Paper: Proton-Coupled Electron Transfer from Tryptophan: A concerted Mechanism with Water as Proton Acceptor
Authors: Ming-Tian Zhang and Leif Hmmarstrӧm
Journal: Journal of the American Chemical Society
PCET (Proton-Coupled Electron Transfer) refers to the transfer of electron thermodynamically coupled to that of proton. The transfer of the electron is in a sense limited by transfer of the 1000-times heavier proton particle; however coupling proton transfer with electron transfer allows for a thermodynamically and kinetically favored pathway. As shown in the graph below, when an electron and proton transfer in separate steps the process involves a high energy intermediate and the coupled pathway can be an alternative. PCET is being hotly debated.
The below diagram represents only one category of PCET – the electron and proton are donated by the same species (X) and accepted by the same species(Y). There are many different types of quantum mechanical tunneling of proton and electron transfer. Biological systems such as Photosystem II and Ribonucleotide Reductases utilize amino acid radicals to fulfill their chemistry.
The important amino acids radicals such as tryptophan and tyrosine need to be studied with consideration of pH. If the pKa of the amino acid (X-H) is lower than the pH, then amino acid will be deprotonated. The deprotonated (X-)amino acid only has to transfer an electron without worrying about a proton (pathway 2). But if pH is very low so that X-H is protonated then whether the electron transfer would occur first depends on the pKa of X-H+ – deprotonation may occur (pathway 1). The most difficult region is where the pH ranges between the two cases.
In the paper, authors claim the one electron and one proton transfer can happen via PCET using water as proton acceptor where driving force and pKa prefer this pathway. Tryptophan residue (hydrogen on an indole nitrogen) has a very high pKa that it is unlikely to be deprotonated while the pKa of Tryptophan radical cation (Trp● H+ – the product after one electron transfer) is 4.7. It is still higher than H3O+ (-1.5) but this means that after ET, PT can occur to yield the final species.
Next we should ask is ETPT (electron transfer followed by proton transfer) always the case?
Figure 1. Sets of Ru complex with modified tryptophan studied. (varying substituents influence pKa and driving force)
The authors tried the four different cases above, where Ru(Bpy)32+ serves as a photooxidant – upon photoexcitation and subsequent quench by a flash quencher, Ru(III) is generated. Ru(III) can takes an electron away from tryptophan, serving as an oxidant. The substituent modification on bipy can vary the Ru(III)/Ru(II) potential while modification on tryptophan can change pKa and oxidation potential (Trp● H+/TrpH).
The authors measured the rate of radical decay as a function of pH. The rate of radical decay is related to the driving force of the entire reaction (Marcus theory can explain this). Interestingly, the variation of pKa and driving force created totally different pathways. This means, as authors claim, proton and electron transfer can happen in concerted (coupled manner). RuTrp(Br)H and RuTrpH becomes pH independent as they pass the pKa and become deprotonated. After deprotonation, ET which does not depend on pH would determine the rate. But for Me4RuTrp(Br)H and Me4RuTrpH, they don’t show the pH independence which RuTrp(Br)H and RuTrpH had at a pH lower than their pKas. Neither the ETPT nor PTET model can explain the data as the authors claim considering also the KIE(kinetic isotope effect). It seems CEP is the only alternative.
Figure 2: The rate of intramolecular oxidation of Tryptophan—Ru complex dependence on pH
In summary, for RuTrp(Br)H and RuTrpH, the ETPT model fits. But for Me4RuTrp(Br)H and Me4RuTrpH, CEP mechanism explains the experimental data.
The result calls the necessity of incorporating the role of water as proton acceptor in PCET mechanism. Further study on the PCET mechanism would deconvolute the complex radical chemistry biological molecules perform.