Publications

Abstract For the first time, a glassy carbon electrode (GCE) modified with novel N-doped carbon nanotubes (CNTN) functionalized with MnFe2O4 nanoparticles (MnFe2O4@CNT-N) has been prepared and applied for the electrochemical determination of caffeine (CF), acetaminophen (AC) and ascorbic acid (AA). The electrochemical behaviour of CF, AC and AA on the bare GCE, CNT-N/GCE and MnFe2O4@CNT-N/GCE were carefully investigated using cyclic voltammetry (CV) and square-wave voltammetry (SWV). Compared to bare GCE and CNT-N modified electrode, the MnFe2O4@CNT-N modified electrode can remarkably improve the electrocatalytic activity towards the oxidation of CF, AC and AA with an increase in the anodic peak currents of 52%, 50% and 55%, respectively. Also, the SWV anodic peaks of these molecules could be distinguished from each other at the MnFe2O4@CNT-N modified electrode with enhanced oxidation currents. The linear response ranges for the square wave voltammetric determination of CF, AC and AA were 1.0 x 10(-6) to 1.1 x 10(-3) mol dm(-3), 1.0 x 10(-6) to 1.0 x 10(-3) mol dm(-3) and 2.0 x 10(-6) to 1.0 x 10(-4) mol dm(-3) with detection limit (S/N= 3) of 0.83 x 10(-6), 0.83 x 10(-6) and 1.8 x 10(-6) mol dm(-3), respectively. The sensitivity values at the MnFe2O4@CNT-N/GCE for the individual determination of AC, AA and CF and in the presence of the other molecules showed that the quantification of AA and CF show no interferences from the other molecules; however, AA and CF interfered in the determination of AC, with the latter molecule showing the strongest interference. Nevertheless, the obtained results show that MnFe2O4@CNT-N composite material acted as an efficient electrochemical sensor towards the selected biomolecules.

Abstract The development of carbon-based metal-free electrocatalysts for the oxygen reduction reaction (ORR) is one of the most attractive topics in fuel cell field. Herein, we report the application of two sustainable sucrose-based activated carbons (ACs), denominated SC800 and SH800, as ORR electrocatalysts. In alkaline medium the ACs showed similar onset potentials at E-onset approximate to -0.20 V vs. Ag/AgCl (0.76 V vs. E-RHE), which are 0.06 V more negative than that observed for 20 wt% Pt/C used as a reference. Higher diffusion-limiting current densities (j(L(-1.0 V, 1600 rpm)) = -3.44 mA cm(-2)) were obtained for the SH800 electrocatalyst, in contrast to SC800 (j(L(-1.0 V, 1600 rpm)) = -3.04 mA cm(-2)). These differences can be related with their different textural properties. The SH800 electrocatalyst revealed a higher specific surface area (A(BET) approximate to 2500 m(2) g(-1)), larger micropores (widths between 0.7 and 2 nm) and sponge-like morphology. Conversely, SC800 showed a spherical shape, A(BET) approximate to 1400 m(2) g(-1) and narrow micropores with pore width <0.7 nm. Both ACs were neither selective to 2- or 4-electron ORR processes, opposing Pt/C which showed selectivity towards direct O-2 reduction to water. SH800 and SC800 showed very similar Tafel plots, but with SH800 showing in both low and high current density regions, the lowest slopes values 53/171 mV dec(-1) vs. 68/217 mV dec(-1). Furthermore, the ACs presented excellent tolerance to methanol, with the SH800 electrocatalyst also showing greater long-term electrochemical stability than the Pt/C electrocatalyst which are very important advantages. The ACs-based electrocatalysts also showed ORR catalytic activity in acidic media, which makes them promising candidates for applications with acidic electrolytes (e.g. proton exchange fuel cells). In this case, E-onset = 0.06 V vs. Ag/AgCl (0.41 V vs. E-RHE) for SC800 and E-onset = -0.01 V vs. Ag/AgCl (0.34 V vs. E-RHE) for SH800, and the diffusion-limiting current densities are very similar for both ACs (jL = -2.59/-2.76 mA cm(-2) at -1.3 V vs. Ag/AgCl, at 1600 rpm). SH800 and SC800 Tafel plots also showed two different slopes, but with higher values in both low and high current density regions, when compared with those obtained in an alkaline medium; still SH800 continues to show the lowest slopes.

Abstract The study of the energetics of phenolic compounds has a considerable practical interest since this family of compounds includes numerous synthetic and naturally occurring antioxidants. In this work, density functional theory (DFT) has been used to investigate gas-phase thermochemical properties of the following tri-substituted phenols: 2,4,6-trimethylphenol, 2,6-dimethyl-4-tert-butylphenol, 2, 6-dimethyl-4-methoxyphenol, 2,4,6-tri-tert-butylphenol, 2,6-di-tert-butyl-4-methylphenol, 2,6-di-tertbutyl-4-methoxyphenol, 2,4,6-trimethoxyphenol, 2,6-dimethoxy-4-methylphenol and 2,6-dimethoxy-4-tert-butylphenol. Molecular structures were computed with the B3LYP and the omega B97X-D functionals and the 6-31G(d) basis set. More accurate energies were obtained from single-point energy calculations with both functionals and the 6-311++G(2df,2pd) basis set. Standard enthalpies of formation of the phenolic molecules and phenoxyl radicals were derived using an appropriate homodesmotic reaction. The O-H homolytic bond dissociation enthalpies, gas-phase acidities and adiabatic ionization enthalpies were also calculated. The general good agreement found between the calculated and the few existent experimental gas-phase thermochemical parameters gives confidence to the estimates concerning the phenolic compounds which were not yet experimentally studied.

Abstract The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and chromone-3-carboxamide scaffolds.

Abstract Reactive species are continuously produced in vivo by all body tissues. However, when an imbalance between the reactive species production and the endogenous pool of antioxidants occurs, the resulting oxidative stress can somehow intensify the pathophysiological mechanisms of several diseases, such as neurodegenerative diseases. Although the aetiology of Parkinson's and Alzheimer's diseases is not yet completely understood, it is accepted by the scientific community that the oxidative stress can act as a trigger or can be involved in the course of both diseases. Therefore, the development of an antioxidant-based therapy could be a helpful approach to ameliorate the deleterious effects of oxidative stress in neurodegenerative diseases. Coumarins and chromones are natural or synthetic chemical entities described as privileged structures with diverse biological activities that have been used to design new drugs with potential anti-Alzheimer and anti-Parkinson profiles. Since some of these compounds also displayed potent antioxidant activity, the rationale approach to developing new drugs based on the benzopyran scaffold, as therapeutic alternatives for neurodegenerative diseases, is a valid and compelling topic. This review provides a medicinal chemistry overview on the discovery and development of benzopyran-based compounds endowed with antioxidant, neuroprotective and anti-Alzheimer or anti-Parkinson activities.

Abstract One of the major hurdles in the development of safe and effective drugs targeting G-protein coupled receptors (GPCRs) is finding ligands that are highly selective for a specific receptor subtype. The search for novel compounds with therapeutic value by targeting the A(3) adenosine receptor (A(3)AR) is still in its early stages. The increasing knowledge about the biological, physiological and pathological role of the A(3)AR subtype was accompanied by the design and development of the A(3)AR ligands, but the particular role of A(3)AR agonists and antagonists is still an open issue. Among the large variety of chemical classes screened towards ARs flavonoids have been indicated as remarkable A(3)AR antagonists. However, the search of A(3)AR ligands based on this framework seems to be discontinued. In this context, our research group focused its investigation into the discovery and development of novel, potent and selective AR ligands based on the chemical core of flavonoids, the chromone scaffold. The ongoing research has shown that chromone-2-phenylcarboxamide derivatives display a remarkable preference for hA(3)AR. In this work we report stimulating results, supported by A(2A)/A(3) molecular docking simulations and structure-affinity-relationship (SAR) studies by which N-(4,5-methylthiazol-2-yl)-4-oxo-4H-chromene-2-carboxamide (compound 31) emerged as the most potent and selective compound, displaying an hA(3) K-i of 167 nM and a selectivity ratio of 590 vs. the hA(1) and 480 vs. the hA(2A)AR subtypes. The chromone-based ligand was obtained by a simple synthetic approach and will enter in a lead optimization program to enhance its potency and drug-like properties.

Abstract The crystal structures of the 3-substituted tertiary chromone carboxamide derivative, C17H13NO3, N-methyl-4-oxo-N-phenyl-4H-chromene-3-carboxamide (1), and the chromone carbonyl pyrrolidine derivatives, C14H13NO3, 3-(pyrrolidine-1-carbonyl)-4H-chromen-4-one (3) and 2-(pyrrolidine-1-carbonyl)-4H-chromen-4-one (4) have been determined. Their structural features are discussed and compared with similar compounds namely with respect to their MAO-B inhibitory activities. The chromone carboxamide presents a -syn conformation with the aromatic rings twisted with respect to each other [the dihedral angle between the mean planes of the chromone system and the exocyclic phenyl ring is 58.48 (8)degrees]. The pyrrolidine derivatives also display a significant twist: the dihedral angles between the chromone system and the best plane formed by the pyrrolidine atoms are 48.9 (2) and 23.97 (12)degrees in (3) and (4), respectively. Compound (3) shows a short C-H center dot center dot center dot O intramolecular contact forming an S(7) ring. The supramolecular structures for each compound are defined by weak C-H center dot center dot center dot O hydrogen bonds, which link the molecules into chains and sheets. The Cambridge Structural Database gave 45 hits for compounds with a pyrrolidinecarbonyl group. A simple statistical analysis of their geometric parameters is made in order to compare them with those of the molecules determined in the present work.