Publications

Abstract Cancer is a major cause of death worldwide and novel anticancer agents for its better management are much needed. Benzopyrone-based compounds, such as chromones, possess several distinctive chemical and biological properties, of which the cytotoxicity against cancer cells seems to be prominent. In this study, two series of compounds based on chromen-4-one (3-10) and chromane-2,4-dione (11-18) scaffolds were synthesized in moderate/high yields and evaluated for cytotoxicity against HL-60, MOLT-4, and MCF-7 cancer cells using MTT assay. In general, the compounds exhibited moderate cytotoxic effects against the cancer cell lines, among which, a superior potency could be observed against MOLT-4 cells. Chroman-2,4dione (11-18) derivatives had overall higher potencies compared to their chromen-4-one (3-10) counterparts. Compound 13 displayed the lowest IC50 values against HL-60 (IC50, 42.0 +/- 2.7 mu M) and MOLT-4 cell lines (IC50, 24.4 +/- 2.6 mu M), while derivative 11 showed the highest activity against MCF-7 cells (IC50, 68.4 +/- 3.9 04). In conclusion, this study provides important information on the cytotoxic effects of chromone derivatives. Benzochroman-2,4-dione has been identified as a promising scaffold, which its potency can be modulated by tailored synthesis with the aim of finding novel and dissimilar anticancer compounds.

Abstract The discovery and development of multitarget-directed ligands (MTDLs) is a promising strategy to find new therapeutic solutions for neurodegenerative diseases (NDs), in particular for Alzheimer's disease (AD). Currently approved drugs for the clinical management of AD are based on a single-target strategy and focus on restoring neurotransmitter homeostasis. Finding disease-modifying therapies AD and other NDs remains an urgent unmet clinical need. The growing consensus that AD is a multifactorial disease, with several interconnected and deregulated pathological pathways, boosted an intensive research in the design of MTDLs. Due to this scientific boom, the knowledge behind the development of MTDLs remains diffuse and lacks balanced guidelines. To rationalize the large amount of data obtained in this field, we herein revise the progress made over the last 5 years on the development of MTDLs inspired by drugs approved for AD. Due to their putative therapeutic benefit in AD, MTDLs based on MAO-B inhibitors will also be discussed in this review.

Abstract The polycondensation of silicic acid, methylsilicic acid, or their mixture was studied by reactive force field simulation. These were found to be feasible systems for the simulation of two-step acid hydrolysis-alkaline condensation of their alkoxysilane counterparts, usually taken experimentally as sol-gel precursors. The approach avoided the alkoxysilane hydrolysis step and allowed high degrees of polycondensation at relatively low temperature (700-1000 K), from the computational efficiency perspective. Being the ultimate interest of the present study the sol-gel polycondensation of templated gels whose microstructural pattern is affected by the presence of a template, the role of the intermolecular forces was decisive, and promoted high polycondensation at the lowest possible temperature. Polycondensation with added damascenone did not result in any perceived templating effect, i.e., damascenone was not able to interact significantly with the growing clusters, in a way that would allow its occlusion or a surface molding effect on the clusters. A possible reason for this is the intermolecular interaction strength being too weak at the temperatures set for the simulations. However, when using luteolin as the template, a molecule with several hydrogen bond interaction points, it was possible to observe different microscopic events involving the template molecules, some of them corresponding to actual templating effects, such as partial enveloping by the network around the template. These restricted events did not allow the inference of any macroscopic property of the final gel. However, it was shown that polycondensates shaped by the template or a template dimer may be obtained. The sites thus obtained will be essential for future in silico studies of the selectivity of such sites.

Abstract Chitosan and chitosan-nanoparticles were combined to prepare biobased and unplasticized film blends displaying antimicrobial activity. Nanosized chitosans obtained by sonication for 5, 15, or 30 min were combined with chitosan at 3:7, 1:1, and 7:3 ratios, in order to adjust blend film mechanical properties and permeability. The incorporation of nanosized chitosans led to improvements in the interfacial interaction with chitosan microfibers, positively affecting film mechanical strength and stiffness, evidenced by scanning electron microscopy. Nanosized or blend chitosan film sensitivity to moisture was significantly decreased with the drop in biocomposite molecular masses, evidenced by increased water solubility and decreased water vapor permeability. Nanosized and chitosan interactions gave rise to light biobased films presenting discrete opacity and color changes, since red-green and yellow-blue colorations were affected. All chitosan blend films exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. The performance of green unplasticized chitosan blend films displaying diverse morphologies has, thus, been proven as a potential step towards the design of nontoxic food packaging biobased films, protecting against spoilage microorganisms, while also minimizing environmental impacts.

Abstract Considering the high incidence level and mortality rate of ovarian cancer, particularly among the European female population, the carbohydrate antigen 125 (CA-125) was selected as the protein target for this study for the development of a MIP-based biosensor. This work presents the development of molecular imprinting polymers (MIPs) on gold electrode surface for CA-125 biomarker recognition. The preparation of the CA-125 imprinting was obtained by electropolymerization of pyrrole (Py) monomer in a gold electrode using cyclic voltammetry (CV) in order to obtain highly selective materials with great molecular recognition capability. The quantification of CA-125 biomarker was made through the comparison of two methods: electrochemical (square wave voltammetry -SWV) and optical transduction (surface plasmon resonance -SPR). SWV has been widely used in biological molecules analysis since it is a fast and sensitive technique. In turn, SPR is a non-destructive optical technique that provides high-quality analytical data of CA-125 biomarker interactions with MIP. Several analytical parameters, such as sensitivity, linear response interval, and detection limit were determined to proceed to the performance evaluation of the electrochemical and optical transduction used in the development of the CA-125 biosensor. The biosensor based in the electrochemical transduction was the one that presented the best analytical parameters, yielding a good selectivity and a detection limit (LOD) of 0.01 U/mL, providing a linear concentration range between 0.01 and 500 U/mL. This electrochemical biosensor was selected for the study and it was successfully applied in the CA-125 analysis in artificial serum samples with recovery rates ranging from 91 to 105% with an average relative error of 5.8%.

Abstract Mesoporous sorbent composites, evolving from previous work on microporous composites of polyanionic polysaccharides were developed with the purpose of increasing the sorptive features of the materials. Using the widely successful classical surfactant micelle approach, it was observed, in this particular case, that the composites remained essentially microporous. The alternative consisted on the application of deep eutectic solvents (DES). The most common DES (choline chloride + neutral hydrogen bond donor), were tested because of their advantages over other possibilities such as imidazolium-based ionic liquids: lower cost, easy in-house preparation, safe constituents and water stability and solubility. Possible mechanisms underlying the observed mesoporosity were discussed. The surface area ranged between 76 and 267 m(2)/g and the average pore size was in the range 3-5 nm. DES had not a negative effect on synthesis yields and, in the case of fucoidan, composites bearing a higher content of the biopolymer were produced. As a consequence and in line with the initial expectations these new composites revealed highly enhanced Pb (II) sorptive features comparatively to their microporous predecessors: chondroitin sulfate composites - up to a 5 fold capacity enhancement; fucoidan composites- up to a 3.5 fold capacity enhancement. The highest capacity was observed for the fucoidan composite prepared with choline chloride-ethyleneglycol DES, 79 mg Pb (II)/g, which is slightly above the highest value (77 mg Pb (II)/g) found in the literature for Pb (II) sorbents based on polysaccharides, sol-gels or their composites.

Abstract Nano carbons, such as graphene and carbon nanotubes, show very interesting electrochemical properties and are becoming a focus of interest in many areas, including electrodeposition of carbon-metal composites for battery application. The aim of this study was to incorporate carbon materials (namely oxidized multi-walled carbon nanotubes (ox-MWCNT), pristine multi-walled carbon nanotubes (P-MWCNT), and reduced graphene oxide (rGO)) into a metallic tin matrix. Formation of the carbon-tin composite materials was achieved by electrodeposition from a choline chloride-based ionic solvent. The different structures and treatments of the carbon materials will create metallic composites with different characteristics. The electrochemical characterization of Sn and Sn composites was performed using chronoamperometry, potentiometry, electrochemical impedance, and cyclic voltammetry. The initial growth stages of Sn and Sn composites were characterized by a glassy-carbon (GC) electrode surface. Nucleation studies were carried out, and the effect of the carbon materials was characterized using the Scharifker and Hills (SH) and Scharifker and Mostany (SM) models. Through a non-linear fitting method, it was shown that the nucleation of Sn and Sn composites on a GC surface occurred through a 3D instantaneous process with growth controlled by diffusion. According to Raman and XRD analysis, carbon materials were successfully incorporated at the Sn matrix. AFM and SEM images showed that the carbon incorporation influences the coverage of the surface as well as the size and shape of the agglomerate. From the analysis of the corrosion tests, it is possible to say that Sn-composite films exhibit a comparable or slightly better corrosion performance as compared to pure Sn films.

Abstract Vanillin is a naturally occurring phenolic aldehyde that is world-wide known for its flavouring properties. This work reports an extensive experimental and computational study of its thermodynamic properties. The vapour pressures of crystalline and liquid phases of vanillin were measured in the following temperature ranges T = (321.0-350.7) K and (324.9-382.3) K respectively, using a static method based on diaphragm capacitance gauge. Additionally, the crystalline vapour pressures were also measured in the temperature interval T = (303.1-325.2) K, using a Knudsen mass-loss effusion technique. The standard molar enthalpies, entropies and Gibbs energies of sublimation and of vaporization, at selected reference temperatures, were derived from the vapour pressure measurements. The enthalpies of vaporization and of sublimation, at T = 298.15 K, were also determined using Calvet microcalorimetry and the standard (p degrees = 10(5) Pa) molar enthalpy of formation, in the crystalline phase, at T = 298.15 K, was derived from its standard massic energy of combustion measured by static-bomb combustion calorimetry. From the experimental results, the standard molar enthalpy of formation in the gaseous phase, at T = 298.15 K, was calculated and compared with the values estimated by employing quantum chemical calculations. To analyse the thermodynamic stability of vanillin, the standard Gibbs energies of formation in crystalline and gaseous phases were calculated. The molar enthalpy of fusion determined using DSC is compared with indirect results determined using Calvet microcalorimetry and vapour pressure measurements. (C) 2018 Elsevier Ltd.