Effect of Microenvironment on the Geometrical Structure of d(A) d(T) and d(G) d(C) DNA Mini-Helixes and the Dickerson Dodecamer: A Density Functional Theory Study.

We report a comprehensive quantum-chemical study on d(A)·d(T) and d(G)·d(C) DNA mini-helixes and the Dickerson dodecamer d[CGCGAATTCGCG]. The research was performed to model the evolution of the spatial structure of d(A)·d(T) and d(G) d(C) DNA mini-helixes all the way from vacuum to water bulk. The influence of external factors such as the presence of counterions and the extent of hydration was included.

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

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.

Experimental and computational study of membrane affinity for selected energetic compounds.

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.

QSAR analysis of the toxicity of nitroaromatics in Tetrahymena pyriformis: structural factors and possible modes of action.

The Hierarchical Technology for Quantitative Structure-Activity Relationships (HiT QSAR) was applied to 95 diverse nitroaromatic compounds (including some widely known explosives) tested for their toxicity (50% inhibition growth concentration, IGC₅₀) against the ciliate Tetrahymena pyriformis. The dataset was divided into subsets according to putative mechanisms of toxicity. The Classification and Regression Trees (CART) approach implemented within HiT QSAR has been used for prediction of mechanism of toxicity for new compounds.