RII Track-4: in situ SSNMR Spectroscopy of Base Catalysts Used to Produce Statin Drugs

The production of pharmaceuticals and pharmaceutical building blocks often is accomplished using traditional chemical synthesis methods. Unfortunately, these methods can produce substantial waste products, and the starting materials are often non-renewable. Recent developments in the availability of biomass and its building blocks (e.g., sugars), however, provides a sustainable feedstock for producing high-value chemicals, such as pharmaceutical precursors.

Previous work has developed catalytic methods for converting sugars into 3-hydroxy-gamma-butyrolactone (HBL), which is an important building block for statin drugs such as Crestor® and Lipitor®. This project is focused on strengthening collaborative efforts between the University of Maine and the Ames Laboratory, which will facilitate elucidation of the chemistry that occurs on these catalysts.

In particular, we will use solid-state nuclear magnetic resonance spectroscopy (SSNMR) to identify the structures of chemical species adsorbed on the surface of the catalyst and to track the reaction progress. Such a molecular-level understanding of the operation of these catalysts is critical for the design of new, improved materials that can further improve the efficiency of pharmaceutical synthesis using renewable resources.

This project seeks to develop a fundamental understanding of the chemistry that occurs at the surface of a solid CaCO3 catalyst used to produce hydroxy-gamma-butyrolactone (HBL) via what is believed to be a retro-Aldol reaction. In collaboration with the nuclear magnetic resonance spectroscopy (NMR) groups at the Ames Laboratory, in situ 13C solid-state NMR (SSNMR) will be used to follow the time-course of HBL production, which will allow for the identification of important surface intermediates in the reaction, and elucidation of the reaction mechanism as carried out by Ca-based catalysts.

Subsequently, the high sensitivity afforded by dynamic nuclear polarization 13C SSNMR will be used to perform homonuclear correlation spectroscopy to identify the configurations of molecules adsorbed on the CaCO3 surface. These fundamental mechanistic insights will be key for the development of solid base catalysts for not only HBL production but also other biomass-related reactions.

Moreover, the collaboration between the PI and the NMR groups at the Ames Laboratory will allow for the development of additional SSNMR expertise at the home institution and will provide further access to advanced SSNMR resources.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.