Foundations and strategies of the construction of hybrid catalysts for optimized performances


Catalysts are generally classified into three categories: homogeneous, heterogeneous and enzyme, each evolved as an independent field. Efforts to bridge these fields are scarce but desirable. In this Perspective, we first describe how numerous classes of reactions can be achieved by all three categories of catalysts. Examples are given based on a selective survey of the literature. Next, a selection of important approaches, the benefits and challenges of constructing heterogeneous–homogeneous, heterogeneous–enzyme and homogeneous–enzyme hybrid catalysts are discussed based on published researches. Hybrid catalysts not only increase the performance, including activity, selectivity, lifetime and recyclability compared to one of the components, but also offer extra functions such as a microenvironment for different reaction pathways, and cascade catalysis for products that are challenging to produce. We expect future tailor-made hybrid catalysts will combine the advantages of the components and be optimized for industrial applications.

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Fig. 1: Schematic of a catalyst space with highlights on the hybrid catalysts.
Fig. 2: Illustrations of existing approaches to construct hybrid catalysts.
Fig. 3: A summary of general advantages and challenges of hybrid catalysts.


  1. 1.

    Ye, R., Hurlburt, T. J., Sabyrov, K., Alayoglu, S. & Somorjai, G. A. Molecular catalysis science: perspective on unifying the fields of catalysis. Proc. Natl Acad. Sci. USA 113, 5159–5166 (2016).

  2. 2.

    Parmeggiani, C. & Cardona, F. Transition metal based catalysts in the aerobic oxidation of alcohols. Green Chem. 14, 547–564 (2012).

  3. 3.

    Brink, G.-Jt, Arends, I. W. C. E. & Sheldon, R. A. Green, catalytic oxidation of alcohols in water. Science 287, 1636–1639 (2000).

  4. 4.

    Enache, D. I. et al. Solvent-Free Oxidation of Primary Alcohols to Aldehydes Using Au-Pd/TiO2 catalysts. Science 311, 362–365 (2006).

  5. 5.

    Tsigos, I., Velonia, K., Smonou, I. & Bouriotis, V. Purification and characterization of an alcohol dehydrogenase from the Antarctic psychrophile Moraxella sp. TAE123. Eur. J. Biochem. 254, 356–362 (1998).

  6. 6.

    Hinnemann, B. & Nørskov, J. K. Catalysis by Enzymes: the biological ammonia synthesis. Top. Catal. 37, 55–70 (2006).

  7. 7.

    Schlögl, R. in Handbook of Hete rogeneous Catalysis (Wiley-VCH, GmbH & Co., KGaA, 2008).

  8. 8.

    Spencer, N. D., Schoonmaker, R. C. & Somorjai, G. A. Iron single crystals as ammonia synthesis catalysts: effect of surface structure on catalyst activity. J. Catal. 74, 129–135 (1982).

  9. 9.

    Yandulov, D. V. & Schrock, R. R. Catalytic reduction of dinitrogen to ammonia at a single molybdenum center. Science 301, 76–78 (2003).

  10. 10.

    Pool, J. A., Lobkovsky, E. & Chirik, P. J. Hydrogenation and cleavage of dinitrogen to ammonia with a zirconium complex. Nature 427, 527–530 (2004).

  11. 11.

    Pappas, I. & Chirik, P. J. Ammonia synthesis by hydrogenolysis of titanium–nitrogen bonds using proton coupled electron transfer. J. Am. Chem. Soc. 137, 3498–3501 (2015).

  12. 12.

    Ertl, G., Knözinger, H. & Weitkamp, J. Handbook of Heterogeneous Catalysis (Wiley-VCH, GmbH & Co., KGaA 2008).

  13. 13.

    Liu, C. et al. Single polymer growth dynamics. Science 358, 352–355 (2017).

  14. 14.

    Yang, Q. & Li, C. in Bridging Heterogeneous and Homogeneous Catalysis 351–396 (Wiley-VCH, GmbH & Co., KGaA, 2014).

  15. 15.

    Gates, B. C. & Lamb, H. H. Supported metals and supported organometallics. J. Mol. Catal. 52, 1–18 (1989).

  16. 16.

    Marks, T. J. Surface-bound metal hydrocarbyls. Organometallic connections between heterogeneous and homogeneous catalysis. Acc. Chem. Res. 25, 57–65 (1992).

  17. 17.

    Copéret, C., Chabanas, M., Petroff Saint-Arroman, R. & Basset, J.-M. Homogeneous and heterogeneous catalysis: bridging the gap through surface organometallic chemistry. Angew. Chem. Int. Ed 42, 156–181 (2003).

  18. 18.

    Herron, N., Stucky, G. D. & Tolman, C. A. The reactivity of tetracarbonylnickel encapsulated in zeolite X. A case history of intrazeolite coordination chemistry. Inorg. Chim. Acta 100, 135–140 (1985).

  19. 19.

    Hench, L. L. & West, J. K. The sol-gel process. Chem. Rev. 90, 33–72 (1990).

  20. 20.

    Seidel, S. R. & Stang, P. J. High-symmetry coordination cages via self-assembly. Acc. Chem. Res. 35, 972–983 (2002).

  21. 21.

    Rungtaweevoranit, B. et al. Copper nanocrystals encapsulated in Zr-based metal–organic frameworks for highly selective CO2 hydrogenation to methanol. Nano Lett. 16, 7645–7649 (2016).

  22. 22.

    Ma, L., Abney, C. & Lin, W. Enantioselective catalysis with homochiral metal–organic frameworks. Chem. Soc. Rev. 38, 1248–1256 (2009).

  23. 23.

    Ye, R., Zhukhovitskiy, A. V., Deraedt, C. V., Toste, F. D. & Somorjai, G. A. supported dendrimer-encapsulated metal clusters: toward heterogenizing homogeneous catalysts. Acc. Chem. Res. 50, 1894–1901 (2017).

  24. 24.

    Sirisha, V. L., Jain, A. & Jain, A. in Adv. Food Nutr. Res. Vol. 79 (eds S.-K. Kim & F. Toldrá) 179–211 (Academic, 2016).

  25. 25.

    Vennestrøm, P. N. R., Christensen, C. H., Pedersen, S., Grunwaldt, J.-D. & Woodley, J. M. Next-generation catalysis for renewables: combining enzymatic with inorganic heterogeneous catalysis for bulk chemical production. ChemCatChem 2, 249–258 (2010).

  26. 26.

    Sheldon, R. A. Enzyme immobilization: the quest for optimum performance. Adv. Synth. Catal. 349, 1289–1307 (2007).

  27. 27.

    Engström, K. et al. Co-immobilization of an enzyme and a metal into the compartments of mesoporous silica for cooperative tandem catalysis: an artificial metalloenzyme. Angew. Chem. Int. Ed 52, 14006–14010 (2013).

  28. 28.

    Jegan Roy, J. & Emilia Abraham, T. Strategies in making cross-linked enzyme crystals. Chem. Rev. 104, 3705–3722 (2004).

  29. 29.

    Cao, L., van Rantwijk, F. & Sheldon, R. A. Cross-linked enzyme aggregates: a simple and effective method for the immobilization of penicillin acylase. Org. Lett. 2, 1361–1364 (2000).

  30. 30.

    Palla, K. S., Hurlburt, T. J., Buyanin, A. M., Somorjai, G. A. & Francis, M. B. Site-selective oxidative coupling reactions for the attachment of enzymes to glass surfaces through dna-directed immobilization. J. Am. Chem. Soc. 139, 1967–1974 (2017).

  31. 31.

    Cabrera, Z., Fernandez-Lorente, G., Fernandez-Lafuente, R., Palomo, J. M. & Guisan, J. M. Novozym 435 displays very different selectivity compared to lipase from Candida antarctica B adsorbed on other hydrophobic supports. J. Mol. Catal. B 57, 171–176 (2009).

  32. 32.

    Brady, D. & Jordaan, J. Advances in enzyme immobilisation. Biotechnol. Lett. 31, 1639 (2009).

  33. 33.

    Denard, C. A., Hartwig, J. F. & Zhao, H. Multistep one-pot reactions combining biocatalysts and chemical catalysts for asymmetric synthesis. ACS Catal. 3, 2856–2864 (2013).

  34. 34.

    Pàmies, O. & Bäckvall, J.-E. Combination of enzymes and metal catalysts. a powerful approach in asymmetric catalysis. Chem. Rev. 103, 3247–3262 (2003).

  35. 35.

    Rudroff, F. et al. Opportunities and challenges for combining chemo- and biocatalysis. Nat. Catal. 1, 12–22 (2018).

  36. 36.

    Huang, X. & Xue, L. in Bridging Heterogeneous and Homogeneous Catalysis 511–552 (Wiley-VCH, GmbH & Co., KGaA, 2014).

  37. 37.

    Wang, Z. J., Clary, K. N., Bergman, R. G., Raymond, K. N. & Toste, F. D. A supramolecular approach to combining enzymatic and transition metal catalysis. Nat. Chem. 5, 100–103 (2013).

  38. 38.

    Bryant, D. E. & Kranich, W. L. Dehydration of alcohols over zeolite catalysts. J. Catal. 8, 8–13 (1967).

  39. 39.

    Vergnolle, O., Hahn, F., Baerga-Ortiz, A., Leadlay, P. F. & Andexer, J. N. Stereoselectivity of isolated dehydratase domains of the borrelidin polyketide synthase: implications for cis double bond formation. Chembiochem 12, 1011–1014 (2011).

  40. 40.

    Northrup, A. B. & MacMillan, D. W. C. The first direct and enantioselective cross-aldol reaction of aldehydes. J. Am. Chem. Soc. 124, 6798–6799 (2002).

  41. 41.

    Ricci, A. et al. Chitosan aerogel: a recyclable, heterogeneous organocatalyst for the asymmetric direct aldol reaction in water. Chem. Commun. 46, 6288–6290 (2010).

  42. 42.

    Takayama, S., McGarvey, G. J. & Wong, C.-H. Enzymes in organic synthesis: recent developments in aldol reactions and glycosylations. Chem. Soc. Rev. 26, 407–415 (1997).

  43. 43.

    White, M. C., Doyle, A. G. & Jacobsen, E. N. A synthetically useful, self-assembling mmo mimic system for catalytic alkene epoxidation with aqueous H2O2. J. Am. Chem. Soc. 123, 7194–7195 (2001).

  44. 44.

    Song, F., Wang, C., Falkowski, J. M., Ma, L. & Lin, W. Isoreticular chiral metal−organic frameworks for asymmetric alkene epoxidation: tuning catalytic activity by controlling framework catenation and varying open channel sizes. J. Am. Chem. Soc. 132, 15390–15398 (2010).

  45. 45.

    Farinas, E. T., Alcalde, M. & Arnold, F. Alkene epoxidation catalyzed by cytochrome P450 BM-3 139–3. Tetrahedron 60, 525–528 (2004).

  46. 46.

    Kalló, D. & Mihályi, R. M. Mechanism of 1-butene hydration over acidic zeolite and ion-exchange resin catalysts. Appl. Catal. A 121, 45–56 (1995).

  47. 47.

    Wuensch, C. et al. Asymmetric enzymatic hydration of hydroxystyrene derivatives. Angew. Chem. Int. Ed 52, 2293–2297 (2013).

  48. 48.

    Xu, R. et al. Iron-catalyzed homogeneous hydrogenation of alkenes under mild conditions by a stepwise, bifunctional mechanism. ACS Catal. 6, 2127–2135 (2016).

  49. 49.

    Argo, A. M., Odzak, J. F., Lai, F. S. & Gates, B. C. Observation of ligand effects during alkene hydrogenation catalysed by supported metal clusters. Nature 415, 623–626 (2002).

  50. 50.

    Müller, A., Hauer, B. & Rosche, B. Asymmetric alkene reduction by yeast old yellow enzymes and by a novel Zymomonas mobilis reductase. Biotechnol. Bioeng. 98, 22–29 (2007).

  51. 51.

    Langdon, S. M., Wilde, M. M. D., Thai, K. & Gravel, M. Chemoselective N-heterocyclic carbene-catalyzed cross-benzoin reactions: importance of the fused ring in triazolium salts. J. Am. Chem. Soc. 136, 7539–7542 (2014).

  52. 52.

    Storey, J. M. D. & Williamson, C. Imidazole based solid-supported catalysts for the benzoin condensation. Tetrahedron Lett. 46, 7337–7339 (2005).

  53. 53.

    Dünkelmann, P. et al. Development of a donor−acceptor concept for enzymatic cross-coupling reactions of aldehydes: the first asymmetric cross-benzoin condensation. J. Am. Chem. Soc. 124, 12084–12085 (2002).

  54. 54.

    Ready, J. M. & Jacobsen, E. N. Highly active oligomeric (salen)co catalysts for asymmetric epoxide ring-opening reactions. J. Am. Chem. Soc. 123, 2687–2688 (2001).

  55. 55.

    Baleizão, C., Gigante, B., Sabater, M. J., Garcia, H. & Corma, A. On the activity of chiral chromium salen complexes covalently bound to solid silicates for the enantioselective epoxide ring opening. Appl. Catal. A 228, 279–288 (2002).

  56. 56.

    Hasnaoui-Dijoux, G., Majerić Elenkov, M., Lutje Spelberg, J. H., Hauer, B. & Janssen, D. B. Catalytic promiscuity of halohydrin dehalogenase and its application in enantioselective epoxide ring opening. Chembiochem 9, 1048–1051 (2008).

  57. 57.

    Koster, R., van der Linden, B., Poels, E. & Bliek, A. The mechanism of the gas-phase esterification of acetic acid and ethanol over MCM-41. J. Catal. 204, 333–338 (2001).

  58. 58.

    Kornberg, A. & Pricer, W. E. Enzymatic esterification of alpha-glycerophosphate by long chain fatty acids. J. Biol. Chem. 204, 345–357 (1953).

  59. 59.

    Carraher, J. M., Fleitman, C. N. & Tessonnier, J.-P. Kinetic and mechanistic study of glucose isomerization using homogeneous organic Brønsted base catalysts in water. ACS Catal 5, 3162–3173 (2015).

  60. 60.

    Moliner, M., Román-Leshkov, Y. & Davis, M. E. Tin-containing zeolites are highly active catalysts for the isomerization of glucose in water. Proc. Natl Acad. Sci. USA 107, 6164–6168 (2010).

  61. 61.

    McKay, G. A. & Tavlarides, L. L. Enzymatic isomerization kinetics of d-glucose to d-fructose. J. Mol. Catal. 6, 57–69 (1979).

  62. 62.

    Furuya, T., Kamlet, A. S. & Ritter, T. Catalysis for fluorination and trifluoromethylation. Nature 473, 470–477 (2011).

  63. 63.

    Pascanu, V. et al. Selective heterogeneous C−H activation/halogenation reactions catalyzed by Pd@MOF nanocomposites. Chem. Eur. J 22, 3729–3737 (2016).

  64. 64.

    Blasiak, L. C. & Drennan, C. L. Structural perspective on enzymatic halogenation. Acc. Chem. Res. 42, 147–155 (2009).

  65. 65.

    Zhang, B. & Breslow, R. Ester hydrolysis by a catalytic cyclodextrin dimer enzyme mimic with a metallobipyridyl linking group. J. Am. Chem. Soc. 119, 1676–1681 (1997).

  66. 66.

    Katz, M. J. et al. Exploiting parameter space in MOFs: a 20-fold enhancement of phosphate-ester hydrolysis with UiO-66-NH2. Chem. Sci. 6, 2286–2291 (2015).

  67. 67.

    Wu, S. H., Guo, Z. W. & Sih, C. J. Enhancing the enantioselectivity of Candida lipase-catalyzed ester hydrolysis via noncovalent enzyme modification. J. Am. Chem. Soc. 112, 1990–1995 (1990).

  68. 68.

    García-Álvarez, R., Díez, J., Crochet, P. & Cadierno, V. Arene–ruthenium(ii) complexes containing inexpensive tris(dimethylamino)phosphine: highly efficient catalysts for the selective hydration of nitriles into amides. Organometallics 30, 5442–5451 (2011).

  69. 69.

    Battilocchio, C., Hawkins, J. M. & Ley, S. V. Mild and selective heterogeneous catalytic hydration of nitriles to amides by flowing through manganese dioxide. Org. Lett. 16, 1060–1063 (2014).

  70. 70.

    MartÍnková, L. & Křen, V. Nitrile- and amide-converting microbial enzymes: stereo-, regio- and chemoselectivity. Biocatal. Biotransform. 20, 73–93 (2002).

  71. 71.

    Mahdi, T. & Stephan, D. W. Enabling catalytic ketone hydrogenation by frustrated lewis pairs. J. Am. Chem. Soc. 136, 15809–15812 (2014).

  72. 72.

    Hu, A., Ngo, H. L. & Lin, W. Chiral porous hybrid solids for practical heterogeneous asymmetric hydrogenation of aromatic ketones. J. Am. Chem. Soc. 125, 11490–11491 (2003).

  73. 73.

    Ni, Y. & Xu, J.-H. Biocatalytic ketone reduction: a green and efficient access to enantiopure alcohols. Biotechnol. Adv. 30, 1279–1288 (2012).

  74. 74.

    Cook, A. K., Schimler, S. D., Matzger, A. J. & Sanford, M. S. Catalyst-controlled selectivity in the C–H borylation of methane and ethane. Science 351, 1421–1424 (2016).

  75. 75.

    Liu, W.-C., Ralston, W. T., Melaet, G. & Somorjai, G. A. Oxidative coupling of methane (OCM): effect of noble metal (M=Pt, Ir, Rh) doping on the performance of mesoporous silica MCF-17 supported Mn x O y -Na2WO4 catalysts. Appl. Catal. A 545, 17–23 (2017).

  76. 76.

    Yoshizawa, K., Ohta, T., Yamabe, T. & Hoffmann, R. Dioxygen cleavage and methane activation on diiron enzyme models: a theoretical study. J. Am. Chem. Soc. 119, 12311–12321 (1997).

  77. 77.

    Chen, C., Dugan, T. R., Brennessel, W. W., Weix, D. J. & Holland, P. L. Z-Selective alkene isomerization by high-spin cobalt(ii) complexes. J. Am. Chem. Soc. 136, 945–955 (2014).

  78. 78.

    Trombetta, M. et al. FT-IR studies on light olefin skeletal isomerization catalysis: iii. surface acidity and activity of amorphous and crystalline catalysts belonging to the SiO2–Al2O3 system. J. Catal. 179, 581–596 (1998).

  79. 79.

    Durchschein, K. et al. Unusual C–C bond isomerization of an α, β-unsaturated γ-butyrolactone catalysed by flavoproteins from the old yellow enzyme family. Chembiochem 13, 2346–2351 (2012).

  80. 80.

    Nguyen, S. T., Johnson, L. K., Grubbs, R. H. & Ziller, J. W. Ring-opening metathesis polymerization (ROMP) of norbornene by a Group viii carbene complex in protic media. J. Am. Chem. Soc. 114, 3974–3975 (1992).

  81. 81.

    Kobayashi, S., Uyama, H. & Kimura, S. Enzymatic Polymerization. Chem. Rev. 101, 3793–3818 (2001).

  82. 82.

    Palucki, M., Hanson, P. & Jacobsen, E. N. Asymmetric oxidation of sulfides with H2O2 catalyzed by (salen)Mn(iii) complexes. Tetrahedron Lett. 33, 7111–7114 (1992).

  83. 83.

    Karimi, B., Ghoreishi-Nezhad, M. & Clark, J. H. Selective oxidation of sulfides to sulfoxides using 30% hydrogen peroxide catalyzed with a recoverable silica-based tungstate interphase catalyst. Org. Lett. 7, 625–628 (2005).

  84. 84.

    Baciocchi, E., Lanzalunga, O., Malandrucco, S., Ioele, M. & Steenken, S. Oxidation of sulfides by peroxidases. involvement of radical cations and the rate of the oxygen rebound step. J. Am. Chem. Soc. 118, 8973–8974 (1996).

  85. 85.

    Wu, C.-Y., Horibe, T., Jacobsen, C. B. & Toste, F. D. Stable gold(iii) catalysts by oxidative addition of a carbon-carbon bond. Nature 517, 449–454 (2015).

  86. 86.

    Sippel, D. & Einsle, O. The structure of vanadium nitrogenase reveals an unusual bridging ligand. Nat. Chem. Biol. 13, 956–960 (2017).

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We acknowledge support from the Director, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geological and Biosciences of the US DOE under contract DEAC02-05CH11231. R.Y. and B.B.W. thank the Student Mentoring and Research Teams (SMART) program at UC Berkeley for financial support in Summer 2017.

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R.Y. and G.A.S. conceived the theme, R.Y. wrote the manuscript, and J.Z. designed the layouts of Fig. 1, Fig. 2, and the table of contents image. All authors contributed data and insights, discussed the argument and edited the manuscript.

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Correspondence to F. Dean Toste or Gabor A. Somorjai.

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Ye, R., Zhao, J., Wickemeyer, B.B. et al. Foundations and strategies of the construction of hybrid catalysts for optimized performances. Nat Catal 1, 318–325 (2018).

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