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Highlights from Faraday discussion 170: Challenges and opportunities of modern Cite this: Chem. Commun., 2015, 51,6248 mechanochemistry, Montreal, Canada, 2014

a b cd e Tomislav Frisˇcˇic´,* Stuart L. James, Elena V. Boldyreva, Carsten Bolm, William Jones,f James Mack,g Jonathan W. Steedh and Kenneth S. Suslicki

The Faraday Discussion Mechanochemistry: From Functional Solids to Single Molecules which took place 21–23 May 2014 in Montreal, Canada, brought together a diversity of academic and industrial researchers, experimentalists and theoreticians, students, as well as experienced researchers, to discuss the changing face of mechanochemistry, an area with a long history and deep connections to manufac- DOI: 10.1039/c5cc90113h turing, that is currently undergoing vigorous renaissance and rapid expansion in a number of areas, including supramolecular chemistry, smart polymers, metal–organic frameworks, pharmaceutical materi- www.rsc.org/chemcomm als, catalytic organic synthesis, as well as mineral and biomass processing and nanoparticle synthesis.

In May 2014, the New Residence Hall of McGill University provided a home to a unique gathering of approximately 100 exp- erts, novices and aficionados of mechanochemistry (Fig. 1).1 Entitled Mechanochemistry: From Functional Solids to Single Molecules, the 256th Faraday Discussion was inspired by the rising importance of mechanochemistry Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. in making, understanding and manipul- ating molecules, and was envisioned as a first step towards bridging the perceived gap

a Department of Chemistry and the Centre for Green Chemistry and Catalysis, McGill University, 801 Sherbrooke St. W., H3A 0B8 Montreal, Canada. E-mail: [email protected] b School of Chemistry and Chemical Engineering, Queen’s University, Belfast, UK c Novosibirsk State University, ul. Pirogova, 2, Novosibirsk, Russia d Institute of Solid State Chemistry and Mechanochemistry SB RAS, ul. Kutateladze, 18, Novosibirsk 630128, Russia e Institut fu¨r Organische Chemie der RWTH Aachen University, Landoltweg 1, 52056 Aachen, Germany f Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK g Department of Chemistry, University of Cincinnati, Fig. 1 Macdonald Physics Building, a hallmark of McGill University, and the site of Ernest Ruther- 301 Clifton Court, Cincinnati, OH 45221-0172, USA ford’s pioneering studies on a-, b-andg-radiation. h Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK i School of Chemical Sciences, University of Illinois at Urbana-Champaign, 600 S. Mathews Av., Urbana, between researchers in diﬀerent sub-areas of Grinding and milling of bulk materials IL 61801, USA mechanochemistry. have traditionally been associated with

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metals,2 inorganic materials,3 specifically Kingdom, France, Germany, Poland, completely solvent-free and quantitative minerals,4 and polymers,5 but has now Slovakia, Croatia, Switzerland) and Asia synthesis of a para-cyclophane (Fig. 2a). also become the focus of chemists wishing (India, China, Russia), representatives of The discussion that ensued, and that was to develop solvent-free and energy-efficient chemical, mining, pharmaceutical and facilitated by the student hosts Patrick A. approaches to molecules and molecular food industries, as well as representatives Julien and Igor Huskic´ (McGill University), materials, or who are simply interested in of manufacturers of milling equipment established that this technique resolves a exploring the properties and advantages of (e.g. Retsch US, Spex). long-standing problem of light penetration a non-conventional reaction medium. in solid-state photochemical synthesis.† Mechanochemistry has found followers The second presentation, by Graeme in broad areas of chemistry and industrial Opening lecture M. Day (University of Southampton), development, ranging from inorganic The conference was opened by William described efforts in computationally 6 7 chemistry to organic and supramolecular Jones (University of Cambridge), who addressing reversible covalent reactions 8 chemistry, with the most recent additions provided a short but elaborate overview by mechanical milling (DOI: 10.1039/ including the synthesis of coordination of the history of mechanochemistry (noting C4FD00162H), specifically the base- polymers (including metal–organic frame- that some of the seminal experiments catalyzed equilibration of aromatic dis- 9 15 works, MOFs) and pharmaceutical solids in mechanochemistry were reported by ulfides. Outcomes of these computa- (e.g. making and screening polymorphs, Michael Faraday) and its future opportunities tional studies show that lattice energy 10 cocrystals, amorphous phases). In con- (DOI: 10.1039/C4FD00162A). The opening calculations, combining anisotropic trast, ultrasonic radiation provides another lecture highlighted the importance of atom–atom potentials with molecular way to expose molecules and particles to mechanical processing in the context of density functional theory (DFT), open a high shear forces suitable for materials industrial and materials manufacture, way to rationalise or even predict the course processing and fundamental studies of and especially in pharmaceuticals materials of reversible mechanochemical transforma- 11 chemical bonding. The most clear-cut science. Prof. Jones described how tions. However, successful modelling and approach to mechanochemistry is mani- sophisticated mechanochemical techniques, prediction of mechanochemical reactivity pulation of individual molecules and such as liquid-assisted grinding, bring about under thermodynamic equilibrium are still atoms by tools of high precision, such as improvements in generating and controlling at a very early stage, with the principle the tip of the atomic force microscope new solid forms of pharmaceuticals, hurdle being the conformational flexibility (AFM), allowing the determination of fun- such as pharmaceutical cocrystals,12 of explored molecules. The discussion† damental properties of individual mole- while at the same time the behaviour that followed was highly positive about cules (e.g. flexibility of protein structures), required of materials and processing this major computational advance in as well as precise surface patterning and parameters during large-scale mechanical modelling mechanochemical reactions, 12 modification. processing remain an open problem. This and highlighted the modelling of reaction Another, very different aspect of kinetics as the next big challenge. In the

Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. inspiring and exciting opening lecture mechanochemistry is understanding the was followed by the first of the four final presentation of this session Tamara processes which occur in different types topical sessions, chaired by Stuart L. D. Hamilton described the application of of mechanical devices, e.g. by in situ James (Queen’s University Belfast) and mechanochemistry to one of the persistently 13 monitoring of reaction progress, or Tomislav Frisˇˇcic´ (McGill University). highly challenging problems of synthetic theoretical modelling of distribution of organic chemistry: the synthesis of por- stress and temperature throughout the phyrins (DOI: 10.1039/C4FD00140G). sample being milled, with the ultimate Session 1: Prof. Hamilton presented a two-step purpose to scale-up and optimise the mechanochemistry of methodology to access a variety of meso- type of mechanical action for a specific substituted porphyrins by mechanochemical transformation. organic molecules, soft chemical reaction of suitable aldehydes Therefore, it was clear from the outset materials and and pyrroles, followed by a mechano- of this meeting that mechanochemistry is pharmaceuticals chemical oxidation step. This protocol of exceptional, as well as growing interest gave porphyrin targets with significant for chemists, physicists, theoreticians and The session was off to a dynamic benefits compared to solution-based industrial researchers. This broadness was start with the presentation by Leonard protocols: reactions are much faster (less reflected in the composition of participants R. MacGillivray (University of Iowa) who than an hour compared to several hours) who spent three days discussing funda- described a novel and experimentally and the use of high temperatures and mentals, applications and problems that simple strategy for coupling photochemistry corrosive reagents is avoided (reflux in distinguish or, perhaps, connect different with mechanochemical milling (DOI: propionic acid is the conventional synthetic aspects of mechanochemistry. The parti- 10.1039/C4FD00006D). This vortex grinding alternative). A mechanochemical first step cipants included researchers from across strategy14 allows mechanochemical grinding North & South America (USA, Canada, of photoactive solids under continuous † Transcripts of all discussions are also published in Mexico, Colombia, Brazil), Europe (United exposure to ultraviolet light, leading to the Faraday Discussions volume 170.

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new strategy for the preparation of ternary (three-component) cocrystals held by a combination of hydrogen and halogen bonds, enabled by mechanochemical cocrystal screening. The next presenter was Manuel Jo¨rres (RWTH Aachen Univer- sity) who presented the use of ball milling for solvent-free organocatalytic Michael additions. Qiwen Su (Barry University) gave a highlight of a novel mechanochemical technique for the preparation of porphyrins, while Daniel Prochowicz outlined an unprecedented technique for the synthesis of isoreticular MOFs (IRMOFs), including the archetypal material MOF-5, that have so far resisted synthesis by mechanochemical means.17 The next presentation was from Canada, given by George Margoutidis (Memorial University, Newfoundland), who described ball milling for depolymerisation of chitin into small amino-substituted molecules. Fig. 2 (a) The para-cyclophane prepared by the MacGillivray group using vortex grinding, combin- Gurpaul Kochhar (Queen’s University, ing simultaneous ball grinding and photochemical [2+2] photodimerisation. Products of mechano- Kingston) gave a brief overview of his work chemistry at diﬀerent scales: (b) a cluster crystal of guanidine carbonate produced by shaking the powder suspended in a saturated solution at 1000 rpm (presented by L. Cuccia) and (c) a composite on theoretical modelling of mechanically-

of lignin matrix and rhenium nanoparticles prepared by the Moores group through milling Re(CO)5Br induced distortions in molecular structure with Kraft lignin. and ring opening of cyclobutene mechanophore. Fre´de´ricLamaty(InstitutdesBio- molećules Max Mousseron, Montpellier) followed by oxidation in chloroform gives importance when considering the purity gave a summary of his poster ‘‘Mechano- yields comparable to those obtained from and control of industrialized mechanochemistry in organic synthesis’’, describing an entirely solution-based process, while chemical processes. Thermal investiga- stoichiometric and catalytic mechano- eliminating a large amount of solvent tion suggested that reactivity under chemistry in the synthesis of amides, Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. and reducing reaction time. The sub- shear treatment may be induced due to amino acids and (oligo)peptides. Next, sequent discussion† revealed that the heating, while a tablet-induced pressure Vladimir Stilinovic´ (University of Zagreb) ‘green’ nature of this methodology can model was suggested as a potential gave details of his systematic investigation be further improved by the using solvent- mechanism for reactions under impact of the role of acetone vapor on forming new free entrainment sublimation for product treatment. The first session was followed crystalline phases in thin layers. Aileen purification. The benefits and simplicity of by a Lightning Session of 14 rapid flash Nielsen (Columbia University) highlighted this mechanochemical approach are presentations selected by the organizers her poster ‘‘High resolution single-molecule reflected in all metrics relevant to sustain- to highlight the most outstanding poster force spectroscopy probes inter-molecular ability and environmentally-friendly nature contributions. interactions’’, on using AFM to evaluate the of chemical reactions. use of intermolecular recognition and non- The effect of different types of mechanical Flash presentations covalent bonding in making two-molecule action on chemical reactivity was demon- The flash presentations were given by junctions. Cristina Mottillo (McGill Uni- strated in the contribution of Adam Katharina Holz (University of Kiel) on versity) presented a novel approach for Michalchuk and co-workers (University ‘‘A 1,2,3-triazole for mechanically induced the synthesis of solid-state fluorescent of Edinburgh and Novosibirsk State Uni- 1,3-dipolar cycloreversion’’, who described materials, by entrapment of BODIPY dyes versity) (DOI: 10.1039/C4FD00150D). mechanical reversal of the popular ‘click into MOFs using either mechanochemistry Mixtures of a-glycine and b-malonic acid reaction’ of an alkyne and an azide by or the recently developed accelerated aging were shown to produce two unique reac- pulling on a triazole fragment using the technique. Next, Matej Bala´ˇz described the tion products when submitted to isolated AFM tip. Next, Robert Schmidt (University synthesis of L-cysteine-capped core–shell impact and shear treatments. This leads of Jena) highlighted his work on assessing luminescent quantum dot nanoparticles to the formation of zones with distinct energetics of the milling aldol reaction CdS@ZnS by a rapid three-step milling chemical reactivity within a single milling between barbituric acid and vanillin. Filip procedure, delineated in his poster vessel,16 an observation of particular Topic´ (University of Jyva¨skyla¨) described a ‘‘Characterization of mechanochemically

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synthesized CdS@ZnS quantum dots: which, although a poor solvent for the by Vladimirˇ Sepela´k (Karlsruhe Institute focus on surface properties and potential reactants, performs several roles in this for Technology), whose group19 has pio- interaction with capping agent’’. The process: as a ‘lubricant’ for kinetic accelera- neered multi-faceted investigations of final presentation was given by Louis tion of the reaction, as a heat sink for this mechanochemically prepared materials, Cuccia (Concordia University), whose exothermic reaction, as a dispersant for combining Mo¨ssbauer and solid-state poster ‘‘Enantiomer-specific oriented product removal from the reaction sites, NMR (SSNMR) spectroscopy with X-ray attachment in conglomerate crystals of and as a suspending agent for the diffraction and high-resolution electron guanidine carbonate’’ demonstrated inter- reactants.† Next, Lucia Maini (University microscopy. The presentation gave a particle collisions as a mechanism of crystal of Bologna) highlighted mechanochemical detailed structural explanation for the growth and spontaneous deracemization synthesis and discovery of new luminescent modification of magnetism in barium in Viedma ripening (Fig. 2b). The rapidly copper(I) iodide (CuI) materials based on hexaferrite by milling (DOI: 10.1039/ concluded Lightning Session was followed the ligand tris(2-pyridyl)phosphine (PN) C4FD00137G). Milling was found to by a rich and social poster session, (DOI: 10.1039/C4FD00164D). Ball milling induce amorphization and distortion of accompanied by an apparently almost was demonstrated as a simple means, the crystal structure of the material down inexhaustible wine reception and a free complementary to solution synthesis, to to ca. 2 nm below the milled particle evening that saw a large number of meeting screen for supramolecular architectures surface. The ability to observe surface participants spontaneously gathering at the with attractive properties, such as phos- deformations in milled particles with McGill University Graduate Student Club, phorescence.18 While conventional solution nanometer resolution, and provide a the (in)famous Thomson House pub. chemistry yields three different CuI archi- detailed description of such deforma- tectures, application of ball milling readily tions by combining spectroscopy, diffrac- expanded this library of luminescent CuI tion and microscopy gave an excellent Session 2: motifs. Solution-achievable phases are illustration of the power of modern ana- mechanochemistry of based either on a monomeric CuI motif in lytical techniques and an inspiration for inorganic compounds CuI(PN)3,adimerinCu2I2(PN)3 or a tetra- further investigations in inorganic, mer in Cu4I4(PN)2. In addition to these, ball metal–organic and organic systems. and coordination-based milling also made accessible new materials Further in the spirit of mechanochemistry materials CuI(PN)2, of still unknown structure, and in the service of inorganic chemistry, CuIPN0.5 with a polymeric CuIN structure. Shalabh Gupta and Vitalij Pecharsky The excitements of the previous night Her presentation also tackled the problem (Iowa State University) presented a new, did not hinder the timely beginning of of structurally characterising mechano- mechanochemical methodology for the the second session on Thursday morning. chemical products, either by crystal growth direct generation of non-solvated alane,

The session, chaired by Leonard MacGillivray in solvothermal synthesis or by structure AlH3, a highly unstable compound of and Laszlo Takacs, was opened by David solution from X-ray powder diﬀraction data considerable appeal for its high gravimetric Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. W. Peters (ATMI, USA), who described using direct space methods. Lisa Tro¨bs hydrogen content (DOI: 10.1039/ the first large-scale synthesis of an impor- (BAM Federal Institute for Materials C4FD00161J). Although mechanochemical tant organometallic compound bis(n-pro- Research and Testing in Berlin) outlined synthesis of alane has been achieved

pyltetramethylcyclopentadienyl)strontium mechanistic studies of mechanochemical previously by milling LiAlH4 with AlCl3, 0 (SrCp 2), by mechanical agitation of SrI2 synthesis of bismuth(III) coordination such procedures were vexed by in situ and KCp0 in diethyl ether (EtOEt) (DOI: frameworks, conducted by rapid stepwise degradation of reactive intermediates 10.1039/C4FD00157A). Development of analysis using Raman spectroscopy and into metallic aluminium. The Ames this first large-scale organometallic X-ray powder diﬀraction (DOI: 10.1039/ group circumvented this obstacle by

mechanosynthetic procedure was based C4FD00163F). The results demonstrated performing AlCl3 addition in several on the unexpected discovery that small time resolution in seconds, so far unpre- small portions, in that way ensuring a scale reactions, stirred by a magnetic stir- cedented in stepwise studies of mechano- continuous excess of hydride reagent. 0 rer, reproducibly gave the product (SrCp 2 chemical reactions. In a twist particularly At the same time, the procedure was EtOEt), whereas large batch reactions stir- relevant for supramolecular solid-state ingeniously simplified by replacing the red by an overhead stirrer did not result in chemistry and pharmaceutical materials, highly reactive and difficult to handle

any product. This revealed that the reac- the presentation also highlighted the LiAlH4 with LiH resulting in the first tion takes place by mechanical crushing use of rapid stepwise analysis for moni- room-temperature, solvent-free approach of the reagent solids in the presence of toring the cocrystallisation of two phar- to generate alane from stoichiometric ether. Realisation of the mechanochemical maceutical ingredients, carbamazepine reagents and without the need for stabilizing nature of this process enabled scale-up to at and indomethacin. organic solvents. least 0.5 kg amounts using a specially Next, the discussions switched to The next two presentations addressed designed large-volume glass reactor inorganic materials, such as magnetic the hot and rapidly developing area of equipped with steel milling balls. The dis- oxides and hydrides for hydrogen nanoparticle20 mechanosynthesis. Audrey cussion focused on the importance of ether storage.† The first presentation was given Moores (McGill University) unveiled a

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methodology for mechanochemical pro- impressive when considered from the resemble 1st or 2nd order reaction kinetics duction of nanoparticles of copper, gold, perspective of extensive research invested of solution reactions (Fig. 3a and b). palladium, ruthenium or rhenium in developing conventional approaches to This confirmed the notion that rapidly embedded within a reductive organic such systems in solution, which demand milled reaction mixtures can behave as matrix (DOI: 10.1039/C4FD00053F). The careful control of reagent choice and ‘pseudo-fluid’ reaction environments.23 mechanochemical synthesis of these nano- addition, and depend on extensive use In addition, the ability to conduct a quan- particles is exceedingly simple, achieved of solvent and additional energy input titative Rietveld analysis of in situ without extensive dilution normally (e.g. rapid shaking or sonication). mechanochemical reaction data provided required by conventional procedures. an unprecedented opportunity to monitor Milling with Kraft lignin led to in situ the participation of amorphous phases in reduction of metal precursors to elemen- Session 3: mechanistic the reactions. Next, Richard Blair (Univer- tary metal nanoparticles with sizes from understanding, catalysis sity of Central Florida) addressed scaling- 2.8 nm (from palladium(II) acetate) to and scaling up up of mechanochemical reactions, with 14.8 nm (from HAuCl4), that remain particular focus on differences between immobilised in the organic lignin matrix. After the lunch break, which gave extensive different types of milling equipment, such Besides providing a rapid, simple and opportunity for further interaction between as shaker, planetary and attrition mills, inexpensive approach to metal nano- presenters and exhibitors, the afternoon and how differences in design of milling particles, this work also revealed the ability session, chaired by Carsten Bolm and Peter equipment affect energy and materials to direct the organisation of nanoparticles Bala´ˇ,z began by addressing the latest transfer in mechanochemical processes either within or onto the organic matrix by development of a technique for quantitative (DOI: 10.1039/C4FD00007B).† The contri- judicious choice of precursor: inorganic real-time monitoring of mechanochemical bution dealt with two industrially relevant precursors led largely to nanoparticles asso- reactions. Ivan Halasz (Institute Ru:er processes: mechanochemical degradation ciated with lignin surface, while more Bosˇkovic´) described the use of high energy of cellulose and mechanochemical edge hydrophobic precursors preferred intimate synchrotron X-ray powder diffraction for oxidation and delamination of graphene. nanoparticle–lignin composites (Fig. 2c). quantitative in situ and real-time monitor- A particularly eye-catching aspect of the Development of a mechanochemical ing of mechanochemical reaction pathways presentation was the simulation of bottom-up procedure21 for solvent-free (DOI: 10.1039/C4FD00013G). The presented the motion of milling media and of the assembly of nanoparticles of binary com- studies, which focused on mechanosynth- distribution of high-energy impacts, pounds was presented by Peter Bala´ˇz esis of zeolitic imidazolate frameworks obtained by discrete element modelling. (Institute of Geotechnics, Slovak Academy (ZIFs), demonstrated that kinetic behaviour Such modelling, a novelty to a large num- of Sciences) who outlined the synthesis of of mechanochemical reactions can strongly ber of participants, offers a means not monodisperse PbS nanoparticles (32– 34 nm diameter) by milling lead(II)acetate Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. with L-cystine (disulfide dimer of the aminoacid L-cysteine). High-resolution transmission electron microscopy revealed that nanoparticles are highly crystalline, with clearly observable lattice fringes, and faceted, adopting the morphology of trun- cated octahedra. Excess cystine was found attached to particle surface, highlighting a simple methodology to obtain group II–VI nanoparticles with biocompatible surfaces. All four presentations in the inorganic materials session inspired active discussions that addressed different aspects of particle structure, formation and advanced techniques for product characterisation in mechanochemical reactions. The presentations formed a neat, high-impact overview of technological and methodological advances in making and understanding Fig. 3 (a) A two-dimensional time-dependent X-ray powder diffractogram for the mechanochemical mechanochemically synthesised nano- synthesis of a zeolitic framework and (b) changes in the composition of the milled reaction mixture containing the product (green), reactants (yellow, blue) and the intermediate amorphous phase (red), particles.22 The effectiveness and simplicity as reported in the paper of Halasz and Frisˇcˇic´. (c) Illustration of the screw design used in the scaling up of mechanochemistry in generating mono- of mechanochemical cocrystallisation of the drug candidate AMG-517 by twin screw extrusion (TSE), disperse nanoparticles are particularly as presented by K. Nagapudi.

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only to understand the motion of milling amorphisation, structure distortion and a central reference point in the design of media in different experiments, but also creation of defects. Such a view of mechanochemical processes in planetary to rationalise and even predict thermal mechanical activation is supported by mills. effects in mechanochemical reactions. detailed investigations of milled particles, The evening after the afternoon session Reaction scale-up was also the topic of presented by theˇ Sepela´kgroup.Conse- saw all participants gather once again, this the presentation by Karthik Nagapudi quently, MSRs provide clear examples of time for the Conference Dinner held in the (Amgen Inc.), who outlined details of mechanochemical transformations in classical environment of the McGill Faculty large scale mechanochemical process which mechanical agitation is primarily Club ballroom. An excellent and high- for the synthesis of pharmaceutical a means to activate, rather than sustain, a spirited mood extended throughout the cocrystals (DOI: 10.1039/C4FD00153A). chemical reaction. evening, enhanced by the traditional Loving This team previously described the first In the final talk of the session Achim Cup ceremony of the Faraday Society application of extrusion24 for scaling up Stolle (Friedrich-Schiller University Jena) (Fig. 4). The dinner was also an excellent of mechanochemical cocrystal formation described a systematic investigation of environment for the acting president of and the current presentation was the first the experimental parameters (conveniently the Faraday Society, Prof. Peter Skabara to highlight the details of the design, divided into chemical, technological and (University of Strathclyde) to announce the focusing on the synthesis of cocrystals process parameters) important for reaction winner of the Best Poster Award, graduate of AMG-517, a potent and selective optimisation, scaling-up and process inten- student Gurpaul S. Kochhar, for his work TRPV1 antagonist, with sorbic acid sification in planetary milling.27 This study Modelling mechanical processes under con- (Fig. 3c). Twin screw extrusion provides an provided a unique overview of the richness stant force and constant extension conditions, efficient, scalable, and environmentally- of experimental parameters that can be performed under the supervision of Prof. friendly process for the continuous pro- varied for fine-tuning a mechanochemical Nicholas J. Mosey at Queen’s University, duction of cocrystals. The presentation, organic reaction, such as the diameter of Kingston. Following an outstanding however, also initiated a lively discussion milling balls, rotation frequency, as well as four-course meal, the scientific discus- on the importance of amorphous phases the filling degree of the milling vessel (with sions (Fig. 4) continued over music and or eutectics as either intermediates25 or respect to packing of milling media and/or pool at the Bar de Pins, a popular venue of necessary activated phases in mechano- the amount of substrate). This work, McGill graduate students. conveniently chemical reactions.† which is of particular relevance to indus- located across the road from the Understanding and modelling of thermal trial researchers, is very likely to become conference site. effects and energy transfer are among the central challenges of mechanochemistry. This topic was addressed by Laszlo Takacs (University of Maryland, Balti- more County) who presented studies of Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. mechanochemically-induced self-pro- pagating reactions (MSRs) (DOI: 10. 1039/C4FD00133D). The MSRs are a unique subset of mechanochemical reactions in which the ratio of reaction enthalpy and heat capacity (DH/C)is sufficiently large to allow the reaction to become a self-sustained thermal process. Such behavior is found in milling thermite mixtures, as well as binary mixtures leading to the formation of borides, carbides, or chalcogenides.26 One aspect of MSRs that particularly captured the attention of the audience was the induction period, where- upon milling leads to little initial chemical changebutisfollowedbyarapidonsetof the reaction. It was noted during the vigorous discussion† that this delay, although Fig. 4 (a) Members of the Organising Committee with the Faraday Society acting president Peter Skabara still poorly understood, corresponds to a (from left to right): C. Bolm, W. Jones, T. Frisˇcˇic´,P.Skabara,S.L.James,K.S.SuslickandJ.Mack.(b)The mechanochemical activation of starting good mood at the Conference Dinner was sustained by a special four-course meal at the McGill Faculty Club, arranged by the chef Pierre Marjois. (c) The Faraday Society acting president Peter Skabara hands the materials, which can take place by different award for the best poster presentation to Gurpaul S. Kochhar (Queen’s University, Kingston, ON) and (d) the mechanisms simultaneously, including Loving Cup of the Faraday Society, brought to Canada by the RSC personnel Heather Montgomery and particle comminution, mixing, surface Michael Spencelayh. Photographs taken by Nenad Judasˇ, University of Zagreb.

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Session 4: sonication and dynamic (or force-ramp) AFMS (DOI: surface of initially completely nitrogen-free macromolecular 10.1039/C4FD00119A), in which bond clea- polymers, such as poly(tetrafluoroethylene) vage is recorded while ramping the force on (PTFE) or polyethylene.† Prof. Galembeck mechanochemistry a molecule stretched between a surface and explained that the extensive coverage of The final session of the meeting took the AFM tip, to force-clamp AFMS, which polymer surface by nitrogen species is most place in the morning of the third day of monitors bond cleavage events with the likely the result of chemisorption from air, 29 the conference and was dedicated to molecule under constant stress. While sparking speculations on possible develop- approaches to mechanochemistry other both methodologies gave similar bond dis- ment of processes for binding atmospheric than milling: molecular cleavage under sociation parameters for acid hydrolysis of nitrogen. The final talk of the session was ultrasonic irradiation, and manipulation amylose esters, which confirmed the pre- delivered by Charles E. Diesendruck from of individual chemical bonds using a tip viously proposed degradation mechanism, the Moore group (University of Illinois at of the atomic force microscope. the force-clamp technique gave a greater Urbana–Champaign),onthedevelopment The duty of chairing this morning ability to identify fine differences in the of a new triphenylsulfinium-based mechan- session belonged to James Mack (Univer- structure of the reactive ester site. The ophore (DOI: 10.1039/C4FD00027G). Theo- sity of Cincinnati) and Richard Blair, and discussions then switched to bulk beha- retical investigation of mechanochemical the opening presentation was given by viour of mechanically treated polymers, scission of this mechanophore indicated Stephen L. Craig (Duke University), who with the talk of Fernando Galembeck that heterolytic bond breaking, generating described a highly efficient design (DOI: (National Center for Energy and Materials phenyl cations, would be slightly preferred 10.1039/C4FD00001C) for incorporating Research, Campinas, Brazil) on the tribo- to the homolytic cleavage, which would give mechanophores, i.e. functional groups electric effect, i.e. the appearance and rise to phenyl cations (Fig. 5b). The predic- sensitive to mechanical tug,28 into poly- distribution of electrical charge on tions were confirmed by sonochemically- mers, leading to materials responsive to rubbed polymer surfaces (DOI: 10.1039/ induced cleavage of the mechanophore mechanical deformation. In particular, it C4FD00118K) (Fig. 5a). placed between poly(methylacrylate) chains, was discovered that the incorporation of Prof. Galembeck provided a detailed with the formation of phenyl cations 1 polybutadiene containing mechanopho- analysis of chemical composition and detected by H NMR and UV/Vis spectro- ric gem-dibromocyclopropane groups as charge on surfaces of rubbed polymers, scopy in trapping experiments. The work a central component in a triblock ABA pointing to the formation of highly clearly illustrated the ability to use theoreti- copolymer with polystyrene leads to at mobile macromolecular fragments that cal modelling for developing new mechan- least a 7-fold increase in mechanochemical readily diffuse across the surface or can ophores for applications in self-healing response compared to mechanophore-rich even be transferred in the form of nano- materials. Anatoly Politov and Olga Golyazi- poly(butadiene) only. Next, Martin Beyer particles. Whereas this study provided an mova (Novosibirsk Institute of Solid State (Leopold-Franzens-Universita¨tInnsbruck) explanation why it has so far not been Chemistry and Mechanochemistry, Russian Academy of Sciences) addressed the effi-

Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. presented the use of atomic force micro- possible to establish a triboelectrical ser- scope spectroscopy (AFMS) for evaluating ies of polymers, a particularly excited ciency of converting mechanical energy into energetics and mechanisms of covalent discussion developed around the demon- useful chemical energy. Focusing on the bond scission. The presentation compared strated presence of nitrogen on the application of ultrasound to lignocellulosic substrates, with the intention to facilitate subsequent fermentative hydrolysis, it was shown that judicious selection of mechanical treatment allows ten-fold increases in reaction yield, even at small inputs of energy. Development of such a targeted mechanochemical approach depends on detailed studies of how mechanical action can be optimised to generate defects and radicals central for a particular transformation.

Closing lecture

The Closing Lecture (DOI: 10.1039/ Fig. 5 (a) Electrostatic potential maps of PTFE film (left) sheared with low-density polyethylene C4FD00148F) was delivered by Kenneth foam slabs, presented by F. Galembeck (DOI: 10.1039/C4FD00118K) and (b) LUMO of the triphenylsulfinium mechanophore compared to the LUMO of the phenyl radical and cation, calculated in Suslick (University of Illinois at Urbana- Spartan’10 at the B3LYP/6-31G* level of theory, presented by C. E. Diesendruck (DOI: 10.1039/ Champaign), a renowned expert and a pio- C4FD00027G). neer in the development of sonochemistry

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(5) the development of smart mechanochemistry, i.e. a highly selective approach to optimise reactivity by judicious application of one or more types of mechanical treatment, based on systematic investigation of how diﬀerent types of mechanical action aﬀect chemical reactivity.

Conference attendees also attempted to outline several questions and potential directions for the future development of mechanochemistry. The first one addressed the definition of mechanochemistry. While IUPAC briefly defines a mechano-chemical reaction as a chemical reaction that is induced by the direct absorption of mechan- 31 th Fig. 6 (a) Physical and chemical consequences of sonochemical and milling processing of inor- ical energy, contributions at the 256 ganic materials are identical; (b) a central problem of modern mechanochemistry is reaching the Faraday Discussion illustrated that level of understanding and modelling that would allow rational scale-up of reactivity demonstrated mechanochemistry is a much broader on a small scale, as illustrated by K. S. Suslick. area which includes, besides conventional modes of organic and inorganic reactivity, processes of molecular organi- of molecules and materials.30 The closing nanoseconds to days or weeks. Different sation and self-assembly in two or three lecture provided an excellent and light- mechanisms will be more dominant in dimensions. It may, therefore, be bene- spirited overview of the development and some reactions and for some configurations ficial to include in the definition of recent advances in sonochemistry, and at than others. The closing lecture also noted mechanochemistry aspects of supramo- the same time highlighted connections to the importance of developing the models lecular chemistry and self-assembly that grinding or milling. Prof. Suslick strongly and understanding of mechanochemistry underlie processes of mechanochemical stressed the analogies and connections that will enable rational, rapid and efficient activation (e.g. amorphisation) or certain between different areas of mechano- scaling up (Fig. 6b). types of reactions (e.g. cocrystallisation chemistry, such as ball milling and sonic or polymorphic transformations).8,10,32 irradiation. Although these areas may Such an attempt to improve the definition appear unconnected on superficial inspec- of mechanochemistry should describe

Published on 18 March 2015. Downloaded 29/07/2015 20:43:46. Conclusions tion, a careful examination of physical and mechanical force (including agitation) as chemical consequences of sonochemical The very end of conference was dedicated a means to enable, either directly or and grinding processing on inorganic mate- to a discussion of the current state and through an intermediate activation pro- rials reveals exactly the same list (Fig. 6a). future developments of mechanochemistry. cess, the assembly or dissociation of Prof. Suslick also noted that modern Several developments in mechanochemical objects ranging in dimensions from nan- mechanochemistry, despite a tremen- research were identified as particularly pro- ometers (molecules, molecular com- dous growth of interest, remains a highly mising for its development: plexes) to millimeters (bulk materials). underdeveloped area, poorly understood Next, it was obvious that understand- by experimentalists and theoreticians (1) exploration of the materials at very ing of the mechanisms remains a central alike. This, to an extent, can be attributed small length scales, such as in micro- problem of modern mechanochemistry to the complex nature of mechano- scopy and nanoindentation studies; and it may be that future studies should chemical processes. While these can be (2) the increased use of concepts of take into account several interacting divided into surface modification, crack supramolecular chemistry and inter- pathways (for example, vapour phase dif- propagation, surface electrification, molecular interactions in understanding fusion simultaneous to amorphisation) plasma-like transients, dislocations and mechanochemical activation and defects; rather than interpret mechanochemical amorphisation, appearance of meta- (3)thedevelopmentofnewmethodolo- behaviour according to one particular stable polymorphs and localised heating, gies for observing mechanochemical reac- mechanism. The complexity of such it is important to remember that no tions as they take place, at different length future studies will require the researchers single mechanism can explain all of scales,frombulktomolecularlevel. of different backgrounds to communicate mechanochemistry. Indeed, a more realistic (4) the development of theoretical and increasingly work together.21 In that picture is obtained by understanding models and simulations addressing context, the conference had brilliantly that all these mechanisms operate all at mass and energy transfer in mechano- served its purpose, to bring together once and at very different timescales, from chemical reactions at different scales. researchers with different interests and

ChemComm Conference Report

background, and encourage their under- E. Ivanov and V. V. Boldyrev, Mater. Sci. 15 A. M. Belenguer, T. Frisˇˇcic´,G.M.Dayand standing, exchange of ideas, collaboration Eng., A, 2001, 304–306, 151–158. J. K. M. Sanders, Chem. Sci., 2011, 2, 696–700. 3 E. Boldyreva, Chem. Soc. Rev., 2013, 42, 16 A. A. L. Michalchuk, I. A. Tumanov and and communication. In that spirit, Prof. 7719–7738. E. V. Boldyreva, CrystEngComm, 2013, 15, Lamaty has kindly invited the attendees 4(a) P. Bala´ˇ,z Int. J. Miner. Process., 2003, 6403–6412. to a future mechanochemistry meeting, 72, 341–354; (b) P. Bala´ˇ,z A. Ala´ˇcova´, 17 D. Prochowicz, K. Sokołowski, I. Justyniak, M. Achimovicˇova´, J. Ficeriova´ and A. Kornowicz, D. Fairen-Jimenez, T. Frisˇˇcic´ planned in Montpellier, France, in the E. Godocˇikova´, Hydrometallurgy, 2005, 77, and J. Lewinski, Chem. Commun., 2015, 51, summer of 2015. 9–17. 4032–4035. 5(a)M.M.Caruso,D.A.Davis,Q.Shen, 18 L. Maini, D. Braga, P. P. 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