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Funding Information: Ana R. Jesus and Ana Rita C. Duarte acknowledge the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme, under grant agreement No ERC-2016-CoG 725034. Publisher Copyright: © 2023 by the authors. Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM]+ cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C2OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability. publishersversion published

The authors are grateful for financial support from project PID2019-106171RB-I00 from the Ministerio de Ciencia e Innovación (MICINN) of Spain . ), Portuguese Foundation for Science and Technology/MCTES ( POCI-01-0145-FEDER-016387 and MIT-EXPL/CS/0055/2021 )). Finally, H.C. thanks financial suport in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of article 23 of the Decree-Law 57/2016 of 29 August, changed by Law 57/2017 of 19 July. Publisher Copyright: © 2022 The Authors This study establishes the photoelectrochromic properties of four diarylethene ionic liquids (DAE-ILs) composed of a diarylethene dicarboxylate (DAE) moiety, as counter-anion, and different organic cations ([C10mim]+, [C16Pyr] +, [N8,8,8,1]+, [P6,6,6,14]+). The synthetized ILs viscous fluids maintain the photochemical and electrochemical properties of this well-known family of photoswitches, as well as the typical features of ILs (e.g., low melting point, and high thermal and electrochemical stability). Our strategy of making multi-stimuli-responsive ionic liquids by ionic exchange opens the door to easily tune the physicochemical properties of smart DAE-ILs in function of the selected cation. Finally, those DAE-ILs are used to formulate smart ionogels (IGs), a type of materials that, by showing good conductive properties and retaining the stimuli-responsive behavior of the embedded DAE molecules, allow the fabrication of photoelectrochemical devices. publishersversion published

The widespread use of RNA for the development of novel therapies has been hindered due to issues associated with its inherent chemical instability and fast degradation by ribonucleases1. In addition, the traditional extraction and purification techniques of this biomolecule are time-consuming and require highly toxic reagents, demanding for improved technologies able to provide RNA with high integrity, purity and biological activity. To overcome the described bottlenecks, ionic-liquid-based aqueous biphasic systems (IL-based ABS), which are mainly composed of water2, are herein investigated as more sustainable and efficient techniques for RNA purification. Due to the high affinity between amino-acids and RNA and the favourable nucleic acids-stabilization properties exhibited by amino-acid-based ILs (AA-ILs)1, they were selected as components of ABS formulations. After identifying the most promising systems able to protect RNA from ribonuclease-mediated degradation, the ultimate goal of this work is to purify RNA from a complex recombinant lysate, envisaging the development of integrated purificationpreservation platforms. AA-ILs comprising L-arginine, L-tryptophan and L-lysine as cations combined with chloride or DL-aspartate ([Arg]Cl, [Trp]Cl, [Lys]Cl, [Arg][Asp], [Trp][Asp], and [Lys][Asp]) were synthesized and characterized, and their ability to form two phases with distinct salts and polymers investigated. With exception of [Trp]Cl and [Lys][Asp] that are unable to form ABS with the compounds in study, all the remaining AA-ILs form ABS with polypropylene glycol 400 (PPG 400). Initial studies on the stability and integrity of RNA have been performed in aqueous solutions of the studied ILs to assess its potential to act as preservation media. Several promising IL-based ABS were found and are currently under investigation as integrated purification-preservation platforms for RNA envisaging its use as biotherapeutics. published

Funding Information: This work was supported by FCT-MCTES (PTDC/QUI-QOR/32406/2017, PEst-C/LA0006/2013, RECI/BBBBQB/0230/2012) and by the Associate Laboratory for Green Chemistry-LAQV (FCT-MCTES UIDB/50006/2020 and UIDP/50006/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project N° 022161 (co-financed by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC). Publisher Copyright: © 2022 by the authors. The development of novel pharmaceutical tools to efficiently tackle tuberculosis is the order of the day due to the rapid development of resistant strains of Mycobacterium tuberculosis. Herein, we report novel potential formulations of a repurposed drug, the antimalarial mefloquine (MFL), which was combined with organic anions as chemical adjuvants. Eight mefloquine organic salts were obtained by ion metathesis reaction between mefloquine hydrochloride ([MFLH][Cl]) and several organic acid sodium salts in high yields. One of the salts, mefloquine mesylate ([MFLH][MsO]), presented increased water solubility in comparison with [MFLH][Cl]. Moreover, all salts with the exception of mefloquine docusate ([MFLH][AOT]) showed improved permeability and diffusion through synthetic membranes. Finally, in vitro activity studies against Mycobacterium tuberculosis revealed that these ionic formulations exhibited up to 1.5-times lower MIC values when compared with [MFLH][Cl], particularly mefloquine camphorsulfonates ([MFLH][(1R)-CSA], [MFLH][(1S)-CSA]) and mefloquine HEPES ([MFLH][HEPES]). publishersversion published

Bisphosphonates are a class of drugs widely used for the treatment of several pathologies associated with increased bone resorption. Although displaying low oral bioavailability, these drugs have the ability to accumulate in bone matrix, where the biological effects are exerted. In the present work, four mono- and dianionic Etidronate-based Organic Salts and Ionic Liquids (Eti-OSILs) were developed by combination of this drug with the superbases 1,1,3,3-tetramethylguanidine (TMG) and 1,5-diazabicyclo(4.3.0)non-5-ene (DBN) as cations, aiming to improve not only the physicochemical properties of this seminal bisphosphonate, but also its efficacy in the modulation of cellular behavior, particularly on human osteoclasts and osteoblasts. It was observed that some of the developed compounds, in particular the dianionic ones, presented very high water solubility and diminished or absent polymorphism. Also, several of them appeared to be more cytotoxic against human breast and osteosarcoma cancer cell lines while retaining low toxicity to normal cells. Regarding bone cells, a promotion of an anabolic state was observed for all Eti-OSILs, primarily for the dianionic ones, which leads to an inhibition of osteoclastogenesis and an increase in osteoblastogenesis. The observed effects resulted from differential modulation of intracellular signaling pathways by the Eti-OSILs in comparison with Etidronate. Hence, these results pave the way for the development of more efficient and bioavailable ionic formulations of bisphosphonates aiming to effectively modulate bone metabolism, particularly in the case of increased bone resorption.