New non-toxic biocompatible dianionic ionic liquids that enhance the solubility of oral drugs from BCS class II

The authors thank Fundação para a Ciência e Tecnologia, FCT/ MCTES (Portugal) for financial support through an Investigator contract (IF/00621/2015 – P.M. Reis), and through projects IF/00621/2015 and CryoDES (PTDC/EQU-EQU/29851/2017). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, under grant agreement No ERC-2016-CoG 725034. This work was also partially supported by the Associate Laboratory for Green Chemistry - LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) The NMR spectrometers are part of The National NMR Facility, supported by FCT/MCTES (RECI/BBB-BQB/0230/2012). The authors are grateful for important discussions with PhD Wagner Silva about two-dimensional NOESY 1H-1H experiments.New dianionic ionic liquids (ILs) based on carboxylic anions and ammonium cations were prepared and characterized. They were used as excipients to increase the solubility of two model oral drugs of BCS class II, ibuprofen and piroxicam. With only 0.2 mol% (≈100 mM) of [N4 1 1 2OH]2[C4H4O4], the solubility increases over 40-fold and 2-fold for ibuprofen, when compared with the parent drug for water and phosphate buffer solution (PBS) 0.01M pH=7.4, respectively. With only 0.02 mol% of [N4 1 1 2OH]2[C4H4O4] it is possible to achieve a water solubility of ≈600 mg/L, in only 5 min at 37°C, corresponding to one dose of ibuprofen that an adult can take. Piroxicam also showed an increase of 20-fold and 1.5-fold for water and PBS respectively, with [N4 1 1 2OH]2[C4H4O4] and [N4 1 1 2OH]2[C5H6O4]. The lipophilicity (logP) of both drugs decreased in the presence of these compounds. The cytotoxicity profile of several of these ILs was determined, and all except [N4 1 1 2OH]2[C3H2O4] have an IC50 higher than 100 mM for fibroblasts L929 cells.publishersversionpublishe

Dark Proteome Database: Studies on Disorder

There is a misconception that intrinsic disorder in proteins is equivalent to darkness. The present study aims to establish, in the scope of the Swiss-Prot and Dark Proteome databases, the relationship between disorder and darkness. Three distinct predictors were used to calculate the disorder of Swiss-Prot proteins. The analysis of the results obtained with the used predictors and visualization paradigms resulted in the same conclusion that was reached before: disorder is mostly unrelated to darkness. (c) 2020 by the authors. Licensee MDPI, Basel, Switzerland