Characterization of Proton Transfer in Co-Crystals by X-ray Photoelectron Spectroscopy (XPS)

Characterization at the molecular level establishes X-ray photoelectron spectroscopy (XPS) as a useful technique for determining the extent of proton transfer in molecular crystals by studying theophylline-citric acid co-crystals alongside solid-state nuclear magnetic resonance (ssNMR) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). A complex has been formed by milling theophylline with either anhydrous or monohydrate citric acid and established as a 1:1 co-crystal by it combination of both conventional and novel analytical methods. The absence of peaks from the starting materials in the X-ray diffraction powder pattern indicates that the product was formed quantitatively, with elemental analysis and XPS revealing it 1:1 stoichiometry. Thermogravimetric analysis demonstrated the complex was anhydrous, with differential scanning calorimetry showing it melting temperature different from that of the starting materials. The absence of a C=NH+ N1s peak in XPS and the small magnitude of N-15 ssNMR and ATR-FTIR shifts relative to anhydrous theophylline revealed that proton transfer. and hence still formation, had not occurred. The combination of analytical techniques allows the complex to be assigned its a 1:1 co-crystal without the need for a single crystal structure.