Nelly L. Jorge

The guinea pig as an animal model for Ipomoea carnea induced α-mannosidosis.

The toxic effects of Ipomoea carnea subsp. fistulosa were evaluated in guinea pigs by administration of dry leaves during 45 days. Swainsonine and calystegines B(1), B(2) and C(1) were isolated and quantified. Clinical signs included emaciated and loss of body weight. Histological evaluation demonstrates numerous vacuoles in the cytoplasm of pancreas, liver and renal cells. Vacuolation was also evident in neurons of brain stem, mainly pontine nuclei. Neuronal lectin binding pattern showed a strong positive reaction to Con-A (Concanavalia ensiformis), WGA (Triticum vulgaris), sWGA (succinylated T. vulgaris) and LCA (Lens culinary). This result is coincident with the lectin histochemistry staining pattern of the vacuoles described in CNS of ruminants. We conclude that I. carnea subsp. fistulosa induces an intralysosomal accumulation of mannose-containing oligosaccharides in guinea pigs, which makes it a valuable animal model for the reproduction of induced alpha-mannosidosis.

Semiempirical study of the conformation of tetroxane and its halogenated derivatives

Abstract We have made a conformational study of tetroxane and its bi- and tetra-halogenated derivatives by means of the semiempirical AM1 and PM3 molecular orbital methods. The results are compared with previous semiempirical and ab initio studies as well as with available experimental data. We have found that in every case the AM1 method underestimates the peroxidic O-O bond length by approximately 12%, while the PM3 procedure describes such a bond in a better way. The degree of accuracy of these two semiempirical methods is discussed in relation with the tetroxane structure.

Experimental and theoretical study of trans-3,6-diphenyl 1,2,4,5-tetroxane molecule

Abstract An experimental and theoretical study of trans -3,6-diphenyl-1,2,4,5-tetroxane molecule is presented comparing the data with the cis -isomer calculations. The different electronic and steric factors which determine the most stable molecular configurations are discussed through semi-empirical AM1 and PM3 methods to obtain the lowest energy conformers and the most characteristic geometrical parameters of the molecule. The results are discussed considering the 1 H NMR spectrum data obtained for the title compound.

Characterization of the Chemical Reactivity and Selectivity of DNA Bases Through the Use of DFT-Based Descriptors

In this chapter, the use of conceptual DFT descriptors for understanding the occurrence and likely mechanisms of formation of DNA lesions is reviewed. After a synthetic presentation of the principal DFT-based descriptors, the global reactivity and selectivity of DNA bases are investigated from global and local descriptors. Then, the formation of several DNA lesions is studied including cytosine compound deamination, intra-strand DNA cross-links, and pyrimidine dimer photoproducts. It appears from the use of the global and local DFT-based descriptors that most of the experimental facts can be theoretically rationalized.

Experimental and Theoretical Study of the Enthalpy of Formation of 3,6-Diphenyl-1,2,4,5-Tetroxane Molecule

We report the results obtained for the experimental determination and the theoretical calculation of the enthalpy of formation of 3,6-diphenyl-1,2,4,5-tetroxane molecule. The experimental work was performed using a macrocalorimeter to measure the combustion heat, and the sublimation enthalpy was determined via the measurement of the vapor pressure at equilibrium with the vapor phase at different temperatures resorting to the Clapeyron-Claussius equation. Theoretical calculations were performed using semiempirical AM1 and PM3 methods as well as ab initio techniques at the 3-21, 6-31G(d,p), and 6-311G(d,p) basis set levels.

THEORETICAL STUDY OF CIS- AND TRANS-3,6-DIMETHOXY-1,2,4,5-TETROXANE MOLECULE

Abstract Results of a theoretical study of cis- and trans -3,6-dimethoxy-1,2,4,5-tetroxane molecules are presented. The different electronic and steric factors which determine the most stable molecular configurations are discussed. We resort to the semiempirical AM1 and PM3 methods to obtain the lowest energy isomers and the most characteristic geometrical parameters for them are given.

Comparison of the mechanism of deamination of 5,6-dihydro-5-methylcytosine with other cytosine derivatives

The mechanism of deamination of 5,6-dihydro-5-methylcytosine has been investigated theoretically and compared to those of other cytosine derivatives. The main goal is to understand the effect of C5-methylation and C5–C6 saturation upon the deamination rate. It is found that C5–C6 saturation tends to increase the local electrophilicity of the cytosine derivative on carbon C4. It is also concluded that C5-methylation displays an opposite effect on saturated versus unsaturated systems: on unsaturated systems, C5-methylation tends to increase the local electrophilicity on C4, while it reduces the local electrophilicity on C4 for saturated ones.

Theoretical study of 1,2,4,5-trioxazines

Abstract A theoretical conformational study of 1,2,4,5-trioxazine and some alkyl and phenyl derivatives was performed with the semiempirical AM1, PM3 and MNDO/3 techniques as well as with an ab initio method with a limited basis set. A reasonable agreement was found among the different calculation procedures, suggesting a chair conformation for the molecular rings of these molecules as the most stable one.

Deamination features of 5-hydroxymethylcytosine, a radical and enzymatic DNA oxidation product

AbstractThe 5-methylcytosine derivative 5-hydroxymethylcytosine (5hmCyt), which is generated via enzymatic oxidation, is sometimes referred to as the sixth nucleobase due to its widespread presence in the DNA of brain and embryonic stem cells. In this study, we used density functional based methods and reactivity indices from conceptual DFT to explore the mechanism and key features of the hydrolytic deamination of 5hmCyt. The data obtained are used to compare and contrast this deamination reaction with those of other cytosine derivatives. The deamination process for 5hmCyt is similar to the corresponding processes for other unsaturated derivatives in that the amino form is the reactive one and water addition is the rate-limiting step. However, several differences due to the rotameric asymmetry of the current system are also noted. FigureExploration of the spontaneous deamination of 5-hydroxymethylcytosine using computational chemistry

Solvent Effect of Oxygen in the Thermolisys Decomposition of the Acetone Diperoxide

In this paper, the kinetics of the thermal decomposition reaction of 3,3,6,6-tetramethyl-1,2,4,5 tetroxane (ACDP) is investigated in various oxygen solvents at different temperatures. Linear relationships are observed between the enthalpy and entropy of activation of the unimolecular reactions of those diperoxides. The isokinetic temperature calculated by Leffler’s treatment is 527.2K, which is consistent with the proposed Exner correlation between the logarithm of the rate constant values for the same reaction in each solvent at two temperatures, where the corresponding AŸ value was 523.5K. A true “isokinetic relationship†for the ACDP thermolysis indicates that their reactions constitute a reaction series with similar interaction mechanisms. This can be related to the capacity for hydrogen bonding between the solvent and the diperoxide molecules. The solvanting properties of the media help the peroxidic bond rupture these molecules.