Theoretical analysis of the electronic properties of the sex pheromone

CHAMORRO, E. R.; SEQUEIRA, A.; ZALAZAR, M. F.; PERUCHENA, N. M.

J. Bioorg. Med. Chem.

ELSEVIER B: V: Pergamon

Año: 2008 vol. 16 p. 8535 - 8545

0968 0896

In the present work, the distribution of the electronic charge density of the natural sex pheromone, the (Z)-13-hexadecen-11-ynyl acetate, in the female processionary moth, Thaumetopoea pytiocampa, and its nine analogue derivatives was studied within the framework of the Density Functional Theory and the Atoms in Molecules (AIM) Theory at B3LYP/6-31G*//B3LYP/6-31++G** level. Additionally, molecular electrostatic potential (MEP) maps of the previously mentioned compounds, were computed and compared. Furthermore, the substitution of hydrogen atoms from the methyl group in the acetate group by electron withdrawing substituents (i.e., halogen atoms) as well as the replacement effect of hydrogen by electron donor substituents (+I effect) as methyl group, were explored. The key feature of the topological distributionof the charge density in analogue compounds, such as the variations of the topological propertiesencountered in the region formed by neighbouring atoms from the substitution site were presented anddiscussed. Using topological parameters, such as electron density, Laplacian, kinetic energy density andpotential energy density evaluated at bond critical points (BCP), we provide here a detailed analysis of thenature of the chemical bonding of these molecules. In addition, the average atomic properties (population,charge, energy, volume, and dipole moment) were determined on selected atoms. These properties wereanalyzed at the substitution site -with respect to the natural sex pheromone- and related to the biologicalactivity and to the possible binding site with the pheromone binding protein, (PBP). Moreover, the Laplacianfunction of the electronic density was used to locate electrophilic regions susceptible to be attacked (by deficient electron atoms or donor hydrogen).Our results indicate that the change in the atomic properties, such as electronic population and atomicvolume, are sensitive indicators of the loss of the biological activity in the analogues studied here. The crucial interaction between the acetate group of the natural sex pheromone and the PBP is most likely to be a hydrogen bonding and the substitution of hydrogen atoms by electronegative atoms in the pheromonemolecule reduces the hydrogen acceptor capacity. This situation is mirrored by the diminish of the electronic population on carbon and oxygen atoms at the carbonylic group in the halo-acetate group. Additionally, the modified acetate group -with electronegative atoms- shows new charge concentration critical points or regions of concentration of charge density in which an electrophilic attack can also occur. Finally, the use of the topological analysis based in the charge density distribution and its Laplacian function, in conjunction with MEP maps provides valuable information about the steric volume and electronic requirement of the sex pheromone for binding to the PBP.