Development of new chemical entities to target neuroinflammatory pathways.

Neuroinflammatory pathways are main culprits of neurodegenerative diseases' onset and progression, including Alzheimer’s disease (AD). On this basis, several anti-inflammatory drugs were repurposed in clinical trials. However, they have failed, probably because neuroinflammation is a complex network, still not fully understood. From these evidences, this thesis focused on the design and synthesis of new chemical entities as potential neuroinflammatory drugs or chemical probes. Projects 1 and 2 aimed to multi-target-directed ligand (MTDL) development to target neuroinflammation in AD. Polypharmacology by MTDLs is considered one of the most promising strategies to face the multifactorial nature of neurodegenerative diseases. Particularly, Project 1 took inspiration from a cromolyn-ibuprofen drug combination polypharmacological approach, which was recently investigated in AD clinical trials. Based on that, two cromolyn-(S)-ibuprofen codrug series were designed and synthesized. Parent drugs were combined via linking or fusing strategies in 1:2 or 1:1 ratio, by means of hydrolyzable bonds. Project 2 started from a still ongoing AD clinical trial on investigational drug neflamapimod. It is a selective inhibitor of p38α-MAPK, a kinase strictly involved in neuroinflammatory pathways. On the other side, rasagiline, an anti-Parkinson drug, was also repurposed as AD treatment. Indeed, rasagiline’s propargylamine fragment demonstrated to be responsible not only for the MAO-B selective inhibition, but also for the neuroprotective activity. Thus, to synergistically combine these two effects into single-molecules, a small set of neflamapimod-rasagiline hybrids was developed. In the end BMX, a poorly investigated kinase, which seems to be involved in pro-inflammatory mediator production, was explored for the development of new chemical probes. High-quality chemical probes are a powerful tool in target validation and starting points for the development of new drug candidates. Thus, Project 3 focused on the design and synthesis of two series of optimized BMX covalent inhibitors as selective chemical probes.

Sewage sludge as organic fertilizer in agriculture. A study of physico-chemical properties, agronomic efficiency and environmental safety, with a specific focus on tannery sludge

In recent decades, the use of organic fertilizers has gained increasing interest mainly for two reasons: their ability to improve soil fertility and the need to find a sustainable alternative to mineral and synthetic fertilizers. In this context, sewage sludge is a useful organic matrix that can be successfully used in agriculture, due to its chemical composition rich in organic matter, nitrogen, phosphorus and other micronutrients necessary for plant growth. This work investigated three indispensable aspects (i.e., physico-chemical properties, agronomic efficiency and environmental safety) of sewage sludge application as organic fertilizer, emphasizing the role of tannery sludge. In a comparison study with municipal sewage sludge, results showed that the targeted analyses applied (total carbon and nitrogen content, isotope ratio of carbon and nitrogen, infrared spectroscopy and thermal analysis) were able to discriminate tannery sludge from municipal ones, highlighting differences in composition due to the origin of the wastewater and the treatment processes used in the plants. Regarding agronomic efficiency, N bioavailability was tested in a selection of organic fertilizers, including tannery sludge and tannery sludge-based fertilizers. Specifically, the hot-water extractable N has proven to be a good chemical indicator, providing a rapid and reliable indication of N bioavailability in soil. Finally, the behavior of oxybenzone (an emerging organic contaminant detected in sewage sludge) in soils with different physico-chemical properties was studied. Through adsorption and desorption experiments, it was found that the mobility of oxybenzone is reduced in soils rich in organic matter. Furthermore, through spectroscopic methods (e.g., infrared spectroscopy and surface-enhanced Raman spectroscopy) the mechanisms of oxybenzone-humic acids interaction were studied, finding that H-bonds and π-π stacking were predominantly present.

Towards the sustainable production of methyl methacrylate: A comparative analysis of industrial chemical production processes using life cycle assessment methodology

Increasing environmental awareness has been a significant driving force for innovations and process improvements in different sectors and the field of chemistry is not an outlier. Innovating around industrial chemical processes in line with current environmental responsibilities is however no mean feat. One of such hard to overhaul process is the production of methyl methacrylate (MMA) commonly produced via the acetone cyanohydrin (ACH) process developed back in the 1930s. Different alternatives to the ACH process have emerged over the years and the Alpha Lucite process has been particularly promising with a combined plant capacity of 370,000 metric tonnes in Singapore and Saudi Arabia. This study applied Life Cycle Assessment methodology to conduct a comparative analysis between the ACH and Lucite processes with the aim of ascertaining the effect of applying principles of green chemistry as a process improvement tool on overall environmental impacts. A further comparison was made between the Lucite process and a lab-scale process that is further improvement on the former, also based on green chemistry principles. Results showed that the Lucite process has higher impacts on resource scarcity and ecosystem health whereas the ACH process has higher impacts on human health. On the other hand, compared to the Lucite process the lab-scale process has higher impacts in both the ecosystem and human health categories with lower impacts only in the resource scarcity category. It was observed that the benefits of process improvements with green chemistry principles might not be apparent in some categories due to some limitations of the methodology. Process contribution analysis was also performed and it revealed that the contribution of energy is significant, therefore a sensitivity analysis with different energy scenarios was performed. An uncertainty analysis using Monte Carlo analysis was also performed to validate the consistency of the results in each of the comparisons.

Improvement of fungal arabinofuranosidase thermal stability by reversible immobilization

A gene encoding a-L-arabinofuranosidase (abfA) from Aspergillus niveus was identified, cloned, and successfully expressed in Aspergillus nidulans. Based on amino acid sequence comparison, the 88.6 kDa enzyme could be assigned to the GH family 51. The characterization of the purified recombinant AbfA revealed that the enzyme was active at a limited pH range (pH 4.0-5.0) and an optimum temperature of 70 degrees C. The AbfA was able to hydrolyze arabinoxylan, xylan from birchwood, debranched arabinan, and 4-nitrophenyl arabinofuranoside. Synergistic reactions using both AbfA and endoxylanase were also assessed. The highest degree of synergy was obtained after the sequential treatment of the substrate with endoxylanase, followed by AbfA, which was observed to release noticeably more reducing sugars than that of either enzyme acting individually. The immobilization of AbfA was performed via ionic adsorption onto various supports: agarose activated by polyethyleneimine polymers, cyanogen bromide activated Sepharose, DEAE-Sepharose, and Sepharose-Q The Sepharose-Q derivative remained fully active at pH 5 after 360 min at 60 degrees C, whereas the free AbfA was inactivated after 60 min. A synergistic effect of arabinoxylan hydrolysis by AbfA immobilized in Sepharose-Q and endoxylanase immobilized in glyoxyl agarose was also observed. The stabilization of arabinofuranosidases using immobilization tools is a novel and interesting topic. (C) 2012 Elsevier Ltd. All rights reserved.

Structured carbons as supports for hydrogenation hybrid catalysts prepared by the immobilization of a Rh diamine complex

A CNF-monolith sample (carbon nanofibres grown on a ceramic monolith), and a granular carbon xerogel have been used as supports for hybrid catalysts where the active species is an Rh diamine complex. The advantages of these supports are their open porous structure and their morphology, which make catalyst handling easier and avoid difficult separation processes. The obtained catalysts are noticeably more active than the homogeneous Rh complex and are stable against leaching. At first use, partial reduction of the Rh complex takes place and nanometer-sized Rh particles develop, which increases the catalyst activity. Despite the open porous structure, mass transport limitations are present, especially in the case of the carbon xerogel based catalyst. Differences in internal mass transfer limitations are essentially due to the different diffusional path lengths.

(Table 8.4, Page 220-223) Chemical composition of different growth structures of manganese nodules, SONNE cruise SO78

In the nodule field of the Peru Basin, situated south of the zone of high bioproductivity, a relatively high flux of biogenic matter explains a distinct redox boundary at about 10 cm depth separating very soft oxic surface sediments from stiffer suboxic sediments. Maximum abundance (50 kg/m**2) of diagenetic nodules is found near the calcite compensation depth (CCD), currently at 4250 m. There, the accretion rate of nodules is much higher (100 mm/Ma) than on ridges (5 mm/Ma). Highest accretion rates are found at the bottom of large nodules that repeatedly sink to a level immediately above the redox boundary. There, distinct diagenetic growth conditions prevail and layers of dense laminated Mn oxide of very pure todorokite are formed. The layering of nodules is mainly the result of organisms moving nodules within the oxic surface sediment from diagenetic to hydrogenetic environments. The frequency of such movements is much higher than that of climatic changes. Two types of nodule burial occur in the Peru Basin. Large nodules are less easily moved by organisms and become buried. Consequently, buried nodules generally are larger than surface nodules. This type of burial predominates in basins. At ridges where smaller nodules prevail, burial is mainly controlled by statistical selection where some nodules are not moved up by organisms.

Impact Of Chemical Changes On The Sensory Characteristics Of Coffee Beans During Storage.

Sensory changes during the storage of coffee beans occur mainly due to lipid oxidation and are responsible for the loss of commercial value. This work aimed to verify how sensory changes of natural coffee and pulped natural coffee are related to the oxidative processes during 15 months of storage. During this period, changes in the content of free fatty acids (1.4-3.8 mg/g oil), TBARS values (8.8-10.2 nmol MDA/g), and carbonyl groups (2.6-3.5 nmol/mg of protein) occurred. The intensity of rested coffee flavour in the coffee brew increased (2.1-6.7) and 5-caffeoylquinic acid concentration decreased (5.2-4.6g/100g). Losses were also observed in seed viability, colour of the beans and cellular structure. All the results of the chemical analyses are coherent with the oxidative process that occurred in the grains during storage. Therefore, oxidation would be also responsible for the loss of cellular structure, seed viability and sensory changes.

Chemical potential and the nature of dark energy: The case of a phantom field

The influence of a possible nonzero chemical potential mu on the nature of dark energy is investigated by assuming that the dark energy is a relativistic perfect simple fluid obeying the equation of state, p=omega rho (omega < 0, constant). The entropy condition, S >= 0, implies that the possible values of omega are heavily dependent on the magnitude, as well as on the sign of the chemical potential. For mu > 0, the omega parameter must be greater than -1 (vacuum is forbidden) while for mu < 0 not only the vacuum but even a phantomlike behavior (omega <-1) is allowed. In any case, the ratio between the chemical potential and temperature remains constant, that is, mu/T=mu(0)/T(0). Assuming that the dark energy constituents have either a bosonic or fermionic nature, the general form of the spectrum is also proposed. For bosons mu is always negative and the extended Wien's law allows only a dark component with omega <-1/2, which includes vacuum and the phantomlike cases. The same happens in the fermionic branch for mu < 0. However, fermionic particles with mu > 0 are permitted only if -1 of-state parameter to be omega <-1/2, a result surprisingly close to the maximal value required to accelerate a Friedmann-Robertson-Walker-type universe dominated by matter and dark energy (omega less than or similar to-10/21).

New constraints on the chemical evolution of the solar neighbourhood and Galactic disc(s) Improved astrophysical parameters for the Geneva-Copenhagen Survey

We present a re-analysis of the Geneva-Copenhagen survey, which benefits from the infrared flux method to improve the accuracy of the derived stellar effective temperatures and uses the latter to build a consistent and improved metallicity scale. Metallicities are calibrated on high-resolution spectroscopy and checked against four open clusters and a moving group, showing excellent consistency. The new temperature and metallicity scales provide a better match to theoretical isochrones, which are used for a Bayesian analysis of stellar ages. With respect to previous analyses, our stars are on average 100 K hotter and 0.1 dex more metal rich, which shift the peak of the metallicity distribution function around the solar value. From Stromgren photometry we are able to derive for the first time a proxy for [alpha/Fe] abundances, which enables us to perform a tentative dissection of the chemical thin and thick disc. We find evidence for the latter being composed of an old, mildly but systematically alpha-enhanced population that extends to super solar metallicities, in agreement with spectroscopic studies. Our revision offers the largest existing kinematically unbiased sample of the solar neighbourhood that contains full information on kinematics, metallicities, and ages and thus provides better constraints on the physical processes relevant in the build-up of the Milky Way disc, enabling a better understanding of the Sun in a Galactic context.

The chemical evolution of IC 10

Context. Dwarf irregular galaxies are relatively simple unevolved objects where it is easy to test models of galactic chemical evolution. Aims. We attempt to determine the star formation and gas accretion history of IC 10, a local dwarf irregular for which abundance, gas, and mass determinations are available. Methods. We apply detailed chemical evolution models to predict the evolution of several chemical elements (He, O, N, S) and compared our predictions with the observational data. We consider additional constraints such as the present-time gas fraction, the star formation rate (SFR), and the total estimated mass of IC 10. We assume a dark matter halo for this galaxy and study the development of a galactic wind. We consider different star formation regimes: bursting and continuous. We explore different wind situations: i) normal wind, where all the gas is lost at the same rate and ii) metal-enhanced wind, where metals produced by supernovae are preferentially lost. We study a case without wind. We vary the star formation efficiency (SFE), the wind efficiency, and the time scale of the gas infall, which are the most important parameters in our models. Results. We find that only models with metal-enhanced galactic winds can reproduce the properties of IC 10. The star formation must have proceeded in bursts rather than continuously and the bursts must have been less numerous than similar to 10 over the whole galactic lifetime. Finally, IC 10 must have formed by a slow process of gas accretion with a timescale of the order of 8 Gyr.

High gravity batch and continuous processes for beer production: Evaluation of fermentation performance and beer quality

This study deals with two innovative brewing processes, high gravity batch and complete continuous beer fermentation systems. The results show a significant influence of the variables such as concentration and temperature on the yield factor of the substrate into ethanol and consequently on the productivity of the high gravity batch process. The technological feasibility of continuous production of beer based on yeast immobilization on cheap alternative carriers was also demonstrated. The influence of process parameters on fermentation performance and quality of the obtained beers was studied by sensorial analysis. No significant difference in the degree of acceptance between the obtained products and some traditional market brands was found. (c) 2008 Institute of Chemistry, Slovak Academy of Sciences.

The influence of immobilized biomass and particle size on the fluid dynamics of an anaerobic fluidized bed reactor

Fluid dynamic analysis is an important branch of several chemical engineering related areas, such as drying processes and chemical reactors. However, aspects concerning fluid dynamics in wastewater treatment bioreactors still require further investigation, as they highly influence process efficiency. Therefore, it is essential to evaluate the influence of biofilm on the reactor fluid dynamic behavior, through the analysis of a few important parameters, such as minimum fluidization velocity, bed expansion and porosity, and particle terminal velocity. The main objective of the present work was to investigate the fluid dynamics of an anaerobic fluidized bed reactor, having activated carbon particles as support media for biomass immobilization. Reactor performance was tested using synthetic residual water, which was prepared using the solution employed in BOD determination. The results showed that the presence of immobilized biomass increased particle density and altered the main fluid dynamic parameters investigated.

Finite element modelling of dissipative structures for nonequilibrium chemical reactions in fluid-saturated porous media

We use the finite element method to model and predict the dissipative structures of chemical species for a nonequilibrium chemical reaction system in a fluid-saturated porous medium. In particular, we explore the conditions under which dissipative structures of the species may exist in the Brusselator type of nonequilibrium chemical reaction. Since this is the first time the finite element method and related strategies have been used to study the chemical instability problems in a fluid-saturated porous medium, it is essential to validate the method and strategies before they are put into application. For this purpose, we have rigorously derived the analytical solutions for dissipative structures of chemical species in a benchmark problem, which geometrically is a square. Comparison of the numerical solutions with the analytical ones demonstrates that the proposed numerical method and strategy are robust enough to solve chemical instability problems in a fluid-saturated porous medium. Finally, the related numerical results from two application examples indicate that both the regime and the magnitude of pore-fluid flow have significant effects on the nature of the dissipative structures that developed for a nonequilibrium chemical reaction system in a fluid-saturated porous medium. The motivation for this study is that self-organization under conditions of pore-fluid flow in a porous medium is a potential mechanism of the orebody formation and mineralization in the upper crust of the Earth. (C) 2000 Elsevier Science S.A. All rights reserved.

Semiochemicals and social signaling in the wild European rabbit in Australia: II. Variations in chemical composition of chin gland secretion across sampling sites

The volatile components of the chin gland secretion of the wild European rabbit, Oryctolagus cuniculus (L.), were investigated with the use of gas chromatography. Studies of the chemical nature of this secretion by previous workers demonstrated that it was important in the maintenance of social structure in this species. This study identified 34 different volatile components that consist primarily of aromatic and aliphatic hydrocarbons. Especially common are a series of alkyl-substituted benzene derivatives that provide most of the compound diversity in the secretion. Samples of chin gland secretion collected from animals at three different geographical locations, separated by more than 100 km, showed significant differences in composition. This work suggests that variation among populations needs to be considered when undertaking semiochemical research. Alternate nonparametric methods are also used for the analysis of chromatographic data.

Integrating toxicity testing in the wastewater management of chemical storage terminals - A proposal based on a ten-year study

Wastewater control at storage terminals of liquid chemical products in bulk is very difficult because of the variety of products handled in the facilities generating effluents of variable composition. The main objective of this work was to verify if the Vibrio fischeri acute toxicity test could be routinely included in the wastewater management of those facilities along with physical and chemical analysis in order to evaluate and improve the quality of the generated effluents. The study was performed in two phases before and after the implementation of better operational practices/treatment technologies. Chemical oxygen demand (COD) and toxicity of treated effluents did not correlate showing that effluents with low COD contain toxic substances and non-biodegradable organic matter, which may be not degraded when discharged into the aquatic environment. Segregation of influents or pre-treatment based on toxicity results and biodegradability index were implemented in the facilities generating significant improvements in the quality of final effluents with reduction of Biochemical oxygen demand (BOD) and toxicity. The integration of physical and chemical analysis with the V.fischeri toxicity test turned out to be an excellent tool for wastewater management in chemical terminals allowing rapid decision making for pollution control and prevention measures. Reuse of rain water was also proposed and when implemented by the facilities resulted in economical and environmental benefits. (C) 2010 Elsevier B.V. All rights reserved.