Multimechanophore Polymers for Mechanically Triggered Small Molecule Release with Ultrahigh Payload Capacity

Polymers that release small molecules in response to mechanical force are promising for a variety of applications including drug delivery, catalysis, and sensing. While a number of mechanophores have been developed for the release of covalently bound payloads, existing strategies are either limited in cargo scope or, in the case of more general mechanophore designs, are restricted to the release of one or two cargo molecules per polymer chain. Herein, we introduce a nonscissile mechanophore based on a masked 2-furylcarbinol derivative that enables the preparation of multimechanophore polymers with ultrahigh payload capacity. We demonstrate that polymers prepared via ring-opening metathesis polymerization are capable of releasing hundreds of small-molecule payloads per polymer chain upon ultrasound-induced mechanochemical activation. This nonscissile masked 2-furylcarbinol mechanophore overcomes a major challenge in cargo loading capacity associated with previous 2-furylcarbinol mechanophore designs, enabling applications that benefit from much higher concentrations of delivered cargo. ; © 2023 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0. ; Financial support from the Arnold and Mabel Beckman Foundation through a Beckman Young Investigator Award and the National Institute of General Medical Sciences of the National Institutes of Health (R35GM150988) is gratefully acknowledged. We thank the Center for Catalysis and Chemical Synthesis of the Beckman Institute at Caltech for access to equipment. We thank Dr. David VanderVelde for assistance with NMR spectroscopy, Dr. Michael K. Takase for assistance with X-ray crystallography, and Yunyan Sun for helpful discussions. L.A.O. thanks the Amgen Scholars Program at Caltech for financial support. P.L. thanks the Swiss National Science Foundation for an Early Postdoc Mobility Fellowship. M.J.R. gratefully acknowledges the Alfred P. Sloan Foundation for a Sloan Research Fellowship and the Camille and Henry Dreyfus ...