Carbohydrate-Based Amphiphiles: Resource for Bio-based Surfactants

International audienc

Regioselective One-pot Protection and Protection-glycosylation of Carbohydrates

Deciphering the roles and structure–activity relationships of carbohydrates in biological processes requires access to sugar molecules of confirmed structure and high purity. Chemical synthesis is one of the best ways to obtain such access. However, the synthesis of carbohydrates has long been impeded by two major challenges – the regioselective protection of the polyol moiety of each monosaccharide building block and the stereoselective glycosylation to produce oligosaccharides of desired length. Here, we review the development of the first regioselective protection-glycosylation and a revolutionary regioselective combinatorial one-pot protection of monosaccharides that can be used to differentiate the various hydroxy groups of monosaccharides with a vast array of orthogonal protective groups in one-pot procedures

Synthesis and characterization of organotriethoxysilanes based on carbohydrates for functional mesoporous organosilica hybrids

Cancer is the second leading cause of death worldwide. Conventional therapies are characterized by clinical inefficiency and serious side effects, like high toxicity in healthy tissues. For these reasons, the investigation for more effective therapies increased in the recent years. With the progress in the area of medicinal chemistry, we read headlines almost every day about potential promising new drugs on the horizon for diseases like cancer, however, these drugs present poor stability, high toxicity, small half-lives, aggregation tendency and the transport is hindered by biobarriers such as the blood brain barrier or cell membranes. To solve these problems, researchers from different areas, such as biology, materials science, pharmacy, medicinal chemistry and chemistry, have oriented their work with the aim to develop more efficient drug delivery systems. In the past decades, the advances of nanotechnology have facilitated the development of several nanovehicles as drug delivery systems, as an advantage in the field of Medicinal Chemistry. Among the nanomaterials proposed, hybrid mesoporous organosilicas have aroused significant interest as candidates for nanomedical applications. The aim of this work was to synthesize mono-organosilanes precursors based on carbohydrates derivatives. The use of carbohydrate as organic part is an innovative work with great potential to prepare anti-tumoral supports for drug delivery, once carbohydrates are involved in numerous important biological processes linked to cancer. In the first part of the present work, was synthesised the carbohydrates derivates, from D-glucose, D-ribose, 1,2:5,6-di-O-isopropylidene-a-D-glucofuranose and methyl-?-D-glucopyranoside. In the second part of the work, was prepared the organotriethoxysilanes involving a cross-link between the carbohydrate derivatives and 3-(triethoxysilyl)propyl isocyanate. Then, these organotriethoxysilanes will be used to functionalized mesoporous hybrids organosilica, with the aim of achieve carrier systems for anti-tumoral drug delivery. The functionalities into the mesoporous materials will interact with potential new drugs or others already in the market, and release them to the specific target sites, giving new and better ways to hit the disease target.Atualmente, o cancro é segunda maior causa de morte no mundo, e a as terapias ditas convencionais, como por exemplo, a quimioterapia, trazem diversos efeitos adversos para o paciente, nomeadamente a elevada toxicidade nos tecidos saudáveis. Este tipo de terapias é ineficaz porque os métodos utilizados não são seletivos para o alvo pretendido. Posto isto, e devido à taxa limitada de sucesso e às consequências não desejadas das terapias convencionais, a procura de novas alternativas, é primordial, nomeadamente a procura de terapêuticas eficazes e seletivas, que promovam uma libertação controlada e uma entrega precisa no sítio-alvo biológico. Estes são os principais objetivos na área da química medicinal. Os avanços na nanotecnologia têm facilitado o desenvolvimento de vários nano-veículos como sistemas de entrega de fármacos, o que se tornou numa vantagem na área da química medicinal. Os materiais híbridos mesoporosos de sílica têm atraído muita atenção devido as suas propriedades únicas, incluindo uma elevada área de superfície especifica, um grande volume de poro, tamanho do poro ajustável, natureza não tóxica, pouca reatividade para quelar grupos presentes no sistema, estabilidade química e a possibilidade de modificação da superfície do poro. A funcionalização destes materiais com precursores organotrietoxisilanos, permite a obtenção de materiais híbridos multifuncionais com características sem precedentes e combinações únicas, que permitiram a interação com fármacos e a sua libertação em locais específicos a uma velocidade controlada. A utilização de hidratos de carbono como componente orgânica na síntese deste tipo de precursores é um trabalho inovador e pode ser uma vantagem na medida em que, são considerados os produtos naturais funcionalmente mais versáteis e podem originar glicoconjugados com grande importância em diversas áreas, particularmente na indústria farmacêutica, uma vez que vez que estão envolvidos em inúmeros processos biológicos, nomeadamente no reconhecimento da superfície celular. Consequentemente, a química medicinal dos hidratos de carbono tem sido incrivelmente desenvolvida ao longo dos anos assim como o seu uso como agentes terapêuticos. Além disso, a facilidade com que este tipo de moléculas tem em estabelecer ligações com outros compostos, faz deles ótimos candidatos para funcionalização de sistemas de entrega de fármacos, aumentando a sua eficácia, atividade e diminuindo possíveis efeitos adversos. Deste modo, por forma a obter precursores organotrietoxisilanos baseados em derivados de hidratos de carbono, foram elaboradas uma série de reações: (1) proteção e desproteção seletiva de açúcares, por forma a melhorar a sua solubilidade no tipo de solventes utilizados nas reações consequentes; (2) reações de formação de precursores organotrietoxisilanos do tipo Z3Si-R, entre os derivados glucídicos e o 3-(trietoxisilil)propil isocianato. A síntese dos derivados de hidratos de carbono foi efetuada com base em três sequências reacionais. A primeira sequência reacional iniciou-se na metil-a-D-glucopiranose e na D-glucose e em cada um destes compostos foram realizadas reações de titilação, seguidas de uma acetilação e por ultimo uma destritilação, originando os compostos 2,3,4–O-triacetil–1–O–metil–ß–D-glucopiranose e 1,2,3,4-tetracetil-ß-D-glucopiranose respetivamente. A segunda sequência reacional iniciou-se com a D-ribose, a qual foi protegida com um grupo metil no hidroxilo do carbono 1 e protegida com o grupo isopropopilideno nas posições dos carbonos 2 e 3, num só passo, originando o metil-2,3-O-isopropilideno-ß-D-ribofuranose. A terceira e ultima sequência reacional iniciou-se com o 1,2:5,6-di-O-isopropilideno-a-glucofuranose que foi benzilado, e de seguida foi feita uma hidrólise, com o objetivo de remover os isopropilidenos das posições referentes aos carbonos 5 e 6. Posteriormente, foi feita uma clivagem oxidativa para a formação do aldeído na posição referente ao carbono 5. Numa fase seguinte, tentou sintetizar-se uma hidrazona através da redução do aldeído anteriormente sintetizado. Contudo, não foi possível obter-se o produto proposto, devido ao excesso de aldeído comparativamente à quantidade de hidrato de hidrazina utilizada na sua reação de síntese, ocorrendo uma dimerização, e formando-se a azina 5-(1’,2’-dimetilenehidrazona)–bis-[3-O-Benzil-1,2:5,6-di-O-isopropylidene-a-D-glucopiranose]. 1,2:5,6-di-O-isopropilideno-a-glucofuranose e 1,2-O-Isopropilideno-a-D-xilofuranose também foram utilizados como componente orgânica para a síntese de precursores. Numa fase seguinte, foi realizada a síntese dos precursores organotrietoxisilanos, sendo a ligação entre o componente derivado de hidrato de carbono e o 3-(trietoxisilil)propil isocianato, efetuada por nós de reticulação de tipo ureia e uretano Devido à impossibilidade de formação da hidrazona, optou-se por sintetizar o precursor 3,5,6-tri-O-metil(3-(trietoxisilil)propil)carbamato-1,2:5,6-di-O-isopropilideno-a–D-glucofuranose. Os compostos propostos foram todos sintetizados com sucesso, com exceção dos compostos Bis(3,5-O-metil(3-(trietoxisilil)propil-carbamato-1,2-O-isopropilideno-a–D-glucofuranose) e 3,5,6-tri-O-metil(3-(trietoxisilil)-propil)carbamato-1,2:5,6-di-O-isopropilideno-a–D-glucofuranose, que por falta de tempo não foi possível uma nova tentativa de síntese, através de uma metodologia diferente. Os precursores organotrietoxisilanos foram obtidos com rendimentos entre 65% e 90%. As sínteses dos precursores organotrietoxisilanos baseados em hidratos de carbono, revelaram um tempo de reação bastante longo e um constante aperfeiçoamento, tanto da temperatura, como do tempo de reação, assim como do solvente a ser utilizado é necessário. O controlo dos parâmetros de reação é essencial, uma vez que neste tipo de compostos pode facilmente haver hidrólise dos grupos etóxidos e consequente perda do precursor. Nesta dissertação são apresentados os resultados da síntese e a caracterização estrutural dos derivados de hidratos de carbono e dos respetivos precursores organotrietoxisilanos, sendo as respetivas estruturas dos compostos obtidos, comprovadas por espetroscopia de 1H-RMN, de 13C-RMN e ainda por espetroscopia de infravermelho

Pyrolysis of Miscanthus and Products Characterization

Miscanthus, an invasive crop, has recently gained attention as an emerging energy crop because of certain features such as adaptability to lower temperature, efficient use of water and nutrients, low or no need of nitrogen fertilizers, high biomass yield, fast growing cycle and less intensive agricultural cultivation practices than other energy crops, such as corn. The literature review is focused on the value-added applications and conversion of Miscanthus for bioenergy and biomaterial applications. The thermochemical conversion technologies reviewed in this chapter include pyrolysis, liquefaction, torrefaction and gasification, whereas biochemical conversion technologies include enzymatic saccharification and fermentation. In this work, Miscanthus was selected as the feedstock for fast pyrolysis carried out in a mechanically fluidized bed reactor at three temperatures (400, 450 and 500°C) and three vapor residence times (1.4 s, 2.7 s and 5.2 s). Miscanthus was efficiently converted to energy-rich bio-oil and value-added biochar through fast pyrolysis. Fast pyrolysis performed at 450°C with 1.4 s of vapor residence time gave the highest yield of bio-oil (\u3e 50 wt%). The biochar obtained at variable pyrolysis temperatures were also activated at 900°C for 1.5 h under CO2 atmosphere to enhance its value as a potential adsorption agent for pollutants. Several characterization techniques were used to study the bio-oils, biochars and activated biochars obtained from the pyrolysis of Miscanthus. The absorption of methylene blue as a model dye (wastewater pollutant) was done to evaluate the performance of activated biochar versus the biochar precursors. Both pyrolysis and physical activation complemented each other as new technologies for energy extraction and material synthesis from Miscanthus

Studies on the Electron Impact Induced Dissociation of Some Organic Compounds

The work discussed in the thesis can be considered In three separate sections: Part I: The Mass Spectra of some Diaryl Ethers. Part II: The Mass Spectra of some Naturally Occurring Phenolic Compounds. Part III: The Mass Spectra of some Carbohydrate Derivatives. Part I: The ethers used in this section are compounds containing fused aromatic rings and homologues of diphenyl ether with methyl substituents on the aromatic nuclei. The spectra of these compounds have been compared with that of diphenyl ether. The degradation of diphenyl ether by loss of carbon monoxide has been noted previously and the extent to which the corresponding reaction takes place in other ethers has been correlated with the structures of these compounds. Other correlations have been made in an attempt to explain the presence of rearranged ions which appear in the ortho-methyl ether spectra. Part II: Some derivatives of tubaic acid were investigated. It was found that mass spectrometric methods can Identify or help to identify the isoprenoid groups present In such molecules. This was confirmed by an examination of the rotenoids. The 2:3-dihydroxyrotenoids can be easily Identified by their mass spectra. Two examples are given of the partial determination of the structure of compounds of this class. An analysis has been mode of the spectra of some flavonoid compounds. Part III: A preliminary examination has been made of the mass spectra of some glycosides and sugar alcohols. Correlations have been made between spectra and structures in each case. Differences in the spectra of two methyl glycosides have been related to differences in the stereochemistry of the compounds. The spectra of all the isomeric inositols are recorded. Proposals have been made for the mechanism of degradation of these compounds

Flavour by design: food-grade lactic acid bacteria improve the volatile aroma spectrum of oat milk, sunflower seed milk, pea milk, and faba milk towards improved flavour and sensory perception

Background The global market of plant-based milk alternatives is continually growing. Flavour and taste have a key impact on consumers’ selection of plant-based beverages. Unfortunately, natural plant milks have only limited acceptance. Their typically bean-like and grassy notes are perceived as“of-favours” by consumers, while preferred fruity, buttery, and cheesy notes are missing. In this regard, fermentation of plant milk by lactic acid bacteria (LAB) appears to be an appealing option to improve aroma and taste. Results In this work, we systematically studied LAB fermentation of plant milk. For this purpose, we evaluated 15 food-approved LAB strains to ferment 4 diferent plant milks: oat milk (representing cereal-based milk), sunfower seed milk (representing seed-based milk), and pea and faba milk (representing legume-based milk). Using GC‒MS analysis, favour changes during anaerobic fermentations were studied in detail. These revealed species-related and plant milkrelated diferences and highlighted several well-performing strains delivered a range of benefcial favour changes. A developed data model estimated the impact of individual favour compounds using sensory scores and predicted the overall favour note of fermented and nonfermented samples. Selected sensory perception tests validated the model and allowed us to bridge compositional changes in the favour profle with consumer response. Conclusion Specifc strain-milk combinations provided quite diferent favour notes. This opens further developments towards plant-based products with improved favour, including cheesy and buttery notes, as well as other innovative products in the future. S. thermophilus emerged as a well-performing strain that delivered preferred buttery notes in all tested plant milks. The GC‒MS-based data model was found to be helpful in predicting sensory perception, and its further refnement and application promise enhanced potential to upgrade fermentation approaches to favour-by-design strategies

Antimicrobial Evaluation of Novel Fatty Acid Derivatives and Other Natural Antimicrobials

The food industry has shown increased interest for novel natural antimicrobials due to consumer demand for foods with fewer synthetic additives, increased safety, quality and shelf-life. Concurrently, the emergence of drug resistant bacteria substantiates the need for newer antimicrobial agents. Alternative strategies include the use of novel antimicrobials, such as fatty acid derivatives, essential oils and bacteriocins, with proven antimicrobial properties against a diverse range of bacteria. This study investigated novel carbohydrate fatty acid (CF A) derivatives for their antibacterial activity against a range of pathogenic and spoilage bacteria. A series of mono-substituted CF A derivatives using lauric and caprylic acids were synthesized. Chemical routes allowing the attachment of the fatty acid as either an ester or ether to the monosaccharide 6-hydroxyl were developed. Structure/activity relationship studies of antimicrobial efficacy allowed some insight into the mechanism of action of these compounds. In addition, selected essential oil (EO) individual components and nisin, both alone and in combination, were also assessed for possible combination strategies with CF A derivatives. Minimum inhibitory concentration (MIC), ICso values, increase in lag phase and decrease in maximum specific growth rate were determined. Leakage of intracellular material absorbing at 260nm, Live/Dead BacLight fluorescence and ATP BacTiterGlo luminescence assays assessed membrane disrupting effects. Furthermore, a Phenotypic MicroArray assay was used to investigate bacterial cell response in the absence and presence of CF A derivatives. The laurate ether of methyl a-D-glucopyranoside (9a) and laurate ester of methyl a-D-mannopyranoside (4c) showed the highest growth-inhibitory effect. CFA derivatives were significantly more effective against Gram positive than Gram negative bacteria. The analysis of both ester and ether fatty acid derivatives of the same carbohydrate, in tandem with alpha and beta configuration of the carbohydrate moiety suggest that the carbohydrate moiety is involved in the antimicrobial activity of the fatty acid derivatives and that the nature of the bond also has a significant effect on efficacy. Membrane damage was observed and may account for at least a component of the mode of action of these compounds. The ATP assay and phenotypic responses suggested that another mechanism of action might also account for the antimicrobial activity of the beta lauric ether derivative (compound 9b). Carvacrol and thymol were found to have the highest antimicrobial activity, followed by citral. Nisin in combination with carvacrol, thymol and citral showed additive effects against Listeria spp. The antimicrobial effect of the combination was improved by lowering the pH from neutral to pH6. CF A derivatives with different structures have great potential for developing antibacterial agents relevant to the food and health care industries. Nisin in combination with individual EO components could lead to useful efficacy as an alternative natural preservative

Alicyclic and Aromatic Carboxylic Acids in Soil Organic Matter: An Investigation of Potential Origin and Association with Plutonium Using Advanced Analytical Techniques

Carboxylic acids are a defining component of soil organic matter, responsible for many of the physical and chemical properties, including metal-organic matter interactions, which govern its role as an important constituent of soils. However, there is a shortage of detailed molecular level information regarding orientation and structural arrangement of carboxylic acids within soil organic matter. This dissertation utilizes electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS) as well as solid-state and multi-dimensional nuclear magnetic resonance (NMR) to investigate the molecular formula composition within several organic matter sources and the primary structures that feature carboxylic acids. Soil organic matter is evaluated in two forms: as the alkali-soluble, acid-insoluble portion of organic matter (humic acids) from a collection of sources, as well as the alkali soluble soil organic material associated with high Fe and Pu metal concentrations at a contaminated munitions facility. Two predominant carboxyl-containing molecular assemblages are found to be common in a wide variety of soil humic acids. Along with lignin-like assemblages, these are carboxyl-containing aliphatic molecules (CCAM) and condensed aromatic molecules. The proportion of these groups relative to lignin-like compounds within samples and the percent of total carboxylic acid molecular formulas among samples are found to increase with increasing humification of the soil. Since CCAM and condensed aromatic molecules have previously been shown to be generated from oxidization of lignin, this represents renewed evidence for lignin as a major source of organic matter in soils. Lignin ring-opening and radical re-polymerization reactions have been proposed to form alicyclic CCAM and condensed aromatic molecules. Detailed evaluation of the aliphatic molecules using multi-dimensional NMR confirms the presence of ring structures, replete with carboxylic acids, heteroatom substitutions in the form of alcohols and ethers, as well as a variety of methyl group substituents. Additionally, condensed aromatic carboxylic acid molecular formulas, primarily those containing nitrogen, were found composed in organic matter with elevated metal ions Pu and Fe. Carboxylic acid oxygens in combination with nitrogen in aromatic structures are suspected to be partially responsible for the high metal affinity. Nitrogen-containing hydroxamate groups were also investigated for their potential to be incorporated into stable organic matter by testing the reaction between an amine-containing hydroxamate siderophore and the biopolymer cutin. While products of this reaction could not be confirmed, carboxylic acid functional groups are identified in this thesis as key molecular components contributing to Pu and Fe metal-binding attributes of organic matter, and potentially formed during the production of condensed aromatic and alicyclic compounds as a result of radical oxidation reactions of lignin