Ronald Breslow (1931–2017) Organic Chemist Who Took Inspiration from Nature
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COMMENT OBITUARY Ronald Breslow (1931–2017) Organic chemist who took inspiration from nature. onald Breslow discovered new chem- In the 1960s, Breslow articulated that a istry at nearly every corner of what he major challenge for organic chemists lay in called the “central science”. At heart selectively adding different atoms or func- an organic chemist, he had a mercurial, intui- tional groups to unactivated carbon–hydro- R THURE CERLING tive understanding of the reactivity of organic gen bonds to make the molecules more useful. molecules. His most significant scientific con- Beginning in 1969, Breslow published a series tribution was his founding of the field of bio- of papers showing that he could selectively organic chemistry, based on his realization activate particular C–H bonds by tethering that, if nature’s reactions followed the rules a catalytic group to the molecule in the right of organic chemistry, then chemists could geometry. His studies laid the groundwork design reactions that are inspired by nature. for today’s field of C–H activation, which is Breslow spent his entire independent important in drug synthesis and beyond. career in the chemistry department at Breslow also pioneered the creation of Columbia University in New York City, ‘artificial enzymes’, which mimic natu- where he oversaw the education of more ral enzymes to catalyse a range of organic than 250 scientists, many of whom are now re actions. Starting in the early 1960s, he leaders in organic chemistry. Away from the showed that artificial enzymes known as bench, one of his proudest achievements cyclodextrins could synthesize amino acids, was chairing the committee at Columbia in cleave bonds and even work in a similar way the 1980s that made the successful case for to vitamin B1. This work inspired the field of the university’s Columbia College to admit chemical biology, which combines organic women. He embodied what an academic in Columbia’s chemistry department. chemistry with molecular biology to build leader could do to mentor younger scientists In the 1950s, Breslow showed how organic molecules with new structures and functions. and promote women professionally, includ- chemistry could reveal the workings of Breslow — with colleague Paul Marks, ing his two daughters, Stephanie and Karen. vitamin B1, a ‘helper’ molecule known as a who was then president and chief executive Breslow, who died on 25 October, was cofactor, which allows enzymes to catalyse of Memorial Sloan Kettering Cancer Center born in Rahway, New Jersey, on 14 March different reactions. At the time, proteins were in New York City — was also instrumental 1931. His mother, Gladys, supported the understood to use the chemistry of their in developing the cancer drug vorinostat. family as a riveter while his father, Alexan- amino-acid building blocks to do the work In the 1970s, chemists had shown that cer- der, served as an army doctor during the Sec- of the cell. But it was not clear how vitamin tain organic solvents arrested the growth ond World War. As a child, Breslow was an B1, or its derivative thiamine pyrophosphate, of cancer cells. Breslow realized that he all-round student, excelling in humanities, allowed proteins to expand their chemical could design more-potent drug molecules sports, student government and music. He repertoire. In 1958, Breslow showed that the by linking together pairs of metal-binding also experimented with chemistry sets in his unique placement of the carbanion between molecules that mimicked the mechanism of family’s basement, and at the age of 17 was a the nitrogen and sulfur atoms in vitamin B1’s the organic solvents. The US drug company finalist in the Westinghouse Science Talent thiazolium ring stabilizes it, enabling cataly- Merck acquired the licence for vorinostat, Search, a prestigious national competition. sis of a broad range of demanding chemical and Breslow and his wife used the proceeds He began to focus on science as an under- transformations. to endow a chair in Columbia’s chemistry graduate and gained a bachelor’s degree As a newly minted professor, Breslow also department. in chemistry from Harvard University in made fundamental contributions in a com- Ron was generous to his students and Cambridge, Massachusetts, in 1952. There, pletely different area of chemistry: a newly colleagues and a champion of women. He he met his future wife, Esther, who went on explored type of chemical bonding called was a keen musician, composing jazz at to have a distinguished career as a biochem- aromaticity. Quantum mechanics had pre- home in the evenings. I first met Ron when ist at Cornell Medical School in New York. dicted that, in addition to classical covalent I was an undergraduate and he took me into Following in his father’s footsteps, Bres- bonds, aromatic molecules could have bonds his laboratory. After I gained my PhD, he low entered Harvard’s graduate programme in which electrons are shared, or delocalized, hired me back to the faculty at Columbia, in medical science. He left with a master’s across multiple atoms. In aromatic molecules where we worked together for almost two degree after one year to focus on academic such as benzene, the cyclic conjugated π-bond decades. He liked to say that chemistry was chemistry. Early in his career, he worked with network contains 4n + 2 electrons, which magical. Professor Breslow, on behalf of two Nobel-prizewinning chemists: Rob- makes the molecules remarkably stable. In so many of your students and colleagues, ert Woodward during his PhD at Harvard, 1957, Breslow became the first to report the thank you for the decades of magic. ■ in which he was trained in the reactivity of synthesis of an aromatic compound with organic molecules; and Alexander Todd as n = 0, the cyclopropenyl cation. In subsequent Virginia W. Cornish is professor in the a postdoc at the University of Cambridge, work, he established that molecules with sim- departments of chemistry and of systems UK, who taught him how to apply the rules ilar conjugated bonds but only 4n electrons biology at Columbia University in New York of organic chemistry to biomolecules. In are destabilized, and he popularized the term City, New York, USA. 1956, aged just 25, he became an instructor antiaromatic to describe the effect. e-mail: [email protected] 176 | NATURE | VOL 552 | 14 DECEMBER©2017 M 2017ac millan Publishers Li mited, part of Spri nger Nature. All ri ghts reserved. .