The effects of molecular weight and orientation on the membrane permeation and partitioning of polycyclic aromatic hydrocarbons: a computational study.

Membrane permeation and the partitioning of polycyclic aromatic hydrocarbons (PAHs) are crucial aspects affecting their carcinogenicity and mutagenicity. However, a clear understanding of these processes is still rare due to the difficulty of determining the details experimentally. Here, the interactions between PAHs and lipid bilayers were studied by molecular simulations, mainly to check the influence of molecular weight and orientation. The liposome-water partition coefficient (), transmembrane time (), and permeability coefficient () of the PAHs were calculated by integrating free energy profiles from umbrella sampling. For selected PAHs, the membrane adsorption is a spontaneous process. The preferred location is near the CC bond and the orientation is related to the molecular structure. The P values of all the PAHs are basically the same order of magnitude, which means that the molecular weight contributes little to the process. As for and , they show obvious increases with different molecular weights. Unconstrained simulations showed that a flat orientation on the membrane surface would prevent PAHs from being transported through the membrane. Highly hydrophobic driving forces are not always good for the absorption of PAHs, especially the formation of aggregates. In addition, the orientations and energetic barriers of PAHs near the midplane of the lipid bilayer explain the different transitions of high- and low-weight PAHs. This work provides molecular level details relating to the interactions of PAHs with lipid membranes, with significance for understanding the health effects of PAHs.