Chemistry: The architecture of electron transfers

Robert Flowers ’91G, the Danser Distinguished Faculty Chair in Chemistry and chair of chemistry, is a physical organic chemist with a wide range of interests from organometallic chemistry and protein renaturation to the development of new methods to study molecular recognition. He is most widely known for his work in the development and mechanistic study of reagents that form carbon-carbon bonds through single electron transfer, and his long-term interests have focused on using rare earths, predominantly samarium and cerium to initiate single electron reduction and oxidation, respectively, to form more complex molecules from readily available starting materials.

For Flowers, who received his Ph.D. from Lehigh, the construction of a complex molecule such as a drug is akin to designing a beautiful building.  

“I’m a mechanistic person. My passion in chemistry is understanding how things work,” he says. “When you are building a structure, you have to understand the basic components and how materials work together to maintain the stability and integrity of a building. As chemists, we have to understand reagents to develop complex molecules from very simple starting materials. If we really understand the mechanisms of these reagents and how they proceed through various steps of a reaction, we can make them more efficient, more environmentally sound, providing a greener approach to chemistry.”

Flowers and his research group investigate compounds that can be used to carry out electron transfer reactions to produce free radicals. Using the appropriate element, reagents can be produced that act as oxidants or reductants or where electrons transfer from a metal to an organic substrate (or vice versa). The researchers can examine how these bond-forming reactions are carried out. They are intrigued by free radicals because of their efficiency and ability to form a new carbon-carbon bond and another intermediate radical. When this occurs, the intermediate radical can be either oxidized to form a cation or reduced to form an anion. With this new reactive intermediate in place, a very different type of reaction can be carried out in the same reaction flask. 

“We view cations, radicals and anions as different oxidation states of carbon that can be interconverted through single electron transfer. Understanding this process gives synthetic chemists great control over reactions and provides the possibility of forming multiple bonds in a reaction sequence with one set of reagents” says Flowers. 

A great deal of Flowers’ work is in collaboration with synthetic chemists at other universities. He is particularly proud of his recent collaboration with Andreas Gansäuer, professor of chemistry at the Kekulé-Institute, University of Bonn in Germany. In most electron transfer processes, the reagent is used in a one-to-one ratio with the substrate so that for each electron transferred, one equivalent of reagent is used. The pair’s work has shown that it is possible to carry out electron transfer reactions catalytically. 

“We generate low valent titanium; it wants to be in the higher valent oxidation state because that’s where it’s more stable, so it transfers an electron to a substrate, undergoes a bond-forming reaction to generate an intermediate high-energy radical, which donates the electron back to the titanium, regenerating the active catalyst.”

The pair’s first paper, funded by the National Science Foundation, piqued the interest of the chemistry world. Using the information found in mechanistic studies, Flowers and his team have made the processes much more efficient, which is important in the development of new synthetic methods in the synthesis of pharmaceuticals and fine chemicals.

Photo by Christa Neu