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

Abstract

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 a 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 a 1:1 stoichiometry. Thermogravimetric analysis demonstrated the complex was anhydrous, with differential scanning calorimetry showing a melting temperature different from that of the starting materials. The absence of a CNH+ N1s peak in XPS and the small magnitude of 15N ssNMR and ATR-FTIR shifts relative to anhydrous theophylline revealed that proton transfer, and hence salt formation, had not occurred. The combination of analytical techniques allows the complex to be assigned as a 1:1 co-crystal without the need for a single crystal structure.

Mechanochemistry: opportunities for new and cleaner synthesis

“…Increasing the relative amount of succinic acid resulted in the progressive replacement of solvent guests with neutral molecules of succinic acid, accompanied by a change in space group. [200] Figure 10 (a) Molecular diagrams of caffeine, succinic acid and pleuromutiline; (b) two-component host of caffeine and succinic acid. [180] A three-component pharmaceutical cocrystal hydrate was obtained while comparing anhydrous and hydrated reactants in mechanochemical cocrystallization of theophylline and citric acid.…”

“…[180] A three-component pharmaceutical cocrystal hydrate was obtained while comparing anhydrous and hydrated reactants in mechanochemical cocrystallization of theophylline and citric acid. [177] Whereas grinding anhydrous theophylline with anhydrous citric acid gives a binary cocrystal (theophylline)·(citric acid), [200] hydrated reactants lead to a ternary solid (theophylline)·(citric acid)·H 2 O.…”

Spectroscopic and physical–chemical characterization of ambazone–glutamate salt

“…13). The component at lower binding energy (397 eV) arises from C=N photoemissions and the other one at 399.2 eV arises from the C-N nitrogen environment [31].…”

Novel Salt of Tinidazole with Improved Solubility and Antibacterial Activity

“…"pKa < 0 is generally considered to be associated with systems that form co-crystals and "pKa > 2 results in salts 7,8,9 . Thermal analysis is frequently utilized to swot up variation in properties of material with temperature.…”