MICROCALORIMETRIC STUDY OF THE INTERACTION OF 1-HEXANOL WITH DIMYRISTOYLPHOSPHATIDYLCHOLINE VESICLES

Partitioning of 1-hexanol into dimyristoylphosphatidylcholine (DMPC) s mall unilamellar vesicles (SUVs) has been evaluated by isothermal titr ation calorimetry (ITC) at various temperatures, the so-called solvent -null method has been used for this purpose. Complementary measurement s with differential scanning calorimetry on multilamellar vesicles (ML Vs) show that the pre-transition disappears and the main-transition te mperature is lowered by the addition of hexanol. Cooling scans show hy steresis which increases rapidly over 5 mM hexanol (molar ratio hexano l to lipid greater than or equal to 1.5). There are indications for th e presence of an interdigitated phase over this concentration in the s ystem, however, this has not been confirmed in this work. The correspo nding phenomena in SUVs is not as explicit but it is clear that the be haviour of the two types of vesicles is different. Implications of ana lysing data in terms of bulk concentrations of alcohol or ratios have been discussed. Light scattering does not indicate any significant cha nge in the size of the SUVs by the action of hexanol in the range of m olar ratio hexanol to DMPC 0.08-0.35. Molal and mole-fraction based pa rtition coefficients have been calculated from the solvent-null experi ments and compared with the literature values. Differences in the valu es have been attributed primarily to the type of vesicles used in the measurements since the SUVs present the lipids in a highly curved, def ect-dense, enthalpically higher stale as compared with the MLVs. The f ree energy, enthalpy and entropy of transfer of hexanol to lipid phase has been calculated, the entropy of transfer indicates a hydrophobic interaction driven process. These transfer parameters have been compar ed with dissolution and show that transfer from aqueous to the lipid p hase is favoured over transfer to a bulk hydrocarbon phase. A van't Ho ff analysis suggests that the interaction of hexanol to SUVs above 25 degrees C is co-operative while a simple binding interaction can be us ed to describe the interaction below this temperature. The solvent-nul l method has been found to be useful in the study of drug-membrane int eractions for non-saturable and non-specific interactions. (C) 1998 El sevier Science Ireland Ltd. All rights reserved.