Métodos semiempíricos para la evaluación rápida de orbitales frontera en la clasificación de agonistas y antagonistas de la subunidad NR1 de los receptores iGluR-NMDA

<p><strong></strong>The ionotropic glutamate receptors activated by N-Methyl-D-Aspartate (iGluR-NMDA) are of great importance in pharmacology since they are involved in neurodegenerative and neuropsychiatric disorders; they even participate in processes such as synaptic plasticity that are essential for memory formation. Subunit NR1 iGluRs-NMDA is of paramount importance for the appropriate activation of this type of receptors; in fact, many of the pharmaceutical products studied for the abovementioned disorders are targeted specifically to the NR1 subunit. Previous studies have shown that the lowest energy unoccupied molecular orbital (LUMO) can be used as a parameter to estimate the agonist and antagonist activity of the NR1subunit. <strong>Objective.</strong> Evaluate the semiemprical method CNDO for the rapid calculation of the LUMO energy with the aim of preparing a simple model for the <em>in silico</em> design of new pharmacological substances. <strong>Materials and methods</strong>. 168 molecules with agonist and antagonist activity in the NR1 subunit were selected. Energy of each structure was optimized and then we calculated the energy of the frontier orbital, the LogP, total energy, capacity of forming hydrogen bonds, binding energy, and dipolar moment. <strong>Results</strong>. We demonstrate that LUMO energy is enough for discriminating agonist and antagonist molecules of the NR1 subunit and that the CNDO method evaluates these properties in a rapid and efficient way. <strong>Conclusions</strong>. The CNDO method facilitates a rapid calculation, enabling a future development of effective procedures for the characterization of potential pharmacological substances acting on this particular site.</p> <p><strong>Key words</strong>: iGluR-NMDA, LUMO, agonist, antagonist, CNDO</p><br />

The Effect of the H-Bond Interactions on the First Hyperpolarisability of (HF)n. A Comparative Study

The effect of H-bond interactions on the first hyperpolarisability (ß) of (HF)„ is discussed. The reported results confirm, computationally, the remarkable sensitivity of this property to intermolecular interactions, which has been found experimentally. Results for the second hyperpolarisability (y) and the total energy (E) are also presented for comparative purposes. The analysis is based on data calculated by the CHFPT- EB-CNDO method.

Relationships of the Polarisability with the Number of Valence Electrons, the Total Energy and the Second Hyperpolarisability of Methylbenzenes

The total energy and polarisability of 12 methylbenzenes have been computed by employing the CHF-PT-EB-CNDO method. The relationships between the normalized polarisability, the total energy, the second hyperpolarisability and the number of valence electrons of the studied compounds are discussed. Variations in the polarisation properties induced by structural changes are also commented upon.

The effect of the water–cation interaction on the polarisability and second hyperpolarisability of hydrated Li+. A comparative study

The CHF-PT-EB-CNDO method has been used to compute the polarisability and second hyperpolarisability of the hydrated lithium cation with one and two hydration shells. The effect of the Li+… (H2O)n interaction on these properties is discussed and the main findings are confirmed in hydrated Na+, Be2+, and Al3+.

The Effect of Intermolecular Interactions in Some Water Clusters and Hydrates of the Hydronium and Hydroxyl Ions, on their Polarisability and Hyperpolarisabilities. A Comparative Study

The polarisability and hyperpolarisabilities of (H2O)n, H3O+ (H2O)n and OH- (H2O)n are computed by the CHF-PT-EB-CNDO method. The basis set has been optimized with respect to the polarisability and second hyperpolarisability of H2O. The effect of intermolecular interactions, in the water clusters and the hydrates of the ions on their polarisability and hyperpolarisabilities, and their variation with charge, shape and size of the aggregates is discussed.