The Contributions of Frank Westheimer to Biological Organic Chemistry

Monday, 22 April 2013 - 1:00pm - 2:00pm
University Library Lilly Auditorium UL 0130

Westheimer Lecture Series

Frank H. Westheimer (1912 - 2007) was Morris Loeb Professor of Chemistry Emeritus at Harvard University. After his Harvard Ph.D., he trained in Columbia with Louis P Hammett, the father of physical organic chemistry, and also studied physics and electrostatics plus statistical mechanics. Those skills equipped him in Chicago to study isotopes and their uses in organic chemistry and led him into a study of enzyme mechanisms.

A renewed interest in organophosphorus compounds and their reaction mechanisms led into problems related to phosphate processes in biochemistry, especially for adenosine triphosphate and ribonuclease. These called for new experimental techniques and their analysis demanded dramatically new concepts in reactivity, especially related to dynamic stereochemistry.

As an Emeritus Harvard Professor, he became committed to understanding the fundamental role of phosphorus in life and attempted to rationalize it in terms of the breadth of his knowledge of phosphates.  Frank Westheimer is regarded as the Father of Mechanistic Biological Chemistry by many of his successors and followers.

The Contributions of Frank Westheimer to Biological Organic Chemistry

I will explore Westheimer’s early work in Harvard on enzyme mechanisms, his quantitative analysis of the reactions of phosphate esters and mechanistic proposals thereby derived, and his engagement with the centrality of phosphorus in life, employing a blend of objective and subjective views. That will lead into a contemporary survey of the possibility of alternatives to phosphate and a critical view of arsenate as a surrogate for phosphate. I shall expose the central paradox of phosphate esters in life as the necessary characteristic of their truly universal deployment. Lastly, I shall survey the range of experimental and computational methods that have been deployed to bring studies on enzyme mechanisms of phosphoryl group transfer to their present advanced state and some of Sheffield University contributions to that knowledge. 


Lynn Gerrard
Department of Chemistry and Chemical Biology