Three novel aqueous soluble fulgimides, trifluoromethyl carboxylic acid indolylfulgimide 4, dicarboxylic acid indolylfulgimide 5, and carboxylic acid indolylfulgimide 6, were synthesized. Both 4 and 5 can switch back and forth between open and closed forms upon illumination with specific wavelengths of light, whereas 6 can only switch from the closed form to the open form. In sodium phosphate buffer (pH 7.4) at 37 degrees C, an unusual hydrolysis of the trifluoromethyl group of the closed form of 4 resulted in 5, which has an additional carboxylic acid group. The closed form of 5 was further decarboxylated to generate 6, which was not photochromic. In buffer, the open form of 4 degraded 20% after 10 days, while the closed form of 4 was converted to 5 rapidly. In buffer, both forms of 5 degraded less than 20% after 21 days at 37 degrees C, and 5 underwent 670 photochemical cycles before degrading by 20%. It is the most robust fulgimide yet reported in aqueous solution.