title: Stereoselective synthesis of perdeuterated phytanic acid, its phospholipid derivatives and their formation into lipid model membranes for neutron reflectivity studies.
abstract: We describe a straightforward method, for synthesis of large scale (gram quantities) of highly deuterated phytanic acid from commercially available phytol while preserving the stereochemistry around the chiral centres. The subsequent synthesis of tail-deuterated analogues of the archeabacterial membrane lipids 1,2-di(3RS,7R,11R-phytanyl)-sn-glycero-3-phosphocholine (DPEPC) and 1,2-di(3RS,7R,11R-phytanoyl)-sn-glycero-3-phosphocholine (DPhyPC) from perdeuterated phytanic acid is also described. Both lipids were employed in construction of two different model membranes, namely Langmuir monolayers and a tethered bilayer membrane (TBM) on a solid substrate, characterised by pressure area isotherm and neutron reflectometry techniques. At 10 mN/m pressure the head-group thickness of both monolayers was similar while the thickness of the tail region was significantly larger for tail-deuterated DPhyPC, which was evident from a smaller area per molecule. At 20 mN/m the thickness of the head and tail regions in both lipids was comparable, yet the area per molecule of tail-deuterated DPhyPC was 10% smaller than tail-deuterated DPEPC. In the TBM bilayer model membrane, the thickness of the lipid tails in both inner and outer leaflets was 8.2 Å, giving a total of 16.4 Å. Deuteration enabled unambiguous determination of the relative proportion of the hydrogenous tether, phospholipid and subphase.
authors.affiliation: National Deuteration Facility, Bragg Institute, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia. Electronic address: raoy@ansto.gov.au.
authors.forename: Nageshwar R
authors.initials: NR
authors.lastname: Yepuri
authors.affiliation: Bragg Institute, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Holt
authors.affiliation: National Deuteration Facility, Bragg Institute, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia.
authors.forename: Greta
authors.initials: G
authors.lastname: Moraes
authors.affiliation: National Deuteration Facility, Bragg Institute, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Holden
authors.affiliation: School of Medical and Molecular Biosciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
authors.forename: Khondker R
authors.initials: KR
authors.lastname: Hossain
authors.affiliation: School of Medical and Molecular Biosciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Valenzuela
authors.affiliation: National Deuteration Facility, Bragg Institute, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia; School of Chemistry, The University of New South Wales, Kensington, NSW 2052, Australia; Australian Synchrotron, 800 Blackburn Road, Clayton, Victoria 3168, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: James
authors.affiliation: National Deuteration Facility, Bragg Institute, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia.
authors.forename: Tamim A
authors.initials: TA
authors.lastname: Darwish
mesh_terms: D003903:Deuterium / Q000737:chemistry*; D008051:Lipid Bilayers / Q000138:chemical synthesis*; D008560:Membrane Fluidity; D008968:Molecular Conformation; D033363:Neutron Diffraction / Q000379:methods*; D010743:Phospholipids / Q000138:chemical synthesis*; D010831:Phytanic Acid / Q000138:chemical synthesis*; D010836:Phytol / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D010831:Phytanic Acid; D010836:Phytol; D003903:Deuterium
keywords: Langmuir monolayer; Perdeuterated phytanic acid; Tail-deuterated 1,2-di(3RS,7R,11R-phytanoyl)-sn-glycero-3-phosphocholine; Tail-deuterated 1,2-di(3RS,7R,11R-phytanyl)-sn-glycero-3-phosphocholine; Tethered bilayer lipid membrane