Illuminating mechanochemical reactions by combining real-time fluorescence emission monitoring and periodic time-dependent density-functional calculations

We provide a proof-of-principle demonstration of the first dual-spectroscopic method for direct and real-time observation of mechanochemical reactions by ball milling, supported by high-level molecular and periodic density-functional theory (DFT) calculations, including periodic time-dependent (TD-DFT) calculations to model solid-state fluorescence spectra. By combining standard Raman and fluorescence benchtop spectrometers in a single readily accessible tandem monitoring technique, we simultaneously observe changes to the supramolecular structure during mechanochemical polymorph transformation and cocrystallization of the model pharmaceutical system indometacin. The observed time-resolved in situ spectroscopic data is supported by ex situ X-ray diffraction and solid-state nuclear magnetic resonance spectroscopy measurements. First principles calculations facilitate the interpretation of both real-time spectroscopic and ex situ data by demonstrating how changes in crystalline environment affect vibrational and electronic excited states.