Direct Evidence of a Tryptophan Analogue Radical Formed in a Concerted Electron−Proton Transfer Reaction in Water

Proton-coupled electron transfer (PCET) is a fundamental reaction step of many chemical and biological processes. Well-defined biomimetic systems are promising tools for investigating the PCET mechanisms relevant to natural proteins. Of particular interest is the possibility to distinguish between stepwise and concerted transfer of the electron and proton, and how PCET is controlled by a proton acceptor such as water. Thus, many tyrosine and phenolic derivatives have been shown to undergo either stepwise or concerted PCET, where the latter process is defined by simultaneous tunneling of the electron and proton from the same transition state. For tryptophan instead, it is theoretically predicted that a concerted pathway can never compete with the stepwise electron-first mechanism (ETPT) when neat water is the primary proton acceptor. The argument is based on the radical pKa (∼4.5) that is much higher than that for water (pKa(H3O+) = 0), which thermodynamically disfavors a concerted proton transfer to H2O. ...