Diarylethene-Based Ionic Liquids: Synthesis and Photo-Driven Solution Properties

Funding text The authors acknowledge Fundação para a Ciência e Tecnologia through the PhD grant SFRH/BD/81693/2011 (M. R. C. Soromenho). This work was supported by the Associate Laboratory for Green Chemistry-LAQV (Portugal) (UIDB/50006/2020, UIDP/50006/2020, and LA/P/0008/2020) and by the Instituto de Investigação do Medicamento (iMed.ULisboa) (UIDB/04138/2020, and UIDP/04138/2020) which are financed by national funds from FCT/MCTES. The NMR spectrometers are part of the National NMR Network (PTNMR) are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).In this work, the design and synthesis of a series of photochromic gemini diarylethene-based ionic liquids (GDILs) with different cationic motifs is reported. Several synthetic pathways were optimized for the formation of cationic GDILs with chloride as the counterion. The different cationic motifs were achieved through the N-alkylation of the photochromic organic core unit with different tertiary amines, including different aromatic amines such as imidazole derivatives and pyridinium, and other non-aromatic amines. These novel salts present surprising water solubility with unexplored photochromic features that broaden their known applications. The covalent attachment of the different side groups dictates their water solubility and differences upon photocyclization. The physicochemical properties of GDILs in aqueous and in imidazolium-based ionic liquid (IL) solutions were investigated. Upon irradiation with ultraviolet (UV) light, we have observed changes in the physico-chemical properties of distinct solutions containing these GDILs, at very low concentrations. More specifically, in aqueous solution, the overall conductivity increased with the time of UV photoirradiation. In contrast, in IL solution, these photoinducible changes are dependent on the type of ionic liquid used. These compounds can improve non-ionic and ionic liquids’ solutions since we can change their properties, such as conductivity, viscosity or ionicity, only by UV photoirradiation. The electronic and conformational changes associated with these innovative stimuli GDILs may open new opportunities for their use as photoswitchable materials.publishersversionpublishe

S100B inhibition protects from chronic experimental autoimmune encephalomyelitis

© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Studies have correlated excessive S100B, a small inflammatory molecule, with demyelination and associated inflammatory processes occurring in multiple sclerosis. The relevance of S100B in multiple sclerosis pathology brought an emerging curiosity highlighting its use as a potential therapeutic target to reduce damage during the multiple sclerosis course, namely during inflammatory relapses. We examined the relevance of S100B and further investigated the potential of S100B-neutralizing small-molecule pentamidine in chronic experimental autoimmune encephalomyelitis. S100B depletion had beneficial pathological outcomes and based on promising results of a variety of S100B blockade strategies in an ex vivo demyelinating model, we choose pentamidine to assay its role in the in vivo experimental autoimmune encephalomyelitis. We report that pentamidine prevents more aggressive clinical symptoms and improves recovery of chronic experimental autoimmune encephalomyelitis. Blockade of S100B by pentamidine protects against oligodendrogenesis impairment and neuroinflammation by reducing astrocyte reactivity and microglia pro-inflammatory phenotype. Pentamidine also increased regulatory T cell density in the spinal cord suggesting an additional immunomodulatory action. These results showed the relevance of S100B as a main driver of neuroinflammation in experimental autoimmune encephalomyelitis and identified an uncharacterized mode of action of pentamidine, strengthening the possibility to use this drug as an anti-inflammatory and remyelinating therapy for progressive multiple sclerosis.This work was funded by grants from Ordem dos Farmacêuticos (AF), Merck KGaA (AF) and Fundação de Ciênciase Tecnologia (UIDB/04138/2020; UIDP/04138/2020) (iMed.ULisboa).info:eu-repo/semantics/publishedVersio

New non-toxic n-alkyl cholinium-based ionic liquids as excipients to improve the solubility of poorly water-soluble drugs

Funding Information: Funding: The authors thank Fundação para a Ciência e Tecnologia, FCT/MCTES (Portugal) for financial support through investigator contract (IF/00621/2015—P.M. Reis) and project IF/00621/2015. This work was also supported by the Associate Laboratory for Green Chemistry—LAQV (UIDB/50006/2020 and UIDP/50006/2020) and by projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences-UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy-i4HB, which are financed by national funds from FCT/MCTES. The NMR spectrometers at FCT-NOVA are part of Rede Nacional de RMN (PTNMR), supported by FCT-MCTES (ROTEIRO/0031/2013—PINFRA/22161/2016) (cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). LRR acknowledges FCT/MCTES project PTDC/CVT-EPI/6685/2014.In this work, we prepared new biocompatible N-alkyl cholinium-based ionic liquids to be used as cosolvents to improve the solubility of poorly water-soluble drugs, namely, sodium diclo-fenac and paracetamol. In this set of ionic liquids, we intend to understand the effect of increasing the asymmetry of the ionic liquid cation/anion by growing the length of one of the alkyl chains attached to the nitrogen center/sulfonate center on the dissolution capacity of the ionic liquid. The addition of these new ionic liquids to water increased the dissolution capacity of the drugs up to four-times that in water, and improved the pharmacodynamic properties of these drugs, especially the case of sodium diclofenac. The intermolecular interactions between the drugs and ionic liquids were investigated by NMR. Two-dimensional1H/1H nuclear overhauser effect spectroscopy (NO-ESY) revealed an interaction between sodium diclofenac and the alaninate anion from the [C2Ch]2[SucAla]. In the case of paracetamol and [C4Ch][C2SO3], it was possible to observe two inter-molecular interactions between the hydroxyl group of paracetamol and two protons from the cation [C4Ch]+. Interestingly, the ionic liquid bearing a succinyl-DL-alaninate anion, [SucAla]2−, and a N-ethyl cholinium cation, [C2Ch]+, which presented the highest ability to dissolve sodium diclofenac, showed no cytotoxicity up to 500 mM. Therefore, this ionic liquid is a potential candidate for drug delivery applications.publishersversionpublishe

Do borrão às aguadas: os engenheiros militares e a representação da Capitania de São Paulo

A análise do papel dos engenheiros militares perpassa as discussões sobre regiões específicas, mesmo quando eles, aparentemente, estão ausentes delas. Sua presença ou ausência sempre foi sinônimo de interesse e de projeto colonizador mais ou menos dirigido. Este ensaio tem como objeto de estudo a cartografia dos engenheiros militares atuantes na Capitania de São Paulo, território comumente visto como economicamente periférico e mais autônomo face aos desígnios da Coroa portuguesa. Com foco no corpus cartográfico de alguns profissionais que aqui atuaram, trata indiretamente da multifacetada atuação desses engenheiros, bem como do processo de feitura das cartas geográficas, corográficas e topográficas, do borrão às aguadas. Investigar a cartografia de alguns desses profissionais permite não apenas explorar a riqueza de suas biografias, como, também, acompanhar o processo de produção técnica dos mapas e os desígnios políticos envolvidos no devassamento e representação das terras descobertas no Novo Mundo.Analyzing the role of military engineers means venturing into discussions about specific regions, even those from which they are apparently absent. Their presence or absence has always been synonymous with interest and a more or less directed colonization project. This essay examines the maps produced by the military engineers working in the Captaincy of São Paulo, a territory often looked upon as one of little economic import and a rather autonomous area in light of the plans of the Portuguese Crown. By focusing on the cartographic corpus bequeathed by certain professionals serving in this region, we deal indirectly with the multifaceted role of these engineers as well as with the process of making geographic, chorographic and topographic charts - all the way from the sketch to watercolored maps. Perusing the charts constructed by some of these professionals enabled us not only to delve into the rich details of their biographies but also to observe the technical mapmaking process and to unravel the political designs behind the exploration and representation of the lands discovered in the New World

Disseminated Lupus Erythematosus. Review of 20 Cases

Os autores reviram 20 casos de L.E.D. estudados no Serviço de 1982 a 1985, sujeitaram-nos a um protocolo baseado nos critérios estabelecidos pela A.R.A. para o diagnóstico desta doença e comentaram, à luz da literatura actualmente disponível, os seus achados clínico-laboratoriais

Effect of Thiouronium-Based Ionic Liquids on the Formation and Growth of CO2 (sI) and THF (sII) Hydrates

LA/P/0008/2020In this manuscript, two thiouronium-based ionic liquids (ILs), namely 2-ethylthiouronium bromide [C2th][Br] and 2-(hydroxyethyl)thiouronium bromide [C2OHth][Br], were tested at different concentrations (1 and 10 wt%) for their ability to affect CO2 (sI) and tetrahydrofuran (THF) (sII) hydrate formation and growth. Two different methods were selected to perform a thermodynamic and kinetic screening of the CO2 hydrates using a rocking cell apparatus: (i) an isochoric pressure search method to map the hydrate phase behavior and (ii) a constant ramping method to obtain the hydrate formation and dissociation onset temperatures. A THF hydrate crystal growth method was also used to determine the effectiveness of the ILs in altering the growth of type sII hydrates at atmospheric pressure. Hydrate–liquid–vapor equilibrium measurements revealed that both ILs act as thermodynamic inhibitors at 10 wt% and suppress the CO2 hydrate equilibria ~1.2 °C. The constant ramping methodology provides interesting results and reveals that [C2OHth][Br] suppresses the nucleation onset temperature and delays the decomposition onset temperatures of CO2 hydrates at 1 wt%, whereas suppression by [C2th][Br] was not statistically significant. Normalized pressure plots indicate that the presence of the ILs slowed down the growth as well as the decomposition rates of CO2 hydrates due to the lower quantity of hydrate formed in the presence of 1 wt% ILs. The ILs were also found to be effective in inhibiting the growth of type sII THF hydrates without affecting their morphology. Therefore, the studied thiouronium ILs can be used as potential dual-function hydrate inhibitors. This work also emphasizes the importance of the methods and conditions used to screen an additive for altering hydrate formation and growth.publishersversionpublishe