title: Investigation of the energy barrier to the rotation of amide CN bonds in ACE inhibitors by NMR, dynamic HPLC and DFT.
abstract: The isomerizations of Enalapril, Perindopril, Enalaprilat and Lisinopril have been investigated using NMR spectroscopic, dynamic chromatographic, unified equation and DFT theoretical calculations. The thermodynamic parameters (ΔH, ΔS and ΔG) were determined by varying the temperature in the NMR experiments. At the coalescence temperature, we can evaluate the isomerization barrier to the rotation (ΔG(≠)) around the amide bond. Using dynamics chromatography and an unified equation introduced by Trap, we can determine isomerization rate constants and Gibbs activation energies. Molecular mechanics calculations also provided evidence for the presence of low energy conformers for the ACE due to restricted amide rotation. With the value of barriers (ΔE) between them of the order of (20kJmol(-1)), which is in agreement with the dynamic NMR results and DFT calculations.
authors.affiliation: Laboratory of Heteroatom Organic Chemistry, Department of Chemistry, Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia. Electronic address: sondes.bouabdallah@laposte.net.
authors.forename: S
authors.initials: S
authors.lastname: Bouabdallah
authors.affiliation: Laboratory of Organic Chemistry: Synthèse et Etude Physico-Chimique, Faculty of Sciences of Tunis, University of El Manar, 1060 Tunis, Tunisia.
authors.forename: M T
authors.initials: MT
authors.lastname: Ben Dhia
authors.affiliation: Laboratory of Heteroatom Organic Chemistry, Department of Chemistry, Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia.
authors.forename: M R
authors.initials: MR
authors.lastname: Driss
authors.affiliation: Laboratory of Heteroatom Organic Chemistry, Department of Chemistry, Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna, Tunisia.
authors.forename: S
authors.initials: S
authors.lastname: Touil
mesh_terms: D000577:Amides / Q000737:chemistry; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004656:Enalapril / Q000737:chemistry; D015773:Enalaprilat / Q000737:chemistry; D007536:Isomerism; D017706:Lisinopril / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015233:Models, Statistical; D020913:Perindopril / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D017706:Lisinopril; D015773:Enalaprilat; D020913:Perindopril
keywords: ACE; DFT; Dynamic chromatography; Isomerization; NMR