This afternoon at the ACS meeting I attended the Analytical Awardees Presentations featuring the four winners of the ACS analytical awards.

The winner of the Award for Outstanding Achievement in Mass Spectrometry was Richard Caprioli of Vanderbilt University. First reported in Nature Medicine in 2001, Professor Caprioli has been developing and applying a technique called MALDI MS Imaging. This is a fascinating technique where a tissue slice is placed directly on a sample plate, prepped with a MALDI matrix, pixilated into discrete spots, and analyzed by MALDI–TOF. The proteins present in each spot can be identified and mapped back to the location in the tissue from where it came. This results in the construction of a protein map of the tissue where different colors can be assigned to various proteins of interest and intensities reflect protein concentrations.

What’s really intriguing about this technique is the potential for a paradigm shift in the way that clinical pathologists and histologists do their jobs. For example, a histologist traditionally would use a stain to define a tumor margin in a biopsy, but the molecular profile revealed by the MALDI MS image can expose oncogenic proteins found out-of-bounds of the tumor. This can help guide surgeons in the removal of all cancerous tissue, reducing the chance of relapse.

Apparently, when Professor Caprioli first told colleagues about his idea of sticking tissue slices into a mass spectrometer, they all thought he was a little nuts. His work is a fine example of how what first seems like a zany idea in analytical chemistry can turn out to have a very practical application in the clinic!

Allison Doerr (Assistant Editor, Nature Methods)

PubChem was created in 2004 as part of the NIH Roadmap – it was intended to be a “”https://nihroadmap.nih.gov/initiatives.asp">new and comprehensive database of chemical structures and their biological activities … [which would contain] compound information from the scientific literature as well as screening and probe data from the [Molecular Libraries Screening Center Network]."

Nature Chemical Biology was one of the first journals to deposit chemical structures into this database, and according to Stephen Bryant, the amount of data is rapidly growing: the database now contains over five million unique structures and more than 190 bioassays.

It sounds like this database will make it easier for chemists and biologists to find interesting bioactive small-molecules. And the best part? Like PubMed, the data is freely available to the entire scientific community…

Joshua

Joshua Finkelstein (Associate Editor, Nature)

Earlier this morning, Professor Larry Overman gave a talk in a session honoring Professor Richard Heck’s contributions to organopalladium chemistry.

Overman talked about intramolecular Heck reactions, and he highlighted the stereocontrolled total synthesis of (/-)-gelsemine, the enantioselective total synthesis of ()-minfiensine, and discussed an unpublished synthesis of guanacastepene N.

If you’re looking for some of his work that’s “hot off the press,” there are two recent papers in Organic Letters from Overman & Watson: “”https://pubs.acs.org/cgi-bin/abstract.cgi/joceah/2006/71/i07/abs/jo052335a.html">Diastereoselection in the Formation of Spirocyclic Oxindoles by the Intramolecular Heck Reaction" and “”https://pubs.acs.org/cgi-bin/abstract.cgi/joceah/2006/71/i07/abs/jo0523363.html">Diastereoselection in the Formation of Contiguous Quaternary Carbon Stereocenters by the Intramolecular Heck Reaction."

The session was packed, and Overman certainly convinced me that intramolecular Heck reactions are a powerful way to make contiguous quaternary carbon stereocenters, even “”https://oasys2.confex.com/acs/231nm/techprogram/P942285.HTM">in situations of considerable steric congestion." If you were there, what did you think?

Joshua

Joshua Finkelstein (Associate Editor, Nature)

As I navigated the halls of the Georgia World Congress Center (yes, all three buildings!) on the first day of the ACS meeting, it was gratifying to see the large number of young faces in the crowd. Although I’m always impressed by senior scientists who share their youthful enthusiasm for chemistry, I am interested in what inspires the current generation of students to pursue careers in chemistry.

The people around us have a lot to do with our choices. I grew up in a family that included three generations of pharmacists. I recall fondly the science lore of the family—my great-grandfather mixing mentholated products in the basement of the house, my grandmother extracting compounds from garden plants right around the time quantum mechanics was making its debut, and my father’s adventures in chemistry lab in the era when NMR was the newest, greatest tool. Although chemistry was already part of my family, I was lucky to have excellent junior high and high school science teachers who nurtured my interests and challenged me scientifically and creatively.

A sense of wonder and curiosity seem equally important. I was fortunate to live in a place where I could enjoy the natural world by wandering off into a forest or sitting by a lake. In addition, when I was growing up, chemistry sets still contained interesting compounds, which allowed some reasonable level of experimentation. Although I was a big fan of crystalline cobalt (II) chloride, sulfur had to be my “go to” reagent bottle for basement experimentation. That easy-to-measure, placid yellow elemental powder made its way into many test reactions and provided hours of amusement for me, but not, I recall, for my parents.

Who or what inspired you to become a chemist? How can we continue to attract young people to chemistry? Tell us your story.

Terry L. Sheppard (Chief Editor, Nature Chemical Biology)

It always takes me awhile to get my bearings at an ACS meeting…figuring out how to catch the shuttle bus to the convention center…finding where to pick up registration materials…searching for that ubiquitous Starbucks for some much-needed caffeine…deciding which one of five interesting symposia to attend… navigating the massive convention center…going back and forth between symposia that seem about a mile apart, only to find the order of the talks have been switched …and so on!

Today was no exception, but I did manage to drop in on one quite interesting symposium given by the Division of Chemical Information. Kicked off by the very entertaining George Whitesides from the chemistry department at Harvard, the symposium was entitled “The nuts and bolts of scholarly publishing”.

As an editor, I would have to say that Professor Whitesides has the writing process down pat (you might even say, down to a science), as he described his views on how to successfully write a research paper. He began by reminding the audience of the mantra that all good journalists know: if you fail to capture the readers’ attention in the first 2-3 sentences, you might as well forget about them reading the rest of your paper. The Introduction should state the principle result, the motivation, importance, and context in reference to prior work (which as Professor Whitesides astutely pointed out, is not only the ethical thing to do, but also a really good idea since the previous work was probably done by the referees reading the paper!). In the Results and Discussion, the principle result should be described first and in as brief of terms as possible (this is not the place to recount the long history of personal struggles in the lab!). Finally, the Conclusion should not be a reiteration of the abstract, but the place to compare the work to previous results, describe the significance of the new work, the benefits and limitations, as well as an opportunity to inject personal opinions. In addition, a good title and interesting and informative figures are absolutely crucial.

Overall, it was an engaging and instructive talk, reminding scientists of the integral role writing plays in research. After all, if you never write up your research and no one ever reads it, it might as well have never been done!

Allison Doerr (Assistant Editor, Nature Methods)

In The Ocean World, Jacques-Yves Cousteau wrote

From the vast expanses of its surface waters to its beaches and marshes and tidelands and mangrove swamps, from its many thousands of miles of rocky shores to its deepest and darkest abyss, the sea produces life in fantastic abundance.

Cousteau’s aquatic adventures ran through my mind when I ate lunch after Professor William Fenical’s talk this morning. He was awarded the “”https://oasys2.confex.com/acs/231nm/techprogram/P926624.HTM">Guenther Award in the Chemistry of Natural Products" and spoke about marine actinomycetes, microorganisms whose terrestrial cousins produce a number of natural products, including streptomycin and actinomycin.

Fenical thought that microorganisms capable of producing interesting, biologically-active natural products lived in the ocean. To find these microbes, his research group constructed new devices to collect samples from the deep sea: the “mud snapper” (200 meters deep), electric reels (1500 meters deep), and an autonomous sampling device that looked like a cross between a syringe and a pogo stick (6000 meters deep). He showed a movie of this last device: it sinks to the bottom of the ocean and the tip of the device plunges into the sediment and collects a soil sample. Then it releases its weights and shoots back up to the surface, where the samples can be retrieved and brought back to the lab.

A few years ago, his research group reported the discovery of a new marine actinomycetes (Salinospora), which produced salinosporamide A, a natural product with a fused gamma-lactam-beta-lactone bicyclic ring structure. They showed that in vitro, this compound was highly potent against a number of cancer cell lines.

Chauhan et al. recently published a Cancer Cell paper where they showed that this compound (renamed NPI-0052) was orally bioavailable and that it prolonged survival in animal tumor model studies. For these reasons, salinosporamide A/NPI-0052 is now scheduled to enter human clinical trials in the late spring or early summer.

In a Chemical & Engineering News article written earlier this year, Fenical said

Oceans not only cover more than 70% of Earth’s surface, but more than 90% of the organisms in the ocean are not found on land … In one cubic centimeter of bottom sediment, there are 1 billion microbial organisms. There is a huge diversity of microscopic organisms [that may produce] potent, biologically active metabolites of unique, unprecedented structures.

Fenical’s research group has identified and cultured 15 new marine phylotypes so far – including Salinispora pacifica, which was reported in a recent issue of Organic Letters and produces cyanosporasides A and B. This is only a fraction of what’s out there, but it looks like Fenical’s research group is off to a good start…

Joshua

Joshua Finkelstein (Associate Editor, Nature)