Development of a Fast and Clean Intercalation Method for Organic Molecules into Layered Double Hydroxides

A new mechanochemical method for the fast and clean preparation of exchanged layered double hydroxides (LDHs) was designed and tested on compounds with different chemical features, to assess its feasibility and applicability, to optimize yields and reaction speeds, and to identify its potential and limitations. Thanks to the simplicity and speed of the proposed method, we were able to upscale the method and produce several hundreds of grams of exchanged hydrotalcite. Moreover, fast in situ X-ray powder diffraction measurements, performed using synchrotron radiation, allowed us to unravel the mechanism and kinetics of the process. This showed that it is possible to carry out the complete reaction in less than 1000 s instead of days. The chosen organic guests were 3-carboxy coumarin and, given their importance, a series of nonsteroidal anti-inflammatory drugs with different pK(a) values and steric hindrance, namely, ketoprofen, flurbiprofen, ibuprofen, indomethacin, and tiaprofenic acid. The method has been applied to different classes of compounds to characterize the reaction in terms of speed, yield, and applicability. The characterization of the obtained nanocomposites, carried out by crystallographic and microscopic techniques, revealed that the synthesis yields are comparable to that of standard methods, but with enormous time, solvent, and energy saving advantages. Moreover, in situ diffraction experiments allowed us to shed some light on the kinetics of the intercalation process with subsecond resolution and to determine the parameters affecting the reaction. Steric hindrance of the molecule proved to be the most relevant parameter to determine the applicability of this method.