Publications

Abstract Neurodegenerative disorders are becoming more prevalent given the increase in the aging population. This has inspired active research in the development of new drugs that could mark an important advance in the treatment of complex diseases such as Alzheimer's and Parkinson's. With the aim of finding new MAO-B-selective inhibitors, we report the synthesis, in vitro evaluation, and docking simulation of a new series of 3-arylcoumarins variously substituted at the 8-position. Most of the studied compounds show high affinity and selectivity for the hMAO-B isoform, with IC50 values in the low micro- to nanomolar range. Some of them have greater hMAO-B inhibitory activity and selectivity than the reference compound, selegiline. Compounds 7 and 8 are the most active of this series, with compound 8 being fivefold more potent against MAO-B and severalfold more selective than selegiline. Docking experiments were carried out with hMAO-B crystal structures, providing new information about the enzymeinhibitor interaction and the potential therapeutic application of the new 8-substituted 3-arylcoumarins.

Abstract Density and viscosity experimental data for binary mixtures of 1-alkyl-3-methylimidazolium alkylsulfates + water are reported using four ionic liquids: 1-butyl-3-methylimidazolium hydrogensulfate [C(4)mim][HSO4], 1-butyl-3-methylimidazolium methylsulfate [C(4)mim] [C1SO4], 1-ethyl-3-methylimidazolium methylsulfate [C(2)mim] [C1SO4], and 1-ethyl-3-methylimidazolium methylsulfate [C(2)mim][C2SO4]. The choice of the ionic liquids allows us to compare the effects of incrementing the alkyl chain length in the cation and the anion on the measured thermophysical properties behavior. The Gardas and Coutinho group contribution methods were applied to the description of the pure component densities and viscosities allowing the estimation of new group contribution parameters, to extend the applicability of these methods to new ILs. Excess molar volumes and viscosity deviations were calculated and correlated by Redlich-Kister polynomial expansions. .

Abstract A full account is given for the total synthesis and the cytotoxic activity against the human lung tumoral cell line NCI-H460 of (+/-)-7-deoxy-pancratistatin and its 2-epi- and 2,4-diepi- unnatural analogues.

Abstract 2-Methoxymethylpyrrolidine best performed, among several other proline derivatives, to control the enantioselective [3+3] annulation of beta-(hetero)aryl-alpha-nitro-alpha,beta-enals with commercial 2,2-dimethyl-1,3-dioxan-5-one, a procedure that renders highly oxygenated nitrocyclohexanes endowed with five new stereocenters. Use of this reaction allowed the development of a total synthesis of the antitumoral natural product (+)-pancratistatin; it also converted our previous racemic route to tetrodotoxin into an enantioselective one.

Abstract This work reports the first data for the vapor pressures at several temperatures of the ionic liquids, [C(N/2)C(N/2)im][NTf2] (N = 4, 6, 8, 10, 12) measured using a Knudsen effusion apparatus combined with a quartz crystal microbalance. The morphology and the thermodynamic parameters of vaporization derived from the vapor pressures, are compared with those for the 1-alkyl-3-methylimidazolium bis-(trifluoromethylsulfonyl)imide series, [C(N-1)C(1)im][NTf2] (N = 3 - 9, 11, and 13). It was found that the volatility of [C(N/2)C(N/2)im][NTf2] series is significantly higher than the asymmetric cation ILs with the same total number of carbons in the alkyl side chains, [C(N-1)C(1)im][NTf2]. The observed higher volatility is related with the lower enthalpy of vaporization. The symmetric cation, [C(N/2)C(N/2)im][NTf2], presents lower entropies of vaporization compared with the asymmetric [C(N-1)C(1)im][NTf2], indicating an increase of the absolute liquid entropy in the symmetric cation ILs, being a reflection of a change of the ion dynamics in the IL liquid phase. Moreover both the enthalpy and entropy of vaporization of the [C(N/2)C(N/2)im][NTf2] ILs, present a clear odd-even effect with higher enthalpies/entropies of vaporization for the odd number of carbons in each alkyl chain ([C(3)C(3)im][NTf2] and [C(5)C(5)im][NTf2]).

Abstract The synthesis of three new quinoxaline mono-N-oxides derivatives, namely, 2-tert-butoxycarbonyl-3-methylquinoxaline-N-oxide, 2-phenylcarbamoyl-3-ethylquinoxaline-N-oxide, and 2-carbamoyl-3-methylquinoxaline-N-oxide, from their corresponding 1,4-di-N-oxides is reported. Samples of these compounds were used for a thermochemical study, which allowed derivation of their gaseous standard molar enthalpies of formation, Delta fHmo(g), from their enthalpies of formation in the condensed phase, Delta fHmo(cr), determined by static bomb combustion calorimetry, and from their enthalpies of sublimation, Delta crgHmo, determined by Calvet microcalorimetry. Finally, combining the Delta fHmo(g) for the quinoxaline-N-oxides derived in this work with literature values for the corresponding 1,4-di-N-oxides and atomic oxygen, the bond dissociation enthalpies for cleavage of the first N-O bond in the di-N-oxides, DH1(NO), were obtained and compared with existing data. Copyright (c) 2011 John Wiley & Sons, Ltd.

Abstract This work reports new experimental thermodynamic results on fluorene. Vapor pressures of both crystalline and liquid phases were measured using a pressure gauge (capacitance diaphragm manometer) and Knudsen effusion methods over a wide temperature range (292.20 to 412.16) K yielding accurate determination of enthalpy and entropy of sublimation and of vaporization. The enthalpy of sublimation was also determined using Calvet microcalorimetry. The enthalpy of fusion was derived from vapor pressure results and from d.s.c. experiments. Static bomb calorimetry was used to determine the enthalpy of combustion of fluorene from which the standard enthalpy of formation in the crystalline phase was calculated. The enthalpy of formation in the gaseous phase was calculated combining the result derived for the crystalline phase with the enthalpy of sublimation.

Abstract Salt-free catanionic surfactants form in water binary systems, thus differing from pseudo-ternary equimolar catanionic mixtures, where salt is present. A miscibility gap, an unusual phenomenon in binary systems, is observed for the lamellar phase of the catanionic surfactant hexadecyltrimethylammonium octylsulfonate. Experimental data show the coexistence of a swollen and a collapsed lamellar phase in a wide two-phase region, while linear swelling is observed for each phase. This phase behavior is suggested to stem mainly from a concentration dependence of the charge density of catanionic bilayer, driven by the much higher solubility of the short chain ionic counterpart (octylsulfonate). Thus, a theoretical cell model based on combined DLVO and short range repulsive potentials is presented in order to provide physical insight into the miscibility gap. Furthermore, the surfactant forms at high dilution a solution phase and exhibits a very low critical micelle concentration (0.0035 wt%). The dilute lamellar phase is in equilibrium with the isotropic solution, and small vesicles can also be observed, apparently as a dispersion of the swollen lamellae in the solution. Upon temperature increase, a vesicle-to-micelle transition occurs. These unusual equilibria can also be qualitatively rationalized by the short chain solubility model. © 2012 by World Scientific Publishing Co. Pte. Ltd.

Abstract In the present work, the standard (p degrees = 0.1 MPa) molar enthalpies of formation of xanthydrol, 9-xanthenecarboxylic acid and 9-xanthenecarboxamide, in the gaseous state, at T = 298.15 K, were determined by experimental and computational studies. The experimental techniques used were the static-bomb combustion calorimetry, which enabled the determination of the standard molar enthalpy of formation, in the crystalline state, and the vacuum drop microcalorimetric and the Knudsen effusion techniques used to derive the enthalpy of sublimation. For comparison purposes, we performed standard ab initio molecular orbital calculations, using the G3(MP2)//B3LYP composite procedure, of the enthalpies of several homodesmotic reactions, allowing to extract the standard molar enthalpies of formation, in the gaseous state, of the three xanthene derivatives considered in this work. The calculated results are in good agreement with the experimental data.

Abstract Two antimicrobial cryptopeptides from the N1 domain of bovine lactoferrin, lactoferricin (LFcin17-30) and lactoferrampin (LFampin265-284), together with a hybrid version (LFchimera), were tested against the protozoan parasite Leishmania. All peptides were leishmanicidal against Leishmania donovani promastigotes, and LFchimera showed a significantly higher activity over its two composing moieties. Besides, it was the only peptide active on Leishmania pifanoi axenic amastigotes, already showing activity below 10 mu M. To investigate their leishmanicidal mechanism, promastigote membrane permeabilization was assessed by decrease of free ATP levels in living parasites, entrance of the vital dye SYTOX Green (MW = 600 Da) and confocal and transmission electron microscopy. The peptides induced plasma membrane permeabilization and bioenergetic collapse of the parasites. To further clarify the structural traits underlying the increased leishmanicidal activity of LFchimera, the activity of several analogues was assessed. Results revealed that the high activity of these hybrid peptides seems to be related to the order and sequence orientation of the two cryptopeptide moieties, rather than to their particular linkage through an additional lysine, as in the initial LFchimera. The incorporation of both antimicrobial cryptopeptide motifs into a single linear sequence facilitates chemical synthesis and should help in the potential clinical application of these optimized analogues.