In situ and real-time monitoring of mechanochemical milling reactions using synchrotron X-ray diffraction

Journal name:
Nature Protocols
Year published:
Published online


We describe the only currently available protocol for in situ, real-time monitoring of mechanochemical reactions and intermediates by X-ray powder diffraction. Although mechanochemical reactions (inducing transformations by mechanical forces such as grinding and milling) are normally performed in commercially available milling assemblies, such equipment does not permit direct reaction monitoring. We now describe the design and in-house modification of milling equipment that allows the reaction jars of the operating mill to be placed in the path of a high-energy (∼90 keV) synchrotron X-ray beam while the reaction is taking place. Resulting data are analyzed using conventional software, such as TOPAS. Reaction intermediates and products are identified using the Cambridge Structural Database or Inorganic Crystal Structure Database. Reactions are analyzed by fitting the time-resolved diffractograms using structureless Pawley refinement for crystalline phases that are not fully structurally characterized (such as porous frameworks with disordered guests), or the Rietveld method for solids with fully determined crystal structures (metal oxides, coordination polymers).

At a glance


  1. Milling equipment for in situ X-ray diffraction measurements.
    Figure 1: Milling equipment for in situ X-ray diffraction measurements.

    (a) An assembled 14-ml PMMA jar, as used in the experiments described herein. (b) Milling jars of different sizes made from steel, aluminum or PMMA. The milling media are steel balls. (c,d) Side view (c) and front view (d) of the modified Retsch MM200 mill with the milling stations lifted above the mill to allow for the X-ray beam to pass above the mill and through the jars.

  2. Chemical reaction and experimental setup.
    Figure 2: Chemical reaction and experimental setup.

    (a) Scheme of the general reaction for the mechanochemical (LAG or ILAG) conversion of zinc oxide into porous ZIFs. (b) Fragment of the crystal structure for the ZIF-8 product based on zinc(II) and 2-methylimidazolate ions. (c) Positioning of the modified Retsch MM200 mill on a motorized stand, movable in the x-, y- (horizontal) and z-directions (vertical).

  3. Experiment preparation.
    Figure 3: Experiment preparation.

    (a) Proper handling of the two halves of the PMMA milling jar before snapping them together. (b) The milling jar after snapping the two halves together. The left side contains the milling liquid and milling balls. The right side contains the reactants (white powder). (c) Horizontal positioning of the PMMA milling jar on the milling station. (d) The positioning of the milling jar with respect to the X-ray beam is verified using a theodolite.

  4. Outside control of mill operation.
    Figure 4: Outside control of mill operation.

    View of the improvised robotic 'finger' for remote switching on and switching off of the modified Retsch MM200 mill. The control is achieved by having the finger press the 'START' or 'STOP' buttons on the horizontal mill control board.

  5. Data processing.
    Figure 5: Data processing.

    Screenshots of Fit2d after opening the data file and at the end of integration data input, with the values for the experimental setup as previously determined from a calibration procedure involving a standard sample.

  6. Data presentation and quantitative analysis.
    Figure 6: Data presentation and quantitative analysis.

    (a) Example of a time-resolved PXRD pattern (diffractogram) for the LAG synthesis of ZIF-8. The simulated powder diffraction pattern of the product is displayed on top. (b) Combined Pawley and Rietveld refinement for reaction a after 9 min and 40 s. The blue tick marks designate calculated positions of reflections for the product. Blue, observed pattern; red, calculated pattern/background; gray, difference pattern. The contribution of ZnO (blue) is inserted below the experimental pattern. Selected reflections of the product, as well as steel from the milling balls, are highlighted.

  7. Qualitative identification of products using Mercury.
    Figure 7: Qualitative identification of products using Mercury.

    (a,b) Screenshots of simulating the PXRD pattern for a known crystal structure (a) and of changing the wavelength for the simulated diffraction pattern (b).


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Author information


  1. Division of Materials Chemistry, Ruđer Bošković Institute, Zagreb, Croatia.

    • Ivan Halasz
  2. Structure of Materials Group, European Synchrotron Radiation Facility, Grenoble, France.

    • Simon A J Kimber &
    • Veijo Honkimäki
  3. Department of Materials Science and Metallurgy, University of Cambridge, Cambridge, UK.

    • Patrick J Beldon
  4. Department of Chemistry, University of Cambridge, Cambridge, UK.

    • Ana M Belenguer,
    • Richard C Nightingale &
    • Tomislav Friščić
  5. Max Planck-Institute for Solid State Research, Stuttgart, Germany.

    • Frank Adams &
    • Robert E Dinnebier
  6. Department of Chemistry and Centre for Green Chemistry and Catalysis, McGill University, Montreal, Quebec, Canada.

    • Tomislav Friščić


The manuscript was composed and research was performed by I.H., S.A.J.K., P.J.B., A.M.B., F.A., V.H. and T.F. Detailed designs for mill modification were provided by R.C.N. Research was organized by T.F., I.H. and R.E.D. Manuscript preparation and submission were organized by T.F.

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The authors declare no competing financial interests.

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Supplementary information

PDF files

  1. Supplementary Manual (526 KB)

    Technical drawings of the mill extension and milling jar.

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