Themed collection Editor’s Collection: Mechanochemistry

Two decades of reactive milling for environmentally benign sustainable production with metals.

Mechanical impact breaks infinitely covalent crystals providing surface plasma with exciting applications. Polymer technology profits from bond breaking with radical formation. Crashed (semi)metals start improved syntheses as do weak-bond molecules including explosives. Strong bonds in small molecules break by shear under Bridgman's anvil and at lubrication. Single bond breaking and nano-dissection are emerging.

In the present study, cocrystallization of a new piprazole analogue drug, brexpiprazole (BREX), with coformers such as succinic acid and catechol was carried out using ball milling to address the poor solubility and dissolution rate of the molecule.

Liquid assisted grinding using imidazolium-based ionic liquids (IL-AG) was found to be effective in isolation of cocrystals and cocrystal polymorphs.

A zinc coordination complex with terpyridyl derivative as ligand exhibits mechanochromic and thermochromic luminescence behaviors with reversible color changes visible to the naked eye from pink to blue-purple upon mechanical grinding and from pink to blue upon heating.

The paper provides a prime example where liquid is required for a reaction, but simultaneously inhibits it. The results offer insights into possible regional, seasonal, polymer additive and temperature effects on mechanochemical synthesis.

Ball milling of blue-emitting crystal 1B of gold(I) isocyanide complex 1 induces a phase transition to yellow-emitting powder 1Y_G, which has the same solid structure as the previously reported 1Y obtained upon photoirradiation of 1B.

Two halogen bonded cocrystals of N-bromosuccinimide and 4,4′-bipyridine, with stoichiometric ratios 1 : 1 and 2 : 1, have been synthesized and characterized. We present the first mechanochemical cocrystallization of N-bromosuccinimide.

Polymorphism has been explored in a second sphere adduct using a racemic ligand that also shows racemic polymorphic behavior. The polar nature of the second sphere adduct allowed us to study NLO phenomena.

In situ investigation and elucidation of the formation of a POM@MOF host guest system obtained by mechanosynthesis.

A Ag(I)-imidazolate coordination polymer showed unique luminescence mechanochromism due to the Ag⋯Ag and C–H⋯π interactions.

Nanoscale cocrystal of CL-20 and HMX with a rounded morphology was prepared by bead milling an aqueous suspension of the coformers.

Mechanically stirring the precursor colloidal dispersion can control the polymorphs of mesoporous calcium carbonate.

Glycine is the simplest achiral amino acid that undergoes spontaneous mirror symmetry and controlled deracemization in its γ-polymorphic modification.

We describe a four-component one-pot mechanochemical reaction which combines the formation of covalent bonds, coordination bonds and halogen bonds to obtain an extended structure based on halogen-bonded metal–organic units.

An X-ray amorphous mixture of carbamazepine and indomethacin transforms upon annealing to produce a novel 1 : 1 cocrystal.

Systematic variation of water activity in the grinding liquid enables a rational strategy to mechanochemically screen for hydrated forms of magnesium-based pharmaceutical derivatives formed in situ from MgO and naproxen.

Co-crystals of dextro-(R,R), levo-(S,S), meso-(R,S) and racemic (R,R–S,S)-tartaric acid with pyrazine were obtained by manual kneading and slurry experiments; upon their reaction with the various tartaric acid forms co-former exchange takes place, according to the sequence of stability [(R,S)-ta]₂·py > (S,S/R,R)-ta·py > (R,R)-ta·py or (S,S)-ta·py.

We describe a model study of “solid + solid” reaction with control over number, energy, duration, and frequency of individual mechanical pulses.

A study of the MOF formation by grinding together solid reactants in a ball mill reveals interesting aspects of morphology and reactivity; the product could also be activated to exhibit appreciable surface areas (>1300 m²g⁻¹) although washing with solvent was required.

Cocrystals of artemisinin, an artificial antimalarial drug lacking sites for forming conventional supramolecular synthons, have been obtained by mechanochemical screening and the results analysed using molecular descriptors derived from the CSD.

Yellow crystals of monomeric structure [Zn(bpdh)₂(H₂O)₄](NO₃)₂·2bpdh (1) convert on heating at ca. 160 °C under grinding and mixing with KSCN or NaN₃ to white and orange 1D coordination polymers, [Zn(µ-bpdh)₂(NCS)₂]_n (2) and [Zn(µ-bpdh)₂(N₃)₂]_n (3), respectively.

Coordination and hydrogen bonding networks of the antibiotic 4-aminosalicylic acid and of the nootropic drug piracetam with silver and nickel cations have been prepared mechanochemically; in the case of silver, solid-state and solution reactions afforded different crystalline materials.

Mechanochemical method of liquid-assisted grinding enables rapid and clean conversion of an inexpensive metal oxide into diverse coordination polymers and porous frameworks for preparative and screening purposes.

The construction of the ternary phase diagram urea–glutaric acid–water has led to the discovery of a new co-crystal form.

Under solvent-free conditions in a ball mill a significant nonlinear relationship between the enantiomeric excess of the catalyst (proline) and that of the product was observed, when solely solid substrates were used.

Synthesis of nicotinamide and fumaric acid supramolecular cocrystals with 1 : 1 and 2 : 1 amide to acid stoichiometries results in the formation of an amide–acid heterosynthon (1 : 1 stoichiometry) and an amide–amide homosynthon (2 : 1 stoichiometry) and different conformations of the fumaric acid moieties.

The solid-state preparation and structural characterization of the first two coordination complexes of the neuroleptic drug gabapentin.

Solvent-free grinding is demonstrated as an effective way to produce a porous 3-dimensional metal–organic framework.

Novel crown ether complexes, 18Crown[6]·[NH₄][HSO₄]·2H₂O and (15Crown[5])₃·[NH₄]₂[H₃O][HSO₄]₃·H₂O have been prepared, respectively, by grinding and kneading of solid 18Crown[6] and of liquid 15Crown[5] with solid [NH₄][HSO₄].

Two solid-state coordination reactions for the polymers g[N(CH₂CH₂)₃N]₂[CH₃COO]·5H₂O and Zn[N(CH₂CH₂)₃N] and their solution counterparts, as well as two discussions of X-ray results are presented.

Two new Na and K coordination polymers with halogen bond, metallophilic and hydrogen bonding interactions were synthesized. These two compounds were synthesized sonochemically and solid-state conversions of them to each other were investigated.

The mechanochemical interconversion of two salts was achieved by the addition of an appropriate amount of one of the corresponding components (HL or CuCl₂·2H₂O), and the progress of dynamic interconversion was revealed by PXRD, fluorescence and Raman spectroscopy.

A combination of the excess enthalpy with the fusion entropy of the pure coformer is suggested to be of interest for coformers screening in order to form a multicomponent system with a given API (cocrystal/co-amorphous).

The effects of milling ball mass, size and material are isolated for a model mechanochemical co-crystallisation.

We demonstrate that solvates obtained through mechanochemistry are the thermodynamic products, and that the kinetics of solvate formation are related to the easiness of breaking the reactant crystals.

Nonporous hybrid metal organic materials have been studied in the solid-state by mechanochemical reactions, chemisorption and release of HCl by heating. The dynamic behavior of the hybrid materials allows the breaking and formation of chemical bonds.

We describe the implementation of chemometric analysis for mechanochemical synthesis monitoring.

Different types of mechanical treatment (tableting, grinding, milling, etc.) are important technological operations in the pharmaceutical industry.

The effect of the ball to reactant ratio on reaction times for a cocrystal formation was studied by in situ PXRD.

A convenient mechanochemical synthesis method has been used to produce luminescent 2D rare-earth coordination polymers.

A systematic study on mechanochemical, thermal and vapochemical cocrystallisation demonstrates the effect of compound properties on the outcome of the reaction.

Three crystal forms of a thermochromic Schiff base derived from o-vanillin and 3-aminoacetophenone were obtained by conventional solution-based methods. Two polymorphs out of three were synthesized by mechanochemical syntheses, under solvent-free conditions.

Mechano-chemical synthesis of Cu-doped BiVO₄ monoclinic nanopowders and investigation of structural, optical and electronic properties.

4-Phenylpyridine-N-oxide and βCD form a stoichiometric inclusion complex with two polymorphs occurring at different crystallisation times. The irreversible conversion of one polymorph into the other was monitored in real time for the first time.

Two new three-dimensional porous Cd(II)-based metal–organic frameworks, TMU-8 and TMU-9, with high performance in adsorption of Congo red.

Mechano-stimuli, which causes mechanochromic luminescence when being applied on crystalline materials, facilitates the annealing crystallization of amorphous materials.

Tolfenamic acid (HTA) is a drug characterized by very poor solubility in water. By mechanochemical methods, new solid-state forms of HTA were obtained, showing better thermal stability than pure HTA and an improved dissolution rate.

[L-serH]₂[ox]·2H₂O form II proved to be an intermediate product in the reaction for obtaining the form I.

A solid-state reaction from a metal organic salt into a coordination complex is achieved via a dehydrochlorination reaction by grinding.

A phase transition, induced by low temperature, facilitates another one, induced by mechanical treatment.

Mechanosynthesis of metal–organic materials from ZnO or CuO proceeds via a stepwise mechanism and can be regulated by the mole fraction and the activity of water in the grinding liquid.

Solid-state adducts of DABCO with aromatic polycarboxylic acids were prepared in the solid state by grinding and kneading techniques; the extent of proton transfer between acids and base reflects the trend of solution acidity of the three polycarboxylic acids.

The ability of solid-state grinding methods, such as neat grinding and solvent-drop grinding, to produce the metastable polymorph of a cocrystal is exemplified by dimorphs of a cocrystal between an analgesic drug, ethenzamide, and saccharin.

The cyanooxime preferentially binds to the moiety with the most negative electrostatic potential in a heteroditopic (benzimidazole-pyridine) hydrogen-bond acceptor.

Annealing assisted mechanochemical grinding of transition metal complexes activates molecules to form coordination polymers, or encourages diffusion/rearrangement of component molecules to form new crystals by way of recognition or transfer of chirality.

We report the first in-depth SFM characterization of a prototype halogen-bonded crystalline system to obtain structural and surface compositional information, and investigate nanoscale properties. We expect this study to impact the rational design of perfluorocarbon–hydrocarbon systems, leading to co-crystals with engineered surfaces and predictable properties.

Investigation of 2-methylphenol and 2-chlorophenol reveals similarities in structure at both low temperature and high pressure. Co-crystallisation of the two components results in the formation of a 0.45 : 0.55 2-methylphenol : 2-chlorophenol co-crystal at low temperature but at high pressure the mixture is separated resulting in the formation of a new polymorph of 2-chlorophenol.

Liquid-assisted grinding (LAG) and sonochemical (SonicSlurry) techniques in cocrystallisation were compared by introducing a parameter (η) that allows interpreting and predicting cocrystal formation in a range of solvents and concentrations by considering reactant saturation levels.

Reactions between metal salts and bridging ligands in a ball mill are found to be remarkably general. Some insights and trends are revealed by studying an array of 60 potential reactions between various ligands and metal salts.