A set of 14 indane carbocyclic nucleosides were synthesized and experimentally assayed for their inhibitory effects in the proliferation of murine leukemia (L1210/0) and human T-lymphocyte (Molt4/C8, CEM/0) cells. The compounds have promising inhibitory activity judging from the IC50 values obtained for all these cellular lines. Multiple linear regression analysis was then applied to build up consistent QSAR models based on quantum mechanics-derived molecular descriptors. The derived models reproduce well the experimental data of both three cells (r(2) greater than or equal to 0.90), display a good predictive power (r(CV)(2) greater than or equal to 0.86) and are, above all, easily interpretable. They show that frontier-orbital energies and hydrophobicity are mainly responsible for the activity of the synthesized compounds and also, suggest similar mechanisms of action. The final QSAR-models involve only two descriptors: the lowest unoccupied molecular orbital energy and the solvent accessible-hydrophobic surface area, but describe a sound correlation between predicted and experimental activity data (r(2) = 0.931, r(2) = 0.936 and r(2) = 0.931 for the cells L1210/0, Molt4/C8 and CEM/0, respectively).

The authors present a hospital-based case-control stydy of the Dupuytren's Disease. The study involved 125 followed-up cases with the disease and 119 controls without the disease that matched on age, sex, ethnicity and residential area, both sets selected among outpatients attending at the hospital. Data was recorded from cases and controls according to several variables and nonparametric analyses was applied to infer the relationship between the variables. Logistic regression was also applied to assess the effect of the collected variables on the appearance of the disease. In this study, Dupuytren's Disease proved to be related to alcoholism, long term duration of diabetes and a positive family history, being the extent of association higher for the latter attribute. However, it should be said that the dependence with alcoholism is only clearly seen in males. Recurrence seems to be only associated with the patients' age at the onset of the disease and is more likely to occur in younger patients rather than in older ones. The results achieved are according to the inevitability of the disease to progress. Nevertheless, when the treatment is performed at the right moment, the outcome results are acceptable.

The meaningful interactions in the contact region of the trypsin-pancreatic trypsin inhibitor complex have been evaluated using free energy simulation methods and appropriate thermodynamic cycles. Consequently, mutations on a few selected residues were performed to destroy the specificity of these interactions preserving the three-dimensional structure of the original species; therefore, the original and mutated residues involved had to be similar from a topological point of view but with opposite chemical properties. The thermodynamic perturbation, conventional thermodynamic integration, thermodynamic integration with end-point perturbational correction and thermodynamic integration conjugated with the extrapolation method of Brooks formalisms have been used in these calculations. The results obtained, with these four alternative approaches, are in reasonable, mutual agreement and reveal that the strength of a specific interaction increases with the charge separation between the amino acid residues involved, and with the hydrophilicity of the surrounding environment.

DFT and ah initio calculations up to the MP2 level have been performed to study the pyrolysis of 2-azidoacetic acid (N3CH2COOH). Several molecular properties, such as conformational equilibrium, optimal geometry, ionization energies, and vibrational frequencies, have been computed for this acid. Other species involved in its pyrolysis were also fully optimized and corrected for zero-point energies. In all cases, the calculated properties agree quite well with the observed experimental data. Two types of mechanisms were analyzed for the decomposition of N3CH2COOH. The first analyzed mechanism is a multistep process analogous to the one traditionally proposed for alkyl azides. First, either the imine NHCHCOOH or the nitrene NCH2COOH is formed by the release of molecular N-2. Then, from these species, ejection of CO2 will produce methanimine (NHCH2), although other reaction channels may be expected. The second mechanism involves, after an initial distortion of the N3CH2COOH minimum geometry, a concerted dissociation step where N-2 and CO2 are simultaneously ejected, yielding directly the imine NHCH2. Accordingly to the present calculations, the second mechanism is the most favorable one, in clear agreement with recent experimental work.

The standard (p(o) = 0.1 MPa) molar enthalpies of combustion in oxygen, at T = 298.15 K, for crystalline 3,5-dimethylpyrazole (Me(2)Pyr), 3,5-dimethyl-4-nitrosopyrazole (Me(2)PyrNO), 1,3,5-trimethyl-4-nitrosopyrazole (Me(3)PyrNO), and 3,5-dimethyl-1-phenyl-4-nitrosopyrazole (Me(2)PhPyrNO) were measured by static-bomb calorimetry. These values were used to derive the standard molar enthalpies of formation of the crystalline compounds. The standard molar enthalpies of sublimation for these four compounds were measured by microcalorimetry. [GRAPHICS] The experimental results obtained allow us to derive the values of the standard molar enthalpies of formation, in the gaseous state, for the monomeric compounds involved in this work. These last values are discussed comparatively with results previously obtained for some aromatic nitroso derivatives. (C) 2001 Academic Press.

The standard (p(o) = 0.1 MPa) molar enthalpies of combustion in oxygen, at T = 298.15 K, for crystalline picolinamide (2-NH2COPy), nicotinamide (3-NH2COPy), isonicotinamide (4-NH2COPy), nicotinamide N-oxide (3-NH2COPyNO), and isonicotinamide N-oxide (4-NH2COPyNO) were measured by static-bomb calorimetry. These values were used to derive the standard molar enthalpies of formation of the crystalline compounds. The standard molar enthalpies of sublimation, at T = 298.15 K, for the three pyridinecarboxamide isomers were measured by microcalorimetry and the standard molar enthalpies of sublimation for the two pyridinecarboxamide N-oxide compounds were measured by a mass-loss effusion technique. From the enthalpies of formation of the gaseous compounds, the molar dissociation enthalpies D-m(o) of the (N+-O-) covalent bonds were derived. Comparison has been made with D-m(o) (N-O) values in pyridine N-oxide derivatives. [GRAPHICS] (C) 2001 Academic Press.

In this paper we analyze the properties of an interface between two immiscible electrolyte solutions. The study is conducted using high concentrations of an ionic salt in the aqueous phase (1 and 3 mol.dm(-3) MgCl2). The profile of the electric potential drop across the interface is calculated, and it is concluded that the surface potential is originated by the orientational anisotropy of the solvents near the interface. The ionic density profile shows a monotonic decrease as the ions approach the interface. The resultant ionic net charge density was found to be null across all the simulation box, within statistical uncertainty, confirming that the potential drop is only caused by the orientation of the solvent molecules. The orientational structure of the solvents is not disturbed by the presence of the ions. The radial distribution functions for the hydration shell of the ions show that the hydration shell remains almost unaffected at the interfacial region. The hydration number is reduced with the increase of the ionic concentration, a fact explained by the decrease of the H2O/ion ratio. Ionic diffusion is anisotropic in all extension of the simulation box, being slower toward the interface than parallel to it. This anisotropy is due to the existence of an impenetrable barrier to displacements normal to the interfacial plane. It was also observed that the diffusion near the interface was faster than in the bulk solution. This effect is mainly caused by the smaller density of the interfacial region.