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The Department of Chemistry and Chemical Biology in the School of Science at IUPUI will host the inaugural Westheimer Lecture Series the week of April 22.

Dr. G. Michael Blackburn of the University of Sheffield will present the first lecture at 1 p.m. on April 22 in the Lilly Auditorium, lower level of the University Library. Titled "The Contributions of Frank Westheimer to Biological Organic Chemistry," the first lecture will discuss the impact of American chemist Dr. Westheimer, former Harvard University proessor. Westheimer, who passed away in 2007, is one of the earliest researchers in the area of physical organic chemistry. Among his honors were the Priestley Medal in 1988, the U.S. National Medal of Science, the U.S. National Academy Award in Chemical Sciences and the Robert A. Welch Foundation Award.

The presentation 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. It will expose the central paradox of phosphate esters in life as the necessary characteristic of their truly universal deployment. Lastly, the presentation will 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. 

Frank H. Westheimer (1912 - 2007) was Morris Loeb Professor of Chemistry Emeritus at Harvard University. After earning his Ph.D. from Harvard, 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.

Blackburn will continue the series at 5 p.m. on April 25 with "Strain Catalysis: Westheimer and Beyond." The second lecture will be held in IT Room 90.

Westheimer was deeply committed to the concept of strain in the reactions of phosphate di- and tri-esters in relation to ribonuclease. This presentation will briefly outline his work on enzyme mechanisms and relate that to present-day studies to show the strength and limits of his work. From there, the presentation will involve a discussion of current opinions on the role of strain in enzyme catalysis and bring that to focus on work in Sheffield on a unique DNA repair enzyme, Uracil DNA Glycohydrolase, which many believe to be a prominent example of Strain Catalysis.

The final lecture, "Resolving Enzyme Mechanisms of Phosphate Transfer," will be at 1 p.m. on April 26 in Lecture Hall 105.

Enzyme catalyzed phosphoryl transfer mechanisms lie at the heart of life. This presentation will illustrate this using the biosynthesis of ATP involving a proton gradient across a membrane, by the polymerisation of RNA using ATP etc., and by energy production from metabolising glucose via 1,3-diphosphoglyceric acid. The strengths and also the shortcomings of analysis of protein structures by crystallography divorced from chemistry will be exemplified. Finally the centrality of studies on transition states to understand mechanisms will be applied to a unified theory of phosphoryl transfer in the isomerisation, hydrolysis, and alcoholysis of phosphate monoesters and anhydrides.

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