Phase transition behavior and molecular structures of monounsaturated phosphatidylcholines. Calorimetric studies and molecular mechanics simulations.

High resolution differential scanning calorimetric studies were performed to investigate the thermotropic phase behavior of 26 molecular species of sn-1 saturated/sn-2 monounsaturated phosphatidylcholines. In parallel with calorimetric studies, the energy-minimized structures and steric energies of the diglyceride moieties of these monoenoic lipids were determined using a molecular mechanics approach. The combined calorimetric and computational studies led to the following results and conclusions. (i) When a single cis-carbon-carbon double bond (delta) is incorporated into a saturated diacylphosphatidylcholine molecule at any position within the central segment of the long sn-2 acyl chain, the resulting monoenoic lipid molecules will, in excess water, exhibit reduced phase transition temperature (Tm) and transition enthalpy (delta H) as they undergo the gel to liquid-crystalline phase transition. The Tm and delta H-lowering effects of the delta bond can be attributed to a decrease in the chain length of the sn-2 acyl chain, a change in the chain length difference between the sn-1 and sn-2 acyl chains, and a local perturbation of the chain-chain van der Waals interaction in the vicinity of the delta bond. (ii) For a series of positional isomers of 1-stearoyl-2-cis-octadecenoylphosphatidylcholine, C(18):C(18:1 delta n)PC, with a delta bond at different positions along the sn-2 acyl chain, the Tm value depends critically on the position of the delta bond. Specifically, the Tm value is minimal as the delta bond is located at the geometric center of the linear segment of the sn-2 acyl chain, and the Tm value is progressively increased as the delta bond migrates toward either end of the sn-2 acyl chain. (iii) The various monoenoic phosphatidylcholines under study can be divided into two groups. The Tm values of most lipids in each group can be correlated in an identical manner with their structural parameters, yielding a common Tm-structure relationship.