A DFT and semiempirical model-based study of opioid receptor affinity and selectivity in a group of molecules with a morphine structural core.

We report the results of a search for model-based relationships between mu, delta, and kappa opioid receptor binding affinity and molecular structure for a group of molecules having in common a morphine structural core. The wave functions and local reactivity indices were obtained at the ZINDO/1 and B3LYP/6-31G(∗∗) levels of theory for comparison. New developments in the expression for the drug-receptor interaction energy expression allowed several local atomic reactivity indices to be included, such as local electronic chemical potential, local hardness, and local electrophilicity. These indices, together with a new proposal for the ordering of the independent variables, were incorporated in the statistical study. We found and discussed several statistically significant relationships for mu, delta, and kappa opioid receptor binding affinity at both levels of theory. Some of the new local reactivity indices incorporated in the theory appear in several equations for the first time in the history of model-based equations. Interaction pharmacophores were generated for mu, delta, and kappa receptors. We discuss possible differences regulating binding and selectivity in opioid receptor subtypes. This study, contrarily to the statistically backed ones, is able to provide a microscopic insight of the mechanisms involved in the binding process.

Influence of aluminum oxide on the prebiotic thermal synthesis of Gly-Glu-(Gly-Glu)(n) polymer.

The effect of the aluminum oxide on the thermal synthesis of the glycine-glutamic acid (Gly-Glu-(Gly-Glu)(n) polymer is described. The thermal synthesis in the molten state was carried out in the absence and presence of the oxide. In both cases, the vibrational spectra showed characteristic group frequencies corresponding predominantly to a Gly-Glu-(Gly-Glu)(n) sequence in the polymeric structure. The theoretical spectral data support the experimental proposed Gly-Glu-(Gly-Glu)(n) sequence for the polymer. The SEM-EDX characterization of the solid phase involved in the thermal synthesis showed that the aluminum oxide participates as a site for nucleation and growth of the polymer, explaining the increase of 25% efficiency in the presence of aluminum oxide. Electrophoresis data show shorter polypeptide chains in the presence of aluminum oxide.

Hacia un modelo neurobiológico del fenómeno de la autoconciencia / Towards a neurobiological model of self-conciousness

En este trabajo se analiza el fenómeno de la conciencia humana desde el punto de vista monista y en base a algunos conocimientos actuales de la neurobiología. Se plantean tres preguntas: 1. Es la conciencia humana localizable en ciertas regiones del sistema nervioso central?. 2. Existen áreas cuyo funcionamiento explique el fenómeno de la autoconciencia?. 3. Es la conciencia un fenómeno unitario o es un fenómeno compuesto?. En un intento por responder estas pregunta, se analiza la conciencia desde un punto de vista neurológico clásico y posteriormente se describe el fenómeno de la autoconciencia desde el punto de vista del asociacionismo cerebral. Los atributos más destacados de la autoconciencia, que son la percepción, la memoria, la planificación, la afectividad, la atención y el lenguaje, son discutidos y analizados de acuerdo a la información relevante actual. Se concluye que en el fenómeno de la autoconciencia son muy importantes las estructuras límbicas y las áreas corticales con las cuales éstas se conectan, especialmente áreas del hemisferio no dominante, lo que da origen al sistema de autoconciencia primario, común al hombre y a algunas especies animales. El sistema de autoconciencia secundario se basa en el funcionamiento de las áreas linguísticas del hemisferio dominante y explica en sus propios términos la contribución del sistema primario, con ciertas limitaciones, lo que ha llevado a producir el fenómeno de la cultura actual.