| An understanding of the distribution of toxic compounds between biological and aqueous media is important to assessing their toxicology and risk to the environment. Of great interest to this problem is the validity of a critical environmental parameter: the octanol-water partition coefficient. Since the usefulness of this parameter has been questioned, we measured the octanol-water, lipid membrane-water, alkane-water, and biomembrane-water partition of nine halogenated phenols (2,4,6-trifluorophenol, pentafluorophenol, 2,4,6-trichlorophenol, 2,3,4,5-tetrachlorophenol, 2,3,4,6-tetrachlorophenol, pentachlorophenol, 2,4,6-tribromophenol, pentabromophenol, and 2,4,6-triiodophenol). We have addressed the role of halophenol charge, concentration, and size as well as ionic strength, membrane composition, and temperature in partition and free energy of transfer of halophenols.; We have confirmed that octanol-water and membrane-water partition coefficients of neutral halophenols are similar. In contrast, we found that membrane-water partition coefficients of ionized halophenols are 800 times greater than octanol-water partition coefficients.; Membrane-water partition exhibits saturation effects that we have modeled using Langmuir isotherms and the Grahame solution to the Gouy-Chapman model of an electrical double layer. The model supports the hypothesis that neutral halophenols saturate membranes via space-filling whereas ionized halophenols saturate membranes electrostatically.; The octanol-water partition coefficient of ionized 2,3,4,6-tetrachlorophenol (2,3,4,6-TeCP) is proportional to ionic strength. This finding is consistent with a cation-TeCP- ion-pair transfer mechanism that maintains electroneutrality of the phases. In contrast, an increase in ionic strength reduces membrane electrostatic saturation, consistent with counter-ion screening of membrane surface charge.; Membrane-water partition of 2,3,4,6-TeCP is nearly independent of lipid acyl length and carbonyl dipole moments. These findings support the hypothesis that the binding domain of halophenols is near the water-membrane interface.; From temperature dependence studies we found that an enthalpy of transfer of about 6--7 kcal/mol dominates both octanol-water and membrane-water partition of 2,3,4,6-TeCP, whereas the entropy of transfer of neutral 2,3,4,6-TeCP is insignificant. This finding contradicts the view that entropy dominates partition via the (classical) hydrophobic effect.; We have constructed models for the free energy of transfer based on halophenol size (surface area and volume), charge, and additional factors such as hydrogen bonding. The models indicate that charge and size are the largest contributing factors to the free energy of transfer. |
