A C-13 solid-state NMR investigation of four cocrystals of caffeine and theophylline

Abstract

We report an analysis of the C-13 solid-state NMR chemical shift data in a series of four cocrystals involving two active pharmaceutical ingredient (API) mimics (caffeine and theophylline) and two diacid coformers (malonic acid and glutaric acid). Within this controlled set, we make comparisons of the isotropic chemical shifts and the principal values of the chemical shift tensor. The dispersion at 14.1 T (600 MHz H-1) shows crystallographic splittings in some of the resonances in the magic angle spinning spectra. By comparing the isotropic chemical shifts of individual C atoms across the four cocrystals, we are able to identify pronounced effects on the local electronic structure at some sites. We perform a similar analysis of the principal values of the chemical shift tensors for the anisotropic C atoms (most of the ring C atoms for the API mimics and the carbonyl C atoms of the diacid coformers) and link them to differences in the known crystal structures. We discuss the future prospects for extending this type of study to incorporate the full chemical shift tensor, including its orientation in the crystal frame of reference.

Publisher

International Union of Crystallography

Publication Date

3-1-2017

Publication Title

Acta Crystallographica Section C: Structural Chemistry

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://dx.doi.org/10.1107/S2053229617000869

Notes

Part 3, Special Issue

Keywords

NMR crystallography, Solid-state NMR, Cocrystal, Caffeine, Theophylline, Active pharmaceutical ingredient (API) minics, Malonic acid, Glutaric acid

Language

English

Format

text

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