title: Reaction Mechanism of Covalent Modification of Phosphatidylethanolamine Lipids by Reactive Aldehydes 4-Hydroxy-2-nonenal and 4-Oxo-2-nonenal.
abstract: 4-Hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) are biologically important reactive aldehydes formed during oxidative stress in phospholipid bilayers. They are highly reactive species due to presence of several reaction centers and can react with amino acids in peptides and proteins, as well as phosphoethanolamine (PE) lipids, thus modifying their biological activity. The aim of this work is to study in a molecular detail the reactivity of HNE and ONE toward PE lipids in a simplified system containing only lipids and reactive aldehydes in dichloromethane as an inert solvent. We use a combination of quantum chemical calculations,1H NMR measurements, FT-IR spectroscopy, and mass spectrometry experiments and show that for both reactive aldehydes two types of chemical reactions are possible: formation of Michael adducts and Schiff bases. In the case of HNE, an initially formed Michael adduct can also undergo an additional cyclization step to a hemiacetal derivative, whereas no cyclization occurs in the case of ONE and a Michael adduct is identified. A Schiff base product initially formed when HNE is added to PE lipid can also further cyclize to a pyrrole derivative in contrast to ONE, where only a Schiff base product is isolated. The suggested reaction mechanism by quantum-chemical calculations is in a qualitative agreement with experimental yields of isolated products and is also additionally investigated by1H NMR measurements, FT-IR spectroscopy, and mass spectrometry experiments.
authors.affiliation: Division of Organic Chemistry and Biochemistry, Rudjer Bošković Institute , Bijenička 54, HR-10000 Zagreb, Croatia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vazdar
authors.affiliation: Division of Organic Chemistry and Biochemistry, Rudjer Bošković Institute , Bijenička 54, HR-10000 Zagreb, Croatia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Vojta
authors.affiliation: Division of Organic Chemistry and Biochemistry, Rudjer Bošković Institute , Bijenička 54, HR-10000 Zagreb, Croatia.
authors.forename: Davor
authors.initials: D
authors.lastname: Margetić
authors.affiliation: Division of Organic Chemistry and Biochemistry, Rudjer Bošković Institute , Bijenička 54, HR-10000 Zagreb, Croatia.
authors.forename: Mario
authors.identifier: 0000-0001-6905-6174
authors.initials: M
authors.lastname: Vazdar
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D013058:Mass Spectrometry; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: C403894:4-oxo-2-nonenal; D000447:Aldehydes; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine; C027576:4-hydroxy-2-nonenal