Triggered degradation of poly(ester amide)s via cyclization of pendant functional groups of amino acid monomers

Abstract

Poly(ester amide)s (PEAs) are of interest for a diverse range of applications as their structures and properties can be readily tuned through the incorporation of a wide variety of monomers. In this work, the incorporation of the amino acids L-2,4-diaminobutyric acid (DAB) and homocysteine (HCY) was investigated with the aim of imparting stimuli-responsive degradation properties to PEAs. First, small molecule model compounds were prepared and studied to demonstrate that upon revealing the pendant γ-amine or γ-thiol of DAB and HCY esters, intramolecular cyclizations to 5-membered lactams and thiolactones respectively were much more rapid than background ester hydrolysis. Subsequently, monomers containing these DAB and HCY self-immolative spacers were prepared and incorporated into PEAs such that cleavage of protecting groups on the pendant moieties by stimuli including acid and the reducing agent DTT induced cyclization reactions that directly cleaved esters in the PEA backbone. The degradation of these polymers both in solution and in films was studied, demonstrating stimuli-triggered degradation was more rapid than background polymer degradation. In addition, to demonstrate that the approach could be readily extended to various stimuli, a photochemically responsive PEA was prepared by simply changing the protecting group on the pendant amine. This intramolecular cyclization strategy involving pendant functional groups should therefore be useful for the development of a wide range of PEAs and other polymers for which it is desirable to initiate degradation under specified conditions.