Diffusion of energetic compounds through biological membrane: Application of classical MD and COSMOmic approximations

Abstract

Computational studies of the potential biological impact of several energetic compounds were performed. The most commonly used explosives were considered in the present studies: trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2,4-dinitroanisole (DNAN), and 5-Nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO). The effect of such factors as ionic strength and presence of DMSO in the water solution on the structure of the membrane were considered using the POPC lipid bilayer as an example. Molecular dynamics (MD) simulations revealed that, even on a short-time scale, the influence of those additives is noticeable, and therefore those factors should always be taken into account. The MD and the COSMOmic approaches were used to elucidate the ability of the energetic compounds to penetrate the living cell. Calculated free energy profiles and partitioning coefficients revealed distributions of the compounds in the lipid bilayer as well as an overall ability to enter the cell. MD in this case provides a better representation of the free energy profile, while the COSMOmic approach works better to predict log(K) values. The effect of the functional group was observed for the profiles that were obtained using the MD method.

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

“…Previously, the octanol–water partition coefficient ( K OW ) was usually used to estimate the bioaccumulation because of the large availability of experimental data and simple measurement of K OW . However, since octanol cannot possess all complexities of a membrane structure, the K OW can characterize only the hydrophobicity and not the lipophilicity and further cannot describe the partition of chemicals between the membrane and water bulk accurately . A new liposome–water partition coefficient ( K LW ) was recently suggested to provide an accurate estimation for the membrane affinity of chemicals .…”

“…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.…”

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Antiseptic Picloxydine, Octenidine, Miramistin [470], Polyhexamethylene Biguanide [471] Insecticide Parathione [132], Fipronil [472], Dibutyl succinate [203] Former Drugs d-sotalol, cisapride [473], piracetam (status varies among countries) [474], ORG-12962 [199] Toxic xenobiotic Polybrominated-diphenyl-ethers [475], Bisphenol [476], Perfluoroalkyls [477], nitroaromatic explosives (TNT,2A, and 24DA) [478][479][480][481], 1,4-Dioxane [482], Benzo[a]pyrene [483] Nanomaterials Graphene [484][485][486][487], Carbon Dots [488], Phosphorene Oxide Nanosheets [489], Gold Nanoparticles [490][491][492], Titanium Dioxide Nanoparticles [493], Generic Nanoparticles (coarse grained) [494], Fullerene [495][496][497][498], Previous reviews [499] Polymers Poly(ethyleneoxide)-Poly-(propylene oxide) [500], polyethylenimine [501], Poloxamer [502,503], Pluronics [504,505], poly(ethyleneglycol)-desferrioxamine/ gallium [506], PEG functionalized with carbochydrates [507] and peptides…”

In Silico Prediction of the Thermodynamic Equilibrium of Solute Partition in Multiphase Complex Fluids: A Case Study of Oil–Water Microemulsion

“…As shown in Figure , most of the predicted values agreed well with the experimental data, having an accuracy within 0.5 in the logarithmic scale. The RMSE values are in line with previous studies on octanol–water, micellar systems, ,, and lipid systems. ,, Only the partition coefficient for p -nitroaniline was severely underpredicted, with an error considerably higher than 0.5 in the logarithmic scale. This is expected given the previously reported inability of COSMO-RS in predicting the properties for secondary and tertiary amines accurately.…”