The shortest route to strychnine

Editor’s note: following on from their previous groundbreaking publication on this blog – in which they provided a comprehensive overview of chemical-free consumer products – Drs Goldberg and Chemjobber submitted another manuscript to Nature Chemistry. Despite being summarily rejected by the editor, many (many) months later – and in the wake of some poetic exchanges on Twitter – the manuscript (and cover letter) are now both posted here on the blog with the permission of the authors. In the spirit of the Christmas papers published by the BMJ, consider this (tongue-in-cheek?) comment on synthetic chemistry by Alex and CJ a holiday-season gift to our readers!

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An expeditious and parsimonious approach to strychnine
Alexander F. G. Goldberg and C.J. Chemjobber

Throughout and following its structural elucidation1-5 strychnine has captured the imagination of synthetic chemists. Beginning with Woodward’s landmark total synthesis, reported in 1954 (ref. 6), this storied molecule has enabled chemists to showcase the state-of-the-art7,8. Advances in the field of organic synthesis over the following decades have culminated in a synthesis as short as six linear steps from commercial materials9. Indeed, each subsequent publication on this strychnine has been a reflection of the leading concepts of the time.

In this vein, we sought in our approach to limit the use of harmful reagents — and harmless reagents — and maximize step economy, atom economy10, redox economy11, word economy12, time economy13, graduate student economy14 and economy15.

Our efforts were initiated and concluded by obtaining commercially available strychnine as a light yellow powder from Sigma-Aldrich. Gratifyingly, all spectral data matched those reported in the literature, and the purity was found, fortuitously, to be as indicated by the vendor.

In summary, we are delighted to have obtained multi-gram quantities of strychnine in the shortest synthetic sequence to date from commercial materials. Future work will likely not be directed toward similar approaches to brucine, cinchonine, and erythropoietin.

Author contributions

A.F.G.G. and C.J.C. contributed equally to the experimental work.

Acknowledgements

We thank Sigma-Aldrich in advance for their sense of humour; A.F.G.G thanks Christine Hansplant for her patience in waiting for this acknowledgement for her contribution to our previous publication.

Affiliations

Stan’s Exchange Secondhand Store, Edmonton, AB.

Competing Financial Interests

A.F.G.G. is handily in the pockets of Big Strychnine.

References

1. Leuchs, H. Über Strychnon und Pseudo-strychnon als Nebenprodukte der Darstellung des Pseudo-strychnins und über weitere Versuche in dessen Reihe. (Teilweise mit Fritz Räck.) (über Strychnos-Alkaloide, 110. Mitteil.) Chem. Ber. 73, 731–739 (1940). [LINK]

2. Briggs, L. H., Openshaw, H. T. & Robinson, R. Strychnine and brucine. Part XLII. Constitution of the neo-series of bases and their oxidation products. J. Chem. Soc. 903 (1946). [LINK]

3. Robinson, R. The constitution of strychnine. Experientia 2, 28–29 (1946). [LINK]

4. Woodward, R. B., Brehm, W. J. & Nelson, A. L. The structure of strychnine J. Am. Chem. Soc. 69, 2250 (1947). [LINK]

5. Woodward, R. B. & Brehm, W. J. The Structure of Strychnine. Formulation of the Neo Bases J. Am. Chem. Soc. 70, 2107–2115 (1948). [LINK]

6. Woodward, R. B., Cava, M. P., Ollis, W. D., Hunger, A., Daeniker, H. U. & Schenker, K. The Total Synthesis of Strychnine. J. Am. Chem. Soc. 76, 4749–4751 (1954). [LINK]

7. Bonjoch, J. & Solé, D. Synthesis of Strychnine. Chem. Rev. 100, 3455–3482 (2000). [LINK]

8. Cannon, J. S. & Overman, L. E. Is There No End to the Total Syntheses of Strychnine? Lessons Learned in Strategy and Tactics in Total Synthesis. Angew. Chem. Int. Ed. 51, 4288–4311 (2012). [LINK]

9. Martin, D. B. C. & Vanderwal, C. D. A synthesis of strychnine by a longest linear sequence of six steps. Chem. Sci. 2, 649–651 (2011). [LINK]

10. Trost, B. M. Atom Economy—A Challenge for Organic Synthesis: Homogeneous Catalysis Leads the Way. Angew. Chem. Int. Ed. 34, 259–281 (1995). [LINK]

11. Burns, N.Z., Baran, P. S. & Hoffmann, R. W. Redox Economy in Organic Synthesis. Angew. Chem. Int. Ed. 48, 2854–2867 (2009). [LINK]

12. Goldberg, A. F. G. & Chemjobber, C. J. A comprehensive overview of chemical-free consumer products. The Sceptical Chymist. [LINK]

13. Hayashi, Y. & Ogasawara, S. Time Economical Synthesis of (–)-Oseltamivir. Org. Lett. 18, 3426–3429 (2016). [LINK]

14. (a) Wang, P., Dong, S., Brailsford, J. A., Iyer, K., Townsend, S. D., Zhang, Q., Hendrickson, R. C., Shieh, J., Moore, M. A. S., Danishefsky, S. J. At Last: Erythropoietin as a Single Glycoform. Angew. Chem. Int. Ed. 51, 11576–11584 (2012) and references therein. [LINK] (b) Nicolaou, K. C., Heretsch, P., Nakamura, T., Rudo, A., Murata, M. Konoki, K. Synthesis and Biological Evaluation of QRSTUVWXYZA’ Domains of Maitotoxin. J. Am. Chem. Soc. 136, 16444–16451 (2014) and references therein. [LINK] (c) Aad, G. et al. (ATLAS Collaboration, CMS Collaboration) Phys. Rev. Lett. 114, 191803 (2015). [LINK]

15. Newhouse, T., Baran, P. S. & Hoffmann, R. W. The economies of synthesis. Chem. Soc. Rev. 38, 3010–3021 (2009). [LINK]

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Cover letter

Dear Stu,

Please find attached our latest manuscript for your consideration for publication in Tetrahedron Letters or whatever it’s called, entitled “An Expeditious and Parsimonious Approach to Strychnine.” This scalable approach features a broadly-applicable method for accessing complex bioactive natural products, and adheres closely to the principles of green chemistry. For instance, our approach to strychnine was solvent-free and atom-economical, and all raw materials were obtained from renewable sources, which were fully incorporated into the final product. We trust that you will find that traditional green chemistry metrics such as atom economy, effective mass yield and E-factor are second to none.

Furthermore, the future of funding for basic research remains uncertain and subject to the whims of oft closed minded and myopic politicians. Pressing, therefore, is the need for cost-effective methods for obtaining important natural products, especially for the purposes of the biological studies which we all say we’re going to get around to.

Indeed, our zero-step synthesis of strychnine from commercially-available materials is a superb model for efficiency in synthetic chemistry. We are confident that the application of this method to other commercially available natural products will accelerate discovery in our own field, as well as in the fields of chemical biology and analytical chemistry; as the 200th anniversary of strychnine’s isolation approaches, we consider this timely and unparalleled manuscript suitable for the broad scientific audience of your publication.

Thank you in advance for your consideration,
Alexander Goldberg & CJ Chemjobber

Chemistry in retrospect: True Grit and the path to a faculty position

mribbe

 

As students and postdocs worldwide gear up for the start of graduate school, a new postdoc, or the beginnings of a long (and often stressful) search for a permanent position, Markus Ribbe reflects on his career path in order to remind us that things often don’t go the way you expect — but that doesn’t mean that things can’t end up better than you could have imagined.

 

 

Nearly 20 years ago, I was sitting on a plane from Munich to John Wayne Airport in southern California. I was on my way to a postdoc position in the research group of Barbara Burgess at the University of California, Irvine. Other than being interested in Barbara’s line of research, I did not know what to expect from this new life far, far away from my small hometown in Bavaria — in fact, I had no idea where I was heading to. As a former weightlifter, I was certainly excited to move a lot closer to Venice Beach, the residency of Arnold Schwarzenegger and the undisputed mecca of my sport. However, my enthusiasm was mixed with trepidation that Irvine was just a ranch in an area with nothing but cattle, a fear supported by a friend’s internet research. Instead of a herd of cattle greeting me at the airport, it was an oversized statue of John Wayne — a former resident of Orange County. At this point, it seemed strange to me that an airport in southern California should be named after a movie star other than Arnold, and that this movie star even deserved a statue of that size. This reaction was probably natural for a clueless postdoc who just arrived with nothing else but a small, half-empty suitcase and very little knowledge about life in SoCal. Little did I know that the statue of John “the Duke” Wayne would have a major impact on my life and career many years later.

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Under a fermium sky

Posted on behalf of Brett Thornton and Shawn Burdette. This blog post is an epilogue to the In Your Element (IYE) article on fermium.

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When exactly was fermium first created by humans? The date for fermium’s initial production is given in some sources as October 1952, while others claim November — both dates are given for the Ivy Mike nuclear weapons test, the first time humans created elements 99 and 100. The discrepancy apparently is because Enewetak Atoll, the site of the test, lies on the other side of the International Date Line from the United States. The Ivy Mike nuclear weapons test there occurred on 1 November 1952 local time, but 31 October 1952 in the U.S. mainland.

The Ivy Mike weapons test was the first thermonuclear device — or ‘hydrogen’ bomb — and this explosion injected large amounts of radioactive debris high into the atmosphere. In the stratosphere, this debris spread over the entire globe as fallout, which was no different than any other above-ground nuclear weapons test. (Concerns about fallout was a major impetus for the the Partial Test Ban Treaty in 1963, which banned all above-ground or above-water nuclear tests). Arkansas was one of the many places the fallout landed and, in 1952, someone there was watching the sky.

After the Ivy Mike test, initial studies had revealed that the fallout contained 244Pu, a previously unknown plutonium isotope with a relatively large number of neutrons compared to 238U, its likely source. Glenn Seaborg at the University of California Radiation Laboratory (UCRL) received a somewhat cryptic telegram informing him that the existence of 244Pu was classified, even if it was produced by unclassified means. The UCRL group had not produced 244Pu yet, but they knew it was possible now. Seaborg and his UCRL group were well-known as leaders in transuranium element research, having already helped with the discoveries of plutonium, americium, curium, berkelium, and californium. If anyone stumbled across or created 244Pu besides the people analyzing nuclear weapon test fallout, the ‘top men’ at UCRL would be the first suspects on the list.

The knowledge that 244Pu existed, even if classified, was enough to get the UCRL group thinking. This probably meant that six neutrons had been almost instantaneously fused into the nucleus of 238U, much faster than was possible in a high-neutron flux reactor. This prompted UCRL researcher Albert Ghiorso to request samples of the Ivy Mike debris. Ghiorso wondered exactly how many neutrons might have been added. Was 244Pu the heaviest isotope in the debris or were much heavier isotopes also present? (ref. 1). Seaborg was skeptical that so many neutrons could be added to a uranium nucleus, but supported the work. This eventually led to the UCRL group finding elements 99 (ref. 2) and 100 in that fallout debris, as we describe in the fermium IYE essay.

Back in Arkansas, Paul (née Kazuo) Kuroda was interested in nuclear fallout. Kuroda was a Japanese radiochemist who had studied natural radioactive soruces in Japan. He emigrated to the United States in 1949, and worked as a postdoctoral researcher at the University of Minnesota in analytical chemistry until 1952 when he received a faculty appointment at the University of Arkansas. At Arkansas, he returned to his previous interest in radioactivity by studying the local hot springs3. Soon after starting his independent career, Kuroda came across a quote from Edward Teller, one of the principal developers of the hydrogen bomb, stating that the ”radioactive and non-radioactive elements” (the fallout) left behind by a nuclear explosion could be studied to ”learn much about the bomb”.

The Teller quotes are found in Harold Urey’s 1952 book The Planets: Their Origin and Development. Teller was paralleling the isotopic signature in bomb fallout with the isotopic signature left by the creation of the solar system and Earth. Kuroda was puzzled that Urey’s book contained no follow-up on these ideas. Kuroda later wrote ”I therefore decided to initiate my own research project on radioactive fallout from nuclear weapons tests.” (ref. 4). In 1952, Kuroda only knew about the American atomic weapons tests in the Nevada desert, and assumed that any fallout in Arkansas came from these tests. Kuroda realized that the radioactive debris from large nuclear explosions would disperse over the entire planet after being injected into the stratosphere.

In the summer of 1953, Kuroda and his co-worker Paul Damon noticed high concentrations of fission products in the Arkansas rain. They published their results quickly5. Their publication ”On the artificial radioactivity of rainfall”, did not go unnoticed. In the autumn of 1953, they were ordered to stop studying fallout, because ”the study of radioactive fallout by non-authorized scientists was strictly forbidden by the U.S. government as a classified military secret” (ref. 4). Damon and Kuroda apparently were mostly silent about the order to stop, but in 1954, they published a report titled ”On the natural radioactivity of rainfall”, which included the pithy statement about artificial radioactivity in rainfall: ”Presumably, considerable work is underway, but has not yet been published.” (ref. 6).

The concentrations of Es and Fm in the fallout reaching Arkansas in 1953 must have been vanishingly small, so Damon and Kuroda would almost certainly not have been able to detect the new elements. They also lacked the huge hint the UCRL group received about the 244Pu produced in the Ivy Mike test, which was the key insight that inspired Ghiorso’s search for elements 99 and 100 (ref. 1). On the other hand, Kuroda and Damon might have noticed 244Pu on their own. We like to envision Kuroda and Damon as characters in a movie asking government agents ”exactly who is investigating the fallout?” Then, like at the end of 1981 film Raiders of the Lost Ark, when Indiana Jones is assured that ”top men” are studying the Ark of the Covenant, Kuroda was being told that ”top men” were looking into it. Unlike Raiders though, the ”top men” were actually looking at the fallout samples7, instead of packing them in a crate and then hiding the crate in a warehouse.

Why would studying radioactive fallout be classified? Likely because, as Ghiorso and Seaborg discovered, the existence of 244Pu was classified. 244Pu is the longest-lived isotope of plutonium, and is not useful for building a nuclear weapon, but as the quote from Teller plainly said, knowledge of the fallout could reveal ”much about the bomb”. In this case, the existance of a neutron-rich isotope like 244Pu found from the fallout analysis might reveal something about the large neutron flux of the weapon. So 244Pu’s existence suggested a high neutron flux — which was key to Ghiorso’s search for elements 99 and 100. In 1953, this was definitely information best kept secret. Of course, the American government could only stop American scientists from studying fallout in rain. Papers began appearing in other countries, especially once knowledge of the hydrogen bomb tests became widely known, and the long range at which fallout could be transported was realized8,9.

Befitting its numerologically significant position on the periodic table, fermium represents the heaviest element which has been forged in a nuclear reactor. The “fermium wall” prevents production of elements heavier than fermium by neutron absorption due to the short half-life (i.e., spontaneous fission) of 258Fm. To go beyond element 100, nuclear scientists had to turn to the same atom-at-a-time techniques — and the same heavy ion beams which were used to produce the first unclassified ”discovery” of fermium (see the IYE article).

In the 1950s though, you didn’t need an nuclear reactor or a convenient hydrogen bomb to find fermium — it fell from the sky.

Brett F. Thornton is in the Department of Geological Sciences (IGV) and Bolin Centre for Climate Research, Stockholm University, 106 91 Stockholm, Sweden. Shawn C. Burdette is in the Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, Massachusetts 01609-2280, USA. e-mail: brett.thornton@geo.su.se; scburdette@WPI.EDU

References

1. Ghiorso, A. Chem. Eng. News 81, 174–175 (2003). [LINK]

2. Redfern, J. Nat. Chem. 8, 1168-1168 (2016). [LINK]

3. Kuroda, P. K., Damon, P. E. & Hyde, H. Am. J. Sci. 252, 76-86 (1954). [LINK]

4. Kuroda, P. K. J. Radioanal. Nucl. Chem. 203, 591-599 (1996). [LINK]

5. Damon, P. & Kuroda, P. Nucleonics 11, 59 (1953).

6. Damon, P. & Kuroda, P. Eos, Transactions American Geophysical Union 35, 208-216 (1954). [LINK]

7. Ghiorso, A. et al. Phys. Rev. 99, 1048-1049 (1955). [LINK]

8. Miyake, Y. Papers in Meteorology and Geophysics 5, 173-177 (1954). [LINK]

9. Miyake, Y. Papers in Meteorology and Geophysics 6, 26-37 (1955). [LINK]

Materials Girl: Hey baby, what’s your h-index?

[Posted on behalf of Materials Girl]

We’re just getting to know each other, but your resume caught my eye and I might be looking to collaborate… How many papers have you published? What’s the typical impact factor of the journals those papers appear in? Or — to be Google Scholar-forward — what’s your h-index? At what rate do you publish? Are you first or corresponding author? Why should we get to know each other better? Is your CV worth a swipe right?

The potential questions regarding one’s publications are endless, and everyone knows that fateful metric by which a researcher is judged. The “publish or perish” approach to evaluating scientists is inescapable — and particularly of note for younger researchers at the beginning of their careers. As a postdoc working for an untenured professor, publication is of tantamount importance for both me and my PI. Those on the prowl for a job outside of academia, however, might find the importance of publication record to be less obvious. A colleague involved in government-run science/funding (e.g., U.S. Department of Energy) insists that 10–20 papers out of graduate school is the minimum number needed to prove one’s scientific worth and land a decent job. Another had the notion that collaborative, non-first author papers held more value, since institutions typically look for team players.

Naturally, the specifics of a position will dictate the need for a strong publishing record.  Regardless of this importance to a particular employer, however, there is an undeniable, strong community expectation to produce papers. Having a low paper count implies low productivity, but how accurate is it to correlate publication statistics with individual labor/intellect/talent? Out of all the graduate students I’ve encountered, the average number of publications is definitively in the single digits – and could be measured on one hand if only first authorship is considered.

So here’s the question: Is this judgement system realistic? My PhD advisor always insisted that Nature and Science papers would definitely come if I worked hard enough. Not intellect or inspiration — just pure, hard labor. However, sometimes a good publication arises from luck — be it a lucky result or experiment, the luck of being on a good project, the luck of having access to equipment or funding at the right time, etc. Labor and brilliance notwithstanding, even the best researcher may not flourish without a dash of good fortune.

No clear-cut right or wrong answers exist to these matters, and it would be interesting to hear TSC reader opinions. What do you think about scientists judging one another on publishing? How heavily scrutinized should an individual’s publication record be? Do you think that the current system is fair?

Reactions: Xin Su

xinsuXin Su studied chemistry in China and the United States and started his career in scholarly publishing with John Wiley & Sons in New Jersey. He just flew across the pond to London to join Nature Chemistry as a Senior Editor, and will ultimately be based out of the Springer Nature Shanghai office.

1. What made you want to be a chemist?

Certainly a biography book of Michael Faraday I read when I was a kid. In retrospect, it is far from being a fine piece on this great scientist, but it did successfully interest me, sparking curiosity and inspiration in me to go and explore chemistry. Throughout my school years, I also had very good chemistry teachers, which reinforced my pursuit.

2. If you weren’t a chemist and could do any other job, what would it be — and why?

I would choose to become a historian, naturally and ideally studying the history of chemistry. I always had an interest in history, as I still do. I minored in history when I was in college, and was attracted to grammatology and classical Chinese literature. I was seriously thinking of apply for a postdoctoral fellowship from the Chemical Heritage Foundation when I was about to finish my PhD. So if I ever get an opportunity to take two half-time jobs, the combination will be publishing and history.

3. What are you working on now, and where do you hope it will lead?

Now that I have just switched to Nature Chemistry, I look forward to serving truly innovative and broadly influential research results to the readers. In the meanwhile, I’m interested in promoting communications and exchanges among chemists and between scientists and the public (with deep-rooted fear for the demonized chemistry).

4. Which historical figure would you most like to have dinner with — and why?

Nikola Tesla. He was such a prolific genius, but a lot of work he did in his later year remains largely unknown. I’d be very eager to learn more from him.

5. When was the last time you did an experiment in the lab — and what was it?

It was after I left research and started in publishing and it wasn’t chemistry at all. I replaced a cracked screen on an iPad in the lab. It would have been quite awkward to maneuver elsewhere, and you could hardly imagine how easy it is with a lab jack, a heat gun and clamps unless you try yourself (DO WEAR GOGGLES).

6. If exiled on a desert island, what one book and one music album would you take with you?

Shishuo Xinyu (Chinese: 世說新語), or literally, A New Account of the Tales of the World, and to complement it, Guangling San (Chinese: 廣陵散), a qin (ancient Chinese zither) melody long enough to be considered as an album. They make the best companion for solitude, I think. Citing the comment by Graham Sanders, a sinologist at University of Toronto, “few works can match the importance of the book…. for its portrayal of cultural attitudes and social practices among elites in China from the second to fourth centuries”, simply a fascinating age.

7. Which chemist would you like to see interviewed on Reactions — and why?

Professor Gordon Gribble at Dartmouth College. He is a highly achieved scholar, as well as an avid winemaker, but  more importantly, he cares about the public image of chemistry and defends against the so-called “chemophobia”.

 

Reactions: Hosea Nelson

Hosea Nelson is in the Department of Chemistry and Biochemistry at UCLA, and works in organic methodology and catalysis.

1. What made you want to be a chemist?

Biology. Early in my career I became fascinated by biomolecules like DNA and protein enzymes. This led to a strong desire to have a more atomistic understanding of how they work and how they interact with small molecules. I found out quickly that I had to study chemistry to do this.

2. If you weren’t a chemist and could do any other job, what would it be — and why?

Valet parking. The second most fun that I ever had working. I did this when I was in my early twenties. I got to drive a lot of nice cars, had the opportunity to interact with cool people, and made cash tips. Working for tips can be fun.

3. What are you working on now, and where do you hope it will lead?

We are working in quite a few areas of catalysis ranging from small molecule activation to asymmetric methodology. My dream is to develop reactions that are broadly applied to solve the many problems that plague humanity!!!

4. Which historical figure would you most like to have dinner with — and why?

Albert Einstein. I may be naive when it comes to physics, but I view the theory of general relativity as one of the most insightful and creative additions to science. I love to rub shoulders with creative scientists…. Maybe some of their magic will rub off on me.

5. When was the last time you did an experiment in the lab — and what was it?

Last month. I screened conditions for a transition metal-catalyzed alkene hydration.

6. If exiled on a desert island, what one book and one music album would you take with you?

For music, the soundtrack to Superfly by Curtis Mayfield. For reading, Fear and Loathing in Las Vegas by Hunter S. Thompson.

7. Which chemist would you like to see interviewed on Reactions — and why?

Ken Houk. He could tell cool stories about Woodward.

Reactions: Jen Heemstra

JenHeemstraCOS crop4Jen Heemstra is in the Department of Chemistry and the Center for Cell and Genome Science at University of Utah, and works on understanding and utilizing the molecular recognition and self-assembly capabilities of nucleic acids for applications in biosensing, bioimaging, and stimuli-responsive materials.

1. What made you want to be a chemist?

I had fantastic mentors. I entered high school thinking that I wanted a career in math. This changed when I joined Science Olympiad, largely because our coach was so effective in conveying to us the joy of scientific discovery and the fact that science is a constantly evolving field. In college, I had the opportunity to work in a chemistry research lab with an outstanding mentor, and after two years thought “hmmm, maybe this is something I want to do with my life.” This was followed by outstanding mentors in graduate school and my postdoc, who nudged me toward academia. I now recognize that l love chemistry because I love to design, build, and explore molecules. But, I think there are many careers that I could have been happy in, and it is interesting to ponder whether things might have ended up differently given a different set of formative influencers in my life.

2. If you weren’t a chemist and could do any other job, what would it be — and why?

I would love to be an architect. Over the past three years, I’ve had the opportunity to serve on the design committee for a new building on our campus, and that has been a really neat experience. I’ve come to appreciate much more of what architects do. Similar to chemists, they have some mundane aspects to their jobs, but they spend significant amounts of time creating, problem solving, and engaging with other people, which are all things that I love about my current job.

3. What are you working on now, and where do you hope it will lead?

Our lab has spent the past seven years developing and studying biomolecular platforms for molecular recognition, self-assembly, and catalysis in vitro. We’re excited to now be pushing these towards applications in living cells, and eventually in vivo. We anticipate that this will open up new avenues in a variety of areas including metabolite imaging, biocatalyst discovery, RNA-based diagnostics, drug delivery, toxin sequestration, and transcript-targeted therapeutics. Over the past few years, I’ve also become increasingly passionate about the challenge of how to educate and prepare students for future success. In particular, I think that we need to help students overcome fear of failure, and encourage them to embrace failure as a necessary step on the path to innovation. My grand hope is that this will lead to an overhaul of how universities assess student success in courses – our current approach teaches students to avoid failure at all costs, which is in dissonance with the values of today’s most innovative workplaces, where we hope our students will end up.

4. Which historical figure would you most like to have dinner with — and why?

Rock climbing has been a passion of mine for the last 20+ years, and so I would choose to have dinner with Lynn Hill. She was one of the few women hanging out in Yosemite’s Camp 4 during the dawn of sport climbing in the 1980s, and has crushed barriers across multiple disciplines of climbing. Right at the time that I was starting to climb, she became the first person, male or female, to free climb The Nose on El Capitan. A year later, she repeated the climb in under 24 hours. When I first subscribed to Rock and Ice magazine, the free gift was a poster of Lynn Hill climbing The Nose – this hung in my dorm room all through college as an inspiration to work hard and push limits.

5. When was the last time you did an experiment in the lab — and what was it?

These days, I’m only in lab to do experiments related to our educational or outreach activities. My last experiment was flooding a plate of GFP-expressing c. elegans and trying to pipet them into a 384-well plate to measure fluorescence intensity. My experiment didn’t work, but then two graduate students from my group tried the same experiment a week later, and they got it to work great. That’s pretty typical these days, and I’m thrilled to be surrounded by a group of people who are all much more competent in lab than I am.

6. If exiled on a desert island, what one book and one music album would you take with you?

Album choice is easy – The Heist by Macklemore & Ryan Lewis. They are one of many artists whose music I enjoy, but what makes them unique is the diversity of emotions that are captured on one album. This album in particular has songs that span the themes of working hard to achieve big goals (“Can’t Hold Us”), the shame that comes with failing yourself and those you care about (“Starting Over”), and not taking yourself too seriously (“Thrift Shop”). I would need a lot of positive energy to survive in exile, and it’s impossible not to smile when singing along to lyrics about rocking flannel zebra jammies from a thrift store. Book choice is much tougher. Most of my favorite books right now (Mindset, Creativity Inc., Give and Take) are focused on how we relate to those around us, so reading one of those on a desert island would make me feel even more lonely. I would probably choose Bossypants by Tina Fey, as that book can still make me laugh out loud, even though I’ve read it at least five times.

7. Which chemist would you like to see interviewed on Reactions — and why?

I would love to see an interview with Cathy Drennan. She is an outstanding researcher, educator, mentor, and advocate for diversity, manages to balance all of this with family life, and seems to be having a blast in everything she does.

Reactions: Elaine O’Reilly

oreillyElaine O’Reilly is in the School of Chemistry at the University of Nottingham, and works on the development of biocatalysts and biocatalytic methodology.

1. What made you want to be a chemist?

I originally went to University to study genetics, having been fascinated with Charles Darwin and his theory of evolution and natural selection from a young age. During my degree at University College Dublin, I took chemistry as one of four choices in first year with the intention of dropping it as soon as possible. I would love to say that the subject captivated me from the onset but in reality, I really struggled with it. Thanks largely to help from one of my lecturers (Prof. Earle Waghorne – thank you!) and a good group of friends, I managed to scrape by. It was in second year that I started to really enjoy chemistry and after spending time in a research lab in my final year, I realized that I was hooked.

2. If you weren’t a chemist and could do any other job, what would it be — and why?

I would love to be an actress on the West End! Aside from the fact that I can’t sing or dance, I would be absolutely perfect! My mum, Phyllis, always told me I was a real ‘abbey actor’ when I was a child and I think I still am.

3. What are you working on now, and where do you hope it will lead?

We are trying to develop biocatalysts that will convert abundant materials into high-value chemicals and pharmaceuticals. Our overall aim is that we will have a ‘toolbox’ of (engineered) enzymes available for a much wider range of synthetic transformations, with a particular focus on those that are challenging or impossible using a more traditional chemical approach. My ambition is for our research to make a real difference in peoples’ lives and if we achieved this directly with our science, I could retire happy. However, perhaps on a smaller scale, I try to be a good mentor to the next generation of scientists, who have the ability to make a powerful impact on people’s lives. I like to think I do the best I can for students who choose to work in my laboratory with the hope that they will become far more capable scientists than I am and truly make a difference.

4. Which historical figure would you most like to have dinner with — and why?

I suspect that he gets a lot of fantasy dinner invites, but it would have to be Charles Darwin. His work has fascinated me for many years and I would love to hear how his theories and ideas were carved out. His research not only directly inspires the work we undertake in our laboratory (directed evolution and protein redesign), but has shaped the way we all look at the world around us.

5. When was the last time you did an experiment in the lab — and what was it?

I have been on maternity leave since August 2016 so between that and being pregnant, I have mostly avoided the lab. The last time I was active was in 2015 and I was trying to develop a high-throughput screening strategy to enable the directed evolution of transaminase biocatalysts. This involved synthesizing some diamines, which should have been easy (it wasn’t). I have since passed the task over to one of my students.

6. If exiled on a desert island, what one book and one music album would you take with you?

I would take How to Survive on a Desert Island’ by Tim O’Shei and Michael Jackson’s Off the Wall.

7. Which chemist would you like to see interviewed on Reactions — and why?

I would like to see Prof. Donald Hilvert interviewed. His group is doing some inspiring work in a similar area to our own.

Reactions: Paolo Melchiorre

foto-pmelchiorrePaolo Melchiorre is an ICREA Research Professor and a Group Leader at the Institute of Chemical Research of Catalonia (ICIQ), Tarragona (Spain). He works on the discovery and mechanistic elucidation of enantioselective organocatalytic and photochemical processes. Paolo recently published a paper in Nature Chemistry entitled “Visible-light excitation of iminium ions enables the enantioselective catalytic β-alkylation of enals.”

1. What made you want to be a chemist?

My father is a medical chemist (now retired) — I guess the fact that his colleagues/friends were often around during my childhood might have had something to do with my decision to study chemistry. As for innate propensity, I was always curious about natural phenomena, their mechanisms and meanings.

2. If you weren’t a chemist and could do any other job, what would it be — and why?

Any activity related to freedom and exploration. But I’ve always liked sports and, when I was a child, I would have loved to have become a sportscaster.

3. What are you working on now, and where do you hope it will lead?

We are exploring the reactivity of chiral organocatalytic intermediates upon light excitation. An electronically excited state can unlock reaction pathways that aren’t available to conventional ground-state chemistry. So combining enantioselective organocatalysis with photochemistry can offer unconventional ways of making chiral molecules. We believe that this approach will not be limited to organocatalysis, but could be applied to other areas of modern synthetic chemistry.

4. Which historical figure would you most like to have dinner with — and why?

It is really hard to choose only one! There are so many historical figures with whom I would love to have dinner: from Julius Caesar and Charles Darwin, to Copernicus, Primo Levi, and Marie Curie. But probably my final choice would be Leonardo da Vinci, a real man of the future – I could even use Italian to talk with him and try to understand how a genius thinks.

5. When was the last time you did an experiment in the lab — and what was it?

A long time ago, in 2010. It was the very beginning of our studies on photochemistry, and I performed a reaction that required UV irradiation. As a light source, I used the UV lamp that was generally used in the lab for thin-layer chromatography visualization. Incredibly, the reaction worked a bit.

6. If exiled on a desert island, what one book and one music album would you take with you?

La Divina Commedia – a long time has passed since I read it at school, and it would be long enough to keep me busy and thinking for a while. As for the music, Radiohead’s full discography, but only if I am alone. Otherwise, my wife and kids would destroy it.

7. Which chemist would you like to see interviewed on Reactions — and why?

Ryan Gilmour and Dieter Seebach. I believe the former will strongly influence Europe’s organic chemistry community; the latter has profoundly done so.

Materials Girl: Life beyond academia

[Posted on behalf of Materials Girl]

Mortality is not a concept that many young scholars are in the habit of considering. Indeed, students tend to pay little thought to their health within a frequently frenetic, sleep-deprived, caffeine-powered existence of procrastination and salty ramen (or are those tears?). Self-care was not an issue that I focused on during grad school, or even in the following year of post-graduation burnout. Sure, I dropped 15 lbs in two weeks while preparing for quals — however, starvation, 20 hour workdays and anxiety attacks are neither a healthy nor sustainable lifestyle (and needless to say, that weight came right back)… Only in retrospect have I realized the depth to which I was depressed, hyper-stressed, and overly isolated in The Dungeon – meanwhile medical specialists wondered why my health was so  poor for a normal-looking student in her early/mid 20’s.

Graduate school was possibly the hardest, most strenuous “activity” in my life. Had I been in good mental and physical shape, I could have graduated in half the time. Perhaps even more quickly, had I not been stumbling through a miserable haze of fatigue, stress, and some sort of masochistic pleasure in overexerting myself (and often focusing on teaching instead of research). Even now, it seems miraculous that I went from having sporadic, disparate projects without a clue what was going on to pulling together a coherent dissertation.

Being a postdoc is just a step above being fodder for the graduate school machine. While my position is still in academia and involves work far more hours than I’m paid for, I’ve also learned to focus on myself. Not just on my work/career and scientific responsibilities, but also me: MG the human. MG with both scientific and extracurricular activities. MG who has amazing friends and is reassembling something one might call a life.

Last year was a defining time for me — personally and professionally, mentally and physically. One step in “real adulthood” has been learning to take nights and weekends off, things that normal people do! Grad-student-MG would’ve been wracked with guilt. Mentally-improved-MG adapts by actually working efficiently and not allowing distractions or exhaustion to overtake the day. Physically-improved-MG changed a sedentary lifestyle into working out six days each week and cooking healthy meals. Instead of late-night languishing in the office with flagging productivity, my work is done more effectively before scampering off to mixed martial arts classes. Afterwards, I scamper home to unpack, eat, shower, sleep early, and drag myself out of bed around 6:30am. Wash, rinse, repeat, and — most importantly — enjoy.

Behind every speck of data and writing is a person with aspirations and feelings — not just a monkey or nameless face who works in the lab and chugs coffee. As Rebecca Schuman aptly says in The Not-So-Splendid Isolation of Doctoral Study, “One of the biggest mistakes many of us make is to forget that our brilliant brains live inside whole, mortal people — and that those people need taking care of”. We must remember to appreciate not only the research, but also the individuals who discover the science. Respect yourself, take breaks, and never lose sight of who you are. And even if that happens, you can come back. Be mindful and give yourself grace, as a wise friend of mine would say. It makes all the difference in the world.