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.

Layered double hydroxides (LDHs) are versatile materials used for intercalating bioactive molecules in the fields of pharmaceuticals, nutraceuticals and cosmetics, with the purpose of protecting them from degradation, enhancing their water solubility to increase bioavailability and improving their pharmacokinetic properties and formulation stability. Moreover, LDHs are used in various technological applications to improve stability and processability. The crystal chemistry of hydrotalcite-like compounds was investigated by X-ray powder diffraction (XRPD), automated electron diffraction tomography (ADT) and thermogravimetric analysis (TGA)-GC-MS to shed light on the mechanisms involved in ion exchange and absorption of contaminants, mainly carbonate anions. For the first time, ADT allowed a structural model of LDH_NO3 to be obtained from experiment, shedding light on the conformation of nitrate inside LDH and on the loss of crystallinity due to the layer morphology. The ADT analysis of a hybrid LDH sample (LDH_EUS) clearly revealed an increase in defectivity in this material. XRPD demonstrated that the presence of carbonate can influence the intercalation of organic molecules into LDH, since CO3 -contaminated samples tend to adopt d spacings that are approximate multiples of the d spacing of LDH_CO3 . TGA-GC-MS allowed intercalated and surface- adsorbed organic molecules to be distinguished and quantified, the presence and amount of carbonate to be confirmed, especially at low concentrations (<2 wt %), and the different types and strengths of adsorption to be classified with respect to the temperature of elimination.

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Layered double hydroxides (LDH) are versatile materials used for intercalating bioactive molecules, both in pharmaceutical and cosmetic fields, with the purpose of protecting them from degradation, enhancing their water solubility to increase bioavailability, and/or obtaining modified release properties. The properties of the intercalation compounds of Mg/Al_LDH and Zn/Al_LDH with different drugs and sunscreens, namely diclofenac, ketoprofen, gliclazide, retinoic acid, furosemide, para-aminobenzoic acid and 2-phenylbenzimidazolsulfonic (Eusolex) acid, have been studied by crystallographic, spectroscopic and thermogravimetric techniques and by solid state NMR, to shed light on their structure, their molecular interactions and their stability from the thermal and chemical viewpoint. The structural features were described with particular attention to the interaction between the organic and inorganic components and to the stability of the intercalation products. For the first time two synchrotron radiation powder diffraction patterns of organic-containing LDH were solved and refined by Rietveld methods to obtain an experimental crystal structure.

A new soft and fast solid state reaction is exploited for the preparation of exchanged layered double hydroxide materials and, in particular, for intercalating bioactive molecules. The characterization of the nanocomposite, carried out by crystallographic and thermogravimetric techniques, revealed that this synthesis yield is comparable to that of standard methods but with time, solvent, and energy saving advantages. Moreover, the in situ diffraction experiments also allowed us to shed some light on the kinetics of the intercalation process.