Table of Contents

In the lab next to mine, the late Welby Courtney was watching silver crystallize from solution. The growth of screw dislocations especially fascinated him. He showed me, under a good microscope, what looked like spiral staircases. And newly minted stereochemist that I was, I showed him that some spiraled clockwise and others spiraled counterclockwise.

In another lab, we were making titanium trichloride because it was useful in catalyzing the recently discovered stereoregular (syndiotactic and isotactic) polypropylenes. Several years later, during a consulting session with Prof. Mark, these two chemistries collided in my head, and I blurted out that I had an explanation for stereoregular polymer growth. “It’s all happening on screw dislocations. Polymer chains are spiraling off these steps and following the same sense as the steps.” Prof. Mark nodded and said, “Possible. You should figure out a way to test that.”

I was reminded of this story by the recently reported findings that asymmetric crystals of sodium chlorate (1) and quartz (2) indeed catalyze stereoselective chemistry. What fascinated me is the authors’ conjecture that such interfacial templating could account for biochemical stereochemistry.

Pharmaceutical futures

In their 1999 report (3), Bryan Reuben and Michael Burstall made many timely observations, but two in particular caught my eye. They make the point that because the path to coming up with a commercial drug is strewn with so many almost-made-its, to be viable a firm must have several candidates in the pipeline all the time. Only a large firm can do that; thus all the mergers. Another factor is that consolidating R&D lends some assurance that your competitors aren’t about to come out with a treatment for the same malady. Whether mergers so motivated can be construed as illegal restraint of trade can keep a lot of attorneys hopping.

And with regard to combinatorial synthesis and screening, the authors caution that it’s all still a glimmer on the horizon. They advise, on the one hand, that reactions accessible to combinatorial synthesis, though increasing in number, are still only a minor fraction of what can be done in a three-neck flask. On the other hand, they indicate that when a library of candidates is produced, screening it may lead to several compounds of equivalent activity, thereby frustrating the deconvolution step.

The doctorate—Italian style

“On the mid-July day I happened to arrive at Il Bo [Palazzo del Bo of Padua University, where Galileo taught], doctoral candidates were taking their final exams. Milling with the crowd, I was carried into a chamber where I inadvertently witnessed one young woman’s dissertation defense before a panel of three robed faculty members. Her entire extended family had shown up to support her in this engagement, from grandparents to infants in arms, and they all stayed remarkably quiet throughout the entire proceedings.

“When the judges passed her, a tumult erupted and spilled down the stairs into the central courtyard, where other triumphant students had already stripped to bathing suits for the reenactment of the time-honored hazing ritual. Wearing peaked caps on their heads and wreaths of real laurel leaves around their necks, the young scholars submitted to face- and body-painting by their parents, and then ran through the ranks of relatives who gleefully kicked, spanked, and spilled water on them, chanting all the while ‘Do-TO-re! Do-TO-re! Do-TO-re!’”

Thus wrote Dava Sobel (4) in describing the research for her book Galileo’s Daughter: A Historical Memoir of Science, Faith, and Love (Walker & Co.: New York, 1999).

References

1. Sato, I.; Kadowaki, K.; Soai, K. Angew. Chem., Int. Ed. 2000, 39, 1510–1512.
2. Soai, K.; Osanai, S.; Kadowaki, K.; Yonekubo, S.; Shibata, T.; Sato, I. J. Am. Chem. Soc. 1999, 121, 11235–11236.
3. Reuben, B.; Burstall, M. L. Outlook for the World Pharmaceutical Industry to 2010; Decision Resources: Waltham, MA, 1999.
4. Sobel, D. Galileo’s Universe. New York Times Magazine, Nov 21, 1999, p 29.