Alkylation of amino acids and glutathione in water by o-quinone methide.: Reactivity and selectivity

o-Quinone methide (1)has been produced in water both thermally:and photochemically from (2- hydroxybenzyl)trimethylammonium iodide (2). Michael addition reactions of 1 to various amines, and sulfides, including amino acids and glutathione have been carried out, obtaining alkylated adducts (3-16) in fairly good to quantitative yields. The reaction rate and selectivity of 1 toward nitrogen and sulfur nucleophiles, in competition with the hydration reaction, have been investigated at different pH by laser flash photolysis technique. The observed reactivity: spans 7 orders of magnitude on passing from water (k(Nu) = 5.8 M-1 s(-1))to the most reactive :nucleophile (2.8 x 10(8) M-1 s(-1), 2-mercaptoethanol under alkaline conditions). These are the first direct reaction rate measurements of nucleophilic addition to the parent o-quinone methide (1). Competition experiments provided strong kinetic support to the involvement of free 1 as an intermediate in both thermal and photochemical reactions. Furthermore, several alkylation adducts regenerate 1 either by heating (9, 10, 13, and 14) or by irradiation(9, 11-13, 16). Such a thermal and photochemical reversibility of the alkylation process opens anew perspective for the use and application of such adducts as o-QM molecular carriers.