A Self-Immolative Spacer That Enables Tunable Controlled Release of Phenols under Neutral Conditions

A current challenge in the area of responsive materials is the design of reagents and polymers that provide controlled release of phenols in environments that are less polar than water. In these contexts, a molecular strategy that enables release of nearly any phenol with predictable and tunable rates and without complication from background hydrolysis would substantially increase the precision with which materials can be designed to respond to a particular signal. This Article addresses this problem at the fundamental level by describing the design, synthesis, and physical-organic characterization of two small molecule self-immolative spacers that are capable of releasing phenols in organic and mixed organic aqueous solutions. The rate of release from these small molecule model systems is predictable and tunable, such that nearly any type of phenol, regardless of pK(a) value, can be released in neutral solutions without complications from nonspecific background release due to hydrolysis. Furthermore, the release properties of the spacers can be predicted from bond length and conformation data (obtained from crystal structures). On the basis of these results, it should now be possible to incorporate these design elements into materials to enable precise response properties in environments that are not 100% aqueous.