Complexation of enalapril maleate with beta-cyclodextrin: NMR spectroscopic study in solution

Abstract

Recebido em 28/3/05; aceito em 14/10/05; publicado na web em 12/4/06 A detailed NMR ( 1 H , COSY, ROESY) spectroscopic study of complexation of enalapril maleate with β-cyclodextrin was carried out. The 1 H NMR spectrum of enalapril maleate confirmed the existence of cis-trans equilibrium in solution, possibly due to hindered rotation along the amide bond. The cis-trans ratio remained almost the same in the presence of β-cyclodextrin but in one case it was found significantly different which suggests a catalytic role of β-cyclodextrin in the isomerization. 1 H NMR titration studies confirmed the formation of an enalapril-β-cyclodextrin inclusion complex as evidenced by chemical shift variations in the proton resonances of both the host and the guest. The stoichiometry of the complex was determined to be 2:1 (guest: host). The mode of penetration of the guest into the β-cyclodextrin cavity as well as the structure of the complex were established using ROESY spectroscopy.

A comparative study of complexation of enalapril with α-, β- and γ-cyclodextrins in aqueous medium: structure elucidation of inclusion complexes using NMR spectroscopic and molecular mechanics methods

“…We studied the complexation of enalapril maleate with b-CD earlier [16] and reported the formation of a 1:2 [b-CD:ENA] complex. Later, Longhi and coworkers [17] reported the formation of 1:1 [b-CD-ENA] complex which was supported by molecular mechanics studies.…”

The Problem of Dynamic Process Manifestation in Identification of Organic Compounds by NMR Spectroscopy

“…Примером соединения, в молекуле которого протекает одновременно несколько внутримолекулярных процессов, является эналаприла малеат. Эналаприла малеат и его аналоги относятся к препаратам, снижающим артериальное давление [41,42]. В молекуле эналаприла малеата наряду с заторможенным вращением вокруг амидной связи присутствует инверсия конфигурации ациклического атома N. Как правило, барьер пирамидальной инверсии атома N существенно ниже барьера вращения Эти экспериментальные данные также можно объяснить различной скоростью пирамидальной инверсии атома азота в зависимости от условий регистрации ЯМР-спектров.…”

UV-Vis Spectroscopic Characterization of β-Cyclodextrin-Vanillin Inclusion Complex

“…Cyclodextrins (CDs) are cyclic oligosaccharides composed of glucose units obtained from the enzymatic degradation of starch [1][2][3] . The most common forms of CDs consist of 6, 7, and 8 glucose units linked by α-1,4 glycosidic bonds and are named α, β and γ CD, respectively (Figure 1a) 4,5 . CD is known to have a truncated cone shape with the characteristic of having a hydrophobic inner cavity and hydrophilic outer surface 2,5,6 (Figure 1b).…”

“…The most common forms of CDs consist of 6, 7, and 8 glucose units linked by α-1,4 glycosidic bonds and are named α, β and γ CD, respectively (Figure 1a) 4,5 . CD is known to have a truncated cone shape with the characteristic of having a hydrophobic inner cavity and hydrophilic outer surface 2,5,6 (Figure 1b). The most significant feature of CDs is their lipophilic cavity which provides a microenvironment to a wide variety of appropriately sized hydrophobic compounds to form inclusion complexes [7][8][9][10][11] through the release of enthalpy-rich water molecules [12][13][14][15] .…”