Frank Westheimer
Encyclopedia
Frank Henry Westheimer was an American
chemist
. He was the Morris Loeb Professor of Chemistry Emeritus at Harvard University
, and the Westheimer medal is named in his honour.
Born in Baltimore, he graduated from Dartmouth College
in 1932 and earned his doctorate in chemistry from Harvard in 1935. He was a member of President Lyndon Johnson's science advisory committee from 1967 to 1970. He also chaired the National Academy of Sciences
Committee for the Survey of Chemistry.
Westheimer started his doctoral research with James Bryant Conant
. When Conant became president of Harvard, he abandoned research and Westheimer finished his Ph.D. with E.P. Kohler. He continued as a postdoctoral fellow with physical chemist Louis P. Hammett at Columbia University
who developed the field of physical organic chemistry, an area that captured Westheimer's interest. His first academic appointment was as a lecturer in chemistry at the University of Chicago
. Here he was influenced by attending a course in physics by Kirkwood on electrostatics
. He applied these ideas to their effects on the properties of organic compounds. He was also influenced by the development of statistical mechanics
by physicists Joseph Mayer and Maria Goeppert-Mayer. He applied the principles of mechanics to the structure of organic molecules, a field that continues as "molecular mechanics
" and finds wide application. He also applied this knowledge to the effects of isotopic substitution on the reactivity of organic molecules. His work on the magnitude of kinetic isotope effects is still the basis of understanding in the field.
In the 1950s, Harvey Fisher, a student of his colleague at Chicago, Birgit Vennesland, was interested in the fate of isotopes in enzyme reactions. Vennesland had developed a project involving the fate of hydrogen atoms in alcohol dehydrogenase
. Vennesland and Fisher's results were puzzling in that a specific hydrogen in the pair at C1 in ethanol appeared to be uniquely reactive in the presence of the enzyme. Westheimer joined the project with Fisher and soon provided an explanation based on what is now known as enantiotopicity. He designed additional experiments that proved the conjecture and established isotope-based chirality
.
Soon after completing the work on alcohol dehydrogenase, Westheimer moved to Harvard where the chemistry department was seeking to broaden the scope of research interests to include biological aspects of organic chemistry. He continued his interest in reaction mechanisms, isotopes and oxidation with a landmark study of chromic acid
oxidations. He then reawakened his interests in phosphate reactions related to biochemical processes, an area related to his original doctoral work with Conant on fragmentation reactions. He proposed that ATP transfers phosphate through a reactive monomeric metaphosphate species. While this did not turn out to be the literal case, many enzymic reactions do proceed through transition states that have this as a significant component. He also approached the reactions of phosphate transfer through mechanisms that involve five-coordinate intermediates. He showed the significance of this route and the importance of stereochemical rearrangements of the intermediates. His work in this area set up the modern field and contributed to the understanding of reactions of RNA, DNA and ribozymes. At the same time, he developed the idea of photoaffinity labeling of the active site of proteins. The identification of an "active site" is difficult in cases where proteins have hydrocarbon-rich sites. The photolabel generates a reactive carbenoid species that inserts into hydrocarbon C-H bonds.
Westheimer's diverse interests led him through many paths in chemistry and politics. He was highly regarded, creative, and rigorous. His combined abilities in diverse areas made him an authoritative presence in any discussion. It is especially valuable to read proceedings of conferences (such as the Welch Foundation Conference on Bio-Organic Chemistry, 1971) in which transcripts of his comments are presented, to get a good idea of his approach. His demeanor of projecting a pessimistic outcome, while hoping for the best, earned him the sobriquet "Black Frank" among students. While he possessed a fine sense of humor, his ability to project a prediction of the worst possible outcome dominated how he was perceived. The attitude enabled him to question results with care and accept outcomes based on fact rather than hope. His approach to research involved attention to the key details that provide solutions to problems, while his papers remain engaging examples of clarity in scientific reporting.
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.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
chemist
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
. He was the Morris Loeb Professor of Chemistry Emeritus at Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...
, and the Westheimer medal is named in his honour.
Born in Baltimore, he graduated from Dartmouth College
Dartmouth College
Dartmouth College is a private, Ivy League university in Hanover, New Hampshire, United States. The institution comprises a liberal arts college, Dartmouth Medical School, Thayer School of Engineering, and the Tuck School of Business, as well as 19 graduate programs in the arts and sciences...
in 1932 and earned his doctorate in chemistry from Harvard in 1935. He was a member of President Lyndon Johnson's science advisory committee from 1967 to 1970. He also chaired the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
Committee for the Survey of Chemistry.
Westheimer started his doctoral research with James Bryant Conant
James Bryant Conant
James Bryant Conant was a chemist, educational administrator, and government official. As thePresident of Harvard University he reformed it as a research institution.-Biography :...
. When Conant became president of Harvard, he abandoned research and Westheimer finished his Ph.D. with E.P. Kohler. He continued as a postdoctoral fellow with physical chemist Louis P. Hammett at Columbia University
Columbia University
Columbia University in the City of New York is a private, Ivy League university in Manhattan, New York City. Columbia is the oldest institution of higher learning in the state of New York, the fifth oldest in the United States, and one of the country's nine Colonial Colleges founded before the...
who developed the field of physical organic chemistry, an area that captured Westheimer's interest. His first academic appointment was as a lecturer in chemistry at the University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...
. Here he was influenced by attending a course in physics by Kirkwood on electrostatics
Electrostatics
Electrostatics is the branch of physics that deals with the phenomena and properties of stationary or slow-moving electric charges....
. He applied these ideas to their effects on the properties of organic compounds. He was also influenced by the development of statistical mechanics
Statistical mechanics
Statistical mechanics or statistical thermodynamicsThe terms statistical mechanics and statistical thermodynamics are used interchangeably...
by physicists Joseph Mayer and Maria Goeppert-Mayer. He applied the principles of mechanics to the structure of organic molecules, a field that continues as "molecular mechanics
Molecular mechanics
Molecular mechanics uses Newtonian mechanics to model molecular systems. The potential energy of all systems in molecular mechanics is calculated using force fields...
" and finds wide application. He also applied this knowledge to the effects of isotopic substitution on the reactivity of organic molecules. His work on the magnitude of kinetic isotope effects is still the basis of understanding in the field.
In the 1950s, Harvey Fisher, a student of his colleague at Chicago, Birgit Vennesland, was interested in the fate of isotopes in enzyme reactions. Vennesland had developed a project involving the fate of hydrogen atoms in alcohol dehydrogenase
Alcohol dehydrogenase
Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide...
. Vennesland and Fisher's results were puzzling in that a specific hydrogen in the pair at C1 in ethanol appeared to be uniquely reactive in the presence of the enzyme. Westheimer joined the project with Fisher and soon provided an explanation based on what is now known as enantiotopicity. He designed additional experiments that proved the conjecture and established isotope-based chirality
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
.
Soon after completing the work on alcohol dehydrogenase, Westheimer moved to Harvard where the chemistry department was seeking to broaden the scope of research interests to include biological aspects of organic chemistry. He continued his interest in reaction mechanisms, isotopes and oxidation with a landmark study of chromic acid
Chromic acid
The term chromic acid is usually used for a mixture made by adding concentrated sulfuric acid to a dichromate, which may contain a variety of compounds, including solid chromium trioxide. This kind of chromic acid may be used as a cleaning mixture for glass. Chromic acid may also refer to the...
oxidations. He then reawakened his interests in phosphate reactions related to biochemical processes, an area related to his original doctoral work with Conant on fragmentation reactions. He proposed that ATP transfers phosphate through a reactive monomeric metaphosphate species. While this did not turn out to be the literal case, many enzymic reactions do proceed through transition states that have this as a significant component. He also approached the reactions of phosphate transfer through mechanisms that involve five-coordinate intermediates. He showed the significance of this route and the importance of stereochemical rearrangements of the intermediates. His work in this area set up the modern field and contributed to the understanding of reactions of RNA, DNA and ribozymes. At the same time, he developed the idea of photoaffinity labeling of the active site of proteins. The identification of an "active site" is difficult in cases where proteins have hydrocarbon-rich sites. The photolabel generates a reactive carbenoid species that inserts into hydrocarbon C-H bonds.
Westheimer's diverse interests led him through many paths in chemistry and politics. He was highly regarded, creative, and rigorous. His combined abilities in diverse areas made him an authoritative presence in any discussion. It is especially valuable to read proceedings of conferences (such as the Welch Foundation Conference on Bio-Organic Chemistry, 1971) in which transcripts of his comments are presented, to get a good idea of his approach. His demeanor of projecting a pessimistic outcome, while hoping for the best, earned him the sobriquet "Black Frank" among students. While he possessed a fine sense of humor, his ability to project a prediction of the worst possible outcome dominated how he was perceived. The attitude enabled him to question results with care and accept outcomes based on fact rather than hope. His approach to research involved attention to the key details that provide solutions to problems, while his papers remain engaging examples of clarity in scientific reporting.
Among his honors were the Priestley Medal
Priestley Medal
The Priestley Medal is the highest honor conferred by the American Chemical Society and is awarded for distinguished service in the field of chemistry. Established in 1922, the award is named after Joseph Priestley, the discoverer of oxygen who immigrated to the United States of America in 1794...
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.
External links
- Medal named in his honour
- Obituary at Chemical & Engineering News, April 23, 2007, Vol. 85, No. 17, p. 10.