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

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.