1,2-oxazine linker as a thermal trigger for self-immolative polymers

We have demonstrated the site-specific thermal activation of self-immolative polymers (SIPs) using a bicyclic oxazine as a temperature-sensitive triggering moiety. The oxazine-based trigger was installed at the junction of a SIP-poly(N,N-dimethylacrylamide) (PDMA) diblock copolymer via oxidation of hydroxyurea end groups on the SIP and in situ [4 + 2] cycloaddition with cyclopentadiene-functionalized PDMA. The trigger undergoes a thermally-driven cycloreversion which ultimately leads to initiation of the depolymerization process. The temperature dependence of activation and depolymerization were investigated, along with the mechanism of activation. The relative rates of depolymerization at different temperatures suggested to us that the thermal trigger design may be a good candidate for on-demand activation of SIPs with minimal background triggering. (C) 2014 Elsevier Ltd. All rights reserved.