Publications

Abstract The outcome of the Suzuki-Miyaura cross-coupling for the direct competition reaction between two boronic acids was evaluated under routine synthesis conditions. The reaction selectivity was found to depend on the amount of the base used, with fewer bases favoring the reactivity of the boronic acid with lower pK(a) (stronger acid). The dependence of the reaction selectivity on base stoichiometry was found to increase with the increase in the difference in the pK(a) values of the competing boronic acids. These results confirm a relationship between acid-base chemistry and the Suzuki-Miyaura reaction catalytic cycle. Moreover, the results indicate that under these specific conditions, the most reactive organoboron species toward transmetalation is the borate anion RB(OH)(3)(-) instead of the neutral boronic acid RB(OH)(2). Hence, the main role of the base in the reaction mechanism is to increase the reactivity of the boronic acid toward the Pd-halide complex by converting it into the respective organoborate. In addition, boric acid, an important reaction byproduct, affects the selectivity in the Suzuki reaction because its gradual formation in the reaction medium disturbs the acid-base equilibrium.

Abstract The self-association equilibrium constants, K-ass, for the dimerization of some small oligothiophenes in acetone, acetonitrile and chloroform were measured by H-1 NMR spectroscopy. The gas phase interaction energies for some oligothiophene dimers were determined by computational quantum chemistry. The H-1 NMR results indicate that K-ass generally increases with the chain length (the number of thienyl rings, n) and solvent polarity; however, K-ass for thiophene (n = 1) was found to be higher than for the bithiophenes (n = 2). The linear oligothiophenes 2,2'-bithiophene and 2,2',5',2 ''-terthiophene were found to self-associate less than their corresponding nonlinear isomers 3,30-bithiophene and 3,2',5',3 ''-terthiophene in solution and in the gas phase. For a-quaterthiophene (n = 4) K-ass in solution was found to be smaller than expected. The non-linear dependence of the standard molar Gibbs energy of self-association, Delta(ass)G(m)(0), on the chain length in solution could be nicely reproduced and related to the conformational entropy change of dimerization. It was observed that the melting properties of oligothiophenes correlate well with their tendency to self-associate, with more self-association leading to increased liquid stability, and thus lower melting temperatures. These results highlight the relevance of self-association in isotropic systems for the correct molecular interpretation of phase equilibria.

Abstract An experimental and theoretical study on the phase and molecular stability of Mq(3) (M = Al, Ga, and In; q = 8-hydroxyquinoline) is presented. The results suggest that the energy difference between the meridional and facial isomers of Mq(3) shall be significantly lower than previously though and provide an explanation for the reported mer-fac solid-solid transition. The first accurate vapor pressure measurements for Alq(3), Gaq(3), and Inq(3) are presented, which are of great relevance for the manufacturing of thin films by vacuum deposition. Phase transition thermodynamics indicates higher cohesive energies of the mer-isomers and an entropic differentiation that can be associated with the different molecular symmetry of the mer- and fac-isomers.

Abstract Vapor pressures of 1,3-dimethylimidazolium bis(trifluoromethylsulfonyl) imide, ([C(1)C(1)im][NTf2]) and 1ethyl-3-propylimidazolium bis(trifluoromethylsulfonyl) imide, ([C(2)C(3)im][NTf2]) ionic liquids were measured as a function of temperature using a Knudsen effusion apparatus combined with a quartz crystal microbalance. Enthalpies and entropies of vaporization were derived from the fitting of vapor pressure and temperature results to the Clarke and Glew equation. [C(1)C(1)im][NTf2] presents a higher enthalpy and entropy of vaporization than the neighboring members of the series. The enthalpy of vaporization of [C(2)C(3)im][NTf2] lies in between the asymmetric and symmetric ionic liquid series, reflecting a decrease in the electrostatic interactions due to a decrease of the charge accessibility between the ionic pairs when the methyl group is replaced by an ethyl group. The obtained higher volatility of [C(2)C(3)im][NTf2] arises from its asymmetric character, leading to an higher entropic contribution that compensates the enthalpic penalty. The border conditions ([C(1)C(1)im][NTf2], [C(2)C(1)im][NTf2] and [C(2)C(2)im][NTf2]), topology ([C(2)C(3)im][NTf2]) and symmetry/asymmetry of the ILs effect were evaluated and rationalized based on a comparative analysis of the thermodynamic properties, enthalpies and entropies of vaporization.

Abstract The standard (p(o) = 0.1 MPa) molar enthalpy of formation of 6-propyl-2-thiouracil was derived from its standard molar energy of combustion, in oxygen, to yield CO2 (g), N-2 (g) and H2SO4 center dot 115H(2)O (I), at T = 298.15 K, measured by rotating bomb combustion calorimetry. The vapor pressures as function of temperature were measured by the Knudsen effusion technique and the standard molar enthalpy of sublimation, Delta H-g(cr)m(o). at T = 298.15 K, was derived by the Clausius-Clapeyron equation. These two thermodynamic parameters yielded the standard molar enthalpy of formation, in the gaseous phase, at T= 298.15 K: -(142.5 +/- 1.9) kJ mol(-1). This value was compared with estimates obtained from very accurate computational calculations using the G3 and G4 composite methods.

Abstract As the prostate cancer (PCa) progresses, sarcosine levels increase both in tumor cells and urine samples, suggesting that this metabolite measurements can help in the creation of non-invasive diagnostic methods for this disease. In this work, a biosensor device was developed for the quantification of sarcosine via electrochemical detection of H2O2 (at 0.6 V) generated from the catalyzed oxidation of sarcosine. The detection was carried out after the modification of carbon screen printed electrodes (SPEs) by immobilization of sarcosine oxidase (SOX) on the electrode surface. The strategies used herein included the activation of the carbon films by an electrochemical step and the formation of an NHS/EDAC layer to bond the enzyme to the electrode, the use of metallic or semiconductor nanoparticles layer previously or during the enzyme immobilization. In order to improve the sensor stability and selectivity a polymeric layer with extra enzyme content was further added. The proposed methodology for the detection of sarcosine allowed obtaining a limit of detection (LOD) of 16 nM, using a linear concentration range between 10 and 100 nM. The biosensor was successfully applied to the analysis of sarcosine in urine samples.

Abstract Dioctadecyldimethylammonium bromide (DODAB):Monoolein (MO) lipoplexes have mainly been studied within the range of high molar ratios of DODAB, with noticeable transfection efficiencies in the Human Embryonic Kidney (HEK, a.k.a. 293T) cell line. In this work, we intend to study the effect of high MO content on the structure and physicochemical properties of pDNA/DODAB:MO lipoplexes to achieve some correlation with their transfection efficiency. Static/Dynamic Light Scattering and Cryo-TEM imaging were used to characterize the size/morphology of DNA/DODAB:MO lipoplexes at different DODAB:MO contents (2:1, 1:1, 1:2) and charge ratios (CRs) (+/-). Nile Red fluorescence emission was performed to detect changes in microviscosity, hydration and polarity of DNA/DODAB:MO systems. Lipoplexes stability at physiological pH values and in the presence of anionic lipids was evaluated by Forster Resonance Energy Transfer (FRET). Physicochemical/structural data were complemented with transfection studies in HEK cells using the beta-galactosidase reporter gene activity assay. This work reports the coexistence of multilamellar and non-lamellar inverted phases in MO-richer lipoplexes (DODAB:MO 1:2 and 1:4), leading to transfection efficiencies comparable to those of multilamellar (DODAB-richer) lipoplexes, but at higher charge ratios [CR (+/-) = 6.0] and without dose-effect response. These results may be related to the structural changes of lipoplexes promoted by high MO content.

Abstract The thermodynamics of the process of self-assembly of cationic gemini surfactants, [C12H25(CH3)(2)N(CH2)(S)N(CH3)(2)C12H25]Br-2, (the spacer S being 2, 6 or 10, assigned as C12CSC12Br2) and the system of oppositely charged mixture of surfactants formed by C12CSC12Br2 and sodium cholate (NaCA) in aqueous solution has been investigated by isothermal titration calorimetry (ITC), conductivity and turbidity measurements. The critical micelle concentration values (cmc) for the gemini surfactants C12CSC12Br2 obtained from calorimetry and conductivity were found to be consistent with values reported in the literature. The enthalpies of micellization (Delta H-mic) of C12CSC12Br2 are all exothermic, presenting a strong negative minimum at S = 6, corresponding to the maximum in the cmc values. For the mixed system of oppositely charged surfactants (C12CSC12Br2(S = 2,6,10)/NaCA), we did obtain from ITC the critical parameters for different events that take place as the concentration of gemini surfactant increases, such as the formation of NaCA-rich mixed micelles (cmc(mix), Delta Hmic-mix), the formation of a precipitate (immiscible liquid crystalline (LC) phase) (C-P, Delta H-P) and its re-dissolution (C-R, Delta H-R), and finally the formation of positive charge-rich mixed micelles (C-M, Delta H-M). It should be stressed that the values of cmc(mix) (gemini) are much smaller than those for pure gemini and pure NaCA. These results also show that there is a stronger synergistic effect between the two surfactants in the NaCA-rich region. The turbidity measurements proved valuable to the determination of the region of immiscible LC phase. The ITC results are combined with those obtained by conductivity and turbidity leading to a thorough discussion of the effect of the gemini spacer length on the aggregation behavior of the mixed systems.

Abstract A different approach to the preparation of microspheric particles of molecularly imprinted xerogels (MIX) is presented here. The technique consisted of filling up the pores of spherical, mesoporous, bare silica particles with a pregelification mixture by applying pressure. Upon gelification and drying, thin layers of MIX were deposited on the mesopores. Spherical composites of S-naproxen (S-NAP) imprints were produced by following this simple strategy. The performance of the imprints was quite satisfactory in terms of recognition ability (ascertained by selectivity against ibuprofen, alpha = 4.9, and an imprinting factor of 13) whereas an outstanding improvement on dynamic features (expressed as column efficiency), as compared to the corresponding bulk format MIX (9 vs. 1.2 theoretical plates/cm), was reached.

Abstract Mycobacterium avium causes respiratory disease in susceptible individuals, as well as disseminated infections in immunocompromised hosts, being an important cause of morbidity and mortality among these populations. Current therapies consist of a combination of antibiotics taken for at least 6 months, with no more than 60% overall clinical success. Furthermore, mycobacterial antibiotic resistance is increasing worldwide, urging the need to develop novel classes of antimicrobial drugs. One potential and interesting alternative strategy is the use of antimicrobial peptides (AMP). These are present in almost all living organisms as part of their immune system, acting as a first barrier against invading pathogens. In this context, we investigated the effect of several lactoferrin-derived AMP against M. avium. Short peptide sequences from both human and bovine lactoferricins, namely, hLFcin1-11 and LFcin17-30, as well as variants obtained by specific amino acid substitutions, were evaluated. All tested peptides significantly inhibited the axenic growth of M. avium, the bovine peptides being more active than the human. Arginine residues were found to be crucial for the display of antimycobacterial activity, whereas the all-D-amino-acid analogue of the bovine sequence displayed the highest mycobactericidal activity. These findings reveal the promising potential of lactoferricins against mycobacteria, thus opening the way for further research on their development and use as a new weapon against mycobacterial infections.