Molecular Simulation Studies on the Interactions of 2,4,6-Trinitrotoluene and Its Metabolites With Lipid Membranes

J Phys Chem B. 2019 Aug 1;123(30):6481-6491. doi: 10.1021/acs.jpcb.9b03033. Epub 2019 Jul 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Lipid Bilayers*
  • Membrane Lipids / chemistry*
  • Molecular Dynamics Simulation*
  • Trinitrotoluene / chemistry*
  • Water


  • Lipid Bilayers
  • Membrane Lipids
  • Water
  • Trinitrotoluene