Westheimer, Frank

Westheimer, Frank, 16 727, 741 Westinghouse AP600 reactor, 17 595 Westinghouse Bettis Laboratory, 17 573 Westinghouse Model 412 pressurized water reactor, 17 574-577 West Nile encephalitis, 14 338 West Nile virus (WNV), 3 135, 137 antiviral therapy, 3 165-168 infection process, 3 164-165 Weston cell, 15 750 Wet adhesion... 

This topic draws from a variety of fields of study. We are grateful for critical comments and thoughtful suggestions on earlier drafts of this chapter from Steven Benner, Peter R. Buseck, Kenso Soai, and Frank H. Westheimer. Any mistakes and omissions remain the responsibility of the authors. 

Whereas many scientists shared Mulliken s initial skepticism regarding the practical role of theory in solving problems in chemistry and physics, the work of London (6) on dispersion forces in 1930 and Hbckel s 7t-electron theory in 1931 (7) continued to attract the interest of many, including a young scientist named Frank Westheimer who, drawing on the physics of internal motions as detailed by Pitzer (8), first applied the basic concepts of what is now called molecular mechanics to compute the rates of the racemization of ortho-dibromobiphenyls. The 1946 publication (9) of these results would lay the foundation for Westheimer s own systematic conformational analysis studies (10) as well as for many others, eg, Hendrickson s (11) and Allinger s (12). These scientists would utilize basic Newtonian mechanics coupled with concepts from spectroscopy (13,14) to develop nonquantum mechanical models of structures, energies, and reactivity. 

Frank H. Westheimer, bom Baltimore, Maryland, 1912. Ph.D. Harvard 1935. Professor University of Chicago, Harvard. Died 2007. 

Acknowledgement. It is a great pleasure for the authors to dedicate this paper to Frank Westheimer. Though most of us have not had the privilege of working in his laboratory, we are all his students nevertheless, since we have learned so much from the crisp clarity and profound wisdom of his publications, his lectures, and his comments on science and life. 

Another of Conant s students was Frank Westheimer (b. 1912), who, after postdoctoral work with Hammett at Columbia, held a post at the University of Chicago (1936-1954) and then returned to Harvard. Westheimer worked in several areas of physical organic chemistry and engaged in other chemistry-based activities, as revealed in an interview conducted in 1995 by Istvan Hargittai.233 For much of his career, Westheimer was essentially a physical organic chemist working in biochemistry and he has himself written reflectively on the discovery of the mechanisms of enzyme action over the period 1947-1963234 and on the application of physical organic chemistry to biochemical problems.235 Westheimer has also contributed, as Tetrahedron Perspective Number 4, an article on Coincidences, decarboxylation, and electrostatic effects , which, he writes, ...allows me to review some of my past .236... 

This monograph is an expansion and revision of the review I wrote earlier with my mentor Jeremy Knowles (Bayley and Knowles, 1977). Jeremy s earlier short review remains an excellent summary of the essential idea of photoaffinity labeling. Another review that will remain valuable is from Frank Westheimer s laboratory where photoaffinity labeling was invented (Chowdhry and Westheimer, 1977). Westheimer has also written a delightful short history and prospectus of the subject (Westheimer, 1980). Several additional reviews concerning special aspects of photochemical reagents are cited in this text. 

Frank Westheimer presents a thought-provoking overview of why nature chose phosphates to make the genetic tape. Even the youngest students have heard of DNA, and most have seen models of the famed double helix wherein hereditary information is encoded, but the current question. Why are phosphates in that helix , is usually passed over. The answer is in this volume. Other significant biochemical concerns, such as hydrolysis mechanisms for phosphate compounds and the NMR spectroscopy of duplex oligonucleotides and DNA complexes, are also addressed. 

To address the funding problem, in February 1964 Frank Westheimer, an organic chemist at Harvard University, was elected to head a committee, under the auspices of the Committee on Science and Public Policy of the National Academy of Sciences, to make a comprehensive study of American basic research in chemistry. The report of the committee, titled Chemistry Opportunities and Needs, came to the basic conclusion that scientific opportunities were being lost for lack of support- ... 

Fundamental work on the stereochemistry of enzyme-catalyzed reactions was done by Frank H. Westheimer. Westheimer was born in Baltimore in 1912 and received his graduate training at Harvard University. He served on the faculty of the University of Chicago and subsequently returned to Harvard as a professor of chemistry. 

At one point in the history of structural chemistry molecular mechanics calculations dominated the computational work for relatively large molecules. The origins of these calculations were intimately connected to another modeling approach that one of its initiators vividly described. Frank Westheimer (Fig. 1.2a) had participated in the American defense efforts during WWII and when the war had ended, he returned to the University of Chicago to resume his teaching and research. He had to start anew and had time to think about basic problems. This is how half a century later he remembered the birth of molecular mechanics [5] ... 

Fig. 1.2 (a) Frank Westheimer in the laboratory (Photograph by MINOT, courtesy of the late Frank Westheimer) (b) Norman (Lou) AUinger (Photograph and by I. Haigittai)... 

Hargittai I (2000) Frank H Westheimer. In Hargittai M (ed) Candid science conversations with famous chemists. Imperial College Press, London, pp 38-53 (the actutil quotation is on pp 41 2)... 

This is an amusing reversal of a quote frequently attributed to Frank Westheimer, a chemist, who said A couple of hours in the library can save you weeks in the laboratory. ... 

Only one actual problem in chemistry was solved using molecular mechanics as we use it now, by hand calculations. In a series of studies, Frank Westheimer described the following situation. Ortho-substituted biphenyl molecules are generally not co-planar because of the steric interference of the ortho substituents. A typical example is 2,2 -dibromo-4,4 -dicarboxybiphenyl. Consider the two structures of this molecule shown in Reaction (1) ... 

Duilio Arigoni You bring back to my memory a discussion that I had with Frank Westheimer on a similar issue. Frank pointed to me that access to scientific libraries is free to everybody. I think it s up to us to take initiative and not to wait for others to teach us what to do. I realize it s a demanding task. 

Historically, Frank Westheimer used 1,3-diketones as mechanistic probes of the enzyme acetoacetate decarboxylase [6]. The active site of acetoacetate decarboxylase has a nucleophilic lysine e-amino group and forms a Schiff base in its catalytic cycle. In his studies, the active site lysine e-amino group of this enzyme reacted covalently vith the 1,3-diketones. Later 1,3-diketones vere used as modification reagents for the nucleophilic lysine e-amino groups of many enzymes [7]. 

This contnbution is dedicated to Frank H Westheimer, on the occasion of his 80th birthday... 

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