JoVE Logo
Faculty Resource Center

Sign In





Representative Results






Discovery and Synthesis Optimization of Isoreticular Al(III) Phosphonate-Based Metal-Organic Framework Compounds Using High-Throughput Methods

Published: October 6th, 2023



1Department of Inorganic Chemistry, Kiel University

The targeted synthesis of new metal-organic frameworks (MOFs) is difficult, and their discovery depends on the knowledge and creativity of the chemist. High-throughput methods allow complex synthetic parameter fields to be explored quickly and efficiently, accelerating the process of finding crystalline compounds and identifying synthetic and structural trends.

High-throughput (HT) methods are an important tool for the fast and efficient screening of synthesis parameters and the discovery of new materials. This manuscript describes the synthesis of metal-organic frameworks (MOFs) from solution using an HT reactor system, resulting in the discovery of various phosphonate-based MOFs of the composition [Al2H12-x(PMP)3]Clx∙6H2O (H4PMP = N,N '-piperazine bis(methylenephosphonic acid)) for x = 4, 6, denoted as Al-CAU-60-xHCl, containing trivalent aluminum ions. This was accomplished under solvothermal reaction conditions by systematically screening the impact of the molar ratio of the linker to the metal and the pH of the reaction mixture on the product formation. The protocol for the HT investigation includes six steps: a) synthesis planning (DOE = design of experiment) within the HT methodology, b) dosing and working with in-house developed HT reactors, c) solvothermal synthesis, d) synthesis workup using in-house developed filtration blocks, e) characterization by HT powder X-ray diffraction, and f) evaluation of the data. The HT methodology was first used to study the influence of acidity on the product formation, leading to the discovery of Al-CAU-60∙xHCl (x = 4 or 6).

Metal-organic frameworks (MOFs) are porous, crystalline compounds whose structures consist of metal-containing nodes, like metal ions or metal-oxygen clusters, which are connected by organic molecules (linkers)1. By varying the metal-containing nodes as well as the linker, a variety of compounds can be obtained that exhibit a wide range of properties and therefore have potential applications in different fields1.

The stability of a material is important for its application1,2,3. Therefore, MOFs contai....

Log in or to access full content. Learn more about your institution’s access to JoVE content here

In this protocol, the HT investigation of chemical systems to discover new crystalline materials, using Al-CAU-6029 as an example, is described.

1. Design of Experiment (DOE)

NOTE: The first step is to set up a synthesis plan, which requires knowledge of the reactor setup (Figure 2), reactants, and solvents used. This synthesis planning procedure is adapted to performing 24 or 48 reactions under a .......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

The PXRD data is shown in Figure 9. For the first evaluation, the results obtained are linked to the synthesis parameters of the investigated parameter space. The investigation was carried out using six different molar ratios of linker to metal and four different molar ratios of NaOH/HCl to Al3+. By linking this information with the obtained PXRD data (Figure 9), it can be seen that products of low crystallinity were obtained from syntheses at a molar.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

Due to the complexity of the HT method, the individual steps and the method itself are discussed in the following sections. The first part covers the critical steps for each working step of the HT workflow (Figure 1), possible modifications, and limitations of the technique, where applicable. At the end, a general discussion also including the significance of the HT method with respect to existing methods and future applications is presented.

In the first step of.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

The work was supported by the Christian-Albrechts-University, the State of Schleswig-Holstein, and the Deutsche Forschungsgemeinschaft (especially STO-643/2, STO-643/5 and STO-643/10).

Norbert Stock would like to thank the B.Sc., M.Sc., and doctoral students, as well as the cooperation partners who have carried out many interesting projects using the high-throughput methodology, in particular Prof. Bein from the Ludwig-Maximilians-Universität in Munich, who played a major role in the development of the reactors.


Log in or to access full content. Learn more about your institution’s access to JoVE content here

Name Company Catalog Number Comments
AlCl3·6H2O Grüssing N/A 99%
Filter block for filtration of max. 48 reaction mixtures In-house made N/A Technical drawings in the supplementary files
Hydrochloric acid Honeywell 258148 Conc. 37 %, p.a.
Multiclaves with 24 individual Teflon inserts In-house made N/A Technical drawings in the supplementary files
N,N ‘-piperazine bis(methylenephosphonic acid Prepared by coworkers N/A H4PMP,  Prepared by coworkers with the method reported by Villemin et al.: D. Villemin, B. Moreau, A. Elbilali, M.-A. Didi, M.’h. Kaid, P.-A. Jaffrès, Phosphorus Sulfur Silicon Relat. Elem. 2010, 185, 2511.
Sample Plate for PXRD In-house made N/A Technical drawings in the supplementary files
Sodium hydroxide Grüssing N/A 99%
Stoe Stadi P Combi STOE Stadi P Combi Cu-Kα1 radiation (λ = 1.5406 Å); transmission geometry; MYTHEN2 1K detector; opening angle 18°; curved  monochromator; xy-table
Forced convection oven Memmert UFP400

  1. Kaskel, S. . The Chemistry of Metal-Organic Frameworks: Synthesis, Characterization, and Applications. , (2016).
  2. Ding, M., Cai, X., Jiang, H. -. L. Improving MOF stability: approaches and applications. Chemical Science. 10 (44), 10209-10230 (2019).
  3. Stock, N., Biswas, S. Synthesis of metal-organic frameworks (MOFs): routes to various MOF topologies, morphologies, and composites. Chemical Reviews. 112 (2), 933-969 (2012).
  4. Shimizu, G. K. H., Vaidhyanathan, R., Taylor, J. M. Phosphonate and sulfonate metal organic frameworks. Chemical Society Reviews. 38 (5), 1430-1449 (2009).
  5. Yuan, S., Qin, J. -. S., Lollar, C. T., Zhou, H. -. C. Stable metal-organic frameworks with group 4 metals: current status and trends. ACS Central Science. 4 (4), 440-450 (2018).
  6. Devic, T., Serre, C. High valence 3p and transition metal based MOFs. Chemical Society Reviews. 43 (16), 6097-6115 (2014).
  7. Rhauderwiek, T., et al. Highly stable and porous porphyrin-based zirconium and hafnium phosphonates-electron crystallography as an important tool for structure elucidation. Chemical Science. 9 (24), 5467-5478 (2018).
  8. Steinke, F., Otto, T., Ito, S., Wöhlbrandt, S., Stock, N. Isostructural family of rare-earth MOFs synthesized from 1,1,2,2-Tetrakis(4-phosphonophenyl)ethylene. European Journal of Inorganic Chemistry. 2022 (34), 2022005562 (2022).
  9. Zhu, Y. -. P., Ma, T. -. Y., Liu, Y. -. L., Ren, T. -. Z., Yuan, Z. -. Y. Metal phosphonate hybrid materials: from densely layered to hierarchically nanoporous structures. Inorganic Chemistry Frontiers. 1 (5), 360-383 (2014).
  10. Glavinović, M., Perras, J. H., Gelfand, B. S., Lin, J. -. B., Shimizu, G. K. H. Orthogonalization of polyaryl linkers as a route to more porous phosphonate metal-organic frameworks. Chemistry. 28 (31), 202200874 (2022).
  11. Yücesan, G., Zorlu, Y., Stricker, M., Beckmann, J. Metal-organic solids derived from arylphosphonic acids. Coordination Chemistry Reviews. 369, 105-122 (2018).
  12. Wharmby, M. T., Mowat, J. P. S., Thompson, S. P., Wright, P. A. Extending the pore size of crystalline metal phosphonates toward the mesoporous regime by isoreticular synthesis. Journal of the American Chemical Society. 133 (5), 1266-1269 (2011).
  13. Zheng, T., et al. Overcoming the crystallization and designability issues in the ultrastable zirconium phosphonate framework system. Nature Communications. 8, 15369 (2017).
  14. Dines, M. B., Cooksey, R. E., Griffith, P. C., Lane, R. H. Mixed-component layered tetravalent metal phosphonates/phosphates as precursors for microporous materials. Inorganic Chemistry. 22 (6), 1003-1004 (1983).
  15. Hermer, N., Reinsch, H., Mayer, P., Stock, N. Synthesis and characterisation of the porous zinc phosphonate [Zn2(H2PPB)(H2O)2]·xH2O. CrystEngComm. 18 (42), 8147-8150 (2016).
  16. Rhauderwiek, T., et al. Crystalline and permanently porous porphyrin-based metal tetraphosphonates. Chemical Communications. 54 (4), 389-392 (2018).
  17. Steinke, F., et al. Synthesis and structure evolution in metal carbazole diphosphonates followed by electron diffraction. Inorganic Chemistry. 62 (1), 35-42 (2023).
  18. Taddei, M., et al. The first route to highly stable crystalline microporous zirconium phosphonate metal-organic frameworks. Chemical Communications. 50 (94), 14831-14834 (2014).
  19. Stock, N. High-throughput investigations employing solvothermal syntheses. Microporous and Mesoporous Materials. 129 (3), 287-295 (2010).
  20. Clayson, I. G., Hewitt, D., Hutereau, M., Pope, T., Slater, B. High throughput methods in the synthesis, characterization, and optimization of porous materials. Advanced Materials. 32 (44), 2002780 (2020).
  21. Clearfield, A., Demadis, K. . Metal Phosphonate Chemistry: From Synthesis to Applications. , (2011).
  22. Mennen, S. M., et al. The evolution of high-throughput experimentation in pharmaceutical development and perspectives on the future. Organic Process Research & Development. 23 (6), 1213-1242 (2019).
  23. Yang, L., et al. High-throughput methods in the discovery and study of biomaterials and materiobiology. Chemical Reviews. 121 (8), 4561-4677 (2021).
  24. Banerjee, R., et al. High-throughput synthesis of zeolitic imidazolate frameworks and application to CO2 capture. Science. 319 (5865), 939-943 (2008).
  25. Reinsch, H., Stock, N. High-throughput studies of highly porous Al-based MOFs. Microporous and Mesoporous Materials. 171, 156-165 (2013).
  26. Reimer, N., Reinsch, H., Inge, A. K., Stock, N. New Al-MOFs based on sulfonyldibenzoate ions: a rare example of intralayer porosity. Inorganic Chemistry. 54 (2), 492-501 (2015).
  27. Tollitt, A. M., et al. High-throughput discovery of a rhombohedral twelve-connected zirconium-based metal-organic framework with ordered terephthalate and fumarate linkers. Angewandte Chemie. 60 (52), 26939-26946 (2021).
  28. Palomba, J. M., et al. High-throughput screening of solid-state catalysts for nerve agent degradation. Chemical Communications. 54 (45), 5768-5771 (2018).
  29. Reichenau, T. M., et al. Targeted synthesis of an highly stable aluminium phosphonate metal-organic framework showing reversible HCl adsorption. Angewandte Chemie. , (2023).
  30. Biemmi, E., Christian, S., Stock, N., Bein, T. High-throughput screening of synthesis parameters in the formation of the metal-organic frameworks MOF-5 and HKUST-1. Microporous and Mesoporous Materials. 117 (1), 111-117 (2009).
  31. STOE & Cie GmbH. WinXPOW v.3.1. STOE & Cie GmbH. , (2016).
  32. Groom, C. R., Bruno, I. J., Lightfoot, M. P., Ward, S. C. The Cambridge structural database. Acta Crystallographica Section B, Structural Science. Crystal Engineering and Materials. 72, 171-179 (2016).
  33. Bruno, I. J., et al. New software for searching the Cambridge Structural Database and visualizing crystal structures. Acta Crystallographica. Section B, Structural Science. 58, 389-397 (2002).
  34. Hermer, N., Wharmby, M. T., Stock, N. . CCDC 1499757: Experimental Crystal Structure Determination. , (2017).
  35. Cawse, J. N. . Experimental Design for Combinatorial and High Throughput Materials Development. , (2003).
  36. Dhanumalayan, E., Joshi, G. M. Performance properties and applications of polytetrafluoroethylene (PTFE)-a review. Advanced Composites and Hybrid Materials. 1, 247-268 (2018).
  37. Lenzen, D., et al. Scalable green synthesis and full-scale test of the metal-organic framework CAU-10-H for use in adsorption-driven chillers. Advanced Materials. 30 (6), 1705869 (2018).

This article has been published

Video Coming Soon

JoVE Logo


Terms of Use





Copyright © 2024 MyJoVE Corporation. All rights reserved