G.L. Estiú

Pharmacophore searching and QSAR analysis in the design of anticonvulsant drugs

Abstract A set a antiepileptic drugs (AED) that are active against the MES test, including structures that are already in clinical use as well as the new compounds recently designed in our lab, is analyzed in this article in relation to the requirements associated with the manifested activity. The strategy involves the identification of the pharmacophoric pattern, by means of a similarity analysis where the structural and electronic characteristics are compared, followed by a QSAR study. The latter shows the importance of the electronic descriptors, and points to the carbonyl group as the most relevant portion for the definition of the activity. Quantum chemical derived descriptors give the best answer for both the similarity analysis and the statistical fitting.

UV-visible spectroscopy in the interpretation of the tautomeric equilibrium of N,N′(bis-3,5-di-bromo-salicyliden)-1,2-diaminobenzene and the redox activity of its Co(II) complex. A quantum chemical approach

Abstract By means of quantum chemical calculations, the origin of the redox capability of N,N′(bis-3,5-di-bromo-salicyliden)-1,2-diaminobenzene Co (II) complexes, of major interest in the catalytic reduction of naphtas, is analyzed. The geometry, electronic structure and UV-vis spectra of both the complex and the ligand are studied. AM1 and INDO/1 hamiltonians are used for the conformational analysis, whereas the UV-visible spectra are accurately reproduced by means of INDO/S-CI calculations, justifying the color of the ligand and offering an explanation to the catalytic redox activity of the Co(II) complex, based on the electronic transitions associated to the spectroscopic features and the electronic characteristics of the redox states.

RESONANCE IN AMIDES. COMPARISON OF AB INITIO AND SEMIEMPIRICAL METHODOLOGIES IN THE DESCRIPTION OF ACETAMIDE

Abstract The electronic description of acetamide is analyzed at different levels of theory, comprising both semiempirical and ab initio methodologies. Regardless of the basis set used, the level of correlation included and the population analysis considered, ab initio calculations always result in a density charge on the nitrogen atom larger than on the oxygen, a fact that seems to be at variance with the predictions of resonance. AM1 and MNDO calculations agree with the ab initio results. PM3 and ZINDO, on the other hand, render the resonance-based description. The study, oriented to select the best semiempirical methodology for the treatment of large aliphatic amides, points to AM1 as the method of choice.

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

Abstract 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 Huckel 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.

A quantum-chemistry approach to the electro-oxidation mechanism of adsorbed carbon monoxide on platinum single-crystal clusters

Abstract A molecular orbital interpretation of the electro-oxidation of CO adsorbed on Pt (100) and Pt (111) single-crystal clusters, based on the extended Huckel method, is presented. The metal surfaces are simulated with different (Pt)N clusters (N = 25 for Pt (100) and N = 19 for Pt (111)), and the influence of the applied potential is introduced by properly shifting the energy of the metal valence band. The multiplicity of the voltammetric peaks resulting for the reaction emerges from the potential-dependent stabilization energies of different ensembles of the type (Pt)N(CO)n(OH)m associated with the different CO coverages and coordination geometries. Data derived from the calculations indicate that only a linearly-bonded CO adsorbate appears to be most likely one involved in the electrochemical oxidative interactions.

Theoretical study of underpotential deposition of foreign metal atoms on Pt(111) single-crystal cluster surfaces: Part 2. The influence of metal underpotential deposition layer structures on the decomposition of co-adsorbed water

Abstract The influence of different bimetallic structures formed by underpotential deposition (UPD) of foreign metal atoms on Pt (111) substrates towards co-adsorbed H 2 O molecule decomposition was studied through semiempirical calculations based on molecular-orbital theory (ASED). Electronic and structural effects are analysed comparatively. The results show that structural effects are quantitatively more important than electronic effects for co-adsorbed H 2 O decomposition. A localized enhancement of the influence of surface-structure effects is produced at surface imperfections formed by foreign atom UPD submonolayers.

Theoretical study of underpotential deposition of foreign metal atoms on Pt(111) single-crystal cluster surfaces: Part I. The stability of the different metal underpotential-deposition layer structures as a function of surface coverage and applied electric potential

Abstract Structures of underpotential deposited (UPD) metal layers on a Pt(111) cluster surface are described through the application of the semiempirical atom superposition and electron delocalization molecular orbital method (ASED-MO). Data predict that before the completion of the first metal monolayer a second layer starts to grow. The growth of the second layer occurs simultaneously with the rearrangement of UPD metal lattice parameters. This process can be interpreted through the adsorption-nucleation and growth model. The early stages of three dimensional nucleation take place in the UPD potential region.

Pharmacophoric pattern of anti-epileptic sulfonamides and sulfamates. Theoretical study of the associated requirements

Abstract A pharmacophoric pattern of sulfonamides is presented, which concerns compounds structurally related to Topiramate (Top) with anti-convulsant activity against the maximal electroshock seizure (MES test). The pharmacophore is characterized by a polar sulfonamide group, whose descriptors are analyzed in order to discern the associated requirements. It has been derived from a conformational study, based on a quantum-chemical calculations, followed by a similarity analysis that include structures synthesized and tested in our lab, together with drugs that are already in clinical use. Different possible mechanisms of action are compared, including carbonic anhydrase inhibition.

Theoretical calculations related to cooperative interaction effects : the H atom-H2O molecule-surface site ensemble at Pt (111) and Pt (100) clusters

Abstract The adsorbate-substrate interaction energies for the H atom-H 2 O molecule at Pt (100) and Pt (111) sites have been evaluated by applying the Extended Huckel Method (EHM). Two cluster approaches were considered, one consisting of 25 atoms for Pt (100) and another one of 19 atoms for Pt (111). For the latter, the cooperative interaction H atom-H 2 O molecule-Pt adsorption site results in a stable configuration which can be represented as a [Pt] N (H 2 O) m (H) n ensemble, whereas no stable configuration results for Pt (100). Data derived from the theoretical calculations can be compared qualitatively to the trends in the energetics of H atom electroadsorption-electrodesorption on different Pt surfaces.

THE ADSORPTION OF THIOPHENE ON A PARTIALLY HYDROGENATED MOS2 CLUSTER. A ZINDO-MRCI STUDY

Abstract Two adsorption geometries of thiophene on a Mo5S14 cluster (η5 and σ) are comparatively analyzed by means of Intermediate Neglect of Differential Overlap (ZINDO program) calculations, at both the self consistent field and the configuration Interaction (Cl) levels. In order to account for the overestimation of the binding energies (BE) by the NDO methods, the calculated raw values for the adsorption system have been corrected to match the experimental (or high level ab initio) BE values for each diatomic bond, counting the number of bonds on the basis of the analysis of the atomic bond Wiberg index matrix. Calculations show that thiophene adsorbs in a η5 coordination on a partially hydrogenated Mo5S14 cluster. This is the active coordination for its cleavage through the C-S bond. Both the σ and η5 coordinations are described as a charge transfer from the adsorbate molecule to the Mo5S14 cluster, which is more remarkable for the flat adsorption.