Electrostatic effects in acylation of hemoglobin by aspirins.

Carboxylate substituents added to the salicylate ring increase the effectiveness of a variety of aspirins and diaspirins in acylating hemoglobin. Even more effective are a series of monoesters of dicarboxylate derivatives. Bis(5-carbomethoxysalicyl)fumarate and -succinate at 5 mM concentrations modify approximately 100% of the hemoglobin in solution and should alter the aggregation behavior of sickle hemoglobin.