The role of residual Cu(ii) from click-chemistry in the catalyzed hydrolysis of Boltorn polyester-based hydrogels

Abstract

In recent times the Cu(I)-catalyzed click reaction between azides and alkynes has been extensively utilized in the preparation of polymers proposed for the use in biomedical applications. There is a potential for some Cu residues to remain in the polymers, and there has been discussion about whether this renders the polymers unsuitable for medical applications. It is well known that the presence of Cu(II) complexed to ester groups can accelerate their hydrolysis. The question then arises as to whether residual Cu(II) from the click reaction can catalyze the hydrolysis of polyesters. In this work the role of residual Cu(II) in the hydrolysis of copolymer hydrogels containing ester groups is elucidated. The copper(I)-catalyzed “click” reaction was used to synthesize a hyperbranched Boltorn-based polyester macromer which was then used in the preparation of a series of copolymer hydrogels formed with PEG diacrylate. Trace amounts of Cu(II) residues were found by AAS and EPR to remain in the hydrogels, even after extensive washing with EDTA solutions. The effect of these residues on the hydrolytic degradation of the hydrogels has been investigated and the presence of complexed Cu(II) was found to accelerate the hydrolysis of the hydrogels and to contribute also to the formation of pits in the pore walls of the hydrogels at intermediate degradation times.