Development of New Bioorthogonal Reactions Based on Rational Computational Design
Final Report Abstract
We have investigated the possible mechanisms of the decomposition of tetrazines in biological conditions. Short benchmarking study was performed in order to establish the appropriate theoretical model for the calculations. Based on the available experimental data, we have identified the probable mechanistic pathways, which are responsible for the decay of the tetrazines in aqueous, protein-containing environs. We propose, that the decreased lifetime of the tetrazines in the presence of proteins, with respect to the stability in buffered water, is due to the reaction of the tetrazines with the thiol-derived radicals. Based on this model, new tetrazines with increased stability were designed. Synthesis, stability testing of these derivatives, and reactivity testing is going to be done during my reintegration period in Germany.
