Strategies for the Mechanically Triggered Release of Small Molecules

The development of force-responsive molecules called mechanophores is a central component of the field of polymer mechanochemistry. Mechanophores enable the design and fabrication of polymers for a variety of applications ranging from sensing to self-healing materials. Nevertheless, an insufficient understanding of structure–activity relationships limits experimental development, and thus computation is necessary to guide structural design. Herein, we use the constrained geometries simulate external force (CoGEF) method to evaluate a library of covalent mechanophores using density functional theory (DFT). We use these results to identify key parameters that accurately predict experimentally determined mechanochemical reactivity. Polymers that release small molecules upon external stimulation are promising for a wide range of applications, including sensing, catalysis, and drug delivery. Mechanophores are uniquely suited to enable molecular release with excellent selectivity and control. We have designed a general platform for mechanically gated small molecule release that leverages a latent 2-furylcarbinol species masked as a mechanically labile Diels–Alder adduct. Here, we describe the computationally guided design of metastable 2-furylcarbinol derivatives through the prediction of activation energy values and construction of structure–activity relationships. These results enable a molecular release platform suitable for a wide scope of cargo molecules across a broad range of chemical environments.