Publications

Abstract Reliable force field (FF) is a central issue in successful prediction of physical chemical properties via computer simulations. While Canongia Lopes-Padua (CL&P) FF provides good to excellent thermodynamics and structure of pure room-temperature ionic liquids (RTILs), it suffers from drastically and systematically underestimated ionic motion. This occurs due to neglected partial electron transfer from the anion to the cation, resulting in unphysically small simulated self-diffusion and conductivity and high shear viscosities. We report a systematic refinement of the CL&P FF for six pyrrolidinium-based RTILs (1-N-butyl-1-methyl-pyrrolidinium dicyanamide, triflate) bis(fluorosulfonyl)imide, bis(trifluoromethanesulfonyl)imide, tetrafluoroborate, chloride). The elaborated procedure accounts for specific cation anion interactions in the liquid phase. Once these interactions are described effectively, experimentally determined transport properties can be reproduced with an acceptable accuracy. Together with the original CL&P parameters, our force field fosters computational investigation of ionic liquids. In addition, the reported results shed more light on the chemical nature of cation anion binding in various families of RTILs.

Abstract In this paper, a review of the literature on the phenolic compounds with anticancer activity published between 2008 and 2012 is presented. In this overview only phenolic antioxidant compounds that display significant anticancer activity have been described. In the first part of this review, the oxidative and nitrosative stress relation with cancer are described. In the second part, the plant-derived food extracts, containing identified phenolic antioxidants, the phenolic antioxidants isolated from plants and plant-derived food or commercially available and the synthetic ones, along with the type of cancer and cells where they exert anticancer activity, are described and summarized in tables. The principal mechanisms for their anti-proliferative effects were also described. Finally, a critical analysis of the studies and directions for future research are included in the conclusion.

Abstract Sorption/desorption experiments in batch and continous flow-through stirred reactor under different experimental conditions were carried out using montmorillonite (< 2 mu m clay fractions). The Sr2+ amount desorbed at pH 4 is only half of the amount desorbed at pH 8, revealing that the retention of Sr2+ onto montmorillonite was enhanced at pH 4. The largest adsorption value was obtained at pH 8.0 ([KNO3] = 10(-3) mol/L) with q (m) = 41.49 mg Sr2+/g from the Langmuir isotherm. The gradient of concentration acted as an increasing driving force since the amount of Sr2+ adsorbed increased as increasing of Sr2+ concentration during the flow-through experiments.

Abstract Zn alloys are considered an alternative to replace Cd in protective coatings. Among Zn alloys, Zn-Ni are those with the higher corrosion resistance and better mechanical characteristics. Although Zn-Ni alloy can be electrodeposited from eutectic-type ionic liquid the morphology of the deposits needs to be improved. The effect of ethylamine and ethylenediamine on the electrodeposition of Zn-Ni alloy was investigated from a eutectic-type ionic liquid (ethaline). The presence of the amines in the plating bath modified the CV and j-t profiles. The nucleation mechanism was also influenced by adding the amines to the solution and the deposition of Zn-Ni in the presence of ethylenediamine followed the 3D progressive mechanism. Electrodeposition of Zn-Ni alloy from ethaline gives origin to a deposit with small grain particles with partial coverage of the electrode. Using the same electrodeposition conditions, the addition of amines allowed the full coverage of the electrode surface. In the presence of ethylamine deposit was formed by globular particles and by hexagonal platelets for deposits obtained in the presence ethylenediamine. Corrosion of the Zn-Ni metallic films was evaluated by potentiodynamic polarization experiments. The lowest value for the corrosion potential was obtained for the deposit prepared in the presence of ethylenediamine.

Abstract The heat of hydrogenation of indenone was measured via two partially independent thermodynamic cycles by carrying out energetic measurements (i.e., electron affinities, proton affinities and ionization potentials) on both negative and positive ions (Delta H degrees(H2), =17.8 +/- 5.5 and 17.5 +/- 5.7 kcal mol(-1), respectively). High level G3 computations were also carried out to provide the heats of formation of indenone (16.8 kcal mol(-1)) and cyclopentadienone (14.0 kcal mol(-1)). These 4n pi electron systems are found to be nonaromatic in contrast to previous views. A recent report on cyclopropenyl anion (J. Org. Chem. 2013, 78, 7370-7372) indicates that this ion is also nonaromatic, and suggests that NMR ring currents and nucleus independent chemical shift (NICS) calculations do not correlate with the energetic criterion for antiaromatic compounds.

Abstract Chromones are 4H-benzopyran-4-one heterocycles that have been thoroughly studied due to their interesting biological activities. Thiazole based compounds have been used in therapeutics as antimicrobial, antiviral and as antifungal agents for a long time but, in the past decades, they have been identified as potent and selective ligands for adenosine receptor. In continuation of our project related to the syntheses of pharmacologically important heterocycles, a new series of chromone-thiazole hybrids have been designed as potential ligands for human adenosine receptors. In this context, new 4-oxo-N-(substituted-thiazol-2-yl)-4H-chromene-2-carboxamides were synthesized from chromone-2-carboxylic acid by two different amidation methods. The development of dissimilar synthetic approaches provided the possibility of working with diverse reaction conditions, namely with conventional heating and/or microwave irradiation. The structure of the compounds has been established on the basis of NMR and MS spectroscopy and X-ray crystallography. Relevant data related to the molecular geometry and conformation of the chromone-thiazole hybrids has been acquired which can be of the utmost importance to understand ligand-receptor binding.

Abstract In recent years, the use of boron-containing reagents in palladium-assisted C-C coupling reactions (the Suzuki reaction) has gained prominence due to the vast array of reagents commercially available. Consequently, the generation of carbon carbon bonds, namely of functionalized biphenyl systems, is at present considered the backbone of organic synthesis. In this context, the design of eco-friendly protocols for the Suzuki reaction employing water as a solvent and the use of microwave-assisted procedures are imperative from an industrial point of view. The series of laboratory experiences described highlight the skillfulness of microwave-assisted synthesis to promote environmentally friendly Suzuki reactions. In the first laboratory class, 1(4-hydroxy-4'-methoxy-[1,1'-biphenyl]-3-yl)ethanone and 1-(4'-chloro-4-hydroxy-[1,1'-biphenyl]-3-yl)ethanone are synthesized, and the crude products are obtained and purified. Students become acquainted with microwave equipment and several laboratory techniques, such as extraction, purification by filtration with celite, column chromatography, and thin-layer chromatography. In the second laboratory class, students check the purity of the compounds and acquire H-1 and C-13 NMR spectral data. The synthesized phenylacetophenone derivatives are key intermediates for the synthesis of many biological active molecules, namely, flavonoids, chromones, or coumarins, which are privileged structures for drug discovery. The experiments can be also performed with diverse arylboronic acids containing different electron donating and withdrawing groups, allowing the synthesis of a small library of benzopyran precursors. The experiments have been tested for three years by 75 graduate students in applied organic chemistry or medicinal chemistry curriculum units.

Abstract In this study, a theoretical approach was used to study the UV absorption of the UVB filter, 4- methylbenzylidene camphor. The main objective of this work was to design new UVA filters based on this rather photo- stable compound, so that photo- degradation in this UV region can be avoided without the use of other molecules. This objective was achieved by the simultaneous addition of two appropriate substituents, which led to red- shifts of up to 0.69 eV while maintaining appreciable oscillator strength. Also, useful structure- energy relationships were derived, which allow for the development of more UVA filters based on 4- methylbenzylidene camphor.

Abstract Hydroxycinnamic derivatives based on ferulic and caffeic acids were designed to meet the pharmacokinetic requirements to cross the blood-brain barrier and to display neuroprotective activity within the central nervous system. Biological screening included the assessment of acetylcholinesterase and glycogen synthase kinase 3b inhibition, iron chelation properties, in vitro blood-brain barrier permeability, evaluation of cytotoxicity and neuroprotection against 6-hydroxydopamine induced damage in SH-SY5Y cells. Although the chemical modifications did not significantly alter the in vitro activity of the parent compounds, the results of the PAMPA-BBB assay show that some derivatives have higher diffusion rates and may reach the brain. The majority of the synthesized compounds did not display cytotoxicity and successfully prevent 6-hydroxydopamine damage. In this series, compound 14 stands out as a promising neuroprotective agent combining a number of key features: iron chelation, neuroprotection against oxidative damage, mild acetylcholinesterase activity and ability to permeate the blood-brain barrier. This biology-oriented approach provides new tools for the generation of new chemical entities to tackle the oxidative damage associated with neurodegenerative disorders.

Abstract New lipophilic hydroxycinnamic acid based derivatives were designed and synthesized and their antioxidant and neuroprotective activities evaluated. The chemical modification introduced in the cinnamic acid scaffold leads to compounds with amplified lipophilicity and in general with increased antioxidant activity when compared to natural models (caffeic and ferulic acids). The compounds did not display cytotoxicity and present a significant neuroprotective effect against 6-OH-DA induced damage to SH-SY5Y cells. Compound 6 stands out as an efficient radical scavenger and iron(II) chelator that ensures drug-like properties. Moreover, neuroprotection against oxidative damage was observed even at low concentration (1 mu M). Therefore, compound 6 developed by a biology-oriented approach displays a combination of important features for a further optimization process that will generate a new effective antioxidant with therapeutic application for oxidative-stress-related events, namely neurodegenerative diseases.