The National Institutes of Health (NIH) has awarded $1,836,375 to Worcester Polytechnic Institute (WPI) researcher Patricia Zhang Musacchio to develop a process that would help medicinal chemists synthesize new drugs by transforming a common chemical bond in small molecules.
Musacchio, an assistant professor in the Department of Chemistry and Biochemistry, will use energy from visible light to break the strong bond that forms in molecules between carbon and hydrogen. Her process would give medicinal chemists a new, green way to customize the structure of small molecules to target disease in the body.
“Drug developers are almost guaranteed to have carbon-hydrogen bonds in a drug compound, so finding a robust way to transform those bonds and change the molecule’s structure, and therefore its medicinal properties, would be a very powerful approach,” Musacchio said. “It would give a drug developer more options to build the kind of molecule they want in a more direct way.”
Small-molecule drugs are organic compounds with low molecular weight that can enter cells to regulate or alter biological processes. Most drugs are made of small molecules, and small-molecule drugs treat a range of human health issues. When developing new compounds, drug developers often alter the structure of an existing small molecule to improve its potency.
Chemists have developed techniques to break carbon-hydrogen (C-H) bonds so that small molecules can be altered, but the process remains challenging and energy-intensive due to the strength of the C-H bond. Historically, organic chemists considered the C-H bond “non-reactive” because of its strength.
Musacchio’s research team has discovered a new way to convert C–H bonds into a reactive intermediate product that is known as a carbocation—a carbon atom that possesses a highly reactive positive charge. The charge can be used to alter a small molecule by installing different groups of atoms at the site where the C-H bond was broken. Musacchio will focus her NIH-funded project on designing platforms that use light-based mild chemical reactions to convert C-H bonds and bypass existing processes that can require multiple steps and large amounts of energy.
A member of the WPI faculty since 2019, Musacchio focuses her research on developing new chemical technologies for the design and synthesis of drug molecules, chemotherapeutics, and biologics. Her five-year project is funded by the NIH’s National Institute of General Medical Science and builds on her previous experience in photochemistry and catalysis.
“This new project is important to me because I believe that small molecules will always make a difference in human health,” Musacchio said. “What my team does is very specialized, and we feel compelled to use our knowledge to make a difference.”
