RSC Mechanochemistry最新文献

Antimony powder is transformed into 2D antimonene in a vortex fluidic device (VFD) at ambient conditions, depending on the choice of solvent (optimised as a 1 : 1 mixture of isopropyl alcohol and dimethylformamide) and the operating parameters of the microfluidic platform which houses a rapidly rotating quartz tube inclined at +45°. It is hypothesised that the Coriolis force from the hemispherical base of the tube, as typhoon like high-shear topological fluid flow down to submicron dimensions, generates localised heating at the quartz interface. This melts the antimony powder (m.p. 630.6 °C) in situ which crystallizes in the β-phase, with semi-conducting antimonene a few layers thick, and demonstrating novel photoluminescence.

An intriguing technique for crystal engineering is mechanochemistry, which frequently yields various solid forms (salts, cocrystals, polymorphs, etc.) that are challenging to acquire using traditional solution-based approaches. However, generating new and potentially beneficial solid forms remains an ongoing task in this field. Moving forward in this demanding arena, several molecular adducts (salts and salt polymorphs) of the model drug ensifentrine (ENSE) with different GRAS (generally recognized as safe) co-former were synthesised for the first time using a mechanochemical technique, followed by a slow evaporation crystallisation procedure. All the newly obtained solid forms were characterized by employing single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Crystal structure analysis verified salt generation, revealing proton transfer from the carboxylic acid group of salt formers to the mesitylimino nitrogen atom of ENSE. Additionally, the phase transition behaviour of the produced salt polymorphs was examined through variable temperature PXRD (VT-PXRD) analysis. Furthermore, a detailed investigation of the physicochemical features of these recently produced entities was carried out, and their solubility in pH 1.2 and pH 7 environments was examined. Results demonstrate that, as compared to the parent drug, the binary adduct's solubility rate significantly increased at pH 7. Moreover, a thorough examination of the residue recovered after solubility confirmed that the majority of the molecular adducts were stable at pH 7 and did not show any phase change or dissociation, whereas at pH 1.2, the majority of the adducts were stable, except for those generated with malonic acid, which moved to a new stable form—a comprehensive study revealed that it was converted into ENSE·Cl salt. To the best of our knowledge, this is the first study to investigate various forms of ENSE, demonstrating that mechanical energy can be employed as a powerful control parameter to produce novel solid forms with superior physicochemical features. We hope that the current discovery will offer a valuable outlook prior to ENSE drug formulation.

Mechanochemistry is increasingly recognized for its sustainability, environmental benefits, and efficiency in synthesizing a wide array of chemicals and materials. This research focuses on advancing our understanding of the factors that influence mechanochemical processes, which remains limited despite the broad application of these techniques in industry and research. Specifically, this paper explores the impact of mass transfer—a parameter previously underexplored in the context of mechanochemistry—on the outcome of chemical syntheses performed without solvents, thus avoiding the use of environmentally harmful substances and complex purification steps. This study introduces a novel multi-functional ball-mill medium design that enhances mass transfer, promotes more uniform kinetic energy distribution and material treatment, and increases overall synthesis efficiency. By analyzing the products of allotrope conversion, co-crystallization, and size reduction, we demonstrate how our new design enhances mechanochemical reactions. The findings indicate that adjusting the geometry of the milling media can significantly influence the chemical transformation processes. This advancement not only contributes to a deeper comprehension of mechanochemical synthesis but also opens avenues for more controlled and scalable production methods. The research underscores the importance of considering mass transfer in developing more effective mechanochemical technologies, paving the way for future innovations in this green chemistry field.

Thioamidation of various classes of carboxamide substrates with Lawesson's reagent under liquid-assisted mechanical activation for the synthesis of relevant building blocks including aromatic thioamides, thiopeptides, thiolactams, and thioenones is described. A thorough analysis of the effect of the specific material of milling jars and milling balls was carried out. The effect of different additives for liquid-assisted grinding (LAG) and the potential of the synthetic protocol for scale-up were explored. The simple and mild reaction conditions involved in this solvent-minimized mechanochemical protocol proved rather effective with a wide variety of substrates. Comparison with the corresponding reactions in solution shows comparable or better yields under mechanochemical activation. Ex situ powder X-ray diffraction (PXRD) monitoring with analysis at multiple points was performed in order to compare the diffraction patterns of reagents and products, to detect potential morphological changes of the reagents induced by milling prior to the reaction, and to perceive the occurrence of phase transitions during the mechanochemical reaction.

Widespread usage of single-use plastics such as polyethylene terephthalate (PET) has heavily contributed to a global plastic pollution crisis, necessitating the improvement and development of recycling methods. We previously established a chemo-microbial degradation process for post-consumer PET plastic, consisting of PET depolymerization to form bis(2-hydroxyethyl) terephthalate (BHET) followed by the complete degradation of BHET by a bacterial consortium found to synergistically degrade PET and BHET. The BHET produced during PET depolymerization consists of two polymorphic forms, the α and δ forms. This work investigates the effect of BHET polymorphism on microbial degradation to further optimize the chemo-microbial process. Reversible interconversion methods for BHET polymorphs were effectively developed using mechanochemistry, achieving pure α and δ forms by modulating milling conditions. When inoculated with the bacterial consortium, the α form was degraded faster than the δ form, indicating solid polymorphism is a significant factor for the biodegradation level. This work paves the way to optimize the chemo-microbial process for an increased degradation rate of post-consumer PET and furthers the effort for sustainable plastic recycling methods.

A solvent-free mechanochemical synthesis of two fluorinated perovskites, KCuF₃ and KNiF₃, including the optimization of milling time at constant rotational speed, was studied as a practical and green alternative to the classical solvothermal synthesis. The presence of KCuF₃ and KNiF₃ in the desired crystalline phase as the main product was observed after 6 h of milling. At higher milling times K₂CuF₄ and K₂NiF₄ were detected as additional crystalline phases for the Cu- and Ni- based perovskites, respectively. The fluorinated perovskites were characterized by using X-Ray Powder Diffraction (XRD), X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM), confirming the selective formation of the fluorinated perovskites. The mechanochemical route was also compared to a new mild solvothermal method. An evaluation of the environmental impact and the energy efficiency was performed; moreover, the effectiveness of the mechanochemical process was compared to that of the solvothermal method. The promising results obtained from this innovative method opened the door to the use of solvent-free mechanochemical syntheses as a suitable approach in the field of crystal engineering also.

A cyanation reaction was performed inside a ball mill system utilizing catalytically active milling balls, while avoiding the use of solvents and ligands. Additionally, replacing the highly toxic cyanide source with potassium hexacyanoferrate(II) leads to a safer reaction environment. Yields of up to 90% were achieved in as little as 4 hours at room temperature. The oxidative addition and transmetalation step could be observed via X-ray photoelectron spectroscopy (XPS) and powder X-ray diffraction (PXRD) analysis, respectively, giving a first indication of the mechanism of this mechanochemical reaction.

Mechanochemistry is a promising approach for chemical recycling of commodity plastics, and in some cases depolymerization to the monomer(s) has been reported. However, while poly(olefin)s comprise the largest share of global commodity plastics, mechanochemical depolymerization of these polymers in standard laboratory-scale ball mill reactors suffers from slow rates. In this work, the observed reactivities of poly(styrene), poly(ethylene) and poly(propylene) are rationalized on the basis of thermodynamic limitations of their depolymerization by depropagation of free radical intermediates. In addition, subsequent phase partitioning equilibria for the removal of monomers from the reactor via a purge gas stream are discussed for these polymers. For poly(styrene), a typical vibratory ball mill supplies just enough energy for its depolymerization to be driven by either thermal hotspots or adiabatic compression of the impact site, but the same energy supply is far from sufficient for poly(propylene) and poly(ethylene). Meanwhile, removal of styrene from the reactor is thermodynamically hindered by its lower volatility, but this is not an issue for either propylene or ethylene. The implications of these thermodynamic limitations for mechanochemical reactor design and potential for mechanocatalytic processes are highlighted.

Beta blockers are a class of ubiquitous cardiovascular drugs that have collectively received little attention from a crystal engineering standpoint. Here, we describe the use of mechanochemistry in the salification of five beta blockers (propranolol, metoprolol, acebutolol, atenolol, and labetalol) with nicotinic and isonicotinic acid. Firstly, liquid assisted grinding (LAG) was used to neutralize the commercial beta blocker salts, enabling the efficient gram-scale formation of the free bases, which are essential for cocrystallization. Thereafter, 1 : 1 mechanochemical cocrystallizations were successful in all but one case and nine salts were characterized, eight of which are novel. Furthermore, the racemic free base crystal structure of acebutolol is reported for the first time, as well as the first multicomponent crystal of labetalol that is not a simple salt. Salification was enabled by the large pK_a differences between the components, which facilitated the protonation of the basic amine on the beta blockers' alkanolamine skeleton. Thereafter, charge-assisted hydrogen bonding promoted cocrystallization. We envisage salification to be applicable to any beta blocker, considering the current study encompasses approximately one quarter of this drug class. Lastly, the role of different liquid additives in the LAG process was assessed, and the solvent identity was found to play a substantial role in the mechanochemical outcome, although it did not strictly correlate with polarity. This study demonstrates that LAG screening with a wide selection of solvents provides a path to achieve full conversion to products, explore the crystal landscape of multicomponent crystals, and assist in identifying additional phases and/or late stage polymorphs in solid form development.

Here, we report the reaction of calcium-based heavy Grignard reagents, which are easily generated by a mechanochemical method, with unactivated alkyl fluorides in the absence of transition metal catalysts to produce the corresponding arylated products in moderate to good yields. This is the first example of the nucleophilic substitution of an inert C(sp³)–F bond by an organocalcium species. Preliminary mechanistic studies based on theoretical calculations indicate that tetrameric aryl calcium species facilitate the unprecedented C(sp³)–F bond arylation.