Hybrid Bilayer Membrane As a Versatile Electrochemical Platform to Modulate Transport Kinetics of Small Molecules Across a Lipid Monolayer

We report our effort to gate molecular transport through lipids. To probe the kinetics of small molecule delivery in and out of a lipid layer, we monitored the electrochemical response of a redox-active moiety covalently attached to a self-assembled monolayer (SAM) on gold. We prepared the first synthetic dicopper electrocatalyst (CuBTT) on a SAM/Au system for the oxygen reduction reaction (ORR) through rational design based on an aminotriazole derivative discovered previously by our group. The kinetically sluggish ORR proceeds via multiple proton-coupled electron transfer (PCET) steps. By appending a monolayer of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) on top of a CuBTT-SAM to construct a hybrid bilayer membrane (HBM, Figure 1), we suppressed the ORR activity of CuBTT. This inhibition in ORR activity is due to the hydrophobic lipid interior which impedes transmembrane diffusion of the hydrophilic positively-charged protons.

In nature, membrane-bound proton carriers deliver protons across lipid bilayers via flip-flop diffusion. Inspired by biological systems, we recovered the ORR activity of CuBTT by incorporating an alkyl phosphate, mono-N-dodecyl phosphate (MDP), in the lipid monolayer of the HBM to facilitate proton transfer to CuBTT. We further discovered that this assisted proton transport behavior can be turned on and off by switching the pH of the bulk solution. This observation allowed us to build a pH-sensitive switch that modulates proton flux to a HBM-embedded ORR electrocatalyst.(1) We believe this HBM platform not only can provide valuable mechanistic insight into PCET reactions, but also lay the foundation for advanced bio-compatible electronics and nanocomputers.

The HBM electrochemical platform allows for the precise and independent control of both the thermodynamics and kinetics of proton transfer to a molecular catalyst. We are in the process of understanding the underlying mechanism of the assisted proton transfer process and in search of a quantitative structure-activity relationship between different proton carriers. Apart from studying related HBM platforms with different lipids and proton carriers, embedding redox and pH markers inside a HBM will provide valuable information about the internal environment of the system. We are also interested in controlling the kinetics of other small molecules through the lipid layer, which offers a unique electrochemical platform for drug screening processes.

References

1.         C. J. Barile, E. C. M. Tse, Y. Li, T. B. Sobyra, S. C. Zimmerman, A. Hosseini and A. A. Gewirth, Nat. Mater., 13, 619 (2014).