A smart ionic co-crystal of urea with KCl and ZnCl2 has been obtained in two polymorphic modifications via mechanochemical and solution methods and proven to be a very efficient urease inhibitor while, simultaneously, able to provide soil nutrients to complement N supply.

The mechanochemical reaction of urea and catechol affords the quantitative formation of a 1:1 urea·catechol (URCAT) cocrystal that can act simultaneously as a urease inhibitor and as a soil fertilizer. The novel compound has been characterized using solid-state methods, and its environmental activity has been assessed using the inhibition of Canavalia ensiformis urease and water vapor sorption experiments at room temperature. The urea molecules within the cocrystal were organized in hydrogen-bonded dimers bridged by two catechol molecules, with the OH groups interacting via hydrogen bonds with the urea carbonyl groups. The inhibition of jack bean urease enzyme by URCAT led to the complete loss of urease activity after a 20 min incubation period. A large difference of water vapor adsorption was observed between urea and URCAT, with the latter adsorbing 3.5 times less water than urea. Our results suggested that cocrystal engineering strategies can be successfully applied to tackle sustainability problems at the food–energy–water nexus.

The novel ternary Zn­(II)-thiourea–urea ionic cocrystal [Zn­(thiourea)­(urea)­Cl2], (ZnTU) has been prepared by both solution and mechanochemical processes and structurally characterized by solid-state methods. ZnTU exhibited improved response properties to water as relative humidity as inherited from thiourea. The results of enzymatic activity measurements provide evidence that ZnTU is effective in modulating urea hydrolysis both in vitro (negatively impacting on the activity of isolated urease) and in vivo (decreasing the ureolytic activity of Sporosarcina pasteurii, a widespread soil bacterium), and that Zn­(II) is the component of the cocrystal acting as the actual urease inhibitor. Concomitantly, the analysis of the ammonia monooxygenase (AMO) enzymatic activity in Nitrosomonas europaea, taken as a representative of soil ammonia-oxidizing bacteria, in the presence of ZnTU reveals that thiourea is the only component of ZnTU able to inhibit ammonia conversion to nitrite. It has also been shown that ZnTU maintains these capabilities when applied to bacterial cultures containing both S. pasteurii and N. europaea working in tandem. The compound can thus act both as a fertilizer via urea and via the Zn­(II) and thiourea components, as a dual action inhibitor of the activities of the enzymes urease and AMO, which are responsible for the negative environmental and economic impact of the agricultural use of urea as soil fertilizer. These results indicate that ZnTU should be considered a novel material to improve N fertilization efficiency, toward a more environment-friendly agricultural practice.

This review is aimed to provide to an “educated but non-expert” readership and an overview of the scientific, commercial, and ethical importance of investigating the crystalline forms (polymorphs, hydrates, and co-crystals) of active pharmaceutical ingredients (API). The existence of multiple crystal forms of an API is relevant not only for the selection of the best solid material to carry through the various stages of drug development, including the choice of dosage and of excipients suitable for drug development and marketing, but also in terms of intellectual property protection and/or extension. This is because the physico-chemical properties, such as solubility, dissolution rate, thermal stability, processability, etc., of the solid API may depend, sometimes dramatically, on the crystal form, with important implications on the drug's ultimate efficacy. This review will recount how the scientific community and the pharmaceutical industry learned from the catastrophic consequences of the appearance of new, more stable, and unsuspected crystal forms. The relevant aspects of hydrates, the most common pharmaceutical solid solvates, and of co-crystals, the association of two or more solid components in the same crystalline materials, will also be discussed. Examples will be provided of how to tackle multiple crystal forms with screening protocols and theoretical approaches, and ultimately how to turn into discovery and innovation the purposed preparation of new crystalline forms of an API.

We report on the mechanochemical synthesis of inclusion complexes obtained by reacting β-cyclodextrin (β-CD) with two widely used sunscreens, namely, avobenzone (AVO) and octinoxate (OCT). Formation of crystalline inclusion complexes was confirmed via a combination of solid-state techniques, including Xray diffraction (XRD), Raman, and ATR-FTIR spectroscopies. A new, metastable polymorph of avobenzone was also isolated and characterized. NMR spectroscopy and thermal analyses (TGA and DSC) allowed us to evaluate the host/guest ratio and the water content (ca. 8H 2 O) in crystalline (β-CD) 2 •AVO and (β-CD) 3 • OCT 2 . Photodegradation of the two sunscreens upon inclusion in the hydrophobic cavity of β-CD was evaluated in solution via mass spectrometry (ESI-MS) and UV−vis spectroscopy and found to be sharply reduced. All findings indicate that the inclusion of AVO and OCT in β-CD might represent a viable route for the preparation of environmentally friendly sunscreens with improved photostability to be used in formulations of sun creams.