A Chemical Mystery: Navigating the Unpredictable Course of Research

Did you know that research scientists and detectives have some things in common? Research often does not go according to plan, and sometimes in the lab you stumble upon something unexpected and mysterious. If you’re lucky, you can follow the clues to solve a mystery that you didn’t originally set out to solve. 

This is the story of how my biggest discovery during my sabbatical year at Seoul National University (SNU) was not in the research area I set out to study. It’s not a disappointment, nor is it something that really surprises me. In this post I’ve described the chemical mystery that I stumbled upon and how I solved it using research methods. It is written at about a 1st-year undergraduate chemistry student level.

A Detour

Because of my own research interest (in the organometallic chemistry of carbon dioxide), I was attracted to work with the Yunho Lee group and their work on organometallic models of the carbon monoxide dehydrogenase CODH enzyme. Yunho and I developed a straightforward idea for a project, but it first required the synthesis of a compound (a proligand) by one of Yunho’s students. That was likely to take a month or so, so on my first day we discussed other possibilities for a short project for me to work on in the meantime.

On the whiteboard beside Yunho’s desk was a hand drawing of a very interesting chemical structure. When I asked about it, Yunho gave me the draft of a manuscript for a journal article about this compound. But he wasn’t satisfied with the draft, believing that with a little work the findings might merit publication in a high visibility journal. I agreed. The manuscript described some surprising chemistry related to the very unusual nickel complex depicted below. (The term nickel complex just refers to a chemical compound featuring a nickel metal atom at the center surrounded by and bonding with other compounds called ligands.)

There are many atoms in this compound, but the most important are the nickel (Ni), nitrogen (N, two kinds), and sodium (Na). They form a ring-like structure around the middle of the compound (highlighted in red). It is a very distorted structure with several weak interactions (dashed lines). Weak interactions mean that the compound is very ready to undergo reactions. Indeed the compound reacts with benzene, one of the simplest compounds in organic chemistry, and breaks one of its strong C-H bonds. That’s not something nickel complexes like this can usually do.

In addition and even more surprising, elemental sodium (Na) is produced. That’s not normal. Elemental sodium metal is quite different from the sodium you use when you salt your fries with sodium chloride. As chemistry students learn, it is the cationic (+ charged ion) form of sodium that is the sodium that we all encounter in our everyday lives (Na⁺). The only difference between sodium metal and sodium cation is the presence of one electron, but what a difference an electron makes. (Elemental sodium famously reacts with water like this– fun!).

This reaction was unexpectedly producing sodium in its elemental form. This was very shocking. My coauthors, especially Jonghoom Choi, ran countless tedious experiments to prove that what we were seeing was indeed elemental sodium.

Also produced is a much more run-of-the-mill nickel phenyl complex. I jumped into the project with the goal of showing that the phenyl complex would react with other simple reagents to result in forming a new carbon-carbon bond. That’s important because while breaking a C-H bond in benzene is great, it is not really useful unless we can then use the resulting phenyl complex to make a new carbon-carbon bond. So I set out to test this phenyl complex under many different conditions.

Long story short, almost nothing I tried worked. The nickel phenyl complex is very stable— very unreactive. I tried for many weeks to get some kind of reaction to take place. This is the part of the story that most every scientist has encountered. The part where nothing you try is working, and you can easily become frustrated and lose motivation. Luckily this phase did not last too long on this project.

The Mystery

I got desperate for something to happen, so I decided to add elemental sodium to the phenyl complex along with a crown ether, hoping to form a new species that would be more reactive. When I did, something happened! I saw a reaction take place (an obvious color change was my first clue), but there was a mixture of products produced, one of which was a never-before-synthesized compound! Exciting! 

This is where the real work began. I carefully repeated the reaction and confirmed that I was consistently seeing the same product. I then figured out how to separate the new product from the reaction mixture. I soon had the new compound isolated, and I set about trying to figure out what it was. One of the best ways to identify an unknown compound is to crystallize it.

Think of the crystal-growing experiments you may have done in grade-school science class with sugar; the process is essentially the same. Once I had grown crystals, which actually required several weeks of trial and error, we used X-ray crystallography to identify the product. This technique literally involves shooting X-rays at a crystal to map the location of each atom in the structure. If you have a high enough quality crystal, you get a picture of the atomic structure. Here is the structure I saw for my unknown compound.

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It is a vinyl complex (Ni1–C30–C31 is the so-called vinyl part), a product whose origin I could not explain. That was a very exciting day. I had solved one mystery but now I had another. How was this compound forming? I needed to design a series of reactions that could pinpoint how the vinyl complex was forming.

Many experiments later, I was able to determine that the vinyl complex is formed after a three-step reaction that involves the same unique nickel complex that I drew above. That complex and phenyl anion are responsible for breaking the carbon-oxygen bonds in the crown ether and extracting a two carbon fragment that becomes the vinyl in the vinyl complex.

Epilogue

By solving the mystery of what the new compound was and where it came from, I proved that the same compound that Yunho had drawn on his whiteboard on my fist day was the key to understanding both the chemistry that the Lee group had already discovered and the new chemistry that I found. We combined both findings into a new manuscript and submitted it for publication to the journal Chemical Science in April. Peer review was quick, but the reviewers had a number of questions which required us to run several more experiments. We (especially Jonghoon) worked hard to quickly address those questions, which enabled the publication to appear online just before my time in Seoul was ending. 

I didn’t plan to make a significant contribution to this project when I first started my sabbatical, but after stumbling onto something new, I was excited to see where the mystery would take me. In my career I’ve had some successful research projects where I set out with a specific goal and was able to follow my plan (usually with some bumps along the way). Other times, like this one, the chemistry led the way, and I struggled to follow along until finally the mystery was revealed. This type of serendipitous discovery is one important way that important research directions can emerge. But first you have to solve the mystery.

The full journal article is available online here:https://doi.org/10.1039/D1SC02210E