Publications

Abstract The present work reports an experimental and computational study of the energetics of 1,2-benzisothiazol-3(2H)-one and 1,4-benzothiazin-3(2H, 4H)-one. The standard (p degrees = 0.1 MPa) massic energy of combustion, at T = 298.15K, of each compound was measured by rotating bomb combustion calorimetry, in oxygen that allowed the calculation of the respective standard molar enthalpy of formation, in the condensed phase, at T = 298.15 K. The standard molar enthalpies of sublimation, at T = 298.15 K, were measured by high-temperature Calvet microcalorimetry. From the combination of data obtained by both techniques we have calculated the standard molar enthalpies of formation, in the gaseous phase, at T =298.15 K. In addition, computational calculations were carried using the density functional theory with the B3LYP functional and the 6-31G* basis set and some correlations between structure and energetics were obtained for the keto and enol forms of both compounds. Using the G3(MP2)//B3LYP composite method and various appropriate reactions, the standard molar enthalpies of formation of 1,2-benzisothiazol-3(2H)-one and 1,4-benzothiazin-3(2H, 4H)-one, at T = 298.15 K. were computationally derived and compared with the experimental data. The aromaticity of 1,2-benzisothiazol-3(2H)-one, 1,4-benzothiazin-3(2H, 4H)-one and that of some related species was evaluated by analysis of nucleus independent chemical shifts (NICS).

Abstract In this work, we have determined the experimental standard (p degrees = 0.1 MPa) molar enthalpies of formation, in the gas phase, of 2,6-dimethy1-4-pyrone -(261.5 +/- 2.6) kJ . mol(-1) and 2-ethy1-3-hydroxy-4-pyrone -(420.9 +/- 2.8) kJ . mol(-1). These values were obtained by combining the standard molar enthalpy of formation in the condensed phase, derived from combustion experiments in oxygen, at T = 298.15 K, in a static bomb calorimeter, with the standard molar enthalpy of sublimation, at T = 298.15 K, obtained by Calvet microcalorimetry. Additionally, high-level density functional theory calculations using the B3LYP hybrid exchange-correlation energy functional with extended basis sets have been performed for these two compounds. Good agreement was obtained between the experimental and computational results. Using the same methodology, we calculated the standard molar enthalpy of formation of gaseous 2-methyl-3-hydroxy-4-pyrone.

Abstract The standard (p(o) = 0.1 MPa) molar energy of combustion in oxygen, at T = 298.15 K, of 7-hydroxycoumarin was measured by static bomb calorimetry. The value of the standard molar enthalpy of sublimation was obtained by Calvet microcalorimetry and corrected to T = 298.15 K. Combining these results, the standard molar enthalpy of formation of the compound, in the gas phase, at T = 29815 K, has been calculated, -(337.5 +/- 2.3) kJ.mol(-1). The values for the temperature of fusion, T(fusion), and for the fusion enthalpy, at T = T(fusion), are also reported. Additionally, high-level density functional theory calculations using the B3LYP hybrid exchange-correlation energy functional with extended basis sets, the MC3BB and MC3MPW methods and more accurate correlated computational techniques of the MCCM suite have been performed for the compound. The agreement between experiment and theory gives confidence to estimate the enthalpy of formation of the remaining hydroxycoumarins substituted in the benzene ring.

Abstract In this paper we report the standard (p degrees = 0.1 MPa) molar enthalpy of formation of quinazoline-2,4(1H,3H)-dione, in the gaseous phase, at T = 298.15 K, which was derived from a combined experimental and computational thermochemical work. The static bomb combustion calorimetry technique was used to determine the standard massic energy of combustion and consequently the standard molar enthalpy of formation, in the crystalline phase, at T = 298.15 K, and the Calvet microcalorimetry technique was employed to determine the standard molar enthalpy of sublimation, at T = 298.15 K. The obtained standard molar enthalpy of formation, in the gaseous phase, at T = 298.15 K, was: Delta(f)H(m)degrees(g) = (271.1 +/- 3.3) kJ . mol(-1). In addition, quantum chemical calculations were performed using the G3(MP2)//B3LYP composite method to assess the relative energetic stabilities of quinazoline-2,4(1H,3H)-dione and its tautomers (4-hydroxyquinazolin-2(1H)-one, 2-hydroxyquinazolin-4(1H)-one, 2-hydroxyquinazolin-4(3H)-one, and quinazolin-2,4-diol). Estimates of the standard molar enthalpy of formation, in the gaseous phase, of the most stable tautomer, quinazoline-2,4(1H,3H)dione, at T = 298.15 K, were obtained from the G3(MP2)//B3LYP calculations using appropriate isodesmic reactions and were further compared with the obtained experimental value. The aromaticity of quinazoline-2,4(1H,3H)-dione has also been assessed through the evaluation and analysis of the Nucleus Independent Chemical Shifts (NICS) and their most significant components for the benzene and pyrimidine rings.

Abstract A novel multi layer film containing a cationic phosphonium-derivatized Ni(salen)-type complex and poly(sodium-4-styrenesulfonate (NaPSS) was assembled onto quartz, mica, and metal surfaces using the layer-by-layer (LbL) technique. Spectroscopic (UV-vis) and gravimetric (QCM) responses for the multilayer films show regular stepwise growth and the signature of strong electrostatic interactions between the component layers. The gravimetric responses indicate the presence of substantial additional (net neutral) material in the PSS layers, which X PS shows is not polyelectrolyte or salt, so charge compensation is intrinsic; we deduce the presence of space-filling solvent. Direct electrostatic interaction of the two-component layers is enhanced by a secondary noncovalent interaction between the delocalized pi-systems of the two components. Permeability of the film to the redox probe [Fe(CN)(6)](3-/4-) was studied by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Qualitatively similar results were obtained in the absence and presence of a precursor PSS/PAH multilayer, but with a general shift in kinetic and diffusional processes to longer time scales (lower frequencies) in the presence of the precursor layer and with increasing numbers of PSS/[Ni(salen)] bilayers. Quantitatively, the EIS data were interpreted using a capillary membrane model (CMM) to yield values of coverage, apparent charge transfer resistance, double-layer capacitance, pore size, and diffusion coefficient. The coverage values were consistent with a model in which there are no preferential growth sites and the surface charge density is independent of the number of bilayers.

Abstract With the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the synthesis and pharmacological evaluation of a new series of bromo-6-methyl-3-phenylcoumarin derivatives (with bromo atom in both different benzene rings of the skeleton) with and without different number of methoxy substituent at the 3-phenyl ring. The methoxy substituents were introduced, in this new scaffold, in the meta and/or para positions of the 3-phenyl ring. The synthesized compounds 3-7 were evaluated as MAO-A and B inhibitors using R-(-)-deprenyl (selegiline) and iproniazide as reference inhibitors, showing, most of them, MAO-B inhibitory activities in the low nanomolar range. Compounds 4 (IC(50) = 11.05 nM), 5 (IC(50) = 3.23 nM) and 6 (IC(50) = 7.12 nM) show higher activity than selegiline (IC(50) = 19.60 nM) and higher MAO-B selectivity, with more than 9050-fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoform.

Abstract Desirability theory (DT) is a well-known multi-criteria decision-making approach. In this work, DT is employed as a prediction model (PM) interpretation tool to extract useful information on the desired trade-offs between binding and relative efficacy of N6-substituted-4'-thioadenosines A(3) adenosine receptor (A(3)AR) agonists. At the same time, it was shown the usefulness of a parallel but independent approach providing a feedback on the reliability of the combination of properties predicted as a unique desirability value. The appliance of belief theory allowed the quantification of the reliability of the predicted desirability of a compound according to two inverse and independent but complementary prediction approaches. This information is proven to be useful as a ranking criterion in a ligand-based virtual screening study. The development of a linear PM of the A(3)AR agonists overall desirability allows finding significant clues based on simple molecular descriptors. The model suggests a relevant role of the type of substituent on the N6 position of the adenine ring that in general contribute to reduce the flexibility and hydrophobicity of the lead compound. The mapping of the desirability function derived of the PM offers specific information such as the shape and optimal size of the N6 substituent. The model herein developed allows a simultaneous analysis of both binding and relative efficacy profiles of A(3)AR agonists. The information retrieved guides the theoretical design and assembling of a combinatorial library suitable for filtering new N6-substituted-4'-thioadenosines A(3)AR agonist candidates with simultaneously improved binding and relative efficacy profiles. The utility of the desirability/belief-based proposed virtual screening strategy was deduced from our training set. Based on the overall results, it is possible to assert that the combined use of desirability and belief theories in computational medicinal chemistry research can aid the discovery of A(3)AR agonist candidates with favorable balance between binding and relative efficacy profiles.

Abstract CdTe quantum dots (QDs), capped with mercaptopropionic acid (MPA), were synthesized and the variation of their fluorescence properties (steady state and lifetime)with pH was assessed in solution and when immobilized in a sol-gel host Three different sizes of CdTe QDs with excited state lifetimes ranging from 42 to 48 ns and with emission maximum at 540 nm (QD(540)). 580 nm (QD(580)) and 625 nm (QD(625)) were selected The solution pH affects the maximum emission wavelength (shifts to higher wavelengths of 23, 24 and 27 nm for QD(540), QD(550) and QP(625), respectively), the excited state lifetime and the fluorescence intensity in a reversible way. Linearization of the maximum emission wavelength variation with the pH allows the estimation of an apparent ionization constant (pK(a)) for each QD: 6.5 +/- 0.1 (QD(540)), 6.1 +/- 0.5 (QD(580)) and 5.4 +/- 0.3 (QD(625)) The variation of the QDs fluorescence properties was further explored using confocal laser scanning microscopy allowing the implementation of a new calibration method for pH imaging in solution QDs were successfully immobilized on the tip of an optical fiber by dip-coating using sal-gel procedure The immobilized QDs showed a similar pH behaviour to the one observed in solution and an apparent lifetime of 80,68 and 99 ns, respectively. The proposed QDs based methodology can be successfully used to monitor pH using wavelength encoded data in imaging and fiber optic sensing applications.

Abstract The Mitsunobu reaction is an important tool in carbocyclic nucleoside chemistry for the direct coupling of alcohols with heterocyclic bases under mild conditions. Chemical evidences for an unusual competitive O-2- vs. N-1-alkylation of 3-substituted pyrimidines is presented.