Estudo conformacional e espectroscópico do dipiridamol : uma visão semiempírica

• Ano de defesa: 2010
• Autor(a) principal: Santos, Luciano
• Orientador(a): Costa Júnior, Nivan Bezerra da
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Sergipe
• Programa de Pós-Graduação: Pós-Graduação em Química
• País: BR
• Palavras-chave em Português: Análise química; Análise espectroscópica; Farmacologia; Dipiridamol
• Palavras-chave em Inglês: Chemical analysis; Spectroscopic analysis; Pharmacology; Dipyridamole
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: https://ri.ufs.br/handle/riufs/6066

Dipyridamole, 2,6 - bis(diethanolamine) - 4,8- dipiperidinedinapyrimide - [5,4-d] pyrimidine (DIP) is a clinically approved drug for use in cardiology, belonging to the class of heterocyclics with interesting antioxidant properties. In this work we studied the relative stability and properties of six conformational structures of DIP and also aimed to understand the effect of the different conformations on some molecular properties such as the ionization potential. In this study, we used semiempirical methods such as AM1, PM3, PM6 and RM1, all available in the MOPAC2009 program. The solvent effect on the relative stabilities of conformations as well as on the properties of the drug was evaluated using the continuum medium approximation and a sequential Monte Carlo procedure and quantum mechanics (MC/QM). The MC procedure has been used in order to yield liquid configurations, allowing the calculation of average values of solution properties which indicated the possibility of hydrogen bonding involving DIP nitrogen atoms. All calculations performed both in vacuum and in implicit solvent suggest the occurrence of a mixture of possible conformations since the energy difference between them is low. The preferential protonation occurs in nitrogens atoms of the heteroaromatic ring but this preference changes with conformation. In general the greater stabilizations occur when the protons bind to N2 and N7 atoms, in agreement with the calculation considering the solvent. The spectroscopic analysis in water has shown that all three DIP bands exhibit a slight solvatochromism and that only the first solvent layer contributes to those shifts. The charge distribution and the ionization potential under the water effect as solvent were carried out for the 125 structures derived from the MC procedure using PM3 and AM1 methods. It has been found that the distribution of Mulliken charges in PM3 points out that the electron leaves the nitrogen atom more effectively, independently of in aromatic or aliphatic position, while the distribution according to AM1 suggests that the electron preferentially leaves the N2 and N7 atoms, according to the HOMO molecular orbital.