Pharmacophore model for antiepileptic drugs acting on sodium channels

Fifteen antiepileptic drugs (AED), active against the maximal electroshock seizure test and able to block the neuronal voltage-dependent sodium channel, have been studied by means of a similarity analysis. Structural and electronic, quantum chemically derived characteristics are compared. Rigid analogs are included, because of the flexibility of some structures, in order to discern the conformational requirements associated with these ligands in the moment of the interaction. An inactive compound (ethosuximide) helps in the definition of the structural factors that are important for the activity. We propose a pharmacophore model that, giving an interpretation of the biological activity, allows the design of new AED with a well-defined mechanism of interaction.Facultad de Ciencias ExactasCentro de Química Inorgánic

A semiempirical quantum approach to possible structures of copper electrodeposits at submonolayer and monolayer levels on Pt(100) and Pt(111) clusters

The development and reconstruction of surface structures formed by underpotential deposition (UPD) of Cu atoms on Pt(100) and Pt(111) clusters are approached through extended Hückel molecular orbital (EHMO) calculations applied to a statistical Cu atom deposition. These results allow us to obtain a qualitative description of the different stable configurations of Cu atoms on the Pt cluster surfaces in terms of the corresponding binding energies.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

A quantum chemical approach to the influence of platinum surface structure on the oxygen electroreduction reaction

The O2 electroreduction reaction (OERR) on Pt behaves as a structure sensitive reaction whose peroxo intermediates are formed in a greater extent on Pt(100) than on Pt(111) surfaces. A semiempirical quantum chemistry interpretation of this behavior is attempted on the basis of the study of [Pt]N02OH systems, where N, the number of atoms in the Pt cluster, equals 18 and 25. Calculations indicate that dissociative O2 electroadsorption on Pt(111) and molecular O2 on Pt(100) are favored. As a result of the interactions of O2 and OH in adjacent positions, hydroperoxide intermediates are formed on Pt(100) leading to the possibility of having H2O2 as product from the OERR.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta

A quantum chemistry description of carbon monoxide and water absorbates on single-crystal rhodium and platinum clusters

Extended Hückel molecular-orbital calculations of CO and HO adsorbed ensembles on single-crystal Pt and Rh clusters are presented. The energy ranges related to the stability of adsorbed ensembles of the type (Me)N(CO)n(OH)m, where Me stands for Rh(100), Rh(111), Pt(100) and Pt(111), were calculated for various coordination geometries and applied potential conditions. A stability inversion potential was found for each ensemble. A correlation was obtained between the stability inversion potentials resulting from the different adsorbed ensembles and the potentials of the current peaks related to the voltammetric oxidation of CO adsorbates on Pt and Rh resulting from comparable potential perturbation conditions.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

A quantum chemistry approach to the electro-oxidation of CO adsorbed on Rh (111) cluster surfaces

A molecular-orbital interpretation of the electro-oxidation of CO adsorbed on Rh(111) single-crystal clusters in the presence of H2O is described. Calculations were based on the atom super-position and electron delocalization method. Different stabilization energies for ensembles of the type [Me]N(CO)n(OH)m for M = Rh or Pt are given. The stability of possible CO adsorbate configurations on Rh(111) surfaces depends on the applied electric potential in a way which is directly comparable with the one reported previously for CO adsorbates on Pt(111). Only linearly bonded CO adsorbates appear to be involved in the electrochemical CO oxidative interaction with H2O molecules on both Rh(111) and Pt(111).Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Teorethical studies of the stability of 8a-alkyll-1,2,3,4,6,8a- hexahydronaphtalen-1-ones using semiempirical methods

The Birch alkylation products are very unstable. We are showing, in this communication, the results of a theoretical study that compares different decomposition reaction mechanisms. The conclusions are in agreement with our experimental results.Facultad de Ciencias Exacta

Synthesis of anticonvulsant sulfamides: theoretical study of the related mechanism

A theoretical study of the mechanisms associated with the synthesis of anticonvulsant symmetric N,N’-substituted sulfamides is presented. Two possible synthetic routes are compared, which mainly differ in the use of pyridine as a nucleophilic agent in the reaction mechanism. Geometry optimization techniques and transition-state detection at the B3LYP/6-31G** level, modeling the solvent by means of an isodensity polarizable continuum approach, allow the most suitable method for the experimental process to be discerned.Facultad de Ciencias Exacta

A quantum chemical approach to the influence of platinum surface structure on the oxygen electroreduction reaction

The O2 electroreduction reaction (OERR) on Pt behaves as a structure sensitive reaction whose peroxo intermediates are formed in a greater extent on Pt(100) than on Pt(111) surfaces. A semiempirical quantum chemistry interpretation of this behavior is attempted on the basis of the study of [Pt]N02OH systems, where N, the number of atoms in the Pt cluster, equals 18 and 25. Calculations indicate that dissociative O2 electroadsorption on Pt(111) and molecular O2 on Pt(100) are favored. As a result of the interactions of O2 and OH in adjacent positions, hydroperoxide intermediates are formed on Pt(100) leading to the possibility of having H2O2 as product from the OERR.Instituto de Investigaciones Fisicoquímicas Teóricas y AplicadasFacultad de Ciencias Exacta

A Semiempirical Quantum Approach to the Formation of Carbon Dioxide Adsorbates on Pt(100) and Pt(111) Cluster Surfaces

The geometries and binding energies of CO2 adsorbates on Pt(100) and Pt(111) cluster surfaces were calculated by means of an improved version of the extended Hückel molecular orbital method. The polarization of the surface by an applied electric potential and coadsorption of H atoms were included in the model. For simulated applied potentials in the range -1.0 to 1.0 V, CO2 coordination geometries (side-on, formate) involving two adsorbate atoms bonded to the surface are favored, regardless the surface topology and the presence of coadsorbed H atoms. In agreement with experiment, larger binding energies are always calculated for the Pt(100) cluster surface.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Pharmacophore model for antiepileptic drugs acting on sodium channels

Fifteen antiepileptic drugs (AED), active against the maximal electroshock seizure test and able to block the neuronal voltage-dependent sodium channel, have been studied by means of a similarity analysis. Structural and electronic, quantum chemically derived characteristics are compared. Rigid analogs are included, because of the flexibility of some structures, in order to discern the conformational requirements associated with these ligands in the moment of the interaction. An inactive compound (ethosuximide) helps in the definition of the structural factors that are important for the activity. We propose a pharmacophore model that, giving an interpretation of the biological activity, allows the design of new AED with a well-defined mechanism of interaction.Facultad de Ciencias ExactasCentro de Química Inorgánic