High-Resolution Imaging Reveals Atomic Structures of Drugs and Materials
Researchers are increasingly leveraging the power of high-resolution nuclear magnetic resonance (NMR) spectroscopy to unlock the atomic-level structures of complex materials, including pharmaceuticals, catalysts, and semiconductors. This advancement, spearheaded by scientists like Aaron Rossini at Iowa State University and Ames National Laboratory, promises to accelerate materials discovery and improve drug formulation—a historically challenging area in the pharmaceutical industry.
The core of this technique involves spinning a solid sample—even a complete drug formulation with both active and inactive ingredients—at an astonishing 50,000 revolutions per second while tilting it at a precise “magic angle” of approximately 55 degrees relative to a powerful magnetic field. This seemingly complex process, conducted at facilities like the National Magnetic Resonance Facility at the University of Wisconsin-Madison, allows researchers to probe the nuclei of the sample’s atoms.
The resulting data appears as a series of peaks on a computer screen, each peak’s position revealing crucial information about the location of atoms like hydrogen, oxygen, and nitrogen within the material’s structure. Rossini’s work focuses on developing methods to improve the sensitivity and resolution of this data, enabling the study of more complex materials and subtle structural differences.
The Power of Magnetic Fields
NMR spectroscopy relies on the “magnetic moment” of atoms. As Rossini explained, the instrument’s magnetic field aligns the nuclei of atoms. Radio pulses then disrupt this alignment, pushing the nuclei to higher energy states. The instrument precisely measures these energy differences, providing a fingerprint of the material’s atomic structure.
While standard NMR instruments, like the 9.4 Tesla model in Rossini’s lab, are powerful tools, even more detailed insights require access to facilities with ultra-high magnetic fields. The National High Magnetic Field Laboratory (MagLab) in Tallahassee, Florida, boasts an instrument capable of generating a 35 Tesla field—over three times the strength of the instrument at Iowa State. Researchers, including Rossini, reserve time at these national facilities for particularly demanding experiments.
Addressing a Pharmaceutical Challenge
The ability to determine the atomic structure of solid drug formulations is particularly significant. According to a project summary from Rossini’s research, a major challenge in the pharmaceutical industry is “the successful design of the formulations for the administration of active pharmaceutical ingredients.” Understanding how these ingredients interact at the atomic level can lead to more effective and stable drug products.
Rossini recently presented his work at a panel discussion, “Pushing the Frontiers of Magnetic Imaging and Spectroscopy,” at the annual meeting of the American Association for the Advancement of Science. He emphasized that solid-state NMR spectroscopy is applicable to a wide range of materials, including catalysts and next-generation semiconductors, highlighting its broad impact on materials science.
New NSF-Funded Research
Rossini is currently leading a three-year, $492,000 study funded by the U.S. National Science Foundation to further investigate the structures of active pharmaceutical ingredients and commercial drug products. This research will focus on developing new methods to enhance the sensitivity and resolution of NMR data. The project will also provide valuable training opportunities for graduate and undergraduate students, equipping them with the skills to prepare samples, conduct experiments, and model atomic structures computationally.
This work aligns with a broader national effort to strengthen high-magnetic-field science and technology in the United States. A report by the National Academies of Sciences, Engineering, and Medicine concluded that the U.S. Needs to reinvest in state-of-the-art NMR research to regain a leadership position in the field. The report specifically calls for increased investment in instruments capable of generating ultra-high magnetic fields, which are essential for achieving the necessary resolution and sensitivity for studying complex materials.
As Rossini explained, the higher the magnetic field, the sharper the resolution and the more easily researchers can study elements like oxygen and nitrogen. “this will help chemists to design better materials and pharmaceutical companies to design improved drug formulations,” he said.
Beyond Pharmaceuticals: New Crystals and Magnetic Textures
The advancements in magnetic field technology are also driving discoveries in fundamental materials science. Researchers at Florida State University, for example, have engineered a new crystal that forces atomic magnets to swirl into complex, repeating patterns. This effect arises from combining two nearly identical compounds with mismatched structures, creating magnetic tension at the atomic level. These swirling textures, known as “skyrmion-like” textures, are prized for their stability and low energy behavior, potentially leading to breakthroughs in data storage, energy-efficient electronics, and quantum computing.
These developments underscore the growing importance of understanding magnetism at the atomic level. As scientists continue to push the boundaries of magnetic imaging and spectroscopy, we can expect further innovations in materials science, drug discovery, and a range of other fields.
