Frank Westheimer

Early life and education Frank Henry Westheimer was born on January 15, 1912, to Henry F. Westheimer (1870–1960) and Carrie C (Burgunder) Westheimer (1887–1972) of Baltimore, Maryland.

He graduated from Dartmouth College in 1932. He went on to Harvard University, where he earned his masters in chemistry in 1933 and his doctorate in chemistry in 1935.

Westheimer came to Harvard hoping to do research with James Bryant Conant. When told that Conant would not take on new students, Westheimer outwaited him and was finally accepted as his last graduate student. Westheimer did some work on semicarbazone at Conant's suggestion.

"The notion that Conant essentially was saying, 'Well, that problem is all right, but good God, you can do better,' was very important to me. From then on, I tried to ask myself about problems, whether they were really worth the investment of time."

In 1935 and 1936, as a National Research Council Fellow, Westheimer worked with physical chemist Louis P. Hammett at Columbia University. Hammett was a founder of the field of physical organic chemistry.

Career Westheimer taught at the University of Chicago from 1936 to 1954, and at Harvard University from 1953 to 1983. Elaborations and fuller testing of their ideas have required forty years and the development of computers. He did research on nitric acid, discovering a new acidity function for nitration reactions. He hesitated to discuss his work on the triphenyl carbinol series with physical chemists because of the secrecy requirements of the project. Other researchers such as Christopher Ingold were first to publish in the area.

In 1943, Westheimer began publishing on the mechanisms of chromic acid oxidations, publishing a "masterly review" of the area in 1949. The phenomenon they reported was not named enantiospecificity until much later. In 2006, their 1953 paper (part I) received a Citation for Chemical Breakthrough Award from the Division of the History of Chemistry of the American Chemical Society.

Harvard University In 1953, soon after completing the work on alcohol dehydrogenase, Westheimer moved to Harvard University. He continued his interest in reaction mechanisms, isotopes and oxidation. In 1955, Westheimer published the first of many articles on the chemistry of phosphate esters and phosphorus derivatives.

In a 1961 article, Westheimer applied ideas from statistical mechanics to the effects of isotopic substitution on the reactivity of organic molecules. Transition state structure's dependence on the kinetic isotope effect is known as the Westheimer Effect. The standard nontunnelling approach to KIEs is developed from Westheimer

Westheimer introduced the idea of photoaffinity labeling of the active site of proteins. The identification of the "active sites" of an enzyme is difficult in cases where proteins have hydrocarbon-rich sites. In 1962, Westheimer and others demonstrated the synthesis of p-nitrophenyl diazoacetate and the subsequent acylation of chymotrypsin to form diazoacetylchymotrypsin, which was then photolyzed. The introduction of an aliphatic diazo group into a bifunctional reagent enabled it to react with the enzyme. The photolabel generated a reactive carbenoid species capable of inserting into hydrocarbon C-H bonds.

Westheimer also approached the reactions of phosphate transfer through mechanisms that involve five-coordinate intermediates. In 1968, Westheimer examined pseudorotation in phosphate ester chemistry He showed the significance of this route and the importance of stereochemical rearrangements of the intermediates. Westheimer developed a set of guidelines, based on experimental observations, also known as Westheimer's rules. They have been widely used for describing and predicting the products and stereochemistry of substitution reactions involving phosphorus.

Westheimer's 1987 paper in Science, "Why nature chose phosphates", discusses the importance of phosphates as signaling and building blocks for living organisms. Phosphates possess a value of pKa that allows them to be doubly ionized at physiological pH. The singly ionized form in the phosphodiester linkages of nucleic acids resists being hydrolyzed by water, but is not so stable that it won't undergo enzymatic hydrolysis. This work continues to challenge and inspire researchers studying biological chemistry and reactions in RNA, DNA, and ribozymes.

Awards and honors Westheimer became a member of the National Academy of Sciences in 1954, a member of the American Philosophical Society in 1976, and a foreign member of the Royal Society of London in 1983.

He chaired the National Academy of Sciences Committee for the Survey of Chemistry from 1964 to 1965. It identified biochemistry as a promising and overlooked area for medical and pharmaceutical research.

Westheimer served on the Council of the National Academy of Sciences for two terms, from 1973 to 1975 and 1976-1978, as well as being a Councillor of the American Philosophical Society (1981-1984), and Secretary of the American Academy of Arts and Sciences (1985-1990). the Robert A. Welch Foundation Award in 1982, the Golden Plate Award of the American Academy of Achievement in 1981, the U.S. National Medal of Science in 1986, the Priestley Medal in 1988; the Repligen Award for the Chemistry of Biological Processes in 1992; and the Nakanishi Prize in 1997.

Family Frank H. Westheimer was married in 1937 to Jeanne E. Friedman. They had two children, Ellen Westheimer and Ruth Susan Westheimer.