Eric Fort

The Art of Making Molecules

It pays to be curious. As in life and art, as in science: Sometimes where you think you’re headed isn’t where you end up.

Since Dr. Eric Fort, an organic chemistry professor in the College of Arts and Sciences at St. Thomas, joined the university in 2010, he has been working with undergraduate students on a research project that continues to journey not only onto roads not taken, but roads (pleasantly) unforeseen.

The project’s goals when it kicked off in 2010 were relatively clear cut: find faster pathways for creating azaborines – synthetic organic compounds created by substituting two carbon atoms in a molecule with boron and nitrogen. The second goal was to then determine if those molecules could be used in solar cells and in the design of drugs.

For several semesters, Fort and a flock of full- and part-time student researchers experimented with different methods of building a type of azaborine molecule called pyrene, known for its ectoplasmic glow. The project was moving along smoothly and meeting its objectives. Then in summer 2013, Fort and the students working with him made a game-changing observation. Out of curiosity they held a test tube containing the product under a black light one step early in the "closing" process. (The building of this molecule is considered "finished" once all the chains of atoms close up together to form a ring.) Only with closure will the molecule glow (and become pyrene). To their surprise, the telltale green fluorescence of a closed, stable pyrene molecule lit up the tube.

This discovery, Fort said, built the foundation for the "exciting new frontier” into which the project has morphed: new molecule creation.

How to build a molecule 101

To understand their moment of discovery, it helps to first know a bit about how the molecule is built.

An azaborine is essentially a carbon molecule that has been skillfully tinkered with in a lab by some tools of the chemist’s trade: starting materials, other small molecules and reagents (compounds used to cause chemical reactions). Chemists build azaborines by replacing the two carbon atoms at the center of a molecule with one atom a piece of nitrogen (aza) and boron.

The ways in which a chemist can build an azaborine are limitless. Fort likened the building of organic molecules to an artist's work, recognizing that amidst the weeks and months of monotonous lab work, an element of surprise is always possible.

“Being an organic chemist is a lot like being a sculptor who says, ‘That’s not just a rock, that’s going to be the Pieta,’ or something like that,” Fort said. “For us, we know that our end goal is in three dimensions, we know the shape and the size it needs to be and how the bonds need to come together; we choose small molecules, starting materials and reagents that build that framework up.” The two central atoms aren’t so much “plucked out,” and replaced he said, but rather laboriously and creatively built in “piece by piece in the proper order with the right chemicals to get everything to talk to each other,” in a process that requires patience, skill and imagination.

In the end, at least in Fort’s project, “the last step is one fell swoop where everything locks up (shape shifts from an open ring to a closed ring of atoms) and the final product is really stable.” The molecule remains the same size and shape as with carbon atoms but its overall properties are changed fundamentally. One of the more dazzling transformations that can happen is that the azaborine can become fluorescent, as is the case with pyrene, which is a flat structure with four fused rings.

An organic chemist's playground

With the rules they believed to govern the  molecule (pyrene) turned upside down, Fort knew he had to redirect his course of action. He and his future student teams would focus on uncovering why their closing mechanism worked. Once that groundwork was laid, they could develop new reactions and new molecules. Soon after the serendipitous discovery, Fort applied for, and received a year later, a $50,000 grant from the American Chemical Society to undertake his new, expanded endeavor.

They succeeded, proving that their molecule didn’t need the catalyst because of the boron-nitrogen bond.

“Putting the boron and nitrogen in changes how the molecule reacts by making the energy needed to close much lower than we had thought,” Fort said. “So, not only does it change the molecules in the final product, but on the pathway to that product it’s changing how the bonds form and break.”

Solving that mystery and laying a fundamental framework meant his students wouldn't be confined to one specific end goal of creating their azaborine as quickly as possible; they could have different end goals based on their interests. While they will continue working with azaborines to make new molecules, Fort’s lab has expanded to building more complicated structures of the compound. Recently one of his biochemistry students built a biologically looking molecule, while another one of his chemistry majors made an electronically structured molecule, and in doing so found another unexpected reaction product and another new mechanism to explore.

“Once we learned those steps to this new way of closing the molecule, in the middle of the process we could say, ‘Instead of putting a swing here, we could put a monkey bar instead and build a whole new playset,’" Fort said. "That’s where we’re at now. We can make molecules! It’s like making playgrounds that kids have never seen before. That was a really exciting development the last year."

Watercolor Molecules

Fort created this watercolor rendering of molecules.

This fall Fort co-wrote (with help from his recent team of students) a paper – the third to come from the study – on their findings, which was published in January.

His students' ability to run with the new finding is important, he noted, because it further proves that undergraduates can do good science.

“We don’t have the funding or man hours to do huge projects but what we do is find these fundamental things that ... helps the entire chemistry community," he said. "We are finding results that though small or incremental in their own right, their implications are grand. Until our paper was submitted, we were the only people who knew the knowledge behind the closing mechanism ... We discovered that.”

For senior biochemistry major Sam Madden, who worked on the project last summer, his outlook on the research took a leap forward after just three months in Fort's lab.

"Being able to conduct research has brought life to my studies in a way that I could not have imagined. Suddenly my mind was searching for connections between the things I would experience in the lab and the new things I learned in classes," he said. Madden also noted that his experience helped him appreciate the larger process involved in conducting research, such as doing preliminary readings of primary literature, writing a grant proposal (a Young Scholars Grant), learning correct safety procedures, becoming accustomed with lab techniques and always searching for ways to improve reactions.

Fort believes he's just stepped foot into this area of research and plans to carry on with it into the foreseeable future. The project is on a yearlong hiatus while Fort takes a sabbatical to work in 3M's hydrogen fuel cell program. But when he returns, he will move forward again, not knowing what new things he and his students will create, only that there will infinite roads waiting for them to discover.