Frank Henry Westheimer. 15 January 1912—14 April 2007

Abstract

Frank H. Westheimer integrated physical and organic chemistry to become an important contributor to the field that came to be called ‘physical organic chemistry’. He then went on to apply physical organic chemistry to the study of biological transformations. He identified fundamental classes of chemical reactions, studied in detail how they occurred in a relevant non-biological format and then investigated corresponding enzymatic reactions. These included oxidation–reduction, decarboxylation and phosphate transfer reactions. In the process, he made fundamental observations in the field of bio-organic chemistry he had helped to create. This line of research led to conceptual advances relevant to the ability of enzymes to distinguish enantiotopic and diastereotopic centres in their substrates, the perturbation of p K a values in enzymatic active sites as a source of catalytic power, and the broad range of transition state structures available for reactions at electrophilic phosphorus. These studies prompted similar work across many classes of enzymatic reactions. These experiments also benefitted from Westheimer's guidance in the application of kinetic isotope effects to probe reaction transition states, his invention of molecular mechanics to understand molecular dynamics, his widely cast studies on how organic reactivity depends on the molecular environment and his demonstration that photochemistry could be used to probe structure in complex biological systems.