PHOSPHORUS

C. DALE POULTER ,UNIVERSITY OF UTAH

Phosphorus, an element of tremendous importance in commerce and research, was first isolated by Hennig Brandt in 1669. Following the standard practice of alchemists of his era, he protected his invention as a "trade secret" in hopes that he had discovered the Philosopher's Stone. Brandt's monopoly was broken a decade later by Robert Boyle, often regarded as the father of chemistry for his insistence on publishing experiments in sufficient detail so they could be reproduced by others. The description that Boyle and his assistant Abrose Godfrey Hanckwitz gave to the Royal Society of London is a fascinating account of their research with phosphorus. It begins with "As is before shewed, take Urine well putrefied in a Tub" and concludes with "If the Privy Parts be therewith rubb'd, they will be inflamed and burning for a good while after." I wonder who volunteered for that experiment!

MAGICAL Joseph Wright's "The Alchemist in Search of the Philosopher's Stone Discovers Phosphorus."

I was introduced to the wonders of phosphorus at the tender age of three. This was near the end of World War II, when Mom and I were living with my grandmother and three aunts, one of whom I convinced to give me a few kitchen matches. My combustion experiment soon got out of control, and I spent the next hour or so at the front window of my grandmother's house nervously watching firemen fight a grass fire in the field across the street. At the same time, phosphate, from Coca-Cola, was an important component in an unrelated set of experiments to develop a concoction I called "chemical dog food." Numerous formulations, most of which featured coffee grounds floating on a highly colored liquid, were prepared from as many different ingredients as I could find in the kitchen. The consumer evaluations I conducted with my grandmother's dog Mitzi were negative, and I eventually dropped the project.

In grade school, my research activities became more organized. Several of my playmates and I formed a "chemistry club." We combined our chemistry sets and set up a laboratory under the front porch of my house--I don't think Mom and Dad ever knew about it. By and large our experiments, many of which were more advanced versions of the earlier combustion study, were successful. We had fun, actually taught ourselves some chemistry, and survived with no permanent injuries. The house survived as well!

I didn't learn very much about phosphorus in college or in graduate school. Phosphorus played a minor role in my graduate and postdoctoral research--P₂O₅ to dry solvents and Wittig reagents to synthesize olefins. Imagine: nine years of advanced education and training with five years of specialization in organic chemistry--the chemistry of compounds from living organisms--and virtually no mention of phosphorus.

I was reintroduced to phosphorus by Hans Rilling, a biochemist at the University of Utah, when we began a long, productive collaboration to study the mechanisms of the reactions used by nature to join isoprene units. The substrates for our enzymes were diphosphate esters--molecules beautifully designed to be stable at physiological pH, but easily activated once inside the active site of an enzyme. One of the first hurdles I faced was how to prepare substrate analogs for mechanistic studies from precious, lovingly synthesized alcohols. The reactions used then gave miserable yields of at most a few milligrams of product. Over the next several years, my students and I developed a practical solution based on a simple displacement using inorganic pyrophosphate. We published a detailed description of the procedure in Organic Syntheses over the objections of a member of the editorial board who regarded our use of a vortex mixer, lyophilization, and chromatography on cellulose to purify the nonvolatile water-soluble products as being "too unfamiliar and biochemical" for organic chemists. Since then, my organic colleagues have become much less hydrophobic.

Over the years, my group has become increasingly dependent on phosphorus. In addition to the isoprenoid diphosphates, we rely heavily on recombinant DNA technology. Consider a few of the beauties of phosphate esters in this regard: reverse transcription for making cDNA libraries from RNA, polymerase chain reaction for synthesizing customized DNA, cutting and pasting of DNA to make templates for generating recombinant proteins, chemical synthesis of DNA, and high-throughput DNA sequencing. These "tools of the trade" for today's chemist studying biosynthesis were unimaginable only three decades ago when I entered the field.

C. Dale Poulter is the John A. Widtsoe Distinguished Professor of Chemistry at the University of Utah. He has received the ACS Ernest Guenther and Repligen Awards for his work on isoprenoid biosynthesis and is editor-in-chief of the Journal of Organic Chemistry.

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