Publications

Abstract The standard molar enthalpies of formation of maleic anhydride and vinylene carbonate in gaseous phase, at T = 298.15 K, were derived from the standard molar enthalpies of formation of the compounds in condensed phase combined with the phase transition enthalpies. The standard molar enthalpies of formation in condensed phase were obtained from the enthalpies of combustion measured using static bomb combustion calorimetry and mini-bomb combustion calorimetry for vinylene carbonate and maleic anhydride, respectively. Phase transition enthalpies were obtained by Calvet micro-calorimetry. High level quantum calculations were performed at the composite G3 level of theory in order to estimate the standard molar enthalpies of formation of both compounds in gaseous phase. Good agreement was obtained between experimental and computational results. In addition, analysis of the factors affecting the relative stability of both systems has been carried out in the framework of the ab initio valence bond (VB) theory in order to clarify the aromaticity/antiaromaticity issues involving these molecular systems.

Abstract Fucoidan, a sulfated polysaccharide extracted from brown seaweed, was, in the form of a silica composite, studied as a prospective cation imprinting matrix. The preparation of such composites in the presence of cations with a strong interaction with the biopolymer chains was expected to direct them towards arrangements, optimized for the sorption of those cations. As expected, the presence of Cu(II), a weakly fucoidan-binding cation, in the synthesis of the composites did not result in the production of significantly stronger Cu(II)-oriented binding arrangements, and therefore the imprinting was not successful. However, with Pb(II), with much stronger affinity for fucoidan, the materials obtained exhibited stronger (22%) binding as compared to the non-imprinted counterparts, and increased selectivity (1.4-1.6 fold) against Cd(II). Although these imprinting features were close to those observed previously with other sulfated polysaccharides, the fucoidan-based Pb(II) imprints developed here presented superior sorption properties, namely a higher capacity and higher binding strength for Pb(II). These features, demonstrated by the material developed here, may easily be put to work in different areas where Pb(II) sensing, determination, separation or remediation is of the utmost importance.

Abstract An electrochemical biosensor was developed by merging the features of Molecular Imprinting technique and Screen-Printed Electrode (SPE) for the simple and fast screening of cardiac biomarker myoglobin (Myo) in point-of-care (POC). The MIP artificial receptor for Myo was prepared by electrooxidative polymerization of phenol (Ph) on a AuSPE in the presence of Myo as template molecule. The choice of the most effective protein extraction procedure from the various extraction methods tested (mildly acidic/basic solutions, pure/mixed organic solvents, solutions containing surfactants and enzymatic digestion methods), and the optimization of the thickness of the polymer film was carefully undertaken in order to improve binding characteristics of Myo to the imprinted polymer receptor and increase the sensitivity of the MIP biosensor. The film thickness was optimized by adjusting scan rate and the number of cycles during cyclic voltammetric electropolymerization of Ph. The thickness of the polyphenol nanocoating of only few nanometres (similar to 4.4 nm), and similar to the protein diameter, brought in significant improvements in terms of sensor sensitivity. The binding affinity of MIP receptor film was estimated by fitting the experimental data to Freundlich isotherm and a similar to 8 fold increase in the binding affinity of Myo to the imprinted polymer (K-F = 0.119 +/- 0.002 ng(-1) mL) when compared to the non- imprinted polymer (K-F = 0.015 +/- 0.002 ng(-1) mL) which demonstrated excellent (re) binding affinity for the imprinted protein. The incubation of the Myo MIP receptor modified electrode with increasing concentration of protein (from 0.001 ng mL(-1) to 100 mu g mL(-1)) resulted in a decrease of the ferro/ferricyanide redox current. LODs of 2.1 and 14 pg mL(-1) were obtained from calibration curves built in neutral buffer and diluted artificial serum, respectively, using SWV technique, enabling the detection of the protein biomarker at clinically relevant levels. The prepared MIP biosensor was applied to the determination of Myo spiked serum samples with satisfactory results.

Abstract The effect of the addition of a group of organic additives on the electrodeposition behavior of zinc was investigated in choline chloride:ethylene glycol (ChC1:EG) eutectic mixture in the molar ratio of 1:2. Cyclic voltammograms recorded on steel electrode showed a cathodic peak is only observed after reversing of the scan. Chronoamperometric measurements indicated that the deposition of zinc occurs through 3D progressive nucleation mechanism. The morphology of the zinc deposits and was evident that additives influence the deposits morphologies. X-ray diffraction confirmed the presence of crystalline zinc and reveal the grain refinement effect obtained by using the additives selected where the smallest grain size of 31.7 nm was obtained in the presence of Dimethyl sulfoxide (DMSO). Moreover the XRD data showed that the addition of additives modified the preferential growth plane. The corrosion resistance properties of the electrodeposited Zn coatings were evaluated in 3% NaCI aqueous solution using potentiodynamic polarization. The results showed that the zinc film deposited with DMSO was the best corrosion resistant coating.

Abstract Targeting mitochondrial oxidative stress is an effective therapeutic strategy. In this context, a rational design of mitochondriotropic antioxidants (compounds 22-27) based on a dietary antioxidant (caffeic acid) was performed. Jointly named as AntiOxCINs, these molecules take advantage of the known ability of the triphenylphosphonium cation to target active molecules to mitochondria. The study was guided by structure-activity-toxicity-property relationships, and we demonstrate in this work that the novel AntiOxCINs act as mitochondriotropic antioxidants. In general, AntiOxCINs derivatives prevented lipid peroxidation and acted as inhibitors of the mitochondrial permeability transition pore. AntiOxCINs toxicity profile was found to be dependent on the structural modifications performed on the dietary antioxidant. On the basis of mitochondrial and cytotoxicity/antioxidant cellular data, compound 25 emerged as a potential candidate for the development of a drug candidate with therapeutic application in mitochondrial oxidative stress-related diseases. Compound 25 increased GSH intracellular levels and showed no toxicity on mitochondrial morphology and function.

Abstract Co-Sn alloy films were electrodeposited from choline chloride (ChC1)-ethylene glycol (EG) and choline chloride (ChCl1)-urea (U) eutectic mixtures. The deposition of Co-Sn alloy on a copper electrode was studied by cyclic voltammetry, which demonstrates that the coelectrodeposition was achieved. For comparison of properties, Co-Sn alloys were deposited from electrolytes with different Co/Sn ratios. The X-ray diffraction patterns (XRD) showed that the phase structure was affected by the Co/Sn ratio; nevertheless, Co3Sn2 was always the predominant phase. Traces of metallic cobalt were also detected. The nature of the electrolyte used and the metallic composition affected the morphologies of the deposits and their corrosion resistance. The best corrosion resistant coating, with a corrosion potential of -617 mV, was composed by 44.4 wt % of Co and 55.6% of Sn, and it was obtained from the ChCl-EG electrolyte. The magnetic properties of the analyzed samples did not present an evident relationship with the metallic ions ratio in solution.

Abstract Oxidative stress and mitochondrial dysfunction have been associated with metabolic and agerelated diseases. Thus, the prevention of mitochondrial oxidative damage is nowadays a recognized pharmacological strategy to delay disease progression. Epidemiological studies suggested an association between the consumption of polyphenol-rich diet and the prevention of different pathologies, including diseases with a mitochondrial etiology. The development of mitochondrialtargeted antioxidants based on dietary antioxidants may decrease mitochondrial oxidative damage. Herein, we report the design and synthesis of two new mitochondriotropic antioxidants based on hydroxybenzoic acids (AntiOxBENs). The results obtained showed that the novel antioxidants are accumulated inside rat liver mitochondria driven by the organelle transmembrane electric potential and prevented lipid peroxidation, exhibiting low toxicity. Some of the observed effects on mitochondrial bioenergetics resulted from an increase of proton leakage through the mitochondrial inner membrane. The new derivatives present a higher lipophilicity than the parent compounds (protocatechuic and gallic acids) and similar antioxidant and iron chelating properties. AntiOxBENs are valid mitochondriotropic antioxidant prototypes, which can be optimized and used in a next future as drug candidates to prevent or slow mitochondrial oxidative stress associated to several pathologies.

Abstract Many computational methods to predict the macromolecular targets of small organic molecules have been presented to date. Despite progress, target prediction methods still have important limitations. For example, the most accurate methods implicitly restrict their predictions to a relatively small number of targets, are not systematically validated on drugs (whose targets are harder to predict than those of non-drug molecules) and often lack a reliability score associated with each predicted target. Here we present a systematic validation of ligand-centric target prediction methods on a set of clinical drugs. These methods exploit a knowledge-base covering 887,435 known ligand-target associations between 504,755 molecules and 4,167 targets. Based on this dataset, we provide a new estimate of the polypharmacology of drugs, which on average have 11.5 targets below IC50 10 μM. The average performance achieved across clinical drugs is remarkable (0.348 precision and 0.423 recall, with large drug-dependent variability), especially given the unusually large coverage of the target space. Furthermore, we show how a sparse ligand-target bioactivity matrix to retrospectively validate target prediction methods could underestimate prospective performance. Lastly, we present and validate a first-in-kind score capable of accurately predicting the reliability of target predictions. © 2017 The Author(s).

Abstract A multidisciplinary approach was used to identify and optimize a quinazolinedione-based ligand that would decrease the flexibility of the substrate-covering loop (catalytic loop) of the type II dehydroquinase from Helicobacter pylori. This enzyme, which is essential for the survival of this bacterium, is involved in the biosynthesis of aromatic amino acids. A computer-aided fragment-based protocol (ALTA) was first used to identify the aromatic fragments able to block the interface pocket that separates two neighboring enzyme subunits and is located at the active site entrance. Chemical modification of its non-aromatic moiety through an olefin cross-metathesis and Seebach's self-reproduction of chirality synthetic principle allowed the development of a quinazolinedione derivative that disables the catalytic loop plasticity, which is essential for the enzyme′s catalytic cycle. Molecular dynamics simulations revealed that the ligand would force the catalytic loop into an inappropriate arrangement for catalysis by strong interactions with the catalytic tyrosine and by expelling the essential arginine out of the active site. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Abstract The paper presents experimental results regarding the electrodeposition and characterization of cobalt and cobalt composites with carbon nanotubes from a choline-chloride-based deep eutectic solvent. Dispersion stability of multi-walled carbon nanotubes (MWCNTs) was excellent in the eutectic solvent used. According to Raman and XRD analysis, the carbon nanotubes were successfully inserted into the metallic matrix. Furthermore, XRD results suggested that the incorporation of CNTs on the deposit promoted a preferred orientation of the Co crystallites on (220) plane. The Co and Co-composites coatings obtained onto a copper substrate are adherent and uniform. Pure Co deposit was formed by sharp edge grains, Co-composites appeared to be less compact and formed by relatively spherical particles connected by MWCNTS. Furthermore, it was found that the presence of MWCNTs contributed to decreasing the deposit's roughness. From corrosion tests, Co-composite films exhibit a comparable or slightly better corrosion performance as compared to pure Co films.