Catalytic Design through Computational Modeling: Exploring the Electrochemical Oxidation of Glycerol By Nitroxyl Radical

Recently there has been an increased interest in the development of small molecule electrooxidation catalysts such as (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), for use in the anodic compartment of a biofuel cell. Some TEMPO derivatives are capable of electrochemically oxidizing short chain alcohols and various sugars to the corresponding aldehydes and carboxylic acids under physiological aqueous conditions. However, building libraries of such a catalyst is difficult due to the limited number of commercially available TEMPO derivatives and the lack of modular synthetic pathways to more complicated TEMPO structures. A promising alternative to the physical preparation of such libraries is the use of computational modeling to allow for in silico catalytic screening of a much wider range of TEMPO compounds.

We have developed a computational model based on simple geometry optimization and population analysis to probe the catalytic activity and oxidation potential of TEMPO-derived species. Redox potentials were calculated from the free energy cycle of TEMPO oxidation while the relative catalytic activity was modeled using multidimensional analysis involving the computed pK_as of various protonation states of the hydroxylamine form of TEMPO along with the corresponding redox potentials. We will also discuss how analysis of the atomic polar tensor (APT) charge of TEMPO can provide insight into the factors that affect its redox potential.