title: The sensitivity of the cis/trans-isomerization of enalapril and enalaprilat to solvent conditions.
abstract: The cis- and trans-isomers of enalapril and enalaprilat can be resolved by HPLC and by capillary electrophoresis. The isomeric content of enalapril is perturbed by the ionization of both its carboxyl and amine groups, while the isomeric content of enalaprilat is only perturbed by the ionization of its amine group. Increasing the hydrophobicity of the analyte solvent, as reflected in its molar polarization, increases the Z (cis) content of enalapril and markedly decreases the kinetics for isomerization. Far UV circular dichroic measurements suggest that the increase in Z (cis) content of enalapril is due to protonation of its carboxylate group. Taken together, the in-vitro properties of enalapril and enalaprilat suggest that the in-vivo transformation of the prodrug enalapril to the inhibitor enalaprilat and its delivery to angiotensin-converting enzyme should not be significantly limited by cis/trans-isomerization.
authors.forename: Robin
authors.initials: R
authors.lastname: Ledger
authors.forename: Earle
authors.initials: E
authors.lastname: Stellwagen
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D019075:Electrophoresis, Capillary; D004656:Enalapril / Q000737:chemistry*; D015773:Enalaprilat / Q000737:chemistry*; D007536:Isomerism; D012997:Solvents
chemical_list: D000959:Antihypertensive Agents; D012997:Solvents; D004656:Enalapril; D015773:Enalaprilat