Estudo da transferência de carga do Maleato de Enalapril no estado sólido por dinâmica molecular

Abstract

Enalapril maleate is an antihypertensive ethyl ester pro-drug with two crystalline forms (form I and form II). A network of hydrogens bond is present in both crystal structures and plays an important participation in the packing of two polymorphs. Enalapril maleate presents high susceptibility to undergo degradation reactions, when exposed to conditions of high humidity, temperature, and pH changes. This work evaluates the effect of maleate on the structural stability of enalapril maleate solid state. The charge transfer process and the mobility of the proton (H+ ) between enalapril and maleate molecules was demonstrate using supramolecular modeling analyses and molecular dynamics calculations. The analyses showed that in both crystalline structures, the moieties of the molecule that exhibited a higher electronic density, and indicate the occurrence of the hydrogens bonds, coincide with the functional groups that are more likely to suffer chemical reactions and cause the degradation of the enalapril maleate, which explains why the crystalline structures of enalapril maleate confer more stability to the drug. Finally, the supramolecular modeling analyses and CPMD calculations, was applied to evaluate the electronic structure of enalapril maleate and the transfer proton process. These analyses showed the charge transfer from enalapril to maleate as well as the mobility of the proton (H+) between the two molecules in the crystalline state.