In the past few years, ionic liquids (ILs) with cyano-functionalized anions have shown to be improved candidates for electrochemical and separation applications. Nevertheless, only scattered data ...exist hitherto and a broad analysis of their structure–property relationship has yet to be attempted. Therefore, in this work, a systematic study of the densities, viscosities and refractive indices of imidazolium-based ILs with cyano-functionalized anions was carried out at 0.1 MPa within a broad temperature range (from 278 to 363 K). The ILs under study are based on 1-alkyl-3-methylimidazolium cations (alkyl = ethyl, butyl and hexyl) combined with the SCN−, N(CN)2−, C(CN)3− and B(CN)4− anions. The selected matrix of cation/anion combinations allows us to provide a detailed and comprehensive investigation of the influence of the −CN group through an analysis of the thermophysical properties of the related ILs. The results show that, regardless of the cation, the densities decrease with an increase in the number of cyano groups or anion molecular weight. Moreover, for a fixed cation and temperature, the refractive index of the ILs decreases according to the rank: SCN− > N(CN)2− ≈ C(CN)3− > B(CN)4−. On the other hand, no clear trend was observed for the viscosity of ILs and the respective number of −CN groups. The viscosity dependence on the cyano-functionalized anions decreases in the order: SCN− > B(CN)4− > N(CN)2− > C(CN)3−. The isobaric thermal expansion coefficient, the derived molar refraction, the free volume, and the viscosity energy barrier of all compounds were estimated from the experimental data and are presented and discussed. Finally, group contribution models were applied, and new group contribution parameters are presented, extending these methods to the prediction of the ILs properties.
This work reports on the systematic investigation of the influence of the cation alkyl side-chain length of 1-alkyl-3-methylimidazolium chloride ionic liquids (C n C1imCl, with n = 1–14), as well as ...the substitution of the most acidic hydrogen in the imidazolium core by a methyl group, in the formation of aqueous biphasic systems. Ternary phase diagrams, tie-lines, tie-line slopes, tie-line lengths, and critical points for the several systems (ionic liquid + water + K3PO4) were determined and reported at 298 K and atmospheric pressure. It is shown that the increase of the cation alkyl chain length enhances the formation of aqueous biphasic systems if alkyl chain lengths until the hexyl are considered. The results for longer alkyl side chains show, nevertheless, that the phenomenon is more complex than previously admitted and that the capacity of the ionic liquid to self-aggregate also governs its ability to phase separate. The effect of the alkyl side-chain length on the phase-forming ability of the studied systems was quantitatively evaluated based on their salting-out coefficients derived from a Setschenow-type behavior. The aptitude of each ionic liquid for liquid–liquid demixing as a function of the cation alkyl side-chain length clearly follows three different patterns. The results obtained for the trisubstituted cation indicate that the hydrogen-bonding interactions between the ionic liquid cation and water are not a relevant issue in the formation of aqueous two-phase systems. In general, for the C n C1imCl series, a multifaceted ratio between entropic contributions and the ability of each ionic liquid to self-aggregate in aqueous media control the phase behavior.
Despite many previous important contributions to the characterization of the liquid−liquid phase behavior of ionic liquids (ILs) plus water systems, a gap still exists as far as the effect of isomers ...(of ILs) is concerned. Therefore, in this work, a comprehensive study of the liquid−liquid equilibria between water and isomeric pyridinium-based ionic liquids has been performed. Atmospheric pressure mutual solubilities between water and pyridinium-based ionic liquids combined with the common anion bis(trifluoromethyl)sulfonylimide were experimentally determined between (288.15 and 318.15) K. The main goal of this work is to study the isomeric effects on the pyridinium-based cation, namely, the structural and positional isomerism, as well as the alkyl side chain length. To the best of our knowledge, the influence of both structural and positional isomerism on the liquid−liquid behavior in ionic-liquid-water-containing systems is an unexplored field and is here assessed for the first time. Moreover, from the experimental solubility data, several infinite dilution molar thermodynamic functions of solution, namely, the Gibbs energy, the enthalpy, and the entropy, were estimated and discussed. In addition, aiming at gathering a broader picture of the underlying thermodynamic solvation phenomenon, molecular dynamics simulations were also carried out for the same experimental systems.
The design of ionic liquids has been focused on the cation-anion combinations but other more subtle approaches can be used. In this work the effect of the branching of the cation alkyl chain on the ...design of ionic liquids (ILs) is evaluated. The mutual solubilities with water and toxicities of a series of bis(trifluoromethylsulfonyl)-based ILs, combined with imidazolium, pyridinium, pyrrolidinium, and piperidinium cations with linear or branched alkyl chains, are reported. The mutual solubility measurements were carried out in the temperature range from (288.15 to 323.15) K. From the obtained experimental data, the thermodynamic properties of the solution (in the water-rich phase) were determined and discussed. The COnductor like Screening MOdel for Real Solvents (COSMO-RS) was used to predict the liquid-liquid equilibrium. Furthermore, molecular dynamic simulations were also carried out aiming to get a deeper understanding of these fluids at the molecular level. The results show that the increase in the number of atoms at the cation ring (from five to six) leads to a decrease in the mutual solubilities with water while increasing their toxicity, and as expected from the well-established relationship between toxicities and hydrophobicities of ILs. The branching of the alkyl chain was observed to decrease the water solubility in ILs, while increasing the ILs solubility in water. The inability of COSMO-RS to correctly predict the effect of branching alkyl chains toward water solubility on them was confirmed using molecular dynamic simulations to be due to the formation of nano-segregated structures of the ILs that are not taken into account by the COSMO-RS model. In addition, the impact of branched alkyl chains on the toxicity is shown to be not trivial and to depend on the aromatic nature of the ILs.
Background Chagas Disease (CD) affects 6-7 million people worldwide and is related to poverty-promoting conditions. Chronic asymptomatic cases are mostly invisible to health systems. Aiming (1) to ...translate CD discoveries into education/information practices to raise alertness and empowerment of affected people; and (2) to perform an active search of CD cases, articulating intersectoral actions to improve the access of infected people to the local health service for the treatment of CD; our research group developed and tested under field conditions as innovative social technology: an itinerant education interdisciplinary setting named "Chagas Express XXI" (CE21). Methodology CE21 was created as an "imaginary train" with ~40 ArtScience workshops, games, laboratory activities and conversation circles. An entry/exit plus six activity modules combined associations of affected people, microscopic observations, One Health education, and wellness activities. CE21 was conceived as a social technology, since all the processes were co-created with CD patients and inter-sector local partners. Descriptive statistics showed quantitative data collected throughout the expeditions (CD knowledge, serological results). Qualitative data accessed the public perceptions about the education activities. Principal findings CE21 was exhibited in local educational institutions (schools, universities) in four cities, engaging 2,117 people that evaluated the 41 activities carried out. Citizens and health professionals enjoyed acquisition of information related to blood, parasites, vectors, reservoirs, environmental changes, and social determinants of CD. Further, local legacies of 600 participants volunteer for health promotion groups and CD associations, local empowerment groups to fight for better health conditions, and 05 mural paintings. We observed that 81% of the participants ignored the possibility of treating CD while 52% of the participants requested a blood test for CD showing seropositivity in 20% of them. Conclusions CE21 is a social technology potentially useful for health and science education and active search of asymptomatic CD chronic cases. Moreover, this technology may be adapted to understand and to cooperate in other potentially epidemic situations, especially NTDs related.
Glioblastoma (GBM) is a deadly and therapy resistant malignant brain tumour, characterized by an aggressive and diffuse growth pattern, which prevents complete surgical resection. Despite advances in ...the identification of genomic and molecular alterations that fuel the tumour, average patient survival post-diagnosis remains very low (∼14.6-months). In addition to being highly heterogeneous, GBM tumour cells exhibit high adaptive capacity to targeted molecular therapies owing to an established network of signalling cascades with functional redundancy, which provides them with robust compensatory survival mechanisms. Here, we investigated whether a multimodal strategy combining multitargeted tyrosine kinase inhibitors (MTKIs) and microRNA (miRNA) modulation could overcome the signalling pathway redundancy in GBM and, hence, promote tumour cell death. By performing a high-throughput screening, we identified a myriad of miRNAs, including those belonging to the miR-302-3p/372-3p/373-3p/520-3p family, which coordinately act with the MTKI sunitinib to decrease GBM cell viability. Two members of this family, hsa-miRNA-302a-3p and hsa-miRNA-520 b, were found to modulate the expression of receptor tyrosine kinase mediators (including AKT1, PIK3CA and SOS1) in U87 and DBTRG human GBM cells. Importantly, administration of mimics of these miRNAs with sunitinib or axitinib resulted in decreased tumour cell proliferation and enhanced cell death, whereas no significant effect was observed when coupling miRNA modulation with temozolomide, the first-line drug for GBM therapy. Overall, our results provide evidence that combining the 'horizontal' inhibition of signalling pathways promoted by MTKIs with the 'vertical' inhibition of the downstream signalling cascade promoted by hsa-miR-302a-3p and hsa-miR-520 b constitutes a promising approach towards GBM treatment.
This work presents and highlights the differentiation of the physicochemical properties of the C1HimNTf2, C2HimNTf2, 1C1 2C1HimNTf2, and 1C4 2C1 3C1imNTf2 that is related with the strong bulk ...interaction potential, which highlights the differentiation on the physicochemical arising from the presence of the acidic group (N–H) as well as the methylation in position 2, C(2), of the imidazolium ring. Densities, viscosities, refractive indices, and surface tensions in a wide range of temperatures, as well as isobaric heat capacities at 298.15 K, for this IL series are presented and discussed. It was found that the volumetric properties are barely affected by the geometric and structural isomerization, following a quite regular trend. A linear correlation between the glass transition temperature, T g, and the alkyl chain size was found; however, ILs with the acidic N–H group present a significant higher T g than the 1C N‑1 3C1imNTf2 and 1C N 3C N imNTf2 series. It was found that the most viscous ILs, (1C1HimNTf2, 1C2HimNTf2, and 1C1 2C1HimNTf2) have an acidic N–H group in the imidazolium ring in agreement with the observed increase of energy barrier of flow. The methylation in position 2, C(2), as well as the N–H acidic group in the imidazolium ring contribute to a significant variation in the cation–anion interactions and their dynamics, which is reflected in their charge distribution and polarizability leading to a significant differentiation of the refractive indices, surface tension, and heat capacities. The observed differentiation of the physicochemical properties of the 1C1HimNTf2, 1C2HimNTf2, 1C1 2C1HimNTf2, and 1C4 2C1 3C1imNTf2 are an indication of the stronger bulk interaction potential, which highlights the effect that arises from the presence of the acidic group (N–H) as well as the methylation in position 2 of the imidazolium ring.
Abstract In a recent study, we demonstrated the immunogenic properties of a new malaria vaccine polypeptide based on a 19 kDa C-terminal fragment of the merozoite surface protein-1 (MSP119 ) from ...Plasmodium vivax and an innate immunity agonist, the Salmonella enterica serovar Typhimurium flagellin (FliC). Herein, we tested whether the same strategy, based on the MSP119 component of the deadly malaria parasite Plasmodium falciparum , could also generate a fusion polypeptide with enhanced immunogenicity. The His6 FliC-MSP119 fusion protein was expressed from a recombinant Escherichia coli and showed preserved in vitro TLR5-binding activity. In contrast to animals injected with His6 MSP119 , mice subcutaneously immunised with the recombinant His6 FliC-MSP119 developed strong MSP119 -specific systemic antibody responses with a prevailing IgG1 subclass. Incorporation of other adjuvants, such as CpG ODN 1826, complete and incomplete Freund's adjuvants or Quil-A, improved the IgG responses after the second, but not the third, immunising dose. It also resulted in a more balanced IgG subclass response, as evaluated by the IgG1/IgG2c ratio, and higher cell-mediated immune response, as determined by the detection of antigen-specific interferon-γ secretion by immune spleen cells. MSP119 -specific antibodies recognised not only the recombinant protein, but also the native protein expressed on the surface of P. falciparum parasites. Finally, sera from rabbits immunised with the fusion protein alone inhibited the in vitro growth of three different P. falciparum strains. In summary, these results extend our previous observations and further demonstrate that fusion of the innate immunity agonist FliC to Plasmodium antigens is a promising alternative to improve their immunogenicity.
Chagas disease is a complex anthropozoonosis with distinct domestic and sylvatic mammal species acting as potential reservoirs. The diversity of vector species and their habitats are among the ...factors that hinder the control of the disease. Control programs periodically monitor the prevalence of T. cruzi infection in insect bugs through microscopical observation of diluted feces. However, microscopy presents limited sensitivity in samples with low parasite numbers, difficulties in examining all evolutionary stages of the insect and may in turn be limited to differentiate T. cruzi from other morphologically similar trypanosomatids. Here, we report two highly sensitive and accurate methodologies to infer T. cruzi infection rates and to quantify parasite load in the gut of field-collected triatomines.
Triatomines were manually collected in the period 2011-2012 and 2014-2015, in domestic, peridomestic or sylvatic habitats in rural areas of 26 municipalities, encompassing three distinct Brazilian biomes: Caatinga, Cerrado and Atlantic Rainforest. Following morphological and taxonomical identification, the search for flagellated protozoa was performed by optical microscopy. A conventional PCR targeting T. cruzi kDNA and a TaqMan qPCR directed to the parasite nuclear satellite DNA (SAT) were developed, both in multiplex, with the triatomine 12S subunit ribosomal RNA gene, used as internal amplification control. Both methods were used for detection (kDNA-PCR) and parasite load quantification (SAT-DNA-qPCR), to investigate T. cruzi infection in captured triatomines.
The combined methods were assayed on a panel of 205 field-collected triatomine samples. Diagnostic analysis revealed 21% positivity for the kDNA-PCR, whereas microscopic examination enabled identification of T. cruzi in only 7.0% of the PCR-positive samples. Negative PCR results were confirmed by the absence of T. cruzi flagellates using microscopy. Caatinga biome yielded the highest T. cruzi infection rate (60%), followed by the Atlantic Rainforest and Cerrado with 7.1 and 6.1%, respectively. In addition, a wide range distribution of parasite load, varying from 8.05 × 10
to 6.31 × 10
was observed with a median of 2.29 × 10
T. cruzi/intestine units. When parasite load was analyzed by triatomine species, a significantly higher median was found for Panstrongylus lutzi in comparison with Triatoma brasiliensis.
Our results demonstrate highly sensitive PCR-based methodologies to monitor T. cruzi infection in triatomines. In addition, the qPCR assay offers the possibility of further evaluation parasite load, as a promising biomarker of the vectorial capacity of triatomines in Chagas disease endemic areas.
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