Accelerated hydrolysis of boronic acid in a modified poly(amidoamine) dendrimer: identification of a factor leading to the production of an impurity in boronic acid containing poly(amidoamine) dendrimers

The preparation of boronic acid containing dendrimers is still a difficult task in dendrimer chemistry. In this investigation, an unanticipated hydrolysis product (4) was identified during the preparation of (G: 2)-PAMAM-dendri-(4-phenyl boronic acid) 14 (3) by acquiring its 1H NMR, 13C NMR, and UV-vis absorption spectra and IR spectra and comparing them with those of 4-hydroxylbenzoic acid (5). Furthermore, an Alizarin Red S staining analysis, ICP-MS, and B-11 NMR spectrum indicated the lack of boronic acid in 4. Finally, treatment of 3 with hydrogen peroxide gave a product that was determined to be identical to dendrimer 4. By analyzing the formation of 4 under various conditions, the presence of numerous primary amines in a PAMAM dendrimer did accelerate the hydrolysis of peripheral boronic acid. This investigation revealed an apparent intrinsic problem that needs to be overcome during the preparation of boronic acid containing dendrimers and related boronic acid containing macromolecules.