Prediction of Solubility Properties from Transfer Energies for Acidic Phosphorus-Containing Rare-Earth Extractants Using Implicit Solvation Model

<p>The differences of thermodynamics energies from the pure phase to a solution were used to predict the solubility properties of acidic phosphorus–containing rare-earth extractants. Four solvents, namely tributylphosphate, <i>n</i>-dodecane, toluene, and <i>n</i>-octanol were used. The thermodynamic cycle of the implicit solvation model and the structure model with short carbon chains were used. The relationship obtained by simulation of the solubility properties and extractant structures agreed qualitatively with reported experimental results. These results provide guidance for the design of new efficient extractants.</p

Metabolism and Bioactivation of Fluorochloridone, a Novel Selective Herbicide, in Vivo and in Vitro

Fluorochloridone (FLC) is a herbicide used worldwide that is thought to be safe. However, due to its potential genotoxicity, cytotoxicity, and even systematic toxicity, there are increasing concerns about human exposure to this compound. Thus, the metabolism and bioactivation of FLC was investigated. After oral administration to mice, 27 metabolites were identified by ultrahigh performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry and with further structural identification by nuclear magnetic resonance spectroscopy. Hydroxylation and oxidative dechlorination were the major phase I pathways, while glutathione (GSH) and <i>N</i>-acetylcysteine conjugations were two major phase II pathways, indicating the formation of a reactive intermediate. In vitro microsomal and cytosolic studies revealed that a GSH conjugate (M13) was the predominant metabolite of FLC formed through a nucleophilic S_N2 substitution of 3-Cl by GSH; this pathway is NADPH independent and accelerated by glutathione <i>S</i>-transferase (GST). Further, a kinetic study showed that M13 formation in both human liver microsomes and cytosols obeyed typical Michaelis–Menten kinetics. The maximum clearance (<i>V</i>_max/<i>K</i>_m) of GSH conjugation in human liver microsomes was approximately 5.5-fold higher than human liver cytosol, thus implying that microsomal GST was mainly responsible for M13 formation. These findings are important for understanding the potential hazard of human exposure to FLC