Publications

Abstract In this work, an advanced oxidation process using ozonation combined with hydrogen peroxide (H2O2) and catalyzed by manganese (Mn2+) in alkaline conditions was investigated to degrade the organic matter present in a synthetic dairy wastewater (SDW) with a chemical oxygen demand (COD) of 2.3 g L-1. The effect of independent factors such as pH (7-13), H2O2/O-3 ratio (0-1), and Mn2+ concentration (0-1.71 g L-1) has been evaluated and the process optimized using a factorial design and a central composite design (CCD) in sequence. The experiment has been made in batch trials using 2 L of SDW in which ozone was bubbled during 2 h and samples collected for COD analyses, used as response variable. In the factorial experiment, the effect of H2O2 was not significant for all the ratios tested (p value > 0.10), and the effects of the pH and Mn2+ were positive and significant (p value = 0.05). In the CCD, the linear (positive) and quadratic (negative) effects of pH and Mn2+ were significant (p values = 0.05 and = 0.10, respectively). According to the response optimizer, the optimal condition for the ozonation catalyzed by manganese at alkaline medium (COD removal of 69.4%) can be obtained in pH 10.2 and Mn2+ concentration of 1.71 g L-1. Moreover, COD removals above 60% can be obtained for pH values of 9.5 to 11 and Mn2+ concentrations of 0.6 g L-1.

Abstract For every lead compound developed in medicinal chemistry research, numerous other inactive or less active candidates are synthetized/isolated and tested. The majority of these compounds will not be selected for further development due to a sub-optimal pharmacological profile. However, some poorly active or even inactive compounds could live a second life if tested against other targets. Thus, new therapeutic opportunities could emerge and synergistic activities could be identified and exploited for existing compounds by sharing information between researchers who are working on different targets. The Mu.Ta.Lig (Multi-Target Ligand) Chemotheca database aims to offer such opportunities by facilitating information exchange among researchers worldwide. After a preliminary registration, users can (a) virtually upload structures and activity data for their compounds with corresponding, and eventually known activity data, and (b) search for other available compounds uploaded by the users community. Each piece of information about given compounds is owned by the user who initially uploaded it and multiple ownership is possible (this occurs if different users uploaded the same compounds or information pertaining to the same compounds). A web-based graphical user interface has been developed to assist compound uploading, compounds searching and data retrieval. Physico-chemical and ADME properties as well as substructure-based PAINS evaluations are computed on the fly for each uploaded compound. Samples of compounds that match a set of search criteria and additional data on these compounds could be requested directly from their owners with no mediation by the Mu.Ta.Lig Chemotheca team. Guest access provides a simplified search interface to retrieve only basic information such as compound IDs and related 2D or 3D chemical structures. Moreover, some compounds can be hidden to Guest users according to an owner's decision. In contrast, registered users have full access to all of the Chemotheca data including the permission to upload new compounds and/or update experimental/theoretical data (e.g., activities against new targets tested) related to already stored compounds. In order to facilitate scientific collaborations, all available data are connected to the corresponding owner's email address (available for registered users only).

Abstract Neurodegenerative diseases affect millions of human lives all over the world. The number of afflicted patients is rapidly growing, and disease-modifying agents are urgently needed. Caffeic acid, an important member of the hydroxycinnamic acid family of polyphenols, has considerable neurotrophic effects. We have previously shown how caffeate alkyl ester derivatives significantly promote survival and differentiation in neuronal cells. In this study, the mechanisms by which these ester derivatives exert their neurotrophic effects are examined. A series of eight caffeic acid esters with different alkyl chain lengths, ranging from methyl (CAF1) to dodecyl esters (CAF8), were synthesized and studied for their influence on neurotrophic signaling pathways. Caffeate esters did not induce tropomyosin-receptor kinase A (TrkA) phosphorylation, which was assessed by immunoblotting up to a concentration of 25 mu M. NIH/3T3 cells overexpressing TrkA were generated to further examine phosphorylation of this receptor tyrosine kinase. None of the esters induced TrkA phosphorylation in these cells either. Assessment of the effect of caffeate derivatives on downstream neurotrophic pathways by immunoblotting showed that the most potent esters, decyl caffeate (CAF7) and dodecyl caffeate (CAF8) caused extracellular signal-regulated kinase (ERK1/2) and Akt serine threonine kinase phosphorylation in PC12 cells at 5 and 25 mu M concentrations. In conclusion, this study shows that caffeate esters exert their neurotrophic action by modulation of ERK1/2 and Akt signaling pathways in neuronal cells, and further demonstrates the potential therapeutic implications of these derivatives for neurodegenerative diseases.

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.