Publications

Abstract Mitochondria are sub-cellular organelles that play a central role in energy metabolism, being these organelles currently recognized as one important target for new drug discovery programs addressed to find innovative therapeutic solutions for diverse pathologic events, such as cancer, cardiovascular, and neurological diseases. Although attractive, the success of the strategies developed so far has been hampered by several challenges and limitations, and until now the Food and Drug Administration (FDA) has not approved a drug for mitochondrial therapy. Currently, the most effective strategy to deliver drugs specifically to mitochondria is the covalent link of a lipophilic cation, namely triphenylphosphonium (TPP), to a pharmacophore of interest. Within this framework two mitochondriotropic antioxidants (MitoQ and SkQ1) have entered in human clinical trials as a therapeutic solution for oxidativestress related diseases. In this chapter, the efforts done so far to target small-molecule antioxidants to mitochondria as potential therapeutics or diagnostic tools have been reviewed. Although TPP cation has been the most extensively used mitochondrial- targeting cation, there are still controversies surrounding this approach, namely related with its intrinsic toxicity. Consequently, efforts must be done in finding new cation carriers, and to guarantee that the cargo does indeed access the mitochondrial matrix and does not merely associate with the mitochondrial membranes. Moreover, in vivo biodistribution, pharmacokinetics and long- term toxic effects studies to provide accurate information about efficacy and toxicity are still an emergent issue to make available the translation from bench to bedside. © Springer International Publishing AG, part of Springer Nature 2018.

Abstract The authors have synthesized water-dispersible NaYF4:Er3+/Yb3+ upconversion particles via a thermal decomposition route and optimized the green upconversion emission through a concentration variation of the Yb3+ sensitizer. The prepared particles were found to be ellipsoid in shape having an average particle dimension of 600 × 150 nm. It is observed that the sample with 18 mmol% Yb3+ ion concentration and 2 mmol% Er3+ ion gives optimum upconversion intensity in the green region under 980 nm excitation. Colloidal dispersibility of the sample in different solvents was checked and hexane was found to be the best medium for the prepared particles. The particle size of the sample was found to be suitable for the preparation of colloidal ink and security writing on a plain sheet of paper. This was demonstrated successfully using ink prepared in polyvinyl chloride gold medium. © 2018 Astro Ltd.

Abstract Because of its high fluorescence quantum yield, high sensitivity and high signal-to-noise ratio, firefly oxyluciferin is widely used in the field of fluorescent probe. However, there are six chemical forms which can possibly co-existence in solution. Reliable relative stability of the different forms in solution made the analysis of their photophysical properties difficult. In order to address this issue and gain insights into the nature of spectra feature observed in the experiments, we designed six oxyluciferin derivatives. The distribution of the species at the ground and excited states demonstrate that only keto(0), keto(-1) and enol(-2) are present for all oxyluciferin derivatives. The majority of molecules are surprisingly more acidic at the ground state than at the excited state, which indicate that they are photobases. The distribution of the species at the excited state indicate that the most pH-sensitive molecules are 2-(6'-hydroxybenzothiazol-2-yl)-2,3-dihydro-4-hydroxypyrrole (Oxyan-1) and 1-(5'-brominated-6'-hydroxybenzothiazol-2-yl)-2-(4-hydroxythiazole) ethylene (Oxyan-4), as their chemical equilibria consist on the same three species: keto(0), keto(-1) and enol(-2). While the first deprotonation occurs at acidic pH, the second occurs at basic pH, with a single deprotonated species existing at more neutral pH. This indicates that both Oxyan-1 and Oxyan-4 can be good candidates for fluorescent pH probing. Exhaustive analyses of the emission spectra in water revealed that the firefly OxyLH(2) analogues can emit in the UV-visible and near-infrared wavelength range.

Abstract In this study, we examined the thickness of the electrical double layer (EDL) in ionic liquids using density functional theory (DFT) calculations and molecular dynamics (MD) simulations. We focused on BF4- anion adsorption from the 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF(4)) ionic liquid on the Au(111) surface. At both DFT and MD levels, we evaluated the capacitance-potential dependence for the Helmholtz model of the interface. Using MD simulations, we also explored a more realistic, multilayer EDL model accounting for the ion layering. Concurrent analysis of the DFT and MD results provides a ground for thinking whether the electrical double layer in ionic liquids is one- or multi-ionic-layer thick.

Abstract Mixing of ionic liquids provides new opportunities for their tuning, enabling the applications of ionic liquid mixtures to expand. At the same time, the genesis of the fundamental properties of ionic liquid mixtures is still poorly understood. In this study we carried out a molecular dynamics simulation of binary mixtures of 1-buthyl-3-methylimidazolium hexafluorophosphate, 1-buthyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, and 1-buthyl-3-methylimidazolium tris(perfluoroethyl)trifluorophosphate ([C(4)mim][PF6] + [C(4)mim][NTf2], [C(4)mim][PF6] + [C(4)mim][FAP], [C(4)mim][FAP] + [C(4)mim][NTf2]) in a wide concentration range at 303.15 K and complemented it with quantum mechanical calculations. Three pure ionic liquids underwent the same kind of analysis for comparison purposes. We found that the addition of the [FAP](-)-anion to a mixture enhances the segregation of non-polar domains and weakens the hydrogen-bond network. The H-bonds in the studied mixtures are rather weak, as follows from QTAIM analysis, with the rarest occurrence for the [FAP](-)-anion. The competition of two anions in the mixtures for the most acidic hydrogen of the 1-butyl-3-methylimidazolium cation is reported. In most of the cases, the smaller anion ([PF6](-) or [NTf2](-)) with stronger charge concentration displaces the bigger one ([NTf2](-) or [FAP](-)) from the preferred coordination site. The existing nano-segregation in some mixtures notably slows down ion diffusion. Our results show that the differences in anion size, shape and nature are the main reasons for nano-segregation and the non-ideal behavior of ionic liquid mixtures.

Abstract Copper (Cu) is an abundant metal in the environment coming from anthropogenic activities and natural sources that, in excess, easily becomes phytotoxic to most species, being its accumulation in plants considered an environmental threat. This study aimed to compare the physiological and molecular responses of Solanum lycopersicum and its wild counterpart Solanum cheesmaniae to Cu stress. In particular, we wanted to address the hypothesis that S. cheesmaniae is more adapted to Cu stress than S. lycopersicum, since the former is equipped with a more efficient antioxidant defense system than the latter. Biomarkers of oxidative status (lipid peroxidation, hydrogen peroxide (H2O2) and superoxide anion (O-2(center dot-)) levels) revealed a more pronounced imbalance in the redox homeostasis in shoots of S. lycopersicum than in S. cheesmaniae in response to Cu. Furthermore, the activity of key antioxidant enzymes clearly differed in both species in response to Cu. Catalase (CAT) activity increased in S. cheesmaniae shoots but decreased in the domestic species, as well as ascorbate peroxidase (APX). Both species preferentially accumulated Cu in the radicular system, although a great increase in the aerial parts of S. lycopersicum was measured, while in leaves of Cu-treated S. cheesmaniae, the levels of Cu were not changed. Overall, results validated the hypothesis that S. cheesmaniae is more tolerant to excess Cu than S. lycopersicum and the data provided will help the development of breeding strategies toward the improvement of the resistance/tolerance of cultivated tomato species to heavy metal stress.

Abstract Disruption of cell-cell communication or quorum sensing (QS) is considered a stimulating approach for reducing bacterial pathogenicity and resistance. Although several QS inhibitors (QSIs) have been discovered so far their clinical use remains distant. This problem can be circumvented by searching for QSI among drugs already approved for the treatment of different diseases. In this context, antibiotics have earned special attention. Whereas at high concentrations antibiotics exert a killing effect, at lower concentrations they may act as signaling molecules and as such can modulate gene expression. In this study, the antibiotic furvina was shown to be able to cause inhibition of the 3-oxo-C12-HSL-dependent QS system of Pseudomonas aeruginosa. Furvina interacts with the LasI/LasR system. The data were validated by modeling studies. Furvina can also reduce biofilm formation and decrease the production of QS-controlled virulence factors.

Abstract Overuse of pesticides has resulted in environmental problems, threating public health through accumulation in food chains. Phytoremediation is a powerful technique to clean up contaminated environments. However, it is necessary to unravel the metabolic mechanisms underlying phytoremediation in order to increase the efficiency of this process. Therefore, growth, physiological and biochemical responses in leaves and roots of Solanum nigrum L. exposed to the commonly used fungicide metalaxyl were investigated. This species shows characteristics that make it valuable as a potential tool for the remediation of organic pollutants. We found that once inside the plant, metalaxyl altered carbon metabolism, which resulted in a reduction of growth and lower biomass accumulation due to impairment of carbohydrate production (total soluble sugar, starch, rubisco) and increased photorespiration (glycolate oxidase, Gly/Ser ratio). A significant increase of antioxidant defenses (polyphenols, flavonoids, tocopherols, ascorbate, glutathione, superoxide dismutase, catalase, peroxidases, monodehydroascorbate-and dehydroascorbate reductase, gluthatione reductase) kept reactive oxygen species (ROS) levels under control (superoxide anion) leaving cell membranes undamaged. The results suggest that enhancing carbon assimilation and antioxidant capacity may be target parameters to improve this species' phytoremediation capacities. Highlights Metalaxyl inhibits growth by reducing photosynthesis and inducing photorespiration Elevated antioxidant defenses protect metalaxyl-treated plants from oxidative damage Ascorbate and glutathione are key antioxidants in metalaxyl tolerance.