[11][12] He received the National Medal of Science in 1986 "For his series of extraordinary, original and penetrating investigations of the mechanisms of organic and enzymic reactions, which have played an unequaled role in the advancement of our knowledge of the ways in which chemical and biochemical processes proceed.
[14]: 17 Conant also suggested that Westheimer work during the summer with Alsoph Corwin at Johns Hopkins University.
Another of Kohler's students, Max Tishler, expanded upon some of Westheimer's research, leading to a co-publication on the derivation of a furanol.
[14]: 17–18 [16] In 1935 and 1936, as a National Research Council Fellow, Westheimer worked with physical chemist Louis P. Hammett at Columbia University.
[14]: 43–47 Kirkwood and Westheimer published four classical papers developing fundamental ideas in enzymology about the theory of the electrostatic influence of substituents on the dissociation constants of organic acids.
He hesitated to discuss his work on the triphenyl carbinol series with physical chemists because of the secrecy requirements of the project.
[14]: 69–71 Westheimer was also influenced by the development of statistical mechanics by physicists Joseph Edward Mayer and Maria Goeppert-Mayer, who moved to the University of Chicago in 1945.
Westheimer first consulted Mayer about applying techniques from statistical mechanics to the racemization of optically active biphenyls.
[1][11] In 1950, University of Chicago biochemist Birgit Vennesland approached Westheimer about a project she and her student Harvey Fisher were doing, involving isotopes in enzyme reactions.
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.
[25] Westheimer designed additional experiments that proved their initial conjecture and established the isotope-based chirality of enzymes.
This work was essential to understanding topicity, the enantiotopic and diastereotopic relationships between groups (or atoms) within molecules.
[27] In a 1961 article, Westheimer applied ideas from statistical mechanics to the effects of isotopic substitution on the reactivity of organic molecules.
[32][28]: 550, 561 The Melander-Westheimer postulate has successfully predicted the ways in which KIEs and transition state (TS) structures vary.
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 photolabel generated a reactive carbenoid species capable of inserting into hydrocarbon C-H bonds.
In 1968, Westheimer examined pseudorotation in phosphate ester chemistry[6] and predicted the occurrence of pseudo-rotation of oxyphosphoranes.
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.
[39] This work continues to challenge and inspire researchers studying biological chemistry and reactions in RNA, DNA, and ribozymes.
[55][2] "Over a span of four decades, Westheimer repeatedly demonstrated an ability to take up a fundamental scientific problem — one that appeared either insoluble or very difficult — and to solve it in an elegant and completely definitive way...