Novel computational tools based on bioinformatic and chemoinformatic data to complement zebrafish embryo teratogenicity test

Abstract

The mole fraction solubility of buprofezin in aqueous co-solvent mixtures of N,N-dimethylformamide (DMF,1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and acetonitrile (1) + water (2) over the temperature range from (273.15 to 318.15) K was reported. At the same composition of DMF, ethanol, isopropanol or acetonitrile and temperature, the buprofezin solubility was highest in DMF (1) + water (2) mixtures. By using the Jouyban-Acree model, the buprofezin solubility was correlated obtaining RAD lower than 5.86% and RMSD lower than 15.60 × 10−4. Quantitative values for local mole fraction of DMF (ethanol, isopropanol or acetonitrile) and water nearby the buprofezin were calculated through the Inverse Kirkwood–Buff integrals method applied to the solubility. The values of preferential solvation parameters (δx1,3) were negative in water-rich mixtures but positive in co-solvent compositions from 0.19, 0.20 (0.25) or 0.25 to 1 in mole fraction of DMF, isopropanol, ethanol or acetonitrile, respectively. It was conjecturable that in water-rich mixtures, the hydrophobic hydration around the nonpolar methyl groups and aromatic ring group of buprofezin played a relevant important role in the solvation. The preference of buprofezin in water-rich mixtures could be explained in terms of the higher basic behaviour of buprofezin molecules interacting with the proton-donor functional groups of the water. In addition, solute-solvent and solvent-solvent interactions of buprofezin in the DMF (ethanol, isopropanol or acetonitrile) + water mixtures were investigated from the solubility data by using the linear solvation energy relationships concept. The variation of buprofezin solubility depended mainly upon the hydrogen bond acidity and cavity term for ethanol (isopropanol) + water mixtures, and the cavity term for DMF (acetonitrile) + water mixtures.