Small angle X-ray diffraction and differential scanning calorimetric studies on O-methyl-(−)-Δ 8-tetrahydrocannabinol and its 5′ iodinated derivative in membrane bilayers

Abstract

We have previously studied and compared the location of (−)- Δ 8-tetrahydrocannabinol (Δ 8-THC) with that of O-methyl-Δ 8-THC (Me-Δ 8-THC) in the membrane using partially hydrated dimyristoylphosphatidylcholine (DMPC) bilayers ((Mavromoustakos et al. (1990) Biophys. Acta 1024, 336–344; Yang et al. (1993) Life Sci. 53, 117–122). Δ 8-THC was found to be located near the membrane interface with its phenolic hydroxyl group anchored near the carbonyl groups of DMPC while the more lipophilic Me-Δ 8-THC is located deeper in the membrane bilayer. Parallel experiments using Me-Δ 8-THC and its 5′-iodo analog (5′-I-Me-Δ 8-THC allowed us to determine the topography of these two molecules in the bilayer. Our results from small angle X-ray diffraction and differential scanning calorimetry (DSC) combined with previous data on the orientation of Me-Δ 8-THC in model membranes, led us to the conclusion that these molecules intercalate between contiguous acyl chains in the lipophilic moiety of the membrane bilayer. The terminal iodo group in 5′-IMe-Δ 8-THC was found to reside in a region extending approx. ± 5 Å from the center of the bilayers. The location of Me-Δ 8-THC in the membranes as well as its orientation may explain its inability to effectively perturb the bilayer lipid chains.