Electrochemical Control of Rapid Bioorthogonal Tetrazine Ligations for Selective Functionalization of Microelectrodes

We demonstrate that bioorthogonal tetrazine ligations can be utilized to rapidly modify electrode surfaces, both with redox probes and enzymes. Furthermore, we show that the redox-active nature of 1,2,4,5-tetrazines can be exploited to gain electrochemical control over surface modification. To our knowledge this is the first demonstration of controlling a tetrazine ligation by changing the redox state of one of the reactants. We utilize the redox-switchable feature of tetrazine ligations for the site-selective functionalization of a 10 μm spaced interdigitated array of microelectrodes. In addition, we were able to achieve potential controlled ligation of the redox enzyme horseradish peroxidase to a macroscopic planar electrode. The rapid kinetics, bioorthogonal reactivity, and electrochemical control provided by tetrazine ligations should lead to numerous applications related to electrode functionalization.