Optimizing the reduction potential of sulfonamides on PAMAM dendrimers

Abstract

p-Toluenesulfonamide serves as an important functional group to protect alkyl amines. However, the electrochemical deprotection of sulfonamides requires relatively high reduction potentials (-2.4V vs SCE) that would interfere with other functional groups. Previous investigations suggest that methods are available to decrease the reduction potential, but no systematic investigation has been conducted that evaluates the reduction potential as a function of aryl-substitution, mediator, or multi-arm grafting. Cyclic voltammetric studies of a library of bis-sulfonamides bearing different aryl substituents in DMF reveals that p-NO2 substituted bis-sulfonamide has the lowest reduction potential. Further investigations aimed at lowering the cathodic potential with polycyclic aromatic hydrocarbon mediators display negligible or no impact. This optimised condition was successfully applied to fully p-nitrobenzenesulfonyl protected generation zero and generation one polyamidoamine dendrimers (G0.0-PAMAM-Ns and G1.0-PAMAM-Ns), demonstrating successful amine protection and deprotection on dendrimers for the first time.