Ronald Breslow was a titan of 20th-century chemistry, a polymath whose work bridged the gap between the rigid structures of physical organic chemistry and the complex machinery of biological systems. Over a career spanning more than six decades at Columbia University, Breslow redefined how we understand the chemistry of life, coining the terms "bioorganic chemistry" and "biomimetic chemistry."
1. Biography: From Rahway to the Ivy League
Ronald Charles David Breslow was born on March 14, 1931, in Rahway, New Jersey. A precocious student, he headed to Harvard University, where he earned his B.A., M.A., and Ph.D. in rapid succession. At Harvard, he studied under the legendary R.B. Woodward, the premier synthetic organic chemist of the era, which provided Breslow with a rigorous foundation in molecular structure.
After a brief postdoctoral fellowship at Cambridge University under Lord Todd (who won the Nobel Prize for work on nucleotides), Breslow joined the faculty of Columbia University in 1956 at the age of 25. He remained at Columbia for his entire professional life, eventually becoming the Samuel Latham Mitchell Professor of Chemistry and a University Professor—the highest academic rank bestowed by the institution. He passed away on October 25, 2017, from pancreatic cancer.
2. Major Contributions: Bridging Biology and Synthesis
Breslow’s research was characterized by an ability to take complex biological phenomena and distill them into fundamental chemical principles.
- The Mechanism of Vitamin B1 (Thiamine): In 1958, Breslow solved a long-standing mystery regarding how Vitamin B1 facilitates decarboxylation reactions. He discovered that the thiazolium ring in thiamine loses a proton to form a "zwitterion" (a molecule with both positive and negative charges). This reactive species, now known as the Breslow Intermediate, explains how the vitamin acts as a catalyst in the metabolism of carbohydrates.
- Antiaromaticity: While chemists had long understood "aromaticity" (the unusual stability of rings like benzene), Breslow explored the opposite. He coined the term antiaromaticity to describe cyclic systems that are destabilized by their electron configuration. His synthesis of the cyclopropenyl cation—the simplest possible aromatic system—remains a landmark in structural chemistry.
- Biomimetic Chemistry: Breslow was a pioneer in creating synthetic molecules that mimic the function of natural enzymes. He famously used cyclodextrins (ring-shaped sugar molecules) as "artificial enzymes" to catalyze reactions with a level of specificity previously seen only in nature.
- Cancer Therapeutics (SAHA): Later in his career, Breslow transitioned into medicinal chemistry. In collaboration with Paul Marks of the Memorial Sloan Kettering Cancer Center, he developed Suberoylanilide Hydroxamic Acid (SAHA). This molecule inhibits histone deacetylases (HDACs), enzymes that control how DNA is packaged. SAHA was approved by the FDA in 2006 as Vorinostat (Zolinza) for the treatment of cutaneous T-cell lymphoma.
3. Notable Publications
Breslow was a prolific writer, publishing over 500 papers. Some of his most influential works include:
- "On the Mechanism of Thiamine Action. IV. Evidence from Studies on Model Systems" (Journal of the American Chemical Society, 1958): The definitive paper on the Breslow Intermediate.
- "Synthesis of the s-Triphenylcyclopropenyl Cation" (JACS, 1957): The first experimental proof of the smallest aromatic system.
- Organic Reaction Mechanisms (1965): A textbook that educated a generation of chemists on the "how" and "why" of chemical reactivity.
- "Biomimetic Chemistry" (Chemical Reviews, 1995): A comprehensive overview of how synthetic chemistry can replicate biological processes.
4. Awards & Recognition
Though the Nobel Prize eluded him—a fact often debated in the chemistry community—Breslow received nearly every other major honor in the field:
- National Medal of Science (1991): Awarded by President George H.W. Bush.
- Priestley Medal (1999): The highest honor bestowed by the American Chemical Society (ACS).
- Wolf Prize in Chemistry (1995): For his work on biological mechanisms and artificial enzymes.
- Arthur C. Cope Award (1987): For outstanding contributions to organic chemistry.
- President of the American Chemical Society (1996): Where he was a vocal advocate for science funding and education.
5. Impact & Legacy
Breslow’s greatest legacy is arguably the creation of the field of Bioorganic Chemistry. Before Breslow, biology and organic chemistry were often treated as separate silos. He demonstrated that the tools of physical organic chemistry (kinetics, isotope labeling, and synthesis) could be used to solve biological puzzles.
Furthermore, his "biomimetic" approach paved the way for modern supramolecular chemistry and nanotechnology. His work on SAHA proved that fundamental chemical research could lead directly to life-saving clinical applications, bridging the gap between the lab bench and the hospital bedside.
6. Collaborations and Mentorship
Breslow was a prolific mentor, training over 100 doctoral students and hundreds of postdocs. His "academic family tree" is a who’s-who of modern chemistry.
- Robert H. Grubbs: One of Breslow’s early students, Grubbs went on to win the Nobel Prize in Chemistry in 2005 for his work on olefin metathesis.
- Paul A. Marks: As President of Memorial Sloan Kettering, Marks was Breslow’s primary partner in the development of Vorinostat, blending chemical synthesis with clinical oncology.
- The Columbia School: Breslow, along with colleagues like Gilbert Stork and Nicholas Turro, turned Columbia University into a global powerhouse for organic chemistry during the mid-to-late 20th century.
7. Lesser-Known Facts
- The "Space Dinosaur" Controversy: In 2012, Breslow published a paper discussing why life on Earth uses "left-handed" amino acids. He speculated that if life evolved on other planets with "right-handed" chemistry, it might have led to "advanced versions of dinosaurs." The media picked up the "space dinosaur" angle, leading to a viral (and slightly sensationalized) moment that Breslow later clarified was a metaphorical illustration of divergent evolution.
- Musical Talent: Breslow was an accomplished pianist and often drew parallels between the creativity required for musical composition and chemical synthesis.
- The Ronald Breslow Award: The American Chemical Society established the "Ronald Breslow Award for Achievement in Biomimetic Chemistry" in 2001. It is rare for a society to name a major award after a living scientist, a testament to his standing in the field.
- Longevity at the Podium: He was famous for his lectures, which he often delivered without notes, weaving complex chemical mechanisms into a narrative that resembled a detective story.