Experimental and computational study of membrane affinity for selected energetic compounds

Abstract

The affinity of various energetic compounds for a biological membrane was investigated using experimental and computational techniques. We measured octanol-water (log(Kow)) and liposome-water (log(Klipw)) partition coefficients for the following chemicals: trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2,4-dinitroanisole (DNAN), 2methoxy-5-nitrophenol (2M5NP), 2,4,6-trinitrobenzene (TNB), and 2,4-dinitrophenol (2,4-DNP). In order to determine log(Klipw) experimentally, we used artificial solid supported lipid liposomes produced under trade mark TRANSIL. Log(Kow) value were predicted with several program packages including the COSMOthermX software. Log(Klipw) were estimated with COSMOmic as implemented in the COSMOthermX program package. In order to verify accuracy of our experimentally obtained results, we performed basic statistical analysis of data taken from the literature. We concluded that compounds considered in this study possess a moderate ability to penetrate into membranes. Comparison of both coefficients has shown that in general, the log(Kow) values are slightly smaller than log(Klipw).

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

“…Generally, the partition coefficient between water and lipid membranes is also chosen to describe the membrane affinity of xenobiotics. 16 Then, this parameter can provide an important theoretical reference to understand the differences of the bioaccumulation of TNT and its metabolites, especially in membranes.…”

“…14 Covalent adducts are attributed mainly to the formation of nitroso and/or hydroxylamino metabolites in the process of two-electron reduction, which may modify the structures of proteins and DNA or induce methemoglobin. 15 However, to the best of our knowledge, the study on the interaction of TNT and its metabolites with lipid membranes is rare, in spite of its vital importance, to understand their adsorption, distribution, and excretion processes in organisms, except for two studies of Golius et al 16,17 They calculated mainly the partition coefficients for several explosives (such as TNT, dinitrotoluene, dinitroanisole, and so on). The detailed information about the interactions between TNT (including its metabolites) and lipid membranes has not been provided yet.…”

Collective absorption of 2,4,6-trinitrotoluene into lipid membranes and its effects on bilayer properties. A computational study

“…16 The results of log K LW demonstrate that the presence of TNT molecules in the headtail interface of membrane would increase the value of log K LW from 1.61 to 2.11, and the higher concentration (40 TNT) resulting in the formation of a membrane-spanning aggregate would lead to the further increase of log K LW to 3.19. Experimentally, Golius et al 48 found that the liposome-water partition coefficient of TNT was 2.18, which was slightly larger than the calculated result from the TNT-0 system, and very close to the one obtained from the TNT-10 system. It indicates that the concentration of solutes may be an important factor in evaluating the partition coefficient by MD simulations.…”