Many chemical and biological processes involve the transfer of both protons and electrons. The complex mechanistic details of these proton-coupled electron transfer (PCET) reactions require independent control of both electron and proton transfer. In this report, we make use of lipid-modified electrodes to modulate proton transport to a Cu-based catalyst that facilitates the O2 reduction reaction (ORR), a PCET process important in fuel cells and O2 reduction enzymes. By quantitatively controlling the kinetics of proton transport to the catalyst, we demonstrate that undesired side products such as H2O2 and O2(-) arise from a mismatch between proton and electron transfer rates. Whereas fast proton kinetics induce H2O2 formation and sluggish proton flux produces O2(-), proton transfer rates commensurate with O-O bond breaking rates ensure that only the desired H2O product forms. This fundamental insight aids in the development of a comprehensive framework for understanding the ORR and PCET processes in general.

In this study, we examine the mechanism of flip-flop diffusion of proton carriers across the lipid layer of a hybrid bilayer membrane (HBM). The HBM consists of a lipid monolayer appended on top of a self-assembled monolayer containing a Cu-based O2 reduction catalyst on a Au electrode. The flip-flop diffusion rates of the proton carriers dictate the kinetics of O2 reduction by the electrocatalyst. By varying both the tail lengths of the proton carriers and the lipids, we find the combinations of lengths that maximize the flip-flop diffusion rate. These experimental results combined with biophysical modeling studies allow us to propose a detailed mechanism for transmembrane flip-flop diffusion in HBM systems, which involves the bending of the alkyl tail of the proton carrier as the rate-determining step. Additional studies with an unbendable proton carrier further validate these mechanistic findings.

In this report, we use a hybrid bilayer membrane (HBM) as an electrochemical platform to study anion diffusion through a lipid monolayer. We first append lipid on a self-assembled monolayer (SAM) that contains a covalently bound Cu(I)/Cu(II) redox center. We then perform cyclic voltammetry (CV) using different anions in bulk solution and extract thermodynamic and kinetic information about anion transport. We analyze the results using linear combinations of fundamental chemical trends and determine that anion transport quantitatively correlates to polarity and basicity, a relationship we formalize as the lipid permeability parameter. In addition, we discuss how our findings can be interpreted according to the two leading mechanisms describing ion permeability through lipids. Our results demonstrate that anion transport in a HBM is best described by the solubility-diffusion mechanism, not the pore mechanism.

We use a hybrid bilayer membrane as an electrochemical platform to study anion diffusion through a lipid monolayer. We first append lipid on a self-assembled monolayer that contains a covalently-bound Cu(I)/Cu(II) redox center. We then perform cyclic voltammetry using different anions in bulk solution and extract thermodynamic and kinetic information about anion transport. The voltammetry is affected by the scan rate and the identity of the anions, but not the bulk anion concentration. An increase in scan rate causes the HBM system to switch from a diffusionless regime to one controlled by anion diffusion. In the latter regime, we test six anions that exhibit a wide range of cathodic peak potentials and cathodic-anodic peak separation values, which reflect the differences in the thermodynamics and kinetics of anion diffusion across the lipid membrane. We analyze the results using factor analysis and determine that anion transport quantitatively correlates to polarity and basicity, a relationship we formalize as the lipid permeability parameter. In addition, we discuss how our findings can be interpreted according to the two leading mechanisms describing ion permeability through lipids. Our results demonstrate that anion transport in a HBM is best described by the solubility-diffusion mechanism, not the pore mechanism. Figure 1