RUI: NMR Crystallography of Co-crystals

Oberlin College, Oberlin OH

Investigators

Abstract

With this award, the Chemical Structure, Dynamics, and Mechanisms (CSDM-A) Program of the Division of Chemistry is funding Professor Manish Mehta at Oberlin College to study the formation of co-crystals - molecular crystals that involve two or more species which retain their molecular identity in the solid state. These structures are of great interest, as they provide a new way to control bulk properties of substances. For example, properties of pharmaceutical substances such as solubility and bioavailability may be altered by co-crystallizing the agent with an excipient. Co-crystals are often made using mechanochemistry (e.g., grinding the co-forming solids together), while others form spontaneously by simply mixing powders. Dr. Mehta seeks to enhance the understanding of these mechanisms using a combination of solid-state magnetic resonance, X-ray and neutron diffraction, and computational methods. The insight gleaned from these studies should help to inform the design and synthesis of co-crystalline materials with desired properties in the future. Participating undergraduate students receive hands-on experience in experimental design and execution and in drafting manuscripts for publication in peer-reviewed journals. Experiences such as these help to prepare interested undergraduates for graduate study in the STEM disciplines. In this work, the PI and his undergraduate research team apply the tools of NMR crystallography to study the synthon structure of co-crystals and their formation using real time in situ solid-state NMR (ssNMR). They (1) investigate the kinetics of co-crystal formation; (2) create a detailed picture of the synthon structure (complementing single-crystal NMR data with neutron diffraction and ab initio calculations); and (3) examine single-crystal reaction dynamics using microscopy and single-crystal X-ray diffraction (scXRD). The NMR-based strategy provides kinetic data, including detection of any transient intermediates (liquid or solid) that might arise in the course of the solid-state reaction. A second goal is to investigate the hydrogen bond synthon structure in model co-crystal systems using neutron diffraction and single-crystal NMR (including assessment of proton shift tensors and their orientation in the crystal frame). Broadly construed, these studies are expected to help bridge the NMR crystallography and crystal engineering communities.