Dynamic Interfacial Properties of Surface-excess Films of Phospholipids and Phosphonolipid Analogs

Abstract

Abstract Dynamic surface pressure-area (π-A) isotherms were measured for dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylethanolamine (DPPE), and 13 chain-equivalent synthetic phospholipid and phosphonolipid diether and etheramide analog compounds structurally related to these glycerophospholipids. Spread interfacial films at a high initial concentration of 15 A2/molecule were studied under continuous cycling to emphasize maximum surface pressure and dynamic respreading behaviors relevant for pulmonary surfactant. Wilhelmy balance subphases containing NaCl and total ionic strength ∼0.15 were used at pH 2.6, 5.6, and 11.5 to give different headgroup ionization states without significantly affecting compound steric bulk. Intracompound changes in isotherm behavior with pH were correlated with variations in headgroup hydrogen bonding and charge for four groups of molecules: (1) DPPC and analog compounds with choline or similar headgroups (Group I) had π-A isotherms with low minimum surface tensions 70 mN/m) at all three pH values, with dynamic respreading on successive cycles that was lowest at pH 2.6 and increased at pH 5.6 and 11.5; (2) DPPE and related compounds with primary amine headgroups (Group II) had higher minimum surface tensions ranging from 5 to 20 mN/m, with respreading that was greater than that of DPPC-related compounds at pH 2.6 and 5.6, and which decreased dramatically at pH 11.5; (3) secondary amine/ammonium compounds with one N-substitution (Group IIIa) behaved similarly to DPPE and its analogs, with higher minimum surface tensions than DPPC-related molecules and respreading that was maximal at low pH and decreased substantially at pH 11.5; and (4) tertiary amine/ammonium compounds with two N-substitutions (Group IIIb) respread better at pH 11.5 than at 5.6 and 2.6, with strikingly altered isotherms and elevated minimum surface tensions (∼30 mN/m) at high pH. The dynamic π-A isotherm characteristics of the majority of phospholipids and phosphonolipids indicated that increased intermolecular hydrogen bonding between headgroups led to increased dynamic respreading in interfacial films. Additionally, in the absence of substantial intermolecular hydrogen bonding, a cationic lipid headgroup charge (neutral phosphate/phosphonate group) correlated with decreased respreading facility for the surfactant molecules studied.