A Redox-Mediated Negative Feedback Loop Based on Tetrazine-Thiol Exchange

The reduction pathways directly compete with the exchange process, as they deplete the source of thiols, thereby constituting a negative feedback mechanism at the molecular level. A microfluidic flow setup was developed to show that the chemical environment of the thiol-containing substratesparticularly when additional thiols or carboxylic acids are present as neighboring groupscould enhance the redox activity of tetrazines.

The method to create a negative feedback loop, integrating thiol-mediated exchange and redox reactivity within the same system, will be applicable to many other dynamic covalent reactions, paving the way to advance our synthetic toolbox for creating out-of-equilibrium reaction networks with ever-increasing complexity.