Synthesis of novel aminoquinolines with potential leishmanicidal and antimalarial biological activity / Síntese de novas aminoquinolinas com potencial actividade biológica leishmanicida e antimalárica

Leishmaniasis is a disease transmitted by different parasite species of the genus Leishmania, while malaria, by protozoa of the genus Plasmodium sp. These diseases affect tropical and subtropical regions, where about half of the world's population live. However, leishmaniasis and malaria are considered neglected diseases because these regions are poor, and consequently have precarious essential sanitation networks. In response to the lack of vaccines and effective medical measures, some natural and synthetic medicines are used as forms of treatment, such as quinoline derivatives necessary to treat malaria. Even so, the parasites have shown resistance to forms of treatment, which makes needed the constant development of new drugs with potential against them. Quinoline derivatives, chloroquine analogues, have potential activity for the diseases of interest, while anilines are molecules used in nucleophilic reactions on different substrates. Therefore, the work consisted of exploring the synthesis between these two compounds through subsequent reactions involving the formation of intermediates that resulted in the products of interest. Twelve novel derivatives with potential leishmanicidal and antimalarial biological activity were synthesized. The molecules produced were purified and rightly characterized by several methods, such as mass spectrometry, infrared spectroscopy, and Nuclear Magnetic Resonance of Carbon (13C) and Hydrogen (1H). Also, were obtained the melting points of the synthesized molecules. Finally, all products were sent for biological tests against the parasites, getting highly effective results for the protozoa responsible for leishmaniasis.

Nb/Sn Liquid-Solid Reactive Diffusion Couples and Their Application to Determination of Phase Equilibria and Interdiffusion Coefficients of Nb-Sn Binary System

Nb3Sn plays an irreplaceable role in superconducting parts due to its stable performance under high field conditions. Accurate phase equilibria and interdiffusion coefficients are of great significance for designing novel Nb3Sn superconductors. However, the related experimental information is still in a state of scarcity because of the difficulty in fabrication of Nb-Sn alloys caused by the large difference in melting points of Nb and Sn. In this paper, a simple but pragmatic approach was first proposed to prepare the Nb/Sn liquid-solid reactive diffusion couples (LSDCs) at 1100 °C and 1200 °C, of which the phase identification of the formed layer and the measurement of composition-distance profiles were conducted. The formed layer in Nb/Sn LSDCs was confirmed to be Nb3Sn compound. While the measured composition profiles were employed to determine the phase equilibria according to the local equilibrium hypothesis and the interdiffusion coefficients with an aid of the latest version of HitDIC software. The determined phase equilibria of Nb3Sn, (Nb) and liquid show good agreement with the assessed phase diagram. While the calculated interdiffusion coefficients and activation energy for diffusion in Nb3Sn are consistent with both experimental and theoretical data in the literature. Moreover, the growth of the formed Nb3Sn layer in Nb/Sn LSDCs was also found to be diffusion controlled. All the obtained phase equilibria and interdiffusion coefficients are of great value for further thermodynamic and kinetic modeling of the Nb-Sn system. Furthermore, it is anticipated that the presently proposed approach of fabricating liquid-solid reactive diffusion couple should serve as a general one for various alloy systems with large differences in melting points.

Application of functional coatings by supersonic thermal plasma flows

Development of modern high-speed technologies for thermal spraying proves that deposition of high-quality dense coatings requires velocity of sprayed particles to be 600 m/s and above. Plasma spraying is the most versatile and highly productive deposition method of various functional coatings without any limitations on the melting points of the sprayed materials. Present work describes a DC plasma torch designed for operation in a supersonic mode. The supersonic plasma torch features de Laval nozzle, utilization of air as a plasma-forming gas, and annular injection unit for delivery of the powder to the plasma jet. The comparison of NiCr and NiAl coatings deposited both in subsonic and supersonic modes are presented. Methods for further increasing the sprayed particles’velocity and the requirements for their heating temperature are proposed.

5-Nitrotetrazol and 1,2,4-Oxadiazole Methylene-Bridged Energetic Compounds: Synthesis, Crystal Structures and Performances

A new structural type for melt cast materials was designed by linking nitrotetrazole ring with 1,2,4-oxadiazole through a N-CH2-C bridge for the first time. Three N-CH2-C linkage bridged energetic compounds, including 3-((5-nitro-2H-tetrazol-2-yl) methyl)-1,2,4-oxadiazole (NTOM), 3-((5-nitro-2H-tetrazol-2-yl)methyl)-5-(trifluoromethyl)-1,2,4 -oxadiazole (NTOF) and 3-((5-nitro-2H-tetrazol-2-yl)methyl)-5-amine-1,2,4-oxadiazole (NTOA), were designed and synthesized through a two-step reaction by using 2-(5-nitro-2H-tetrazole -2-yl)acetonitrile as the starting material. The synthesized compounds were fully characterized by NMR (1H, 13C), IR spectroscopy and elemental analysis. The single crystals of NTOM, NTOF and NTOA were successfully obtained and investigated by single-crystal X-ray diffraction. The thermal stabilities of these compounds were evaluated by DSC-TG measurements, and their apparent activation energies were calculated by Kissinger and Ozawa methods. The crystal densities of the three compounds were between 1.66 g/cm3 (NTOA) and 1.87 g/cm3 (NTOF). The impact and friction sensitivities were measured by standard BAM fall-hammer techniques, and their detonation performances were computed using the EXPLO 5 (v. 6.04) program. The detonation velocities of the three compounds are between 7271 m/s (NTOF) and 7909 m/s (NTOM). The impact sensitivities are >40 J, and the friction sensitivities are >360 N. NTOM, NTOF and NTOA are thermally stable, with decomposition points > 240 °C. The melting points of NTOM and NTOF are 82.6 °C and 71.7 °C, respectively. Hence, they possess potential to be used as melt cast materials with good thermal stabilities and better detonation performances than TNT.

A Review of the electrochemical corrosion of metals in choline chloride based deep eutectic solvents

Deep eutectic solvents (DESs) are a class of mixtures with melting points notably lower than those of their raw constituent components. These liquids have found a tremendously wide spectrum of applications in the last two decades of their research, so their contact and interaction with technical metals and alloys are inevitable. Therefore, the corrosivity of DESs towards metals is an extremely important topic. This review summarizes research efforts collected in the last two decades related to the corrosion rate of various metals in different DESs. Since the DESs are mainly composed of organic raw compounds, and by their physicochemical properties they may be regarded as a separate class of ionic liquids, the literature data about DESs corrosivity has been compared to the data related to the corrosivity of various organic solvents and ionic liquids as well. All the results gained until now show significantly low corrosivity of DESs. This observation is discussed in relation to the chemical composition of DESs. The absence of the oxidizing agents, the inhibitory action of organic ions and molecules, high viscosity and low electrical conductivity have been recognized as the main factors contributing to the low metal corrosion rate in DESs.

Dissimilar Rotary Friction Welding of Inconel 718 to F22 Using Inconel 625 Interlayer

Dissimilar metal joining has always been a challenging task because of the metallurgical incompatibility and difference in melting points of alloys being joined. Diffusion and mixing of alloying elements from dissimilar base metals at the weld often cause unwanted metallurgical changes resulting in unsuccessful welds or underperformance of the weldment. Solid-state dissimilar friction welds of Inconel 718 and F22 were prepared in this study with an Inconel 625 interlayer to address the carbon enrichment of Inconel 718 during the welding. Defect-free rotary friction welds were produced in this study. Microstructural and mechanical properties investigation of the weldments and base metals was carried out, and results were analysed. Intermixing zone was observed at the weld interface due to the softening of the metal at the interface and rotatory motion during the welding. The high temperatures and the plastic deformation of the intermixing zone and thermo-mechanically affected zone (TMAZ) resulted in the grain refinement of the weld region. The highest hardness was observed at the Inconel 718/F22 weld interface due to the plastic strain and the carbon diffusion. The tensile specimens failed in the F22 base metal for the weld prepared with and without the Inconel 625 interlayer. Inconel 718/F22 welds exhibited lower toughness values compared to the Inconel 718/F22 welds prepared with Inconel 625 interlayer.

Strategic synthon approach in obtaining cocrystals and cocrystal polymorphs of a high-Z′ system deferiprone – an anti-thalassemia drug

Compounds with more than one molecule in the crystallographic asymmetric unit (Z′ > 1) display a noticeably stronger propensity to form cocrystals. Deferiprone is an anti-thalassemia drug known to exhibit polymorphic behaviour. Previously, three polymorphs were reported out of which one of them exhibited Z′ > 1. In the present manuscript, a fourth polymorph of deferiprone was identified and it also possessed Z′ > 1. All the four polymorphs showed similar hydrogen bonding features and differed in crystal packing. The ability of deferiprone to crystallize as Z′ > 1 prompted us to investigate the hydrogen bonding and synthon variation upon cocrystallization of deferiprone with hydroxyl-group-containing coformers such as catechol, hydroquinone, phloroglucinol, resorcinol and pyrogallol. Crystallization attempts along with PXRD analysis aided in obtaining 11 new cocrystal structures which involve different stoichiometric cocrystals and some polymorphs. Synthon analysis, crystal packing as well as thermal behaviour were assessed and compared. The presence of multiple phases in each cocrystal system in its respective bulk powders was identified and quantified using PXRD and Rietveld analysis. Homosynthons were observed in three co-crystal systems, while a heterosynthon was observed in five systems. The combination of both homo- and heterosynthon was observed in three cocrystal systems. The phase transformation events were observed in most of the systems. In nine co-crystal systems, the melting points were observed intermediate between those of the API and the coformers.

The Crystallization of Active Pharmaceutical Ingredients with Low Melting Points in the Presence of Liquid–Liquid Phase Separation

Liquid–liquid phase separation (LLPS) during the crystallization of active pharmaceutical ingredients (APIs) often causes agglomeration and other quality issues in crystal products; thus, it should be avoided if possible. However, LLPS in the crystallization of APIs with low melting points cannot be circumvented in some cases due to yield considerations. The crystallization of ibuprofen in an ethanol/water mixture was studied to explore methods to reduce agglomeration in the presence of LLPS. It was found that unseeded crystallization produced agglomerates when LLPS took place. The two liquid phases resulting from LLPS underwent LLPS again when they were cooled separately, indicating the dynamic nature of LLPS. Seeding and seed ageing at a low supersaturation were very effective in mitigating agglomeration. The effects of two widely used surfactants, i.e., Tween 80 and hydroxypropyl methylcellulose (HPMC), on LLPS and crystallization were confirmed preliminarily. More work needs to be conducted to explore their usefulness in LLPS handling. The findings and techniques presented in this study may be applicable to the crystallization of other APIs with low melting points.