Development of catalysts for the addition of N-H and O-H to carbon-carbon double bonds

The addition of O-H and N-H bonds across carbon-carbon double bonds offers a direct way of synthesising a variety of organic molecules. These reactions have attracted considerable interest in academic research and the chemical/pharmaceutical industry in recent years due to its atom economy. Nevertheless, there remains a considerably challenge to control the regioselectivity and the stereoselectivity of this reaction. This PhD thesis describes the investigation into the discovery and development of a general method for catalytic hydroamination (HA), hydroalkoxylation and hydrooxyacylation of olefins. Air- and moisture-stable transition metal catalysts were the main focus of this study. The introductory Chapter provides an overview of recent advances in N-H addition reactions involving late transition metal catalysts. In Chapter 2, rhodium and ruthenium complexes were examined as catalysts for the addition of N-H bonds to alkenes. The combination of (RuCl2)n/dppb/AgOTf generated a catalyst effective for the addition of methyl carbamate to norbornene in a modest yield. Copper (II) trifluoromethanesulfonate was discovered to be an efficient catalyst for the addition of carboxylic acids, phenols and alcohols to norbornene. A selection of norbornyl esters and ethers were formed in good to excellent yields. In the following Chapter, the combination of copper (II) trifluoromethanesulfonate and diphosphine ligands was successfully applied to the addition of sulfonamides and carbamates to vinylarenes, 1,3-dienes and norbornene in good to excellent yields. In Chapter 4, the intramolecular hydroamination reaction was developed. The synthesis of several acyclic precursors were described, along with attempts to cyclise them. The chapter ends with the attempted synthesis of tricyclic molecules using a palladium-catalysed methodology. The last Chapter contains experimental procedures and characterisation data of all the compounds synthesised during the course of this project

Preliminary studies of the cytotoxicity and photoprotective properties of Benzophenone and Lactone derivatives.

A Radia??o solar ultravioleta(RUV) pode induzir efeitos ? pele devidos a sua a??o direta ou indireta, por meio da gera??o de radicais livres. Esses efeitos podem provocar diversas les?es na pele humana como o c?ncer de pele. Como medida de prote??o da pele contra os efeitos da radia??o solar pode-se citar o uso de protetores solares, produtos t?picos adicionados de filtros solares UV sint?ticos com propriedades de absor??o e reflex?o de raios solares.Um fotoprotetor org?nico ideal deve proteger a pele contra os raios UVB (290-320 nm) e UVA (320-400 nm), possuir um fator de prote??o solar (FPS) seguro, ser fotoest?vel e n?o ser fotot?xico. Este trabalho objetiva em estudos preliminares de fotoprote??o dos derivados das Benzofenonas e Lactonas. Os produtos obtidos foram sintetizados e caracterizados por t?cnicas espectrosc?picas usuais e foram submetidos a ensaios de viabilidade celular frente ao MTT e determina??o do valor de prote??o solar (FPS) in vitro pelo m?todo espectrofotom?trico UV/VIS. Os espectros de IV, RMN de 1 H e RMN de 13C mostraram bandas e sinais em conformidades com as estruturas propostas para os compostos estudados. Os compostos 1 e2 apresentaram um FPS proporcional ? concentra??o analisada, ou seja, quanto maior a concentra??o, maior ? o Fator de Prote??o, por?m o composto 3 apresentou fator prote??o menor em concentra??es mais elevadas. No estudo de viabilidade celular, os compostos 1 e 2 n?o foram citot?xicos nas concentra??es avaliadas neste trabalho.Ultraviolet solar radiation can generate free radicals that damage skin and cause skin lesions or skin cancer. Sunscreens are a protective measure against the effects of solar radiation that protects the skin by absorbing or reflecting solar rays. Ideally, the sunscreen should protect the skin against UVB (290-320 nm) and UVA (320-400 nm) rays, be photostable and non-toxic. This work describes a preliminary study on the SPF of a benzophenone and a lactone derivative. The synthesized compounds were characterized by spectroscopic techniques, submitted to cell viability assays against MTT and SPF determined in vitro by UV/VIS spectroscopy measurements. The spectroscopic data was in agreement with the proposed structures of the compounds studied. The SPF was proportional to concentration, and in one case, the sun protection factor was lower at higher concentrations. The benzophenone derivatives were evaluated for toxicity by a cell viability study, and found to be non-cytotoxic at the tested concentrations

Preparation and characterization of a quercetin-tetraethyl ether-based photoprotective nanoemulsion.

Although Quercetin absorbs in the UVA/UVB electromagnetic region, it is limited for applications as a UV filter due to its low lipophilicity and capacity to penetrate the epidermis. In order to overcome this limitation, we synthetized and evaluated the photo protective properties of a derivative obtained from Quercetin. The derivative was prepared by alkylation of Quercetin with iodoethane and characterized by IR and NMR spectroscopy. The in vitro Solar Protection Factor was determined by the Mansur method and the cytotoxicity was evaluated using hepatocellular cell (Hep G2) cells. Finally, Quercetin and the corresponding derivative were incorporated in nanoemulsions. Nanoemulsions with particles sizes between 53 and 73 nm were obtained, and polydispersity indexes were around 0.1, indicating good homogeneity of the nanoemulsion particles. The cell viability study for the Quercetin derivative indicated a very low cytotoxicity profile. The chemical modification of Quercetin resulted in a promising compound with improved properties desirable for skin penetration and incorporation into sunscreen formulations

Baccharis trimera (Carqueja) Improves metabolic and redox status in an experimental model of type 1 diabetes.

Diabetes mellitus is a metabolic disorder that causes severe complications due to the increased oxidative stress induced by disease. Many plants are popularly used in the treatment of diabetes, e.g., Baccharis trimera (carqueja). The aim of this study was to explore the potential application of the B. trimera hydroethanolic extract in preventing redox stress induced by diabetes and its hypoglycemic properties. Experiments were conducted with 48 female rats, divided into 6 groups, named C (control), C600 (control + extract 600 mg/kg), C1200 (control + extract 1200 mg/kg), D (diabetic), D600 (diabetic + 600 mg/kg), and D1200 (diabetic + 1200 mg/kg). Type 1 diabetes was induced with alloxan, and the animals presented hyperglycemia and reduction in insulin and body weight. After seven days of experimentation, the nontreated diabetic group showed changes in biochemical parameters (urea, triacylglycerol, alanine aminotransferase, and aspartate aminotransferase) and increased carbonyl protein levels. Regarding the antioxidant enzymes, an increase in superoxide dismutase activity was observed but in comparison a decrease in catalase and glutathione peroxidase activity was noted which suggests that diabetic rats suffered redox stress. In addition, the mRNA of superoxide dismutase, catalase, and glutathione peroxidase enzymes were altered. Treatment of diabetic rats with B. trimera extract resulted in an improved glycemic profile and liver function, decreased oxidative damage, and altered the expression of mRNA of the antioxidants enzymes. These results together suggest that B. trimera hydroethanolic extract has a protective effect against diabetes

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Multiethnic Meta-Analysis Identifies Ancestry-Specific and Cross-Ancestry Loci for Pulmonary Function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

The Eighteenth Data Release of the Sloan Digital Sky Surveys: Targeting and First Spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Comment: Accepted to ApJ

The eighteenth data release of the Sloan Digital Sky Surveys : targeting and first spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Publisher PDFPeer reviewe