addition. Here we describe a simple method of accessing olefins with any substitution pattern or geometry from one of the most ubiquitous and variegated building blocks of chemistry: alkyl carboxylic acids. The activating principles used in amide-bond synthesis can therefore be used, with nickel- or iron-based catalysis, to extract carbon dioxide from a carboxylic acid and economically replace it with an organozinc-derived olefin on a molar scale. We prepare more than 60 olefins across a range of substrate classes, and the ability to simplify retrosynthetic analysis is exemplified with the preparation of 16 different natural products across 10 different families.

Design and stereoselective preparation of a new class of chiral olefin metathesis catalysts and application to enantioselective synthesis of quebrachamine: catalyst development inspired by natural product synthesis.

A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. A key catalytic ring-closing metathesis of an achiral triene is used to establish the all-carbon quaternary stereogenic center and the tetracyclic structure of the natural product; the catalytic transformation proceeds with reasonable efficiency through the use of existing achiral Ru or Mo catalysts. Ru- or Mo-based chiral olefin metathesis catalysts have proven to be inefficient and entirely nonselective in cases where the desired product is observed. In the present study, the synthesis route thus serves as a platform for the discovery of new olefin metathesis catalysts that allow for efficient completion of an enantioselective synthesis of quebrachamine. Accordingly, on the basis of mechanistic principles, stereogenic-at-Mo complexes bearing only monodentate ligands have been designed. The new catalysts provide significantly higher levels of activity than observed with the previously reported Ru- or Mo-based complexes. Enantiomerically enriched chiral alkylidenes are generated through diastereoselective reactions involving achiral Mo-based bispyrrolides and enantiomerically pure silyl-protected binaphthols. Such chiral catalysts initiate the key enantioselective ring-closing metathesis step in the total synthesis of quebrachamine efficiently (1 mol % loading, 22 degrees C, 1 h, >98% conversion, 84% yield) and with high selectivity (98:2 er, 96% ee).

Type-2 alkenes mediate synaptotoxicity in neurodegenerative diseases.

Synaptic dysfunction appears to be an early pathogenic event in Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease. Although the molecular mechanism of this synaptotoxicity is not known, evidence suggests that these diseases are characterized by a common pathophysiological cascade involving oxidative stress, lipid peroxidation and the subsequent liberation of alpha,beta-unsaturated carbonyl derivatives such as acrolein and 4-hydroxy-2-nonenal (HNE). A diverse body of in vivo and in vitro data have shown that these soft electrophilic chemicals can cause nerve terminal damage by forming Michael-type adducts with nucleophilic sulfhydryl groups on presynaptic proteins. Therefore, the endogenous generation of acrolein and HNE in oxidatively stressed neurons of certain brain regions might be mechanistically related to the synaptotoxicity associated with neurodegenerative conditions. In addition, acrolein and HNE are members of a large class of structurally related chemicals known as the type-2 alkenes. Chemicals in this class (e.g., acrylamide, methylvinyl ketone, and methyl acrylate) are pervasive pollutants in human environments and new research has shown that these alpha,beta-unsaturated carbonyl derivatives are also toxic to nerve terminals. In this review, we provide evidence that the regional synaptotoxicity, which develops during the early stages of many neurodegenerative diseases, is mediated by endogenous generation of acrolein and HNE. Based on a presumed common nerve terminal site of action, we propose that the onset and progression of this neuropathogenic process is accelerated by environmental exposure to other type-2 alkenes.

Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes.

BACKGROUND: Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV) form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP) encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. RESULTS: Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G), were established for Thogoto virus (THOV) GP and Autographa california multiple NPV (AcMNPV) GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. CONCLUSION: These results suggest that proteins in the GP64 superfamily are class III penetrenes.

Quantitative and mechanistic read across for predicting the skin sensitization potential of alkenes acting via Michael addition.

Read across is a powerful tool to predict toxicity from structure: It relies on "obvious" chemical similarities to allow for interpolation of activity. This study has extended the read across concept within a known mechanism of action to be quantitative. The chemicals that have been chosen are skin sensitizers and are considered to elicit this response by direct interaction through a direct-acting Michael type addition electrophilic mechanism of action. The Michael addition domain is well-defined for skin sensitizers; however, developing quantitative models for predicting potency within the domain has proven to be difficult. This study highlights the ability of an electrophilicity index (omega) to be used as a measure of similarity for sensitizing chemicals acting through the Michael addition mechanism. The index is shown to offer a chemically interpretable qualitative ranking of the chemicals within the Michael acceptor domain, enabling potentially nonsensitizing and extremely sensitizing chemicals to be easily identified. This study also demonstrates the utility of omega to make predictions of skin sensitization using a mechanism-based read across model. Predictions were made for 19 chemicals within the Michael acceptor domain, with the majority being in good agreement with the experimentally determined values. The mechanism-based read across predictions are in keeping with the OECD principles of transparency and simplicity for quantitative structure-activity relationships and are likely to be of significant benefit to regulators and risk assessors.

Fragrance material review on damascenone.

A toxicologic and dermatologic review of damascenone when used as a fragrance ingredient is presented.

Proteomics computational analyses suggest that the carboxyl terminal glycoproteins of Bunyaviruses are class II viral fusion protein (beta-penetrenes).

The Bunyaviridae family of enveloped RNA viruses includes five genuses, orthobunyaviruses, hantaviruses, phleboviruses, nairoviruses and tospoviruses. It has not been determined which Bunyavirus protein mediates virion:cell membrane fusion. Class II viral fusion proteins (beta-penetrenes), encoded by members of the Alphaviridae and Flaviviridae, are comprised of three antiparallel beta sheet domains with an internal fusion peptide located at the end of domain II. Proteomics computational analyses indicate that the carboxyl terminal glycoprotein (Gc) encoded by Sandfly fever virus (SAN), a phlebovirus, has a significant amino acid sequence similarity with envelope protein 1 (E1), the class II fusion protein of Sindbis virus (SIN), an Alphavirus. Similar sequences and common structural/functional motifs, including domains with a high propensity to interface with bilayer membranes, are located collinearly in SAN Gc and SIN E1. Gc encoded by members of each Bunyavirus genus share several sequence and structural motifs. These results suggest that Gc of Bunyaviridae, and similar proteins of Tenuiviruses and a group of Caenorhabditis elegans retroviruses, are class II viral fusion proteins. Comparisons of divergent viral fusion proteins can reveal features essential for virion:cell fusion, and suggest drug and vaccine strategies.

Design of acyclic triaryl olefins: a new class of potent and selective cyclooxygenase-2 (COX-2) inhibitors.

A new class of acyclic 1,1-diphenyl-2-(4-methylsulfonylphenyl)-2-alkyl-1-ethenes were synthesized, via a short two-step McMurry olefination reaction and then oxidation of the thiomethyl intermediate using Oxone, in 62-76% yield. The title compounds possess identical C-1 phenyl substituents which precludes the possibility of (Z)- and (E)-stereoisomers. 1,1-Diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene exhibited highly potent (IC(50)=0.014 microM) and selective COX-2 (Selectivity Index >7142) inhibitory activity.

Factors influencing the distributions of polyunsaturated terpenoids in the diatom, Rhizosolenia setigera.

Polyunsaturated highly branched isoprenoid (HBI) hydrocarbon distributions of laboratory cultures of five strains of the planktonic diatom Rhizosolenia setigera (Brightwell) are shown herein to be highly variable. Some strains produced both haslenes with from three to five double bonds and rhizenes. The haslenes comprised not only Delta5 alkenes but also those with C7(20) unsaturation, including hasla-7(20),9E,Z, 23-trienes and hasla-7(20),9E,Z-13, 23-tetraenes. The rhizenes contained C7(25) unsaturation and the vinyl moiety common to all algal haslenes so far characterised. The effects of temperature and salinity on HBI composition, along with isotopic content, were determined in strain CS 389/A. Increase in growth temperature from 18 to 25 degrees C increased the degree of unsaturation in the haslenes and E to Z isomerisation in the triene. There was also an increase in unsaturation in the rhizenes at the highest growth temperature, with hexaenes dominant over the pentaenes but in the rhizenes, Z to E isomerisation increased. Increased salinity from 15 to 35 psu increased cell growth and rhizene production but decreased haslene production. Unsaturation in haslenes was not changed by increased salinity but unsaturation in the rhizenes decreased. These may reflect growth rate differences. The carbon isotopic compositions of the haslenes and rhizenes were similar to that of the major sterol at 18 degrees C, but the major HBI isomers were 3-4 per mil depleted relative to phytol released by saponification from chlorophyll a. This suggests biosynthesis of HBIs from a different isotopic pool of isopentenyl biphosphate to that from which phytol is biosynthesised. At 25 degrees C, further isotopic differences were observed. The variables controlling HBI distributions in R. setigera are still not fully understood and rationalisation of the environmental controls on the sedimentary distributions of the HBIs from R. setigera may only be possible once such factors are established.