EFFECT OF A POLAR ENVIRONMENT ON THE CONFORMATION OF PHOSPHOLIPID HEAD GROUPS ANALYZED WITH THE ONSAGER CONTINUUM SOLVATION MODEL

The effect of the polarity of the environment on the conformation of t he zwitterionic membrane lipid head groups phosphoethanolamine (PE) an d phosphocholine (PC) has been investigated with calculations at the H artree-Fock level using the 3-21G(), 6-31G*, and 6-31+G* basis sets t ogether with the Onsager continuum solvation model. Results suggest th at in the gas phase both PE and PC adopt cyclic minimum energy conform ations, in which an ammonium or N-methyl hydrogen closely approaches o ne of the nonesterified phosphate oxygens. In the case of PE, intramol ecular interactions result in a proton transfer from the ammonium grou p to the phosphate oxygen, which however is suppressed by a moderate i ncrease in the polarity of the surrounding medium. With increasing pol arity of the environment, the cyclic structures of PE and PC still rem ain low-energy conformers but simultaneously for both head groups an a lmost identical extended conformer, typical of crystal structures, bec omes increasingly favored. Already at epsilon = 10, the extended confo rmer of PC is favored (-2.4 kcal/mol) relative to the cyclic one, whil e for PE the relative energy of the extended conformer approaches that of the cyclic one at epsilon = 80. The similarity and increasing stab ility of the extended PE/PC conformers in the monomeric state and the fact that this conformer is also adopted in all crystal structures of PE/PC lipids, regardless of hydration and interaction pattern, indicat e that the geometry of this conformer is determined by energetics intr insic to the phosphoethanolammonium backbone. In lipid aggregates or a membrane environment the extended conformer becomes additionally stab ilized by intermolecular ionic and hydrogen bond interactions with nei ghboring molecules substituting for the internal interaction that in t he monomeric state constrains the zwitterionic dipole into a cyclic st ructure.