Acute toxicity and n-octanol/water partition coefficients of substituted thiophenols: determination and QSAR analysis.

The acute toxicity (-log EC(50)) to Photobacterium phosphoreum and the n-octanol/water partition coefficient (log K(ow)) of 31 kinds of substituted thiophenols were determined at 298.15K. The -log EC(50) values of studied chemicals are between 4.26 and 5.89. Their log K(ow) values are between 1.34 and 4.02. Comparative molecular field (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models established were successful in predicting -log EC(50) and log K(ow) values of halogenated, methylic, amino and methoxy thiophenols. The size of molecule is the main factor influencing the properties. No correlation was found between the properties and their structural and thermodynamic descriptors from DFT calculation.

Environment-related properties of polyhydroxylated dibenzo-p-dioxins.

Polyhydroxylated dibenzo-p-dioxins (PHODDs) are important metabolic and synthetic products of polychlorinated dibenzo-p-dioxins (PCDDs). Two types of hydrogen bonds exist in PHODD molecules: one between a hydroxyl group (HO) and an oxygen atom of the ether bond, and the other between two ortho hydroxyls of a benzene ring. By fully optimized calculation with density functional theory (DFT), their bond energies were ascertained to be approximately 9-14 kJ/mol and 15-19 kJ/mol respectively by the comparison of standard Gibbs energy of formation (Δ(f)G(θ)) between different molecules, which was experimentally verified. The two types of hydrogen bonds affect the hydrophilicity and stability of the molecules. The torsional potential of hydroxyls and the orientation making the congener most stable were obtained. The octanol-water partition coefficients (logK(ow)s) were calculated based on the group contribution method, and the standard state entropy (S(θ)), standard enthalpy (Δ(f)H(θ)) of formation and Δ(f)G(θ) were obtained from the combination of DFT calculation and isodesmic reaction for the stable PHODD congeners. The number and position of hydroxyl substitution (N(PHOS)) were employed as descriptors to establish quantitative structure-property relationship (QSPR) models. Although the hydrophilicity of PHODDs increases with the number of hydroxyl groups, it is impaired by the intramolecular hydrogen bonds. The logK(ow)s of PHODDs are much smaller than those of PCDDs, and the variation trend with the number of substituents is different. In addition, the relative stability order of PHODD congeners was theoretically proposed, which is quite different from that of PCDDs. Considering the ionization in water, first-order ionization constants of PHODDs were calculated according to the results of SMD method of Self-Consistent Reaction Field Theory (SCRF), and they were influenced by the hydrogen bonds.

Studies of thermodynamic properties and relative stability of a series of polyfluorinated dibenzo-p-dioxins by density functional theory.

The thermodynamic properties of 75 polyfluorinated dibenzo-p-dioxins (PFDDs) in the ideal gas state at 298.15K and 1.013x10(5) Pa have been calculated at the B3LYP/6-311G* level using Gaussian 03 program. The isodesmic reactions were designed to calculate standard enthalpy of formation (DeltaH(f)(degrees)) and standard free energy of formation (DeltaG(f)(degrees)) of PFDDs congeners. The relations of these thermodynamic parameters with the number and position of fluorine atom substitution (N(PFS)) were discussed, and it was found that there exist high correlations between thermodynamic parameters (entropy (S(degrees)), DeltaH(f)(degrees) and DeltaG(f)(degrees)) and N(PFS). According to the relative magnitude of their DeltaG(f)(degrees), the relative stability order of PFDD congeners was theoretically proposed.