Publications

Abstract The standard molar enthalpy of formation in the gas phase of 2H-1,4-benzoxazin-3(4H)-one was derived from the standard energy of combustion determined by static bomb combustion calorimetry in oxygen atmosphere and from the standard sublimation enthalpy determined by Calvet microcalorimetry. In addition, we report the results of a systematic theoretical study of the keto and enol tautomers in benzoxazinones and diones using density functional theory. The keto tautomers are computed to be more stable than the enols. Tautomerization energies are reported.

Abstract The standard (p degrees = 0.1 MPa) molar enthalpy of formation for solid benzanilide was derived from the standard molar enthalpy of combustion, in oxygen, at T = 298.15 K, measured by static bomb combustion calorimetry, and the standard molar enthalpy of sublimation, at T = 298.15 K, measured by Calvet microcalorimetry. From these experiments the standard molar enthalpy of formation of benzanilide in the gaseous phase at T = 298.15K was calculated. In addition density functional theory calculations with the B3LYP functional and a variety of basis sets have been performed for benzanilide and some auxiliary molecules.

Abstract Cancer, one of the major causes of death across the world, has shown to be a largely preventable disease, highly susceptible to modulation by dietary factors. Phenolic compounds, abundant in vegetables and fruits ubiquitous in diet, were described to play an important role as chemopreventive agents. Since conventional therapeutic and surgical approaches have not been able to control the incidence of most cancer types, the development of chemopreventive strategies is an urgent priority in public health. The current diet phenolic intake is often insufficient to protect from mutagens (either exogenous or endogenous), which leads to the need for dietary supplementation as an alternative approach. Research efforts are placing increasing emphasis on identifying the biological mechanisms and in particular the signal transduction pathways related to the chemopreventive activities of these compounds. These effects are believed to occur by the regulation of signaling pathways such as nuclear factor-kappa B (NF-kappa B), activator protein-1 (AP-1) or mitoacn-activated protein kinases (MAPK). Dietary polyphenols can exert their effects on these pathways separately or sequentially and in addition the occurrence of crosstalk between these pathways cannot be overlooked. By modulating cell signaling pathways, polyphenols activate cell death signals and induce apoptosis in precancerous or malignant cells resulting in the inhibition of cancer development or progression. However, regulation of cell signaling pathways by dietary polyphenols can also lead to cell proliferation/survival or inflammatory responses due to increased expression of several genes. The present review summarizes the most recent advances providing new insights into the molecular mechanisms underlying the promising anti carcinogenic activity of dietary polyphenols. (c) 2006 Wiley Periodicals, Inc.

Abstract Methamphetamine (METH), leading to striatal dopamine (DA) nerve terminal toxicity in mammals, is also thought to induce apoptosis of striatal neurons in rodents. We investigated the acute effects induced by multiple injections of METH (4 X 5 mg/kg, i.p.) at 2-h intervals or a single injection of METH (20 mg/kg, i.p.) on terminal dopaminergic toxicity markers, including DA levels, DA turnover, and tyrosine hydroxylase (TH) immunoreactivity in rat caudate-putamen (CPu). We further investigated whether both treatment paradigms would change Bax and activate caspase-3 expression, thus triggering striatal apoptotic mitochondria-dependent biochemical cascades. The first injection of METH (5 mg/kg, i.p.) produced a significant release of DA that peaked 30 min and stayed above control levels up to 1.5 h within CPu. In another set of experiments, rats were killed 1 and 24 h following the last injection, for tissue DA and metabolite content measurement and Western blot analysis (24 h). Multiple doses induced DA depletion and increased turnover at both endpoints. Single-dose METH reproduced these effects at 24 h; however, turnover was significantly higher than that evoked by the multiple doses at 24 h. Although both paradigms evoked similar DA depletion, however, none of the dosing regimens induced changes in TH expression at 24 h. The former paradigm produced an increase in Bax expression in CPu not sufficient to induce cleavage of caspase-3 proenzyme at 24 h. This study suggests that both paradigm induced changes in striatal dopaminergic markers that are independent of terminal degeneration and striatal apoptotic mitochondria-dependent caspase-3 driven cascade within 24 h.

Abstract A multidisciplinary project was developed, combining the synthesis of a series of beta-nitrostyrene derivatives and the determination of their physicochemical parameters (redox potentials, partition coefficients), to the evaluation of the corresponding antibacterial activity. A complete conformational analysis was also performed, in order to get relevant structural information. Subsequently, a structure-property-activity (SPAR) approach was applied, through linear regression analysis, aiming at obtaining a putative correlation between the physicochemical parameters of the compounds investigated and their antibacterial activity (both against standard strains and clinical isolates). The beta-nitrostyrene compounds displayed a lower activity towards all the tested bacteria relative to the beta-methyl-beta-nitrostyrene analogues. This was observed particularly for the 3-hydroxy-4-methoxy-beta-methyl-beta-nitrostyrene (IVb) against the Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium). The SPAR results revealed the existence of a clear correlation between the redox potentials and the antibacterial activity of the series of beta-nitrostyrene derivatives under study.

Abstract The toxicological and redox profiles of MDMA and its major metabolites (MDA, alpha-methyldopamine, N-methyl-alpha-methyldopamine, 6-hydroxy-alpha-methyldopamine, 3-methoxy-alpha-methyldopamine) were studied to establish a structure- toxicity relationship and determine their individual contribution to cell death induction by apoptosis and/or necrosis. The results of the comparative toxicity study, using undifferentiated PC12 cells, strongly suggest that the metabolites possessing a catecholic group are more toxic to the cells than MDMA and metabolites with at least one protected phenolic group. Redox studies reveal that an oxidative mechanism seems to play an important role in metabolite cytotoxicity. Nuclear features of apoptosis and/or necrosis show that most of the metabolites, particularly N-methyl-alpha-methyldopamine, induce cell death by apoptosis, largely accompanied by necrotic features. No significant differences were found between MDMA and the metabolites, concerning overall characteristics of cell death. These results may be useful to ascertain the contribution of metabolism in MDMA neurotoxicity molecular mechanisms.

Abstract Catanionic surfactants result from the pairing of oppositely charged amphiphilic molecules, forming a new class of surfactant molecules with various interesting lyotropic and thermotropic properties. With the aim of probing the role of both headgroup chemical nature/structure and molecular shape, a series of catanionic surfactants were synthesized. The cationic portion of the molecule is kept constant, being the dioctadecyldimethylammonium double chain. Different single-chained surfactants with varying headgroups and chain lengths are used as the anionic pair. The thermotropic behavior has been studied by DSC and the mesophase structural investigated by polarizcd light microscopy. The results indicate that, for a given chain length, parameters such as headgroup polarity and charge density, as well as volume, influence the catanionic surfactant behavior. The thermodynamic parameters are qualitatively evaluated, considering the headgroup chemical nature and the overall molecular structure.

Abstract We present the phase behavior and thermodynamics of the catanionic mixture of the gemini surfactant hexanediyl-alpha,omega-bis(dodecyidimethylammonium bromide), designated here as 12-6-12Bn(2), and sodium dodecyl sulfate (SIDS) over the full range of composition, at the water-rich corner. Visual and turbidity measurements of the mixtures provide some basic macroscopic information on phase behavior. The structure of the aggregates formed spontaneously in the mixtures has been observed with TEM. As the molar fraction of SDS, X(SDS), is increased, at constant total surfactant concentration, the aggregation morphologies change gradually from gemini-rich micelles, through multiphase regions containing a precipitate (catanionic surfactant) and a vesicle region, to SDS-rich micelles. From isothermal titration calorimetry measurements, the phase boundaries and corresponding enthalpy changes for phase transitions have been obtained. The formation of the different microstructures, in particular, the spontaneously formed vesicles in the SDS-rich side, is discussed on the basis of geometric and electrostatic effects occurring in the SDS-gemini mixture.

Abstract The lyotropic phase behavior for the neat cationic gemini surfactants alkanediyl-alpha,omega-bis(alkyldimethylammonium bromide), designated here as in-s-m, has been investigated previously in several works, but the thermotropic behavior has not been well characterized. Only for 15-s-15 and 14-s- 12 have thermotropic liquid crystals (Lc) been reported. In this work, for the first time and in contrast to previous reports, we observe thermotropic Lc formation for m-2-m geminis with in = 12, 14, 16, and 18, by means of polarizing microscopy and differential scanning calorimetry (DSC). Furthermore, we investigate mixtures of m-2-m and SDS, m-2-m Br(2)center dot 2SDS, which exhibit crystal-to-crystal phase transitions at lower temperature and, at high temperature, smectic Lc phases. The transition temperatures and enthalpies for Lc phases, obtained by DSC, present clear trends upon increase of the chain lengths. Combining Langmuir film experiments, possible lamellar arrangements for the different phases are tentatively discussed.

Abstract A confon-national analysis of ethyl 3-(3,4,5-trihydroxyphenyl)-2-propenoate (ethyl 3,4,5-trihydroxycinnamate, ETHPPE), a polyphenolic cinnarnic ester which displays antiproliferative activity towards human adenocarcinorna cells, was carried out by Raman spectroscopy coupled to ab initio MO calculations. Apart from the optimised geometrical parameters for the most stable conformations of this compound (both for the trans and cis isomers), the corresponding harmonic vibrational frequencies were obtained. Eighteen distinct geometries were found, 12 for the lowest energy trans isomer and six for the cis species. The conformational preferences of this system were verified to be mainly ruled by the stabilising effect of pi-electron delocalisation, a planar geometry being favoured. The orientation of the ester moiety showed to be the most determinant factor for the overall stability of the molecule. In the light of these results, a complete assignment of the corresponding Raman pattern was performed.