Ronald Breslow

was born in Rahway, New Jersey, on March 14, 1931. His chemical career started with undergraduate and graduate training at Harvard University, where he also did his Ph.D. research with R. B. Woodward. He then spent a year in Cambridge, England, as a postdoctoral fellow with Lord A. R. Todd and came to Columbia University in 1956 as Instructor in Chemistry, where he now holds the chair of the Samuel Latham Mitchill Professor of Chemistry. He is also University Professor, one of 12 at Columbia, and member and honorary member of several learned societies, among those the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, the New York Academy of Sciences, the Royal Society of Chemistry (UK), the Royal Society (UK), the World Innovation Foundation, and the Chemical Society of Japan. His research is published in more than 400 papers and was acknowledged with numerous scientific awards, among those the ACS Award in Pure Chemistry (1966), the Fresenius Award of Phi Lambda Upsilon (1966), the Remsen Prize (1977), the Roussel Prize in Steroids (1978), the ACS James Flack Norris Award in Physical Organic Chemistry (1980), the Arthur C. Cope Award (1987), the Kenner Award (1988), the Nichols Medal (1989), the National Academy of Sciences Award in Chemistry (1989), the Allan Day Award (1990), the Paracelsus Award and Medal of the Swiss Chemical Society (1990), and the U.S. National Medal of Science (1991). He was recently named one of the top 75 contributors to the chemical enterprise in the past 75 years by Chemical & Engineering News (1997) and won the Priestley Medal (1999). In 2000 he won the New York City Mayor’s Award in Science, and in 2002 he received the ACS Bader Award in Bioorganic or Bioinorganic Chemistry and the Esselen Award for Chemistry in the Public Interest. He served as president of the American Chemical Society (in 1996) and belongs to the editorial board of a number of scientific journals.

Scientific Sketch

Breslow’s research interests involve on the one hand the design and synthesis of new molecules with interesting properties, and on the other hand the study of these properties. Examples include the cyclopropenyl cation, the simplest aromatic system and the first aromatic compound prepared with other than six electrons in a ring. His work establishing the phenomenon of anti-aromaticity has involved the synthesis and characterization of novel molecules. Even in the work on purely mechanistic questions, such as the discovery of the chemical mechanism of thiamine (vitamin B-1) in biochemical reactions, the synthesis and study of novel molecules has played an important role. Although he continues his interest in unusual conjugated systems, his major emphasis in recent years has been associated with the understanding of mechanisms in enzymes and enzyme model systems and the development of good artificial enzymes. Some work is focused on understanding the detailed mechanisms of carboxypeptidases and ribonucleases and some on the enzymes that utilize coenzyme B12 as a cofactor. Based on this experience, new artificial enzymes are produced by combining good binding sites, such as hydrophobic pockets of cyclodextrins, with appropriately placed catalytic groups. Recently, Breslow has shown the power of artificial cytochrome P-450 enzymes for catalytic oxidations of steroid substrates (Fig. 1, J. Org. Chem. 2002, 67, 5057).

Figure 1. Catalytic oxidations of steroid substrates by artificial enzymes.

An example that also demonstrates the second major effort of Breslow and coworkers is the application of templates (see Fig. 1, group R¹) that achieve geometric control of the point of attack on a complex molecule, resulting in re-gio-specifity (see also Chemtracts Org. Chem. 2002, 15, 59). Investigations of the complex geometries are supported by molecular and computational models.

Figure 2. An effective cancer cell differentiating agent.

Beside the synthesis of artificial enzymes, Breslow and coworkers study the physical effects of reactions, e.g., the antihydrophobic cosolvent effects for alkylation reactions in water solutions (J. Am. Chem. Soc. 2002, 124, 3622), as well as the development of a computational model to probe the relative hydrophobicity of aromatic surfaces.

Breslow is also interested in developing new agents against cancer. He has shown an approach of using cyclodextrine dimers for a photodynamic therapy (J. Am. Chem. Soc. 2001, 123, 12488) and is involved in a fruitful collaboration with Marks and Rifkind at the Sloan Kettering Institute for Cancer Research. Here they have developed cytodifferentiating agents for cancer chemotherapy, that are able to induce undifferentiated or de-differentiated cells to transform to an adult noninvasive form (Fig. 2, Helv. Chim. Acta 2000, 83, 1685).

Veal and Sausage Stew

Starting materials:

425 g veal sausage (Italian style, with anise)

425 g veal chunks

425 g sliced mushrooms

425 g sliced carrots

2 large onions

2 cloves garlic

2 bay leaves

chopped parsley

salt

pepper

red or white wine

olive oil

pasta

salad

In a coverable kettle, sauté the veal sausage (cut into bite-sized chunks) in a little olive oil and pour off the fat when it is done. Remove it to a bowl, and sauté the onions, the chopped garlic, and the veal chunks in more olive oil until they are brown, then remove to the bowl. Add the sliced mushrooms and cook until the water is driven off, return the meat and onions to the pot, and cover the contents with ordinary red or white wine and simmer (covered) for at least two hours after adding two bay leaves, a handful of chopped parsley, some salt and pepper, and the sliced carrots. Then cool the stew and reheat it before serving (it is much better after this cooling and reheat cycle, which brings the sauce into the meat; for this reason, the stew is even better the second day). Serve with appropriate pasta and a good salad.

«A variation incorporates some tomatoes as well before the simmering step. In another variation, uncooked peas are added 10 minutes before the end of the simmering step. The garlic should have its bitter core removed before chopping.»

Ronald Breslow