Publications

Abstract A system of dimethyl ester of 3,3 ''''-bisdecyl[2,2 ':5 ',2 '':5 '',2 ''':5 ''',2 '''':5 '''',2 ''''']sexithiophene-5,5 '''''-dicarboxylic acid, with polyethylene oxide, copolymer (ST) and [6,6]phenyl-C61-butyric acid methyl ester (PCBM) is of photochemical interest. A focus is on dynamics within the ST/PCBM donor/acceptor system as a solution and as a film by means of fluorescence spectroscopy, cyclic voltammetry, and atomic force microscopy. ST forms intra-molecular rod-coil aggregates in the solution and terraces of aggregates in the film. ST/PCBM fluorescence spectra from the solution:film result in a spectral red shift of 60 nm and intensity decrease with a ratio of 17:8, respectively. The fluorescence decay times tau(1) increase with increasing PCBM concentration from 17.0 to 25.5 ps and from 5.8 to 19 ps in the solutions and the films, respectively. Interestingly, the decay time tau(2) result for the solutions and for the films to be on average 491 ps and 78 ps, describing the slower and the faster overall process, respectively. HOMO/LUMO levels for ST and PCBM are - 7.27 eV/- 4.42 eV and - 6.68 eV/- 4.43 eV, respectively. Excitation energy transfer between ST and PCBM is observed as radiative quenching and static quenching through the disaggregation of the ST aggregates by PCBM molecules.

Abstract Polypharmacology is a new trend in amyotrophic lateral sclerosis (ALS) therapy and an effective way of addressing a multifactorial etiology involving excitotoxicity, mitochondrial dysfunction, oxidative stress, and microglial activation. Inspired by a reported clinical trial, we converted a riluzole (1)-rasagiline (2) combination into single-molecule multi-target-directed ligands. By a ligand-based approach, the highly structurally integrated hybrids 3-8 were designed and synthesized. Through a target- and phenotypic-based screening pipeline, we identified hit compound 6. It showed monoamine oxidase A (MAO-A) inhibitory activity (IC50 = 6.9 mu M) rationalized by in silico studies as well as in vitro brain permeability. By using neuronal and non-neuronal cell models, including ALS-patient-derived cells, we disclosed for 6 a neuroprotective/neuroinflammatory profile similar to that of the parent compounds and their combination. Furthermore, the unexpected MAO inhibitory activity of 1 (IC50 = 8.7 mu M) might add a piece to the puzzle of its anti-ALS molecular profile.

Abstract Non-alcoholic fatty liver disease (NAFLD) is a health concern affecting 24% of the population worldwide. Although the pathophysiologic mechanisms underlying disease are not fully clarified, mitochondrial dysfunction and oxidative stress are key players in disease progression. Consequently, efforts to develop more efficient pharmacologic strategies targeting mitochondria for NAFLD prevention/treatment are underway. The conjugation of caffeic acid anti-oxidant moiety with an alkyl linker and a triphenylphosphonium cation (TPP+), guided by structure-activity relationships, led to the development of a mitochondria-targeted anti-oxidant (AntiOxCIN(4)) with remarkable anti-oxidant properties. Recently, we described that AntiOxCIN4 improved mitochondrial function, upregulated anti-oxidant defense systems, and cellular quality control mechanisms (mitophagy/autophagy) via activation of the Nrf2/Keap1 pathway, preventing fatty acid-induced cell damage. Despite the data obtained, AntiOxCIN4 effects on cellular and mitochondrial energy metabolism in vivo were not studied. In the present work, we proposed that AntiOxCIN4 (2.5 mg/day/animal) may prevent non-alcoholic fatty liver (NAFL) phenotype development in a C57BL/6J mice fed with 30% high-fat, 30% high-sucrose diet for 16 weeks. HepG2 cells treated with AntiOxCIN4 (100 mu M, 48 h) before the exposure to supraphysiologic free fatty acids (FFAs) (250 mu M, 24 h) were used for complementary studies. AntiOxCIN(4) decreased body (by 43%), liver weight (by 39%), and plasma hepatocyte damage markers in WD-fed mice. Hepatic-related parameters associated with a reduction of fat liver accumulation (by 600%) and the remodeling of fatty acyl chain composition compared with the WD-fed group were improved. Data from human HepG2 cells confirmed that a reduction of lipid droplets size and number can be a result from AntiOxCIN4-induced stimulation of fatty acid oxidation and mitochondrial OXPHOS remodeling. In WD-fed mice, AntiOxCIN(4) also induced a hepatic metabolism remodeling by upregulating mitochondrial OXPHOS, anti-oxidant defense system and phospholipid membrane composition, which is mediated by the PGC-1 alpha-SIRT3 axis. AntiOxCIN4 prevented lipid accumulation-driven autophagic flux impairment, by increasing lysosomal proteolytic capacity. AntiOxCIN(4) improved NAFL phenotype of WD-fed mice, via three main mechanisms: a) increase mitochondrial function (fatty acid oxidation); b) stimulation anti-oxidant defense system (enzymatic and non-enzymatic) and; c) prevent the impairment in autophagy. Together, the findings support the potential use of AntiOxCIN4 in the prevention/treatment of NAFLD.

Abstract <jats:p>The production of useful chemicals by electroreducing CO2 it is a promising approach to reduce the levels of this greenhouse gas in the atmosphere. This is not a straightforward process due to the high stability of the CO2 molecule and low selectivity however, these barriers can be overcome by using an appropriate catalyst. This research focus on the effect of pre-treating the carbon supports before incorporating the catalyst on the electroreduction of CO2. We found that the electrochemical behaviour of the carbon supports is modified by the nature of the pre-treatment used. From the structure perspective, the results showed partial destruction of the carbon structure mainly after the oxidative treatments nevertheless, the introduction of defect sites in the carbon structure contributed to catalyst performance. This improvement was proved by the LSV data that showed the reduction of the current associated with the hydrogen reduction reaction.</jats:p>

Abstract Diclofenac (DCF) is a very common pharmaceutical that, due to its high use and low removal rate, is considered a prominent contaminant in surface and groundwater worldwide. In this study, Solanum lycopersicum L. cv. MicroTom (tomato) was used to disclose the role of glutathione (GSH)-related enzymes, as GSH conjugation with DCF is a well reported detoxification mechanism in mammals and some plant species. To achieve this, S. lycopersicum plants were exposed to 0.5 and 5 mg L-1 of DCF for 5 weeks under a semi-hydroponic experiment. The results here obtained point towards an efficient DCF detoxification mechanism that prevents DCF bioaccumulation in fruits, minimizing any concerns for human health. Although a systemic response seems to be present in response to DCF, the current data also shows that its detoxification is mostly a root-specific process. Furthermore, it appears that GSH-mediated DCF detoxification is the main mechanism activated, as glutathione-S-transferase (GST) activity was greatly enhanced in roots of tomato plants treated with 5 mgL(-1) DCF, accompanied by increased glutathione reductase activity, responsible for GSH regeneration. By applying a targeted gene expression analysis, we provide evidence, for the first time, that SlGSTF4 and SlGSTF5 genes, coding for GSTs from phi class, were the main players driving the conjugation of this contaminant. In this sense, and even though tomato plants appear to be somewhat tolerant to DCF exposure, research on GST activity can prove to be instrumental in remediating DCF-contaminated environments and improving plant growth under such conditions.

Abstract Photocatalysis has received special attention from researchers that focus on evaluating its potential applications in the fields of energy, environment, and therapeutics, in an economically sustainable way. The photocatalysts that are most often discussed in literature are the ones composed of semiconductors, such as TiO2, ZnO, CdS, ZnS, CeO2 and WO3, since they possess an exquisite combination of optical, physical and chemical properties. Among these semiconductors, TiO2 has been amply studied due to its high refraction index, bandgap of 3.0-3.2 eV, high chemical and photostability, low cost and high range of potential applications. Within this scope, the obtainment of hollow spherical structures of micro- and nanometer size has been heavily motivated by an array of advantages such as high surface area, low density, high charge capacity, high shell permeability, amongst others. When compared to their bulk counterparts, literature data indicates a significant increase in photonic efficiency by using hollow spheres, mostly due to multiple processes of diffraction and reflection of light. Moreover, selectivity is an important feature of photocatalysts, that also enhances photonic efficiency. It may be expressed in two different manners. The first one concerns with selective photocatalysts to the substrate, which focus on the required surficial phenomena of adsorption of a target molecule by the photocatalyst before the catalysis reaction can take place. The second one concerns the selective photocatalysts to the desired product. In this review, the developments accomplished in recent years (mostly 2018 onwards) are addressed, encompassing a quite productive period, both regarding selectivity, hollowness and their synergisms. Product selectivity has been relying mainly on the utilization of metallic dopants, mostly noble metals. However, doping with non-metallic elements (N, F, P) and pairs of metallic elements, such as Pd/Cu and Au/Ag, appears to be gaining an increased acceptance. New insights into the mechanisms of selectivity by doping, besides the usual consideration of the reduction of band gap, were produced. A great vitality could also be found in the usage of cocatalysts (metal, metal/polymer, graphene). Concerning substrate selectivity, morphology and surface structuring have been the approaches of choice since a long time already. A recent trend was also identified, namely that of seeking synergisms between increasing photonic efficiency and increasing selective capacity, although this has presented itself as a challenge. An additional trend recently observed was that of attempting a simultaneous substrate and product selectivity, in order to make the photocatalytic process even more effective. In the case of hollow TiO2, this review addresses the control of crystallinity of the shell which is frequently under the risk of bursting due to the harsh conditions applied. To circumvent the possibility of bursting, two main strategies have been proposed, "silica-protected calcination" and "acid pretreatment". Finally, the combination of hollowness and selectivity has captured the attention of researchers. Molecular imprinting took the lead when it came to structuring the hollow shell, mostly via the post-calcination deposition of an imprinted polymer. To introduce product selectivity, modifications both of the outer and of the inner surface of the shell were reported. The possibility of tuning the properties of the outer and inner surfaces separately, opens new creative avenues in the field of TiO2-supported photocatalysis, with subsequent modification of reaction mechanisms.

Abstract <jats:p>This work introduces a method specially developed to produce a biorecognition element based on modified Stöber silica nanoparticles by the covalent immobilization of the human IgG. The sensing structure is based on long period fiber gratings (LPFG), specially developed to allow the interaction of the electromagnetic wave with the target analytes through its evanescent field. The surface was modified by the immobilization of the IgG-modified nanoparticles serving has recognition elements for specific target molecules. The resulting configuration was tested in the presence of anti-human IgG, recording the refractometric response of the modified LPFG in contact with different amounts of analyte. The selectivity of the sensor was also assessed.</jats:p>

Abstract The complex nature of electrode charge screening is well-known for ionic liquids (ILs). Due to strong ionion correlations, these electrolytes form a distinctive layered structure at interfaces. Variations in electrode potential cause structural changes that are reflected in a peculiar shape of differential capacitance-potential dependence with characteristic peaks. Although the differential capacitance for various ILs in conjunction with metal electrodes accessed via molecular dynamics (MD) simulations has been reported in the literature, retrieving a capacitance-potential curve, C(U), from the MD trajectories is not a trivial task. In this work, we present the results of the MD simulations of the IL 1-butyl-3-methylimidazolium hexafluorophosphate at a single-crystalline Au (100) surface. The discussion focuses on the simulation data treatment for C(U) curve fitting. It is shown that the resulting C strongly depends on the fitting method used. Four capacitance peaks and three structural reorganization types were identified in the studied system. With the help of a semi-quantitative approach in the framework of the original bilayer model of electric double layer (EDL), it is argued that the ions' reorientation is in the origin of the capacitance peaks. Also, it is shown that under the conditions of this study, the multilayer structure, characteristic of EDL in ILs on the whole, is far from the "lattice saturation" regime. The multilayer structure possesses a steric packing effect that impedes structural changes, decreasing the capacitance.

Abstract Deep eutectic solvents (DES) are often regarded as greener sustainable alternative solvents and are currently employed in many industrial applications on a large scale. Bearing in mind the industrial importance of DES-and because the vast majority of DES has yet to be synthesized-the development of cheminformatic models and tools efficiently profiling their density becomes essential. In this work, after rigorous validation, quantitative structure-property relationship (QSPR) models were proposed for use in estimating the density of a wide variety of DES. These models were based on a modelling dataset previously employed for constructing thermodynamic models for the same endpoint. The best QSPR models were robust and sound, performing well on an external validation set (set up with recently reported experimental density data of DES). Furthermore, the results revealed structural features that could play crucial roles in ruling DES density. Then, intelligent consensus prediction was employed to develop a consensus model with improved predictive accuracy. All models were derived using publicly available tools to facilitate easy reproducibility of the proposed methodology. Future work may involve setting up reliable, interpretable cheminformatic models for other thermodynamic properties of DES and guiding the design of these solvents for applications.</p>