Neighbouring group participation hindered by force as a molecular design for covalent catch bonds

Abstract

Abstract Catch bonds—dynamic molecular interactions whose lifetimes increase under mechanical load—are central to biological mechanotransduction but remain challenging to replicate synthetically. Here, we report a covalent catch-bonding mechanism in a low-molecular-weight motif based on hydroxyethyl phosphate (HEP) triesters. Our design uses force-mediated inhibition of a neighboring group participation (NGP) pathway: mechanical tension suppresses intramolecular assistance, thereby increasing the reaction barrier and prolonging bond lifetimes. Density Functional Theory calculations confirm that tensile force hinders the geometric contraction required for NGP, providing a mechanistic basis for catch-bond behaviour. Single-molecule force spectroscopy reveals that HEP triester lifetimes increase over threefold at 400 pN. This work establishes a molecular mechanism for engineering covalent catch bonds, offering opportunities to design force-responsive polymer networks. By translating a biological concept into a synthetic framework, our findings open new avenues for adaptive materials and mechanochemical sensing.