Octanol/Water Partition Coefficients as a Model System for Assessing Antidotes for Methylmercury(II) Poisoning, and for Studying Mercurials with Medicinal Applications

Abstract

l-Octanol/water partition coefficients, mercury concentration in octanol divided by mercury concentration in water, provide a simple but limited model system for aspects of the biological behavior of methylmercury and commonly used organomercury medicinal compounds. In an octanol/water system some widely studied antidotes for mercury poisoning at least partly displace the biological thiols L-cysteine and glutathione from binding to methylmercury at pH 6.9. Addition of the antidote meso-dimercaptosuccinic acid to methylmercury in the presence of glutathione results in formation of metallic mercury. For organomercury (RHg) derivatives of L-cysteine and glutathione, octanol/water partition coefficients fol1ow the order R = Ph > Et > Me. An exceptional1y high value for diphenylmercury, compared with PhHg derivatives of L-cysteine and glutathione, is consistent with reported results of the distribution of mercury compounds in rats. Ethylmercury(II) is partly displaced from thimerosal by L-cysteine and glutathione in the octanol/water system, indicating that the active form of thimerosal in vivo may involve binding of ethylmercury to biological ligands.