Synthesis and supramolecular properties of conformationally restricted and flexible phospholipids.
Short synthetic routes are described to produce structurally related phospholipids that are either conformationally restricted or flexible. The conformationally restricted structures have a cyclopropyl ring in the interfacial region of the phospholipid. The key synthetic step is a cyclopropanation reaction between 2(5H)-furanone and a stabilized chloroallylic phosphonate anion. The synthetic routes enable the incorporation of different polar headgroups as well as nonpolar tails at late stages in the sequence. The phosphoethanolamine derivatives 1b and 2b readily form encapsulating vesicles, however, dye leakage from vesicles composed of the restricted phospholipid 1b is significantly slower than from vesicles composed of flexible analogue 2b. Physicochemical analyses using 31P NMR, differential scanning calorimetry, fluorescence anisotropy, and Langmuir-Blodgett films suggest that the decreased permeability of membranes composed of conformationally restricted 1b is due to its ability to pack more closely in a bilayer assembly.
Vares
Lauri
L
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Koulov
Atanas V
AV
Smith
Bradley D
BD
D002152:Calorimetry, Differential Scanning; D003521:Cyclopropanes / Q000737:chemistry; D005453:Fluorescence; D005456:Fluorescent Dyes; D008081:Liposomes / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D010063:Ovum / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D010743:Phospholipids / Q000138:chemical synthesis / Q000737:chemistry*; D011312:Pressure; D013499:Surface Properties
D003521:Cyclopropanes; D005456:Fluorescent Dyes; D008081:Liposomes; D010713:Phosphatidylcholines; D010743:Phospholipids; C030797:cyclopropane; C017251:1,2-oleoylphosphatidylcholine