Nucleophilic reactivity of terminal amino groups of PAMAM dendrimers

Abstract

Kinetics of aminolysis of 4-nitrophenyl acetate and 2,4-dinitrofluorobenzene by PAMAM dendrimers of four generations (G0, G1, G3 and G4) and a reference compound, N-acetyl ethylenediamine (AcEn), have been studied within a pH range of 6 to 11. Observed rate constants per one amino group for dendrimers are close to those for AcEn at high pH but in neutral solutions a 10-fold dendritic effect is observed with both substrates. For G0 and G1 the individual rate constants of dendrimer species in different protonation states were determined analyzing the pH-rate profiles by multiple linear regression using the species distribution diagrams obtained from the potentiometric titrations of dendrimers. Although the protonation of dendrimers induces a decrease in pK_a values of protonated amino groups, the rate constants remain unaffected by protonation and the dendritic effect can be attributed entirely to an increased relative fraction of neutral amino groups in partially protonated species due to a decrease in pK_a. A similar conclusion can be drawn for G3 and G4 dendrimers analyzing the dependencies of the observed rate constants based on potentiometrically determined concentrations of free amino groups at variable pH. The reaction with 2,4-dinitrofluorobenzene can be used for a quantification of dendrimers in a µM concentration range in DMSO solution.