Synergistic Effects of IMX-104 Components in Membrane Absorption: A Computational Study

New insensitive munitions such as IMX-104 formulations are being developed to improve the safety suffering from accidental stimulations. Experimental data indicated the synergistic toxicity of 2,4-dinitroanisole (DNAN) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in IMX-104, which increased the concern about its environmental and health threats. Indeed, little is known about the synergistic mechanism. Here, we investigated the membrane absorption of DNAN and RDX as the first step toward uncovering synergistic toxicity. The permeability coefficient, transmembrane time, and liposome–water partition coefficient were calculated by the umbrella sampling technique. The results show that component RDX in the IMX-104 formulation promotes the membrane absorption of another more toxic component DNAN, suggesting that the synergistic toxicity effect of IMX-104 may emerge from their membrane adsorption stage. In detail, the integrating free-energy curves show that DNAN, RDX, or their mixture in membranes would promote subsequent molecules passing through membranes. For the mixture of DNAN and RDX, RDX was absorbed by the membrane before DNAN. Postabsorbed DNAN tends to stay around RDX, which is due to the strong van der Waals (VDW) interaction between them. RDX stabilized under phospholipid headgroups limits the overflow of DNAN from the membrane, which results in 11% more absorption of DNAN by the membrane than in the case of the pure DNAN system.