Uncoupling properties of a chlorophenol series on Acer cell suspensions: a QSAR study

A series of 22 chlorinated phenols was investigated for their uncoupling effect on Acer cell suspensions. All the studied molecules were able to enter the cell and had instantaneous uncoupling properties: pentachlorophenol was the best uncoupler of the series (the concentration required to uncouple by 50% was 5 microM), being 200-fold more effective than 3-Cl or 2-Cl phenol, which were the molecules having the lowest activity. The QSAR (quantitative structure-activity relationship) study gave good equations for the uncoupling activity with the steric and electronic parameters taken together. The electronic parameter sigma was always present with a positive sign, whereas A, the angular parameter, was always negative. The general steric parameters (sigma D, 1 chi v, MR) represented the third component of the equations and each of them played practically an equivalent role. Equations of quality (r greater than 0.9), which were statistically significant, could be obtained after four compounds in F (2,5-diCl phenol; 2,4,5-triCl phenol; 2,4-diCl 6-NO2 phenol; and 2-Cl 4,6-diNO2 phenol) had been excluded and when quadratic terms were not present. The best equation (r = 0.940) was obtained with sigma D, A, and sigma 1. The comparison of the significant equations with those previously established with isolated mitochondria led us to suppose that there were no selective limiting steps during the transfer of the studied compounds from the reaction medium to mitochondria inside the cells. The major difference between the uncoupling results obtained with isolated mitochondria and with cells was that the concentrations needed to uncouple by 50% were always higher in cells.