Organic Electrochemistry and the Use of Microelectrode Arrays to Probe Small-Molecule Protein Interactions

Abstract

While electrochemical methods offer many unique opportunities for synthesis,1 the relationship does work in both directions. As part of an effort to develop microelectrode arrays as tools for monitoring small molecule – receptor interactions in real time, but have been working to show how synthetic chemistry can be used in order to build two-dimensional addressable surfaces on an array. The reactions themselves work nicely. But the overall strategy that has as its focus the construction of addressable molecular libraries that can be used to guide synthetic efforts brings with it not only synthetic challenges, but analytical ones as well. Many of the common direct detection methods used on microelectrode arrays and other electrochemical sensors are not compatible with a polymer coated electrode surface that has a lifetime consistent with using electrochemistry interactively with a synthetic endeavor. The surfaces required are thicker and more robust than typical SAMs that need to survive for months and be stable to a myriad of synthetic efforts.The result is a need to develop indirect methods for detecting binding events on the arrays. These methods are modeled after electrochemical impedance experiments and take advantage of redox mediators in the solution above the array. A current is established for the mediator at each electrode in the array and then that current used to monitor binding events between molecules on the surface of the electrodes and biological targets in solution. In the talk to be presented, a quick review of how the surface used, how those surfaces can be functionalized, and how molecules on an array can be characterized will be presented along with a guide for how to conduct the analytical experiments used, how those methods can be calibrated, the problems that can arise, and how those problems can be recognized and addressed.