Logic‐Gated Release of a Dual Payload from a β‐Lactam Mechanophore with a Rotaxane Actuator

Abstract

Abstract The force‐controlled release of functional molecules has attracted interest due to its potential use in drug delivery and self‐healing applications. Clever mechanochemical devices have been developed to that effect, but most are limited by the payload (type, number) they can deliver and their responsiveness to a single stimulus (force). However, the applications envisaged above require the precise delivery of a complex payload. In this context, a device able to release a diverse set of cargo molecules in response to a varied number of stimuli is desired. Here, we present a rotaxane‐based device that can release a dual payload in response to two different stimuli: force and water. The first payload is released mechanically, while the release of the second cargo requires both force and water in a way reminiscent of a logic AND gate. Our device is built around a β‐lactam mechanophore that is activated by a rotaxane actuator to release a ketene and reveal an imine that anchors the second cargo to the axle of the rotaxane; hydrolysis of the imine releases the second cargo molecule. The concept was demonstrated with the efficient release of two drugs, hymecromone and gemcitabine, both in solution and in bulk. We anticipate that our device should find applications in a variety of contexts where precise release is required.