Intermolecular crosslinking of fatty acyl chains in phospholipids: use of photoactivable carbene precursors

Abstract

Phospholipids containing photolysable carbene precursors (β -trifluoro-α-diazopropionoxy and m-diazirinophenoxy groups) in ω-positions of sn-2 fatty acyl chains were prepared. Photolysis of their vesicles produced crosslinked products in 40-60% yields. Crosslinking was mostly intermolecular and occurred by carbene insertion into the C-H bonds of a second fatty acyl chain. Crosslinking products were characterized by (i) their gel permeation behavior, (ii) analysis of products formed by base-catalyzed transesterification, (iii) degradation with phospholipases A2 and C, (iv) gas chromatography/mass spectrometry, and (v) use of mixtures of phospholipids carrying the carbene precursors and a phospholipid containing radioactively labeled fatty acyl groups. Nitrenes generated from the aliphatic or aromatic azido groups in phospholipids were unsatisfactory for forming crosslinks by insertion in C-H bonds.