Articles by: Kenneth Hanson

The Life Cycle of a North American Research Project

Simply reading a research article doesn’t provide any insight into how a project progresses from inception to fruition/publication. Sometimes projects start as a good idea. Other times they begin from interesting or unexpected results. Every so often, it is an accident.

These auspicious origins are further clouded by the tendency of authors to present their results as if they were intentional from the very beginning, even if they stumbled upon them. To a younger scientist reading these papers it can feel overwhelming to begin research. They may ask “how could I ever possibly get from here to there?”

A project that I started four years ago at the beginning of graduate school was finally published last week. It was by far my favorite project. Not only because of the content but also because of the journey. In response to a question posed by masterm on the chemistry subreddit, I am going to share my experience with the process between inception and publication for this project and hopefully provide some insight for the uninitiated.

My graduate career can be broken down into two categories: 1) research that pays the bills and 2) purely scientific research. In 2005 when I started graduate school my adviser, Mark Thompson, came to me with a not so simple request: “Find a molecule that exhibits efficient (>10%: more than 10 out of every 100 photons that are absorbed are then emitted) phosphorescence between 750 and 900 nm.” This project fell into category 1 because it had specific, short-term, grant dictated goals along with a long term goal of producing a commercially viable product.

Unfortunately/fortunately the number of published molecules that efficiently phosphoresce in that wavelength range is limited. During the years that followed my colleges and I (team IR) became entrenched in the idea of taking known molecules and extending the π-conjugation to red-shift emission. This strategy was based on a common tenet in small molecule photophysics that says if you extend the π-conjugation of a molecule (add more benzene rings) you will lower the energy of absorption/emission (changing from blue/high energy/shorter wavelength towards red/low energy/longer wavelength). It is a ‘particle in the box’ mentality. That is, if you extend the box you will lower the energy of the system. The words “let’s just add some benzene rings to it” became our regular chorus. With this mantra we had a considerable amount of success, adding benzene rings (benzannulating) platinum porphyrins. Attempts at benzannulating other systems were less successful in that they either did not shift the emission or they were unstable.

At the 2006 ACS meeting in San Francisco I presented my results on one of these “failed” pursuits. I also made an effort to go to as many talks and poster secessions as possible hoping that I would come across a new molecule/ligand that might help reach our goal. I kept seeing 1,3-bispyridylisoindole (BPI) ligand in various catalysis presentations. It caught my attention because it has many of the components that we have in our near-infrared emitters: a pyrrole like our iridium dipyrrins (λem = 672 nm) and platinum porphyrins (λem = 650 nm), an isoindole like platinum tetrabenzoporphyrins (λem = 765 nm) and phthalocyanines (λem = ~1000 nm). It is a simple concept in chemistry that, more often than not, if things look similar they will exhibit similar behaviors.

Before we ever go to the bench and synthesize a new molecule we first perform a DFT calculation to get an estimate of its phosphorescence wavelength (Etriplet-Esinglet or EHSOMO(triplet) – EHOMO(singlet)). In my hotel room that night I performed this high yield “reaction” (Titan: B3LYP, LACVP**) and inserted a platinum chloride into BPI and found the calculated emission wavelength was 675 nm. That is way out into the deep red but not quite to the 750-900 nm we were looking for. So what’s next? The chorus comes around again: “BENZANNULATE!” Adding three benzene rings (bottom right) to the parent structure (top middle) resulted in a modest red-shift in the emission wavelength from 675 nm to 697 nm. Needless to say, this was an anticlimactic result. I was disappointed and wanted to understand why there was only a small shift, so I calculated a series of these molecules (above). A clear trend can be observed, benzannulating the pyrrole ring results in a blue shift, benzannulating the pyridyl ring results in a red shift. The calculated blue shift is counter to the common expectation that benzannulation results in red shifted absorption/emission.

Between my advisers interest in the two molecules predicted to emit above 800 nm and his desire to find out if the calculations were correct, he gave me permission to pursue the project. Following published procedures or slightly modified versions of these reactions I was able to produce several similiar molecules. In both absorption and emission, the predicted trends were correct. In fact, even without taking a measurement it was obvious to the naked eye that the absorption and emission were blue shifting upon benzannulation of the pyrrole ring (left).

So now that we knew that the phenomenon was real, the question was “Why the blue shift?” Turning to literature we were able to find several examples of molecules that exhibit this behavior but the explanations given were either incomplete or molecule specific. No generalized explanation could be found.

So we had a mystery on our hands. Between our preliminary calculations, photophysical and electrochemical measurements we were able to conclude that an unchanging HOMO energy (similar oxidation potential) and a destabilized LUMO energy (increasing reduction potential) with each benzannulation was responsible for the observed trend.

Proud of our result and the conclusion we had reached at this point, I was excited to present the results at the Southern California Inorganic Photochemistry Conference (SCIP). I explained the story and results of the discovery and at the end of my talk Professor Jeffery Zink (UCLA) asked a simple but profound question that I was unable to answer: “Why does the LUMO go up?”

Reflecting on the question I experienced a flashback to constructing orbital diagrams in undergraduate chemistry classes. For the sake of people not to familiar with the topic, I will quickly review molecular orbitals. The interaction between two orbitals can be broken down into three categories: bonding, antibonding and nonbonding. In cases where the energies and symmetries of two orbitals are similar they will interact to produce a stabilized bonding and a destabilized antibonding interaction. The shape and energy of these bonding/antibonding orbitals will be dependent on the energies of the two interacting orbitals. In cases where the orbital energies are extremely unequal no interaction will occur. Similarly, if the symmetry of two orbitals are not similar they will not interact (example: px and py are orthogonal and thus will never interact).

Using thus basic principle to construct an orbital diagram of naphthalene from the combination of benzene and butadiene you will find that a HOMObezene-HOMObutadiene bonding/antibonding interaction destabilizes the HOMO (increases the energy) and a LUMObezene-LUMObutadiene bonding/antibonding interaction stabilizes the LUMO (decreases the energy), as shown below.

The HOMO destabilization and LUMO stabilization inevitably leads to a red-shifted absorption (smaller ΔE for the HOMO to LUMO transition) of napthalene relative to benzene. This type of orbital interaction is the reason behind the common expectation that benzannulation will red-shift absorption/emission.

Without an answer to the question (“Why does the LUMO go up?”) I presented these results again at the 2008 ACS meeting in New Orleans. At the meeting I had a chance to catch up with one of my closest friends and a fellow graduate from the St. Cloud State University’s  chemistry department, Luke Roskop (St. Cloud State is a small university in Minnesota that you have probably never heard of unless you enjoy college hockey). It just so happens he was/currently is a graduate student at Iowa State under one of the world’s foremost theoretical chemists, Mark Gordon. After a conversation that night and permission from both of our advisers we decided we were going to combine our expertise and do our best to come up with an answer.

Over the several months that followed and through a combination of time-dependent DFT calculations, photophysical measurements and a bunch of reading we were leaning towards an argument that involved orbital diagrams. However, it was not until holiday break while both of us were back in Minnesota at Luke’s parent’s dinning room table that we had a break through. As a synthetic chemist, I often pigeon-hole myself into only thinking about molecules that can be made. In fact, I sometimes get an uncomfortable feeling when looking at a molecule that “feels” unstable. One of the things that I love about theoreticians is that if it can be dreamed of they can calculate it. Luke’s ability to imagine the “impossible” became infinity useful on that particular day. Utilizing his remote access to Iowa States computing cluster, Luke just started making changes to the BPI motif to figure out the effects of structural changes on the HOMO/LUMO orbitals and energies. After looking at dozens of molecules a tremendous feeling of clarity hit me. It was one of those rare moments that all scientists search for. My internal conflict floated away and for a brief moment I felt as if the universe made sense. I turned to Luke and said “You are going to love this!” What followed was my tentative explanation of the phenomena and then a long discussion between us to iron out the details. By the end of the night we had outlined what as of last week became our publication.

Ignoring the importance of justifying the use of molecular orbitals (beyond the scope of this summary but is discussed in the paper) our rationalization can be reduced down to a simple molecular orbital argument. In the orbital diagram for benzene we find that a LUMO-LUMO interaction leads to destabilization of the LUMO of naphthalene as compared to benzene. In the system described here, the HOMO of (BPI)PtCl (middle) has very little orbital density at the sites of butadiene addition and as a result no mixing occurs and the HOMO energy/orbital remains unchanged.

The LUMO however, is energetically similar to both the HOMO and the LUMO of butadiene thus the type of interaction that occurs is dictated by the symmetry of butadiene addition. The nodal plane of the LUMO at the end of the isoindole ring of (BPI)PtCl is the same symmetry as the HOMO of butadiene (also has a nodal plane) and thus a bonding/antibonding interaction occurs that destabilizes the LUMO. The unchanged HOMO and the destabilized LUMO results in a blue-shifted absorption of the benzannulated product (right) relative to the parent molecule. Alternatively, the lack of a nodal plane on the pyridine ring at the sight of butadiene addition results in the expected LUMO-LUMO interaction resulting in a stabilized LUMO of the isoquinoline derivative (left) and red shifted absorption relative to the parent molecule. Similar arguments hold true for not only for benzannulating the other positions of (BPI)PtCl but also the previously published examples of blue-shifted absorption upon benzannulation.

In short, we found an unexpected but straight forward visual manifestation of molecular orbital theory.

We finished up the paper (an ordeal in itself), submitted it, and it was accepted after revisions.

Take home message from this project:

  1. Go to presentations that are unrelated to your research/expertise.
  2. Pay attention to your unusual results.
  3. Gather knowledge. The more knowledge you have in a subject matter, the more likely you are to recognize something unusual.
  4. Find an adviser that will let you pursue an interesting project (I have no idea how to make this happen other than word of mouth or just get lucky).
  5. Don’t rule out the imaginary molecules. Sometime they are exactly what you need.
  6. Try not burn any bridges in pursuit of your goals; you might need help later.

Inquiring Minds Need Your Help

My current adviser has successfully managed a research group for more than 30 years. He has produced hundreds of publications and acquired a wealth of chemistry knowledge. Last week, when the group moved into a new lab, we boxed and unboxed the tools that helped build this knowledge: a grand collection of equipment, glassware and chemicals.

It has become abundantly clear that with much knowledge comes much glassware.

And not simply your everyday beakers or Erlenmeyer flasks, but unique glassware created for specific experiments. While this glassware once had high utility, it is now a fossil of long-ago projects gathering dust in the archives (and by archives I mean that drawer full of weird glassware that no one uses).

The graduate student or postdoc who preformed the long-forgotten experiment has moved on and taken with them the explanation of the glassware’s function.

The inquiring minds of my research group would like your help in identifying/explaining the five of the most interesting specimens.

1) The Immersion Condenser
The first item is an immersion condenser or cold finger with an o-ring connector and an inlet/outlet for cold water. The question is why does it have the weird tip at the end?


Since many of you are currently trying your hardest to come up with a funny/witty comment, I will make a preemptive, unclever strike: PENIS! PENIS! PENIS!

2) The Pitch Fork
Each of the glass rods in this image has a small (~1-2 mm) tube inside so it behaves as a four-way junction. Why this specific shape?

3) The Meth Pipe
This item has two openings. The smaller one has a long stem that encircles the larger opening several times until they both meet in a conical chamber. As you can tell from my label, our guesses on this glassware’s purpose were limited.

4) The all-in-one Reflux/Distillation/Addition Funnel Apparatus
The form of this item is relatively straight forward with the exception of the absent Teflon or glass stopcock just above the lowest round bottom flask. What is it for?

5) The Bubbler
This is the piece that I am most curious about. At first glance it appears to be a plain bubbler with a smaller inlet tube that runs to the bottom of the larger chamber which has an outlet near the top. Upon further inspection, we find that there is an additional, independent piece of glass in the inner tube that is free to move vertically (inset). The independent piece of glass is a sealed chamber either filled with a gas or is simply a vacuum. On the top of this piece is a ground-glass ball joint. The counter to this ball joint is a socket with an opening from the top inlet. Our best guess for this piece is that, unlike a normal bubbler, the inlet is reversed and is for liquid to flow directly into the larger chamber. As that chamber fills, the freely moving piece is buoyant and will continue to move upward with the solvent. Once the chamber has filled with enough solvent it will push the ball and socket joint together preventing the further flow of liquid. If this guess is indeed correct, what would you use it for?

Any insight you can offer is greatly appreciated.

By October 17, 2010 16 comments fun, Uncategorized

$cience is Important

Last week Kei Koizumi, Assistant Director for Federal Research & Development for the White House Office of Science and Technology Policy, paid a visit to the University of North Carolina-Chapel Hill (my new home as of mid-June). The visit included a tour of several laboratories where everyone did their very best to convince him that our funding (e.g. my salary) is worthwhile as well as a presentation by Mr. Koizumi that outlined the Presidents plans/goals/vision for scientific funding.

On many occasions, President Obama has voiced his strong support of the sciences. In an address to the National Academy of Sciences on April 27, 2009 he emphasized the importance of science by stating “Science is more essential for our prosperity, our security, our health, our environment, and our quality of life than it has ever been before.” In addition to this type of powerful dialogue we have seen significant action.  Perhaps the most obvious example of this is the scientific funding boost that came through with the American Recovery and Reinvestment Act (ARRA, purple block in the graph below). In addition to this quick funding boost there is a continuing effort by the administration to double the 2006 budget for the Department of Energy, the National Institute of Standards and Technology and the National Science Foundation by the year 2017. The approved 2011 budget continues with this upward funding trend as outline in the graph below.

So what does the future hold? Every year a memorandum is sent from the Office of Management and Budget to the major funding agencies requesting their budget proposals for the upcoming year. In this memorandum the current administration outlines how they intend to direct their funding. In the 2012 memorandum, the Obama administration emphasized the following six areas of focus:

  • Promoting sustainable economic growth and job creation.
  • Defeating the most dangerous diseases and achieving better health outcomes for all while reducing health care costs.
  • Moving toward a clean energy future to reduce dependence on energy imports while curbing greenhouse gas emissions.
  • Understanding, adapting to, and mitigating the impacts of global climate change.
  • Managing the competing demands on land, fresh water, and the oceans for the production of food, fiber, biofuels, and ecosystem services based on sustainability and biodiversity.
  • Developing the technologies to protect our troops, citizens, and national interests.

The proposal writing process is no doubt an exercise in balancing wishful thinking and self control. Along these lines it is not unusual for an agency to submit several versions of their budget (above, below and the same as the previous year). However, due to the recent economic issues, the administration was particular in asking all agencies to submit a funding request that is reduced by 5 percent relative to the previous year. As of Monday, September 13th the new budget proposals for the 2012 fiscal year were due. Over the next several months negotiations between the Office of Management and Budget and the Office of Science Technology Policy will determine the 2012 funding situation.  The 2012 budget will then be announced in the first week of February 2011. Although it is unlikely that every agencies budget will be reduced by 5% , 2012 is likely to be a tough year for many researchers.

tl;dr: All you have to do to guarantee funding in 2012 is submit a solid proposal for a commercially viable, bulletproof, CO2 detecting solar energy converter that cures diseases while still maintaining the ecosystem.

By September 19, 2010 6 comments science policy

Finding a Postdoc Position is a Difficult Journey but here are 15 Tips to Help You Along the Way.

My impression, from the anecdotes of others as well as my own experience, is that finding a postdoctoral position is a widely unknown and undiscussed process that one learns about via “trial by fire.” For example, Mitch wrote about the surprises he experienced during his interview last January.

Unlike applying for college or graduate school, there is no formal application process for obtaining a postdoc. From what I have been told it more closely resembles the job search process, but for further complication, many postdoc openings are not advertised and only become available when the right applicant inquires. In an effort to support future postdoctoral hopefuls, I am going to expand on Mitch’s prior post with insight and advice I acquired through trial and error and gleaned from the stories of others. It is a long list but hopefully some of this information will be helpful.

Get your foot in the door…
1. Begin your search one to two years before graduation. A few professors shared this insight with me after they learned I began my postdoc search only nine months before my own graduation (oops). It makes sense now when I think about it because potential advisors need time to allocate money, resources and a project for your estimated date of arrival.

2. Find four or five research groups you are interested in working with. I focused primarily on finding groups working in the flavor of research I am interested in. Other searchers may prioritize location. Another variable, more important than either, is whether the lab you are interested in will serve as a stepping stone for your long-term professional goals.

3. Write a cover letter to each professor. This letter should include a brief overview of the research you have conducted and why you are interested in their work. I recommend subtly incorporating the skills, tools, and ideas you would bring to their research. I would also mention a willingness to pursue external funding sources or to request recommendations for any fellowships they may know that you could apply for.

4. Ask your advisor to send a short email on your behalf. It is not unusual for a top research professor to get several postdoctoral applications each week. Regardless of how good your qualifications may be it can be difficult to differentiate your email from the others. If your advisor is willing, have them send a truncated recommendation email saying something like, “I have a spectacular graduate student that is interested in being a postdoc in your research group and you would be a fool to pass them up. They will be sending you their CV and cover letter shortly.” If the professors know each other it can be huge advantage in your favor and sometimes this email is all it takes to get an offer.

5. Send an email with cover letter and CV attached. Example email text: “I am a fifth year graduate student in the …. research group at the University of …. This email is to express my interest in joining your research group as a postdoc starting in Month 201x. Attached are a cover letter and curriculum vitae. Letters of recommendation are soon to follow. I am happy to provide any other information you may find helpful.”

6. Send a hard copy of the cover letter and CV. Even if your email gets ignored you can pretty much guarantee that a physical letter will at least be opened and your name will cross the professor’s mind at least one more time.

7. Wait for a reply. Hopefully you hear back from the professor with good or at least a neutral (not no) reply. In the best case scenario you get a job offer or an interview. If they do not extend an invitation for a campus visit, you can insist on paying for your own visit and offer to give a talk. This option of course depends on how badly you want the position, as well as the state of your bank account. My theory is that it would be much more difficult to say no after a person has demonstrated that they are highly interested and competent (assuming you demonstrate these qualities). If you do not hear back in several weeks you should send a follow up email asking for an update on the postdoctoral position.

You have planned a visit. Before you go…
8. Do your homework. Looking into the research group’s goals and methods should be a no-brainer. It is unlikely that you will get a pop quiz on their research. However, your general dialog with the adviser and group members will flow much better and you will leave a better impression. Nothing says “I have a scientific mind” like asking a really insightful question. If possible, think of a proposal or direction they could shift their research. They might not want to pursue your ideas but it does show that you have them.

9. Have a one hour talk prepared. Instinctively you might feel the need to include as much of your PhD work as you can cram into an hour but it is much more effective to present a small subset of your research with a coherent storyline. This talk should also be tailored in a similar manner as your cover letter as to clearly demonstrate skills/tools/ideas you can bring to their research.

During the visit…
10. Consider how to dress. This is a point where I respectfully disagree with Mitch. If you are someone that is comfortable or enjoys wearing a suit by all means look more professional. However, I am not willing to sacrifice my comfort for appearance. The more relaxed I am the better I will perform in both my presentation and one-on-one meetings. For my postdoc interviews (and defense) I wore a nice pair of jeans and a suite coat.

11. What to expect. Your visit will most likely be comprised of a lab tour, possibly a short campus tour, a meeting with the adviser/grad students/postdocs, lunch and a presentation (either to the group or the entire department). Not necessarily in that order. If there are in-house collaborators, a meeting with them can be expected but thanks to Mitch I now know that you might also be asked to meet with other professors in the department.

12. Be prepared for a long, energy consuming day. You will likely be putting in an 8-hour day of constant discussions. I have heard rumors that when veteran professors are interviewing a candidate they will set up a meeting in the morning and one at the end of the day. The reason they do this is to first catch you in the morning to see how awake and energetic you are, and then at the end of the day to see if you are the same way. It is a method of finding out who you really are. It is very difficult to keep up a facade for 8 hours. Also if you can keep up your energy that entire time you are probably going to get a lot of work done.

After your visit…
13. Send a follow-up email. A few days after the interview I sent a follow-up email thanking the professor and their group members for their time, reemphasized my interest in their research group and closed by asking for updates on the position. If I did not hear back within a month I sent a second email asking for an update.

14. Funding. Even if you have received an offer that includes full financial support it is still a good idea to apply for postdoc fellowships not only for the money but also the prestige that comes with receiving a fellowship. Most advisors are willing to help you write a proposal based on their work or an original proposal idea. Whether or not you get the fellowship you will still learn a lot about your future projects.

15. Making a decision. Believe it or not, this might be one of the more difficult parts of the process. If you only receive one offer out of several attempts it greatly simplifies your decision. However, if you get a few offers it may be more difficult. This is the time to ask some honest questions about your future advisor and group members. Will they help you find a job? Do they like the area? What is it like working their? Many of us also have to consider the two body problem. Can my significant other find a job there?

The final advice I will give is that the process is so individualized that you should consult everyone you can that has undergone their own postdoc adventure. If others have any more information to share, please do so.

By July 18, 2010 15 comments Uncategorized