How Does Electronic Activity Drive Chemical Reactions? Insights from the Reaction Electronic Flux for the Conversion of Dopamine into Norepinephrine

Hydrogen atom transfer (HAT) is a crucial step in the physiological conversion of dopamine into norepinephrine catalyzed by dopamine beta-monooxygenase. The way the reaction takes place is unclear, and a rational explanation on how the electronic activity drives the HAT seems to be necessary. In this work, we answer this question using the reaction electronic flux (REF), a DFT-based descriptor of electronic activity. Two reaction mechanisms will be analyzed using the REF's decomposition in polarization and electron transfer effects. Results show that both mechanisms proceed as follows: (1) polarization effects initiate the reactions producing structural distortions; (2) electron transfer processes take over near the transition states, triggering specific chemical events such as bond forming and breaking which are responsible to push the reactions toward the products; (3) after passing the transition state, polarization shows up again and drives the relaxation process toward the product. Similar polarization effects were observed in both reactions, but they present an opposite behavior of the electronic transfer flux disclosing the fact that electron transfer phenomena govern the reaction mechanisms.