Modification of hemoglobin with analogs of aspirin

A variety of acyl esters of salicyclic acid and 3,5-dibromosalicylic acid have been prepared and examined for their ability to place the acyl group on hemoglobin. In general, short chain acyl groups (C2 and C3) are more reactive than longer chains (C4 to C10), but longer chains may be more effective with intact red cells because of their enhanced ability to permeate the erythrocyte membrane. The brominated salicyl esters also exhibit enhanced permeation of the membrane, as well as increased activity due to activation at the acyl site. Bis(salicyl) esters, nonbrominated and brominated, are more reactive than corresponding monoesters, and those from C4 dicarboxylic acids connect beta subunits by covalent bridges. These double-headed aspirins have the attractive features of being bound selectively by hemoglobin and of forming a covalent cross-link that may influence the conformation of the tetramer.