Molecular Recognition in Mechanochemistry: Insights from Solid-State NMR Spectroscopy

Molecular-recognition events are highly relevant in biology and chemistry. In the present study, we investigated such processes in the solid state under mechanochemical conditions using the formation of racemic phases upon reacting enantiopure entities as example. As test systems, alpha-(trifluoromethyl)lactic acid (TFLA) and the amino acids serine and alanine were used. The effects of ball-milling and resonant acoustic mixing (RAM) on the formation of racemic phases were probed by using solid-state Nuclear Magnetic Resonance (NMR) spectroscopy. In a mixer mill, a highly efficient and fast racemic phase formation occurred for both TFLA and the two amino acids. RAM led to the racemic phase for TFLA also, and this process was facilitated upon employing pre-milled enantiopure entities. In contrast, under comparable conditions RAM did not result in the formation of racemic phases for serine and alanine. Mechanochemically-induced molecular recognition processes have been studied by solid-state NMR spectroscopy using alpha-(trifluoromethyl)lactic acid (TFLA), serine, and alanine as representative substrates. To disentangle different mechanochemical effects, a mixer mill and a resonant acoustic mixer were applied as mixing devices. image