As this is a new research project, in 2024 there will be 12 participants.
Drug discovery has a long history dating back thousands of years. Native peoples curated (and still curate) plants for their medicinal use, plant breeders have selected for unique metabolic capabilities, and the drugs produced by microbes have been coopted for human use. Many of these compounds are simple organic chains, but others are far more complex. Some of these, called macrocyclic compounds, form not a chain but a ring. In biology, structure is linked to function – and therefore these cyclic compounds have unique functions. They have been exploited as antibiotics, antifungals, immunosuppressants, and as anti-cancer compounds. The discovery and characterization of these compounds from natural products is one path forward, but what if we could synthesize these compounds from scratch? What possibilities open when we’re not limited by what we’ve found in nature?
Participants will learn the fundamentals of organic and inorganic chemistry along with the denovo synthesis and downstream characterization of organic and inorganic molecules. Each team of three will complete bench experiments to create a novel macrocyclic compound ‘from scratch’ and then each participant will (ideally) create a unique macrocyclic ligand analog by including a metal ion to stabilize the structure. These techniques have been in use by our 2024 Academic Director for over a decade, while they’re setting their (and therefore SSPers’) sights on a new base structure. With this, groups will be diving into a brand-new synthesis, checking whether each step in the multi-step synthesis reaction is successful, and eventually arrive at an untested compound that will have unknown and possibly beneficial effects. By the end of the program, each group will complete and present a professional poster and draft a manuscript that summarizes their efforts.
The project starts with concepts (typically) covered in 200-level Organic I and Organic II college courses and ends with the topics of inorganic and coordination chemistry often only taught in 300- to 400-level courses for chemistry majors. The laboratory work required attention to detail, safety, and unbroken focus as even a single miss-step could affect the final synthesis yield. The classroom and overall project demand an in-depth understanding of the underlying chemical reactions, a critical eye analyzing the characterization spectra, and the ability to work closely with your peers to accomplish a goal. Finally, this first year of the Synthetic Chemistry program will be an excellent opportunity for participants to learn how trained professionals pivot, optimize, and troubleshoot research problems on the fly.
Topics covered in SSP Synthetic Chemistry will include: