Molecules can be like people, with their own unique personalities and quirks. In some cases, these differences can lead to significant changes in their behavior or properties. Take, for example, the cancer drug doxorubicin, which can have heart-damaging side effects in a small percentage of patients. However, a diastereomer of the drug, known as epirubicin, which has a single alcohol group that points in a different direction, is much less toxic to heart cells. This phenomenon is not unique to pharmaceuticals. Many biological molecules exist as diastereomers, which are molecules with the same chemical structure but different spatial arrangements of their atoms. These differences can have significant effects on the molecules’ functions or chemical properties.
“There are a lot of examples like that in medicinal chemistry where something that seems small, such as the position of a single atom in space, may actually be really profound,”
says Alison Wendlandt, an associate professor of chemistry at MIT. Wendlandt’s lab is focused on designing new tools that can convert these molecules into different forms. Converting Molecules
One of the key tools that Wendlandt’s lab is developing is a way to convert a molecule into its mirror image or an isomer of the original. This is known as interconversion. Traditional chemical synthesis techniques typically require starting from scratch and building the desired molecule.
- Imagine you want to make a new molecule, but the existing one is a diastereomer. You’d have to start over and build it from the ground up.
- But what if there was a way to convert the existing molecule into the desired isomer? That would allow you to make the molecule without starting from scratch.
Wendlandt’s lab is developing a tool that can achieve this interconversion. This tool uses a combination of catalysts and energy to manipulate the chemical groups in the molecule.
| Tools for Interconversion | Using a combination of catalysts and energy | Catalysts work by lowering the activation energy required for a chemical reaction | Energy is used to manipulate the chemical groups in the molecule |
This approach can have a significant impact on how molecules are made. Instead of thinking of molecules as static structures, Wendlandt’s lab is thinking about them as dynamic entities that can change and adapt. Math and Chemistry
Wendlandt’s interest in chemistry began when she was a child, watching her parents work in the geology lab. She found math to be more appealing than chemistry, but her interests changed when she encountered abstract math in college.
“I was good at calculus and the kind of math you need for engineering, but when I got to college and I encountered topology and N-dimensional geometry, I realized I don’t actually have the skills for abstract math. At that point I became a little bit more open-minded about what I wanted to study,”
she says. She began working in a lab focused on total synthesis, where she developed strategies to synthesize complex molecules from scratch. However, a lab accident led her to change her direction and pursue chemical biology instead.
| Wendlandt’s Educational Background | The University of Chicago (math major) | The University of Yale (master’s degree in chemistry) | The University of Wisconsin (PhD in chemistry) | Harvard University (postdoc in chemistry) |
Edit Molecules
Since joining the MIT faculty, Wendlandt has worked on developing tools that can edit molecules. She has developed a tool called a stereo-editor, which can alter the arrangement of chemical groups around a central atom.
“If you have a molecule with an existing stereocenter, and you need the other enantiomer, typically you would have to start over and make the other enantiomer. But this new method tries to interconvert them directly, so it gives you a way of thinking about molecules as dynamic,”
she says. Wendlandt has also developed tools that can convert common sugars into other isomers, including allose and other sugars that are difficult to isolate from natural sources. She is now working on ways to convert six-membered carbon rings to seven or eight-membered rings. Dynamic Molecules
Wendlandt’s approach to chemistry is focused on thinking of molecules as dynamic entities, rather than static structures. This approach has significant implications for how molecules are made and how they interact with other molecules. Uncharted Chemical Space
Wendlandt’s tools can also open up the possibility of creating new molecules that haven’t been seen before. This could be useful, for example, to create drug molecules that interact with a target enzyme in just the right way.
“There’s a huge amount of chemical space that’s still unknown, bizarre chemical space that just has not been made. That’s in part because maybe no one has been interested in it, or because it’s just too hard to make that specific thing,”
she says. Wendlandt’s work is a prime example of how chemistry can be used to create new and innovative molecules. By thinking of molecules as dynamic entities, Wendlandt’s lab is pushing the boundaries of what is possible in the field of chemistry.
