TETRAETHER BOLAFORM AMPHIPHILES AS MODELS OF ARCHAEBACTERIAL MEMBRANE-LIPIDS - SYNTHESIS, DIFFERENTIAL SCANNING CALORIMETRY, AND MONOLAYER STUDIES

Four racemic tetraether lipids containing a single 1,omega-polymethylene chain (omega = 16, 20) bridging two glycerophosphate headgroups (bolaform amphiphiles) have been synthesized. These materials have been characterized at the air-water interface by monolayer balance methods and in buffered solution by differential scanning calorimetry (DSC) and negative stain transmission electron microscopy (TEM). Molecular areas in excess of 100 angstrom 2/molecule at 40 mN/m2 were observed for all bolaamphiphiles studied, suggesting a U-shaped molecular conformation that places both phosphate headgroups in the water subphase. Aqueous dispersions of these lipids have thermal and morphological properties that depend on molecular structure and solution pH. Phase transition temperatures (T(c)) of the structural isomers, 2,2'-di-O-decyl-1,1'-O-eicosamethylene-rac-diglycero-3,3'-diphosphate (PS20) and 1,1'-di-O-decyl-2,2'-O-eicosamethylene-3,3'-diphosphate (SS20), were 49 and 38-degrees-C, respectively, at pH 2.5. A reduction in the observed T(c) of approximately 14-degrees-C occurred when the pH was raised to 8.1. The closely related structural analogue, 1,1'-O-eicosamethylene-2-O-eicosyl-rac-diglycero-3,2',3'-diphosphate (PA20), has a T(c) of 85-degrees-C. No phase transition was observed above 5-degrees-C for 2,2'-O-dioctyl-1,1'-O-hexadecylmethylene-rac-diglycero-3,3'-diphosphoric acid (PS16). Multilamellar structures with hydrocarbon-region spacings of 24-30 angstrom and overall lengths approaching 0.3-mu-m were observed by negative stain electron microscopy. The observed lamellae distance is in good agreement with the membrane thickness expected for a bolaamphiphile in its all-anti conformation.