Publications

Abstract The derivatives of 1,4-benzodioxan are found widely spread in nature and have great biomedical importance. The present work reports ail experimental and Computational study on the thermochemistry of 1,4-benzodioxan and several of its 6-R derivatives in the gaseous phase, at T = 298.15 K. Our current results were obtained from measurements of combustion energies, at T = 298.15 K, using a static bomb calorimeter. The standard molar enthalpies of vaporization/sublimation were measured by Calvet microcalorimetry and corrected to T = 298.15 K. Additionally, estimates were performed of the enthalpies of formation of all the studied compounds in the gas phase, using DFT and other more accurate correlated calculations, together with appropriate isodesmic or homodesmic reactions. There is a reasonable agreement between computational and experimental results.

Abstract The standard molar energies of combustion, at T = 298.15 K, of crystalline 1,4-benzodioxan-2-carboxylic acid and 1,4-benzodioxan-2-hydroxymethyl were measured by static bomb calorimetry in an oxygen atmosphere. The standard molar enthalpies of sublimation, at T = 298.15 K, were obtained by Calvet microcalorimetry. These values were used to derive the standard molar enthalpies of formation of the compounds in the gas phase at T = 298.15 K: 1,4-benzodioxan-2-carboxylic acid -(547.7 +/- 3.0)kJ.mol(-1) and 1,4-benzodioxan-2-hydroxymethyl -(374.2 +/- 2.3)kJ.mol(-1). In addition, density functional theory calculations using the B3LYP hybrid exchange-correlation energy functional with extended basis sets, 6-31IG(center dot center dot) and cc-pVTZ, have been performed for the compounds studied. We have also tested two more accurate computational procedures involving multiple levels of electron structure theory in order to get reliable estimates of the thermochemical parameters of the compounds studied. The agreement between experiment and theory gives confidence to estimate the enthalpies of formation of other 2-R derivatives of 1,4-benzodioxan (R = -CH(2)COOH, -OH, -COCH(3), -CHO, -CH(3), -CN, and -NO(2)).

Abstract Amino acid-derived gemini surfactants arise as a potentially good alternative to the more conventional lipid and synthetic catanionic systems in view of their enhanced interfacial properties, increased chemical stability, and low toxicity. The presence of an amino acid as the polar headgroup allows toxicity reduction, with the simultaneous increase of biodegradability. For these compounds, the establishment of structure/function relationships from the assessment of their basic aggregation properties is therefore of the utmost interest, e.g., in the design of operative self-assembled systems (e.g., liposomes, nanotubes, etc). In this context, the study of the thermal phase behavior of the dry surfactants is a natural, straightforward first step, the more so as thermotropic liquid crystals are also relevant for practical applications. In this work, several lysine-based amphiphiles with a gemini-like configuration have been synthesized, with the amino acid side chain as the spacer group. The molecules are either esters (neutral, with C6-C12 even chains) or sodium carboxylates (anionic, with C6-C12 even chains). Upon increasing the temperature, different crystalline (cr) and liquid-crystalline (1c) phases have been detected and the corresponding thermodynamic and structural parameters determined by a combination of differential scanning calorimetry, polarizing light microscopy and small-angle X-ray scattering. The phase behavior of the amphiphiles is highly dependent on both the chain length and the presence of charge on the headgroup, with significant differences occurring within and between each group of molecules. The C6 and C8 esters form reverse hexagonal cr and lc phases, while C10 and C12 self-assemble into smectic cr and lc structures, with C10 showing also a reverse hexagonal lc phase prior to isotropization. All the carboxylate derivatives form smectic lc phases at high enough temperature prior to isotropization. The rationalization of the phase behavior and phase transition energetics of the compounds has been put forth on the basis of the intermolecular interactions at stake (van der Waals, H-bonding, electrostatic, and packing) and the molecular shape of the amphiphile.

Abstract The use of amino acids for the synthesis of novel surfactants with vesicle-forming properties potentially enhances the biocompatibility levels needed for a viable alternative to conventional lipid vesicles. In this work, the formation and characterization of catanionic vesicles by newly synthesized lysine- and serine-derived surfactants have been investigated by means of phase behavior mapping and PFG-NMR diffusometry and cryo-TEM methods. The lysine-derived surfactants are double-chained anionic molecules bearing a pseudogemini configuration, whereas the serine-derived amphiphile is cationic and single-chained. Vesicles form in the cationic-rich side for narrow mixing ratios of the two amphiphiles. Two pairs of systems were studied: one symmetric with equal chain lengths, 2C(12)/C(12), and the other highly asymmetric with 2C(8)/C(16) chains, where the serine-based surfactant has the longest chain. Different mechanisms of the vesicle-to-micelle transition were found, depending on symmetry: the 2C12/C12 system entails limited micellar growth and intermediate phase separation, whereas the 2C(8)/C(16) system shows a continuous transition involving large wormlike micelles. The results are interpreted on the basis of currently available models for the micelle-vesicle transitions and the stabilization of catanionic vesicles (energy of curvature vs mixing entropy).

Abstract Double-chained surfactants with potential biocompatibility have been prepared in high yields by lysine acylation with four natural saturated fatty acids (C(6) to C(12)) and with cis-undec-5-enoic acid. The surfactants were found to assemble into nanotubules in aqueous medium and, when mixed with a commercial cationic surfactant, to spontaneously form liposomes.

Abstract The activating and stabilizing effects of inorganic pyrophosphate, tripolyphosphate and nucleoside triphosphates on firefly luciferase bioluminescence were studied. The results obtained show that those effects are a consequence of the luciferase-catalyzed splitting of dehydroluciferyl-adenylate, a powerful inhibitor formed as a side product in the course of the bioluminescence reaction. Inorganic pyrophosphate, tripolyphosphate, CTP and UTP antagonize the inhibitory effect of dehydroluciferyl-adenylate because they react with it giving rise to products that are, at least, less powerful inhibitors. Moreover, we demonstrate that the antagonizing effects depended on the rate of the splitting reactions being higher in the cases of inorganic pyrophosphate and tripolyphosphate and lower in the cases of CTP and UTP. In the case of inorganic pyrophosphate, the correlation between the rate of dehydroluciferyl-adenylate pyrophosphorolysis and the activating effect on bioluminescence only occurs for low concentrations because inorganic pyrophosphate is, simultaneously, an inhibitor of the bioluminescence reaction. Our results demonstrate that previous reports concerning the activating effects of several nucleotides (including some that do not react with dehydroluciferyl-adenylate) on bioluminescence were caused by the presence of inorganic pyrophosphate contamination in the preparations used.

Abstract Trihydroxycinnamic derivatives were synthesized and evaluated for their antioxidant and cytotoxic activities. The ester derivatives exhibited a higher radical-scavenging activity, when liposomes were used as target systems, a fact which may be related to their lipophilicity and conformational preferences. These compounds were found to display significant growth inhibition and cytotoxic effects towards a human cervix adenocarcinoma cell line (Hel,a). The partition coefficients presently obtained for the trihydroxycinnamic derivatives correlate well both with their structural characteristics and with their antioxidant/cytotoxic activities. A positive structure-activity-property relationship between cytotoxic and antioxidant activities, which is intrinsically related with physico-chemical and conformational properties, is anticipated, as a noteworthy study that must be done for phenolic systems. As damage events are frequently correlated with oxidative stress, the prevalence of both properties in a single compound could be beneficial in terms of rationale preventive or therapeutic purposes.

Abstract A Raman study of hydroxycinnamic and hydroxybenzoic esters (caffeates, ferulates and gallates) displaying antioxidant and anticancer properties was undertaken, with particular emphasis on the analysis of the effect of the ring substituents and the nature of the ester alkyl chain on their spectroscopic features. A complete assignment of the spectra was carried out for all the compounds investigated, in the light of the corresponding calculated wavenumbers (at the density functional theory level). Distinct vibrational patterns were observed for each type of ester, thereby allowing their ready characterisation and identification by Raman spectroscopy. Evidence of the occurrence of intermolecular hydrogen bonds, leading to the formation of dimers in the condensed phase, was also obtained. Copyright (c) 2007 John Wiley & Sons, Ltd.

Abstract Adenosine A(2A) receptors are members of the G protein-coupled receptor family and mediate multiple physiological effects of adenosine, both at the central nervous system (CNS) and at peripheral tissues, by activating several pathways or interacting with other receptors or proteins. Increasing evidence relate A(2A) receptors with pharmacological stress testing, neurodegenerative disorders (such as Parkinson's disease) and inflammation, renewing the interest in these receptors, increasingly viewed as promising therapeutic targets. Series of agonists and antagonists have been developed by medicinal chemistry artwork either by structure activity relationship (SAR) or quantitative structure activity relationship (QSAR) studies. These studies have allowed identification of the structural and electrostatic requirements for high affinity A(2A) receptor binding and, therefore, contributing to the rational design of A(2A) receptor ligands. Additional rational chemical modifications of the existing A(2A) receptor ligands may further improve their affinity/selectivity. The purpose of this review is to analize and summarize aspects related to the medicinal chemistry of A(2A) receptor ligands, their present and potencial therapeutic applications by exploring the molecular structure and physiological and pathophysiological roles of A(2A) receptors.

Abstract A comparison of linear and non-linear regression method in selecting the optimum isotherm was made to the experimental equilibrium data of methylene blue sorption by activated carbon. The r(2) was used to select the best fill linear theoretical isotherm. In the case of non-linear regression method, six error functions, namely coefficient of determination (r(2)), hybrid fractional error function (HYBRID), Marquardt's percent standard deviation (MPSD), average relative error (ARE), sum of the errors squared (ERRSQ) and sum of the absolute errors (EABS) were used to predict the parameters involved in the two and three parameter isotherms and also to predict the optimum isotherm. For two parameter isotherm, MPSD was found to be the best error function in minimizing the error distribution between the experimental equilibrium data and predicted isotherms. In the case of three parameter isotherm, r2 was found to be the best error function to minimize the error distribution structure between experimental equilibrium data and theoretical isotherms. The present study showed that the size of the error function alone is not a deciding factor to choose the optimum isotherm. In addition to the size of error function, the theory behind the predicted isotherm should be verified with the help of experimental data while selecting the optimum isotherm. A coefficient of non-determination, K-2 was explained and was found to be very useful in identifying the best error function while selecting the optimum isotherm.