Characterisation of polymeric surfactants that are glutathione transferase mimics

Abstract

Catalysts that can detoxify reactive organic chemicals (electrophiles) could be of potential beneficial use. Electrophilic compounds are common toxic agents that are conjugated to endogenous nucleophiles (i.e. glutathione) in an enzyme catalysed reaction (by glutathione transferases). Here, the properties of newly synthesised polymeric surfactant catalysts, which are glutathione transferase mimics, are described (which are not limited to the glutathione thiol donor). Reactions studied were nucleophilic aromatic substitution with 1-chloro-2,4-dinitrobenzene (CDNB) and thiolysis of p-nitrophenyl acetate. Polymeric quaternary ammonium salts synthesised starting from 2-(dimethyl-amino)ethylmethacrylate or 1,3-bis(dimethylamino)isopropylmethacrylate were used as surfactants. Five polysoaps were studied possessing different charge density and different density of hydrophobic chains. In comparison with cetyltrimethylammonium bromide, the polymeric surfactants were clearly more efficient catalysts (i.e. 4.9 vs. 150 (10 3 per M 2/s) with benzyl hydrosulfide and CDNB). Polymers with high charge and hydrophobic density were most efficient. With a given catalyst, increasing hydrophobicity of the thiol substrate parallels increasing reaction rates (e.g. 0.7–≥37 (10 3 per M 2/s) with CDNB). Concentration of the substrate in the micellar pseudophase together with solvent shielding is suggested as the underlying rate enhancement mechanism. Dead-end Meisenheimer complex stabilisation, where an extremely electrophilic compound (1,3,5-trinitrobenzene) reversibly interacts with glutathione is seen both with glutathione transferases and the polymeric surfactant catalysts. The degree of stabilisation follows catalytic efficiency and thus supports the above structure activity relationships. In conclusion, polymeric materials that can perform biological functions in detoxication are described, as well as their optimal properties.