Orientador: Prof. Dr. Fabio Furlan Ferreira / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2017. / A malária, apesar de ser uma doença tratável, ainda continua causando um grande número de mortes, principalmente no continente africano, sendo considerada uma das doenças parasitárias mais prevalecentes no mundo. A recomendação da organização mundial da saúde (OMS) para o tratamento da malária consiste na utilização de terapia combinada de artemisinina (artemisinin combined therapy - ACT). A ACT visa combinar a artemisinina ou um derivado com outro fármaco antimalárico que tenha um maior tempo de meia-vida e, assim, tornar o tratamento mais eficaz e evitar o aparecimento de resistência dos parasitas aos antimaláricos. O MEFAS é um novo sal híbrido derivado do artesunato e da mefloquina ¿ dois compostos antimaláricos ¿ que apresenta dois mecanismos de ação diferentes e promissoras características que viabiliza a sua utilização no tratamento da malária. Neste contexto, foi realizado um estudo estrutural do MEFAS em estado sólido e foi proposta uma síntese mecanoquímica para sua obtenção. Com o uso da difração de raios X por policristais (DRXP) foi verificado que uma das amostras de MEFAS estudadas, apresenta uma fase amorfa. A estabilidade química do MEFAS também foi estudada, visto que fases amorfas tendem a ser instáveis; os resultados mostraram que o MEFAS se degradou após dezoito meses de armazenamento, formando a diidroartemisinina (DHA). Isto foi evidenciado com o uso das técnicas de espectroscopia vibracional na região do infravermelho por transformada de Fourier (FTIR), ressonância magnética nuclear de estado sólido (RMN) e também pelos dados de DRXP e método de Rietveld. A estabilidade química do MEFAS em solventes orgânicos também foi estudada. Para os solventes testados, o MEFAS demonstrou ser estável quimicamente apenas em éter etílico. Por fim, uma rota de síntese via mecanoquímica é proposta para a obtenção do MEFAS, com a possibilidade de utilização de pequenas quantidades de solventes. Essa é uma boa estratégia, pois é uma rota de síntese mais rápida, comparada com a obtenção do MEFAS via reação química em solução, e ainda é uma síntese considerada "química verde", ou seja, um método sustentável. Os resultados obtidos pelas técnicas de FTIR e RMN indicaram que a síntese mecanoquímica foi promissora na formação do MEFAS, sendo que após quinze minutos de moagem foi obtido o sal hibrido desejado. / Malaria, despite being a treatable disease, still continues to cause a large number of deaths, especially on the African continent, and is considered one of the most prevalent parasitic diseases in the world. The recommendation of the World Health Organization (WHO) for the treatment of malaria is the use of artemisinin combination therapy ¿ ACT. ACT aims to combine artemisinin or derivative with another antimalarial drug that has a longer half-life and thus make treatment more effective and prevent the emergence of parasite resistance to antimalarials. The MEFAS, a new hybrid salt derived from artesunate and mefloquine ¿ two antimalarials compounds ¿ has two different mechanisms of action and presents promising characteristics that make its use feasible in the treatment of malaria. In this context, a structural study of MEFAS in solid state was performed and a mechanochemical synthesis was proposed to obtain this hybrid salt. With the use of X-ray powder diffraction data (XRPD) it was verified that the MEFAS is in the amorphous form. The chemical stability of MEFAS has also been studied, since that the amorphous phases tend to be unstable; the results showed that MEFAS degraded after eighteen months of storage. When degradation of this hybrid salt occurs, dihydroartemisinin (DHA) is formed. This was evidenced by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) as well as by the Rietveld method with X-ray powder diffraction data. Finally, a route of synthesis via mechanochemistry is proposed to obtain the MEFAS, with the possibility of using catalytic amounts of solvents. This is a good strategy and is still a synthesis considered "green chemistry", that is, a more ecologically correct method. The results obtained by FTIR and NMR techniques indicated that the mechanochemical synthesis was promising in the formation of MEFAS, after fifteen minutes of milling the desired hybrid salt was obtained.

Mechanochemically synthesized cobalt oxide-based particles are employed for the catalytic reduction of 4-nitrophenol (4NP), a toxic water contaminant. This reduction produces 4‑aminophenol (4AP), a less toxic, pharmaceutical precursor for drugs such as paracetamol. The indicated reduction has been completed previously using noble metals and/or catalysts requiring extensive solvent use, and time as part of their preparation. The cost and synthesis of these noble metal catalysts hinders the sustainable broad scale application as an environmental remediation solution. The catalyst synthesis explored in this study utilizes the green chemistry technique of vibratory ball-milling and annealing cobalt oxide-based particles at different temperatures, producing unique agglomerates with differing surface structure and catalytic properties. Additional investigation into the mechanism through temperature, pH, and change in pressure over the reaction is completed. Further analysis shows that these catalysts are efficient for the reduction of 4-amino-3-nitrophenol and 2-amino-5-nitrophenol with unique catalytic rates. Finally, it is found that the application of this reduction in a flow process has potential for use on a broader scale.

Yes / A study on the translation of a solid-state synthetic reaction from a mechanochemical mixer-mill to a continuous twin-screw extruder is discussed herein. The study highlights some considerations to be made and parameters to be tested in the context of a model fluorination reaction, which is the first organic fluorination to be attempted using extrusion. Upon optimization, which features the first use of grinding auxiliary solids to enable effective synthetic extrusion, the difluorination reaction was successfully translated to the extruder, leading to a 100-fold improvement in Space Time Yield (STY); 29 kg m−3 day−1 in a mixer mill to 3395 kg m−3 day−1 in a twin screw extruder. / D. L. B is grateful to the EPSRC for a First Grant (D. L. B. EP/P002951/1), CRD for a studentship award to J. L. H., Queen’s University Belfast for a Visiting Research Fellowship and the School of Chemistry at Cardiff University for generous support. S. L. J. is grateful to EPSRC for support (EP/L019655/1).

No / Mechanochemical synthesis has been applied to the rapid synthesis of Deep Eutectic Solvents (DESs), including Reline 200 (choline chloride : urea, 1 : 2), in a continuous flow methodology by Twin Screw Extrusion (TSE). This gave products in higher purity and with Space Time Yields (STYs), four orders of magnitude greater than for batch methods

Nanostructured fayalite (α-Fe2SiO4) with a large volume fraction of interfaces is synthesized for the first time via single-step mechanosynthesis, starting from a 2α-Fe2O3 + 2Fe + 3SiO2 mixture. The nonequilibrium state of the as-prepared silicate is characterized by the presence of deformed polyhedra in the interface/surface regions of nanoparticles. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The oxidation of lignin model compounds was studied in conventional solvents in parallel with oxidations in ionic liquid solvents. Catalyst systems were investigated in ionic liquid solvents to determine how reaction rates and the selectivity for benzylic carbon oxidation were affected. Oxidation rates were often lower in ionic liquids than in conventional solvents ‒ as indicated by lower conversion in a standard reaction time ‒ likely due, at least in part, to the higher viscosity of ionic liquids. Mechano chemical treatment of Indulin AT kraft lignin by ball milling with KOH and toluene produced significant carbonyl functionality, among other changes. The chemical reactivity of the lignin was increased, resulting in greater lignin degradation from porphyrin oxidation followed by Baeyer-Villiger oxidation. The mechanochemical treatment produced a level of lignin oxidation that was similar to that produced by porphyrin-catalyzed oxidation. Combining mechanochemical treatment with porphyrin oxidation produced a synergistic positive effect on the depolymerization of lignin, as demonstrated by a significantly higher yield of monomers. The methyl ester of vanillic acid was obtained as the main monomeric product (after methylation), along with a small amount of methyl 5-carbomethoxyvanillate.

Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, previous computational models have succinctly reproduced components of the EMT program. In this work, we have developed a computational framework to evaluate the mechanochemical signaling dynamics of EMT at the molecular, cellular, and tissue scale. First, we established a model of cell-matrix and cell-cell feedback for predicting mechanical force distributions within an epithelial monolayer. These findings suggest that tensional homeostasis is the result of cytoskeletal stress distribution across cell-cell junctions, which organizes otherwise migratory cells into a stable epithelial monolayer. However, differences in phenotype-specific cell characteristics led to discrepancies in the experimental and computational observations. To better understand the role of mechanical cell-cell feedback in regulating EMT-dependent cellular processes, we introduce an EMT gene regulatory network of key epithelial and mesenchymal markers, E-cadherin and N-cadherin, coupled to a mechanically-sensitive intracellular signaling cascade. Together these signaling networks integrate mechanical cell-cell feedback with EMT-associated gene regulation. Using this approach, we demonstrate that the phenotype-specific properties collectively account for discrepancies in the computational and experimental observations. Additionally, mechanical cell-cell feedback suppresses the EMT program, which is reflected in the gene expression of the heterogeneous cell population. Together, these findings advance our understanding of the complex interplay in cell-cell and cell-matrix feedback during EMT of both normal physiological processes as well as disease progression.

The aim of this study was to produce zirconium diboride (ZrB2) and other metal borides such as lanthanum hexaboride (LaB6) and cerium hexaboride (CeB6) by magnesiothermic reduction (reaction of metal oxide, boron oxide and magnesium) using volume combustion synthesis (VCS) and mechanochemical process (MCP). Production of ZrB2 by VCS in air occurred with the formation of side products, Zr2ON2 and Mg3B2O6 in addition to MgO. Formation of Zr2ON2 was prevented by conducting VCS experiments under argon atmosphere. Wet ball milling was applied before leaching for easier removal of Mg3B2O6. Leaching in 5 M HCl for 2.5 hours was found to be sufficient for removal of MgO and Mg3B2O6. By MCP, 30 hours of ball milling was enough to produce ZrB2 where 10% of excess Mg and B2O3 were used. MgO was easily removed when MCP products were leached in 1 M HCl for 30 minutes. Complete reduction of ZrO2 could not be achieved in either production method because of the stability of ZrO2. Hence, after leaching VCS or MCP products, final product was composed of ZrB2 and ZrO2. Formation of LaB6 and CeB6 were very similar to each other via both methods. Mg3B2O6 appeared as a side product in the formation of both borides by VCS. After wet ball milling, products were leached in 1 M HCl for 15 hours and pure LaB6 or CeB6 was obtained. As in ZrB2 production, 30 hours of ball milling was sufficient to form these hexaborides by MCP. MgO was removed after leaching in 1 M HCl for 30 minutes and the desired hexaboride was obtained in pure form.

The mechanical treatment of solids is one of the most common and widely used operations. The volume of solids subjected to chemical treatment is very large too. Therefore, combining these two ways into one seems to be a logical solution. This method is called the mechanochemical processing of materials. Processing materials in this way has many advantages. On the one hand, this processing is economically as well as technologically feasible. Even the materials that not react together in conventional way can be prepare in this way. The mechanochemistry/mechanochemical synthesis utilizes the mechanical energy to activate chemical reactions and structural changes. The aluminothermic reduction reactions induced by the high – energy ball milling are gaining importance because of the potential applications like the synthesis of microcrystalline and nanocrystalline in – situ metal matrix composites. The mechanical activation of the chemical reactions by high energy ball milling often changes the reaction mechanism and produces metastable materials. Changes of reaction mechanisms during mechanical alloying on four different systems were studied. The system was based on this composition: Al - B2O3 - X (X = C, Ti, Nb, Cr). The possibility of another in – situ reactions during spark plasma sintering process (SPS) was also investigated. All systems were mechanically alloyed under the same conditions. After alloying, on each system scanning electron microscopy was performed and qualitative and quantitative analysis was performed using X-ray diffraction. The indentation hardness and the indentation modulus of elasticity were evaluated using nanoindentation. All analyzes were performed after mechanical alloying as well as SPS and the results were compared to each other. Based on the results, a change of reaction mechanisms was proposed for all systems. It has been found that metal matrix composites are formed and, when chromium is used, hybrid composite material reinforced with intermetallic phase and aluminum borate has been developed.

<p>Tantalum, niobium, stainless steels, and nickel are corrosion-resistant metals that have become critical in many industrial sectors. Due to the demanding environments and temperatures in which they operate, few materials can serve as substitutes. The advantages of these materials are offset by the difficulties in their machining. Belonging to a group of metals and alloys often referred to as ‘gummy’, their poor machinability or gumminess is manifest as thick chip formation, large cutting forces, and poor finish on cut surface. Hence, machining costs can be prohibitive, and applications limited. The gumminess has been attributed broadly to their high strain-hardening capacity.</p> <p>To examine why these metals are difficult to machine, we used direct <i>in situ</i> observations of the cutting process with a high-speed imaging system, complemented by force measurements. The observations showed that chip formation occurred by repeated large-amplitude folding of the material – sinuous flow – with vortex-like components and extensive redundant deformation. The folding was particularly severe in Ta and Nb. Although Ta and Nb displayed a higher rate of fold nucleation than the Ni and stainless steel, the flow dynamics underlying chip formation across the metals was the same – sinuous flow nucleated by a plastic (buckling-type) flow instability on the workpiece surface just ahead of the advancing tool. The large strains and energy dissipation associated with sinuous flow is the reason for the poor machinability of these metals. </p> <p>Prior work with Cu and Al has shown that sinuous flow can be disrupted and replaced by an energetically more favorable (segmented) flow mode, characterized by quasi-periodic fracture, when suitable chemical media are applied to the initial workpiece surface – a mechanochemical effect. The segmented flow is beneficial for machining processes since it involves much smaller forces and plastic strains. It has been hypothesized that the chemical media influence the flow through their adsorption onto the workpiece surface, thereby altering the surface energy and/or surface stress, and effecting a local embrittlement (ductile-to-brittle transition). </p> <p>We demonstrate similar media (mechanochemical) effects and segmented flow development in cutting of the corrosion-resistant metals, with significant benefits for their machining. These benefits include > 35 percent reduction in the cutting force/energy, and an order of magnitude improvement in cut surface quality (finish, tears and residual strain). Importantly, the experiments with the corrosion-resistant metals provide strong evidence that it is indeed adsorption – not corrosion, as in case of hydrogen embrittlement – that underpins the mechanochemical effect. The experiments used chemical agents well-known for their strong adsorption to metal surfaces, namely green corrosion inhibitors (e.g., plant extracts, propolis) and other natural organic molecules (e.g., dyes, antibacterial drugs, cow’s milk). Lastly, the suitability and application of the mechanochemical effect at industrial cutting speeds is explored in turning experiments with these corrosion-resistant metals. Collectively, our observations, measurements, and analysis show that the gumminess of metals in cutting is due to sinuous flow; the gumminess can be eliminated by use of chemical media; and adsorption is the key to engendering the mechanochemical effect. Implications of the results for industrial processes ranging from machining to particle comminution, and for sustainable manufacturing are discussed.</p> <br>