Elucidation of the crystal structure of a solid compound is incredibly telling about its physical and chemical properties. For example, crystal packing affects its thermodynamic stability as well as its solubility. These two properties are important considerations for industrial chemistry applications, especially with respect to crystalline pharmaceuticals. Stability and solubility of compounds give researchers an idea of how long the shelf-life of a drug will be, as well as how bioavailable the substance will be upon entering the body. In order to improve these properties, the polymorphic forms of drugs are studied and compared to find the one(s) with the most desirable properties. Drugs can also be co-crystalized with other compounds to improve stability and solubility. Solid state NMR (SS-NMR), which uses magic-angle spinning to achieve high resolution, can provide structural information on microcrystalline samples. NMR crystallography is a technique that combines SS-NMR, diffraction data, and computer modeling to determine crystal structures of organic crystals. One approach utilizes the chemical shift anisotropy (CSA) that can be measured through a technique called magic-angle turning (MAT). The three principal components of the CSA can be modeled by electronic structure methods to provide structural insight. Conformational polymorphism and structural variation in co-crystals can arise from the flexibility of torsion angles or changes in the hydrogen bonding network. In many cases, these structural changes occur at nitrogen-containing functional groups. Such variations in structure can be captured by 15N NMR chemical shift. In this work, natural abundance 15N CSA of carbamazepine and fluoxetine were measured using SS-NMR with MAT. More specifically, distinct polymorphic forms of carbamazepine and co-crystal types of fluoxetine were studied.

Investigating pharmaceutical crystal structures by 15N chemical shift anisotropy

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.