The
penetration of chemicals into biological membranes is a key factor in the determination of their
possible effects on organisms; this complex process involves mainly
the interaction between chemicals and membranes. Here, we reported
the interaction between a highly toxic class of explosives [2,4,6-trinitrotoluene
(TNT) and its metabolites] and lipid membranes using molecular dynamics
simulations. We calculated the permeability coefficient, transmembrane
time, and liposome–water partition coefficient by integrating
free-energy curves for all species. The results showed that TNT had
a lower transmembrane capacity than its metabolites. Based on the
liposome–water partition coefficient, we demonstrated that
the membrane affinity of TNT is larger than that of its diamino metabolites
but less than that of its monoamino metabolites. This result can qualitatively
explain the difference of bioconcentration factors in experiments.
The accumulation of TNT and metabolites in membranes can change the
membrane structure, such as the area per lipid, the thickness of lipid
bilayers, and the order of lipid tails and, further, the penetration
of water. All of these are closely related to the interactions (mainly
hydrogen bonds) of TNT and metabolites with lipid and water molecules.
This work has a certain significance for understanding the toxicity
of TNT and its metabolites.