Publications

Abstract Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN(3)) based on the dietary antioxidant gallic acid was developed. AntiOxBEN(3) accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN(3) showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN(3) presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN(3) strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN(3) can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders. [GRAPHICS] .

Abstract Background: Oncology drugs are only effective in a small proportion of cancer patients. Our current ability to identify these responsive patients before treatment is still poor in most cases. Thus, there is a pressing need to discover response markers for marketed and research oncology drugs. Screening these drugs against a large panel of cancer cell lines has led to the discovery of new genomic markers of in vitro drug response. However, while the identification of such markers among thousands of candidate drug-gene associations in the data is error-prone, an appraisal of the effectiveness of such detection task is currently lacking. Methods: Here we present a new non-parametric method to measuring the discriminative power of a drug-gene association. Unlike parametric statistical tests, the adopted non-parametric test has the advantage of not making strong assumptions about the data distorting the identification of genomic markers. Furthermore, we introduce a new benchmark to further validate these markers in vitro using more recent data not used to identify the markers. Results: The application of this new methodology has led to the identification of 128 new genomic markers distributed across 61% of the analysed drugs, including 5 drugs without previously known markers, which were missed by the MANOVA test initially applied to analyse data from the Genomics of Drug Sensitivity in Cancer consortium. Conclusions: Discovering markers using more than one statistical test and testing them on independent data is unusual. We found this helpful to discard statistically significant drug-gene associations that were actually spurious correlations. This approach also revealed new, independently validated, in vitro markers of drug response such as Temsirolimus-CDKN2A (resistance) and Gemcitabine-EWS-FLI1 (sensitivity). © 2018 The Author(s).

Abstract In this work, we report for the first time the accumulation activity by energized rat heart mitochondria and the ionic transfer process at a liquid liquid interface of a novel mitochondria-targeted antioxidant, named as AntiOxCIN(4), which is structurally based on a hydroxycinnamic acid. Lipophilicity studies conducted at the water/1,6-dichlorohexane (DCH) interface allowed the building up of an ionic partition diagram of AntiOxCIN(4) in accordance with the electrochemical data obtained. The partition coefficients of both positively charged (-2.3) and zwitterionic (0.2) forms of the antioxidant were determined. This study contributed to gaining an insight about the ability of the synthesized antioxidants to cross biomembrane barriers by using an interface between two immiscible electrolyte solutions (ITIES) as a model system.

Abstract L-tyrosine controlled release systems, based on imprinted polymers radically polymerized in modified organic solvents (dimethyl sulfoxide and methanol) were developed. A set of copolymers synthesized with different functional monomers and the crosslinker ethylene glycol dimethylacrylate were evaluated regarding both the imprinting and controlled release features. Those prepared in modified-DMSO were mesoporous (surface area ranging 370-690 m(2)/g) but not the ones prepared in modified methanol with the exception of the imprinted polymer prepared with the monomer vinylbenzoic acid (209 m(2)/g). The swelling degree ranged 32 to 64% and appeared to be mostly dependent on the functional group employed in the synthesis of the polymers. When tested in dynamic mode a clear imprinting effect has been observed in some of the imprinted polymers. However, selectivity for L-Tyr against similar compounds could not be found in these conditions. Selectivity could be observed when carrying out the isothermal analysis, with selectivity factors up to 2.7. A few polymers exhibited also other remarkable features such as high L-Tyr load capacity (up to 253 mg L-Tyr/g) and large binding strength (up to 55 L(m)mg((1-m)))/g). Therefore, imprinted polymers capable of a selective sorption of L-Tyr upon equilibration, containing stronger binding sites for L-Tyr, appeared promising vehicles for its controlled release. In fact, the release assays with L-Tyr impregnation by adsorption, showed profiles corresponding to controlled release systems, with high yield (40-50%) and continuous release (up to at least 7 h). In addition, release mechanisms recommended for controlled release systems were deduced from kinetic data fitting to the Korsmeyer and Order 0 models.

Abstract The principle of operation, concepts and recent developments of the Knudsen effusion methodology for the vapour pressure measurement of ionic liquids and other low volatile liquids and solids are presented. A new version of a Knudsen effusion apparatus, coupled with a quartz crystal microbalance, which is used for a reliable measurement of the mass flow from a Knudsen effusion cell, is described in detail. In the new system, designed and optimized for the vapour pressure measurement of ionic liquids, it is possible to measure the vapour pressure of small samples using very short effusion time over a wide temperature range. This apparatus allows the vapour pressure measurements using step-temperature and continuous-temperature modes that have the advantage of reducing the measurement time interval and minimize the effect of a sample degradation. A significant number of improvements on the performance and capability for the vapour pressure measurements of ionic liquids has been implemented: in situ temperature control of the vacuum chamber for a better stability of background signal; a new design of a stainless steel effusion cell to decrease the reactivity and sample decomposition; dual temperature control ensuring a positive temperature gradient between bottom and top of the cell in order to avoid the ionic liquids condensation on the effusion cell lid and significantly improved stability of the time frequency derivative at high temperatures; Installation and test of a mass flow tube, on the top of the outlet of the cell lid oven block in order to increase the mass sensitivity coefficient of QCM. The tests and benchmarking concerning the measurement of vapour pressures of ionic liquids performed with [C(2)mim][NTf2] indicate that the described Knudsen effusion apparatus and methodology is able to produce reproducible and reliable experimental vapour pressure data with an accuracy and quality similar than the achieved in the measurements with low volatile solids. The effect of the improvements on the performance of the Knudsen effusion apparatus was tested and evaluated by the comparison of the vapour pressure results of 1,3,5-triphenylbenzene and 1-ethyl-3-methylimidazolium with the available literature data. (C) 2018 Elsevier Ltd.

Abstract The sublimation vapor pressures of three metallic (group 6) hexacarbonyls, Cr(CO)(6), Mo(CO)(6), and W(CO)(6), were measured using the Knudsen mass-loss effusion method. The standard (p (o) = 0.1 MPa) molar enthalpies, entropies, Gibbs energies, and heat capacity difference between the gas and solid state, at T = 298.15 K, were derived from the experimental results combined with selected literature ones covering a wide range of temperature. The temperatures and molar enthalpies of fusion of those compounds were measured using differential scanning calorimetry. The thermodynamic stability of the hexacarbonyls was evaluated taking into account the standard Gibbs energies of formation in the crystalline and gaseous phases. Gas-phase absolute entropies, heat capacities, and enthalpies of formation of the three compounds studied as well as the bond distances M-C and C-O were calculated.

Abstract This study aimed at assessing the learning effects of different ways of integrating digital educational resources in chemistry education. The alternative hypothesis is that digital educational resources contribute more effectively for students’ learning than pen-and-paper consolidation worksheets. A sample of 61 students participated in a pretest-posttest quasi-experimental design with four conditions (control, and three digital-based approaches: Outside the classroom individual approach, inside the classroom individual approach, inside the classroom group approach). Three digital educational resources were developed to address three chemistry themes (particle motion, gas pressure, and electric current through a solution). Results revealed that the inside the classroom individual digital-based approach and the outside the classroom individual digital-based approach were more effective in helping students to perform better, thus partially supporting the alternative hypothesis. The study contributed for the progress of the state of the art by drawing our attention to the plethora of phenomena around the use of computer-based technologies in education, in particular, highlighting the need to consider carefully the resources and pedagogical strategies underpinning one-to-one computing. © Springer Nature Switzerland AG 2019.