Surface and interfacial properties of clomethiazole

The surface and interfacial properties of clomethiazole (CMZ) were investigated by means of several techniques. Drop-volume measurements showed that CMZ is surface active, with an estimated area per molecule at the aqueous/air surface of about 5D Angstrom(2). Surface balance experiments revealed that CMZ, originally in the subphase, mixes with spread monolayers of dimyristoylphophatidylcholine (DMPC) and dipalmitoylphophatidylcholine (DPPC). The interaction of CMZ with lipids was further illustrated using X-ray investigations of lamellar crystalline and liquid crystalline phases, where the repeat distance was shown to decrease with increasing amount of CMZ. The large decrease of the repeat distance was interpreted as an effect of the CMZ molecules residing in the lipid bilayer close to the interface. The hydrocarbon chains of the phospholipids fill the voids behind the small CMZ molecules, which in turn leads to a decrease in the bilayer thickness. This interpretation was also supported by the fact that large amounts (>10% w/w) of CMZ could be incorporated into the bicontinuous cubic phase of monoolein and water. Furthermore, CMZ decreases the chain melting temperatures of DMPC and DPPC as revealed by X-ray and DSC.