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Thomas Bruice (1925–2019)
Thursday, 2019/11/07 | 08:16:53
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Stephen J. Benkovic PNAS November 5, 2019 116 (45) 22418-22419
Figure: Thomas Bruice. Image courtesy of Tony Mastres (University of California, Santa Barbara, CA).
Thomas Bruice, one of the fathers of bioorganic chemistry, died on February 15, 2019, at the age of 93. He was born on August 25, 1925, in Los Angeles, California. He is survived by his wife, Paula Yurkanis Bruice, a renowned author of undergraduate organic chemistry textbooks.
The founding and maturing of the bioorganic chemistry field coincided with the golden era of physical organic chemistry, when chemists strove to describe the plausible mechanisms for organic reactions. Papers were being published that described novel methods for revealing the reaction’s kinetic coordinates, its stereochemistry, and for the detection of very short-lived, unstable intermediates. Biochemists were now in possession of the first enzyme crystal structures (urease, pepsin, chymotrypsin), but how did such proteins catalyze their reactions? Their active sites showed various candidates for acid/base chemistry but how did they act collectively? For the simple hydrolysis of amides and esters, the textbooks of that time showed their hydrolysis only by strong acids and bases. How could an enzyme, such as chymotrypsin that readily cleaves amide bases, accomplish such a feat?
Tom earned his doctorate at the University of Southern California, resuming an education that had been interrupted by his service as a Marine medical corpsman during the World War II island campaigns in the South Pacific. His doctoral thesis with Norman Kharash on sulfenic acids provided no hint that in his first papers as an assistant professor at Yale he would report that the imidazole base in histidine could catalyze the hydrolysis of esters. From then on to the end of his career, Tom was intensely focused and unsparingly driven to decipher the mechanisms of enzyme action. After nine years at Yale, Johns Hopkins, and Cornell, Tom joined the faculty at the University of California, Santa Barbara, in 1964, where his laboratory was near the beach and ocean. A waxed surfboard was propped handily against his office wall, ready for immediate use.
Tom’s productivity was prodigious, as was his creativity that led to more than 600 papers, whose wealth of discovery contributed to a foundation for the development of the field. His papers fell broadly into several distinct categories: How do enzymes achieve their enormous catalytic rate advantages relative to a nonenzymatic reference state? What are the mechanisms used by various enzymic cofactors to promote specific transformations? How are general acid-base catalysis and transition-state stabilization harnessed by enzymes to facilitate various hydrolytic reactions? Tom’s papers featured the construction of insightful intramolecular models to mimic enzyme active sites, novel azomethines to model the transamination reactions supported by pyridoxal, a series of cleverly designed synthetic flavins to identify 4-aflavin adducts at the heart of flavin cofactor catalysis and chemical luminescence, and the importance of nearest-neighbor reactive conformations in boosting the efficiency of enzyme catalysis. There were others: Reactions in ice to study hydrogen bond effects, in micelles to mimic the intermolecularity of enzyme processes, and the synthesis of microgonadotropins to bind selectively in the minor groove of DNA as a first step in interrupting DNA transcription. For me, one of the outstanding remembrances of Tom derives from our collaboration to write the “Bioorganic Mechanisms” texts that served to help establish this field (1, 2).
Tom’s research was recognized by the election to both the National Academy of Sciences and the American Academy of Arts and Sciences. Among his many awards were the National Academy of Sciences Award for Innovative Research in the Chemical Sciences, the Linus Pauling Medal, The Tolman Medal, the Repligen Medal for the Chemistry of Biological Processes, the Alfred Bader Medal for Bioorganic Chemistry, and the James Flack Norris Award in Physical-Organic Chemistry.
Tom was a man of intense energy. All his activities (work or play) were to be pursued with passion, whether it was his science, his driving a Corvette at unsafe speeds, or playing touch football against hapless graduate students, who lacked his physical strength. To many perceived competitors, Tom was combative and aggressive. He was uniquely honest and demanded the best from his graduate and postdoctoral associates; he did not tolerate incompetence. Those who met his standards were rewarded with the joy and deep satisfaction from learning how to accomplish excellent science. Tom was a strong supporter of one’s career choice and for many of us, a close personal confidant. He befriended us when we encountered failures and losses (even to the passing of parents), revealing a warm tender side often not visible. He rejoiced with us in our accomplishments. Like many who have pioneered new areas in science, Tom’s discoveries are no longer specifically cited. They now underpin so much present research in bioorganic, bioinorganic, and chemical biology that they are taken for granted. I, who enjoyed a special kinship with Tom Bruice, will miss brainstorming his insightful judgments and, most of all, his unselfish, warm friendship.
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