BIO

Hi! My research interests include NMR, organic chemistry, and medicinal chemistry. I am originally from Miami and enjoy working at the MagLab.

Probing Hydrogen Atom Positions in Organic Salts and Co-Crystals Using Solid-State NMR Spectroscopy

Abstract

Organic salts and co-crystals play a key role as matrices that encapsulate active pharmaceutical ingredients (APIs), influencing stability and solubility for enhanced efficacy. Acid-base salts and cocrystals are frequently distinguished based on the position of a hydrogen atom between a hydrogen bond donor and acceptor. A precise determination of the hydrogen atom position will allow the accurate identification of the protonation state of such systems. However, it is challenging to precisely measure the hydrogen atom positions using standard X-ray diffraction techniques.
Here, we focus on determining hydrogen atom positions in organic salts and co-crystals using solid-state NMR spectroscopy. Specifically, we measure N-H bond distances to clearly distinguish the protonation state of a base using a model system involving pyridine and a series of acids. Nitrogen-14 is an attractive isotope for probe N-H bonds and interactions due to its high isotopic abundance (99.6 %). However, 14N is a spin-1 quadrupolar nucleus which results in broadening of 14N solid-state NMR spectra. Here, we use fast magic angle spinning proton detection solid-state NMR experiments to measure 1H-14N bond distances in these salts and cocrystals. Solid-state NMR can be used to measure dipolar couplings between two spins (in our case 14N-1H bonds) which corresponds to the distance between the two spins. Our experimental results will be supported by density functional theory calculations. Ultimately, a combination of solid-state NMR spectroscopy, X-ray diffraction, and quantum chemical calculations, in an NMR crystallography approach, will provide an atomistic picture of hydrogen bonding interactions in pharmaceutical salts and cocrystals.

Keywords: NMR, Chemistry, Pharmaceuticals