Microelectrode arrays: a general strategy for using oxidation reactions to site selectively modify electrode surfaces.

Oxidation reactions are powerful tools for synthesis because they allow for the functionalization of molecules. Here, we present a general method for conducting these reactions on a microelectrode array in a site-selective fashion. The reactions are run as a competition between generation of a chemical oxidant at the electrodes in the array and reduction of the oxidant by a "confining agent" in the solution above the array. The "confining agent" does not need to be more reactive than the substrate fixed to the surface of the array. In many cases, the same substrate placed on the surface of the array can also be used in solution as the confining agent.

Microelectrode arrays and ceric ammonium nitrate: a simple strategy for developing new site-selective synthetic methods.

Conditions for a site-selective ceric ammonium nitrate oxidation have been developed. The reactions proceed nicely on both 1K- and 12K-microelectrode arrays. The procedure for developing the reactions was very simple and demonstrated that the same reagents used for a solution-phase reaction can be used for a related site-selective reaction on a microelectrode array.

Building addressable libraries: site-selective formation of an N-acyliminium ion intermediate.

A strategy for site-selectively generating reactive N-acyliminium ion intermediates on a microelectrode array has been developed. The route capitalizes on the use of an electroauxiliary for building a methoxylated amino acid substrate, and then the electrochemical generation and solution phase confinement of acid in order to form the N-acyliminium ion. Keys to this strategy were the stability of an N-alpha-methoxyalkyl amide to basic reaction conditions and the generality of the electrogenerated acid conditions for conducting microelectrode array reactions in a site-selective fashion.

Building functionalized peptidomimetics: use of electroauxiliaries for introducing N-acyliminium ions into peptides.

A series of silyl-substituted amino acids have been synthesized, inserted into peptides, and then employed as precursors for oxidatively generating reactive N-acyliminium ions. Both electrochemical and chemical oxidation procedures have been employed. N-Acyliminium ion generation in a solid-phase substrate as well as application to a small library of functionalized dipeptides has been demonstrated. Limitations in terms of how electron-rich the silyl groups can be as well as the compatibility of multiple silyl groups within a longer peptide are defined.