Monitoring Co-Crystal Formation via In Situ Solid-State NMR

Abstract

A detailed understanding of the mechanism of organic cocrystal formation remains elusive. Techniques that interrogate a reacting system in situ are preferred, though experimentally challenging. We report here the results of a solid-state in situ NMR study of the spontaneous formation of a cocrystal between a pharmaceutical mimic (caffeine) and a coformer (malonic acid). Using 13C magic angle spinning NMR, we show that the formation of the cocrystal may be tracked in real time. We find no direct evidence for a short-lived, chemical shift-resolved amorphous solid intermediate. However, changes in the line width and line center of the malonic acid methylene resonance, in the course of the reaction, provide subtle clues to the mode of mass transfer that underlies cocrystal formation.

Publisher

American Chemical Society

Publication Date

10-2-2014

Publication Title

Journal of Physical Chemistry Letters

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://dx.doi.org/10.1021/jz501699h

Language

English

Format

text

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