LUMIBOR: Expanding the Chemical Toolkit with Organoboron Molecules
With the support of an ERC Starting Grant, Dr. John J. Molloy will use light to design 3D organoboron molecules with tailored properties. His project, LUMIBOR, exploits the hybridization of boron—an element that can switch between planar and tetrahedral atomic configurations—to fine-tune its reactions via light activation. The envisioned molecules will provide versatile building blocks with enhanced reactivity for both fundamental research and industrial applications.
For most of us, boron conjures up images of 'borax,' a well-known compound used to kill ants and pests. We’d probably never think of this element as having great potential in pharmaceuticals—and beyond. However, Dr. John J. Molloy begs to differ. He has been studying boron compounds since joining the Max Planck Institute of Colloids and Interfaces in 2021. The European Research Council has awarded him a 1.5 million EUR Starting Grant to pursue his ambitious research project, LUMIBOR. Let’s have Dr. Molloy take us on a journey to learn more about his favorite element and how he plans to create innovative and versatile chemical tools with it.
Congratulations, Dr. Molloy!
Tell us more about your project and what makes boron so special.
Thank you! I’m always happy to talk about boron. The full title of the project is 'Illuminating Routes to 3D Organoboron Molecules.' My goal is to develop innovative strategies to synthesize 3D organoboron structures using light as an activation tool. Simply put, what will come out of my lab is a set of new reactions and methods to make molecules with a boron handle in a specific 3D arrangement. Organoboron groups serve as excellent 'functional handles,' which are essentially add-ons that provide specific properties and additional sites of reactivity . The more sites a molecule has for forming chemical bonds, the more useful it becomes for exploring chemical space—a term that captures the countless possible combinations and orientations of atoms that can occupy a given 3D space.
These new molecules will be versatile building blocks in many areas of fundamental research and industry. Think of organoboron molecules as transformers — they can change their shape and, as a result, their properties and behavior depending on how we adjust their chemical composition. I want to capitalize on these varied properties to fine-tune light-activated chemical reactions. Strategically placed boron atoms can selectively interact with biomolecules, or the boron atom can be easily replaced with other chemical groups.
Can you explain the role of light in your project?
Chemical reactions require energy to occur. In our case, light provides the initial energy input, and all subsequent reactivity is energetically downhill. What makes organoboron molecules so valuable to a chemist’s toolkit is the hybridization of boron—it can switch between different atomic configurations. One is flat (trigonal planar), and the other is pyramidal (tetrahedral), each with contrasting properties. In its flat form, boron attracts negatively charged molecules, while in its pyramidal form, the atoms next to boron have a high electron density. LUMIBOR will exploit these differing properties to manipulate chemical reactions that occur after the absorption of a photon. Controlling the hybridization state will be key to discovering new modes of reactivity. In addition to being precise, light is inexpensive and sustainable, and we will use devices like ordinary LEDs or aquarium lights to set up experiments.
One of the many potential applications of organoboron compounds is in pharmaceuticals.
What are some examples?
This brings me back to the ant poison you mentioned earlier, which is why boron was not considered for use in medicine for a long time. While it is toxic to ants, we now know that boron is as harmless to humans as table salt—with an interesting twist. Boron forms strong covalent bonds (where electrons are shared) with sugars and certain amino acids, making it a promising component for future drug development. In fact, organoboron molecules are already being used to treat pathogens as diverse as bacteria, fungi, and viruses. Perhaps the best-known example is Bortezomib, a highly effective drug for treating certain types of cancer that has become a blockbuster in the USA. In LUMIBOR, we strategically place the boron group in molecules to enable site-specific interactions with biomolecules. The idea is to provide medicinal chemistry with an additional tool for designing boron-based drugs. Beyond pharmaceuticals, organoboron molecules have a wide range of applications, from semiconductors and agrochemicals to catalysts and LED displays.
You are no stranger to receiving grants, being both a Liebig Fellow and a Daimler Benz Fellow.
What does the ERC funding mean for you?
The ERC is an incredible opportunity to put together a team with combined strengths. The plan is to hire three PhD students and one postdoc, each responsible for a specific aspect of the overall project. I’m thrilled to create a group where each member has the freedom to grow as a scientist while collaborating on a common challenge. While grants and fellowships are important personal milestones, it's ultimately the team's accomplishments that matter most. Thanks to the funding, I’ll also be fostering both long-standing and new collaborations, particularly with theorists who can predict the structure and reactivity of my compounds, and with experts in X-ray crystallography who can precisely analyze their atomic arrangements.
How did you prepare for the ERC grant application?
As with all ideas in science and beyond, exchanging thoughts with peers was essential from the start. When I learned that I had been invited for an interview, I rehearsed extensively with colleagues. I asked them to be as mean as possible in their questions, which sometimes took a toll on my confidence, but ultimately, it was the best way to prepare for the final stage. I was fortunate to have the guidance of Prof. Peter Seeberger, who helped me navigate the entire selection process.
Rehearsing and talking to people who are not as big fans of boron as I am provided a crucial external perspective. Sometimes, though, it can backfire. I asked my father—who is not a scientist—what he thought of the short title LUMIBOR and he said it sounded like a mountain in a Tolkien novel! Hopefully, our journey into the world of boron won’t be as fraught with danger as Tolkien’s tales, but I dare say that the pursuit of knowledge about boron deserves to be described as epic!
How did your passion for boron begin, and how does it fit into the Biomolecular Systems Department at the Institute?
I think my interest was sparked when I was an undergraduate at the University of Strathclyde. What has always fascinated me about boron is its synthetic utility, or its ability to be used to make other compounds. I like that my research enables further scientific endeavors and that my topic lends itself to many collaborations. Joining Peter Seeberger's Department of Biomolecular Systems meant having access to state-of-the-art automation and flow technology to perform syntheses. In addition, boron can bond to some of the sugars that are the department's specialty. So, my research fits well into my colleagues’ interest in developing new diagnostic and therapeutic tools based on the recognition of sugars in biomolecules.
To join the MPICI, you had to leave your home country for Germany.
What was the hardest part?
I am probably not the only one to say that learning German was one of the biggest challenges. But coming from Glasgow, I also had to work on making myself understood in my native English. My accent can be unforgiving, and I remember when I first moved to Germany as a visiting scholar at the University of Münster. Prof. Ryan Gilmour (also Scottish) was perhaps the only person who could understand me! Even though I believe my accent has softened over time, I still occasionally have students in my lectures at Freie Universität asking me to repeat a sentence or word.
If it was not boron, what other chemical element might have piqued your interest and why?
It would be silicon or germanium, which I have also worked on. They offer unique orthogonal reactivity, perfect for exploring chemical space. Essentially, this allows you to systematically activate different elements one by one and branch off from the core molecule into different regions of the chemical space.
What do you do when you are not in the lab?
My favorite way to unwind from science is through sports. When I move to new places, joining sports clubs is a great way to meet locals and integrate outside the research bubble. I play a lot of football here in Potsdam. Who knows, maybe the upcoming LUMIBOR team will learn from boron’s versatility and double as a sports team, too!
Wissenschaftlicher Ansprechpartner:
Dr. John J. Molloy
John.Molloy@mpikg.mpg.de
Originalpublikation:
Hao Fang, Alejandro García-Eguizábal ,Constantin G. Daniliuc, Ignacio Funes-Ardoiz, John J. Molloy
Regioselectivity of non-Symmetrical Borylated Dienes via EnT Ca-talysis: Unveiling the Relationship between Structure and Reactivity
ChemRxiv. (2024)
DOI: 10.26434/chemrxiv-2024-3hsm9