Shallow Distance Dependence for Proton-Coupled Tyrosine Oxidation in Oligoproline Peptides

We have explored the kinetic effect of increasing electron transfer (ET) distance in a biomimetic, proton-coupled electron-transfer (PCET) system. Biological ET often occurs simultaneously with proton transfer (PT) in order to avoid the high-energy, charged intermediates resulting from the stepwise transfer of protons and electrons. These concerted proton-electron-transfer (CPET) reactions are implicated in numerous biological ET pathways. In many cases, PT is coupled to long-range ET. While many studies have shown that the rate of ET is sensitive to the distance between the electron donor and acceptor, extensions to biological CPET reactions are sparse. The possibility of a unique ET distance dependence for CPET reactions deserves further exploration, as this could have implications for how we understand biological ET. We therefore explored the ET distance dependence for the CPET oxidation of tyrosine in a model system. We prepared a series of metallopeptides with a tyrosine separated from a Ru(bpy)32+ complex by an oligoproline bridge of increasing length. Rate constants for intramolecular tyrosine oxidation were measured using the flash-quench transient absorption technique in aqueous solutions. The rate constants for tyrosine oxidation decreased by 125-fold with three added proline residues between tyrosine and the oxidant. By comparison, related intramolecular ET rate constants in very similar constructs were reported to decrease by 4-5 orders of magnitude over the same number of prolines. The observed shallow distance dependence for tyrosine oxidation is proposed to originate in part from the requirement for stronger oxidants, leading to a smaller hole-transfer effective tunneling barrier height. The shallow distance dependence observed here and extensions to distance-dependent CPET reactions have potential implications for long-range charge transfers.