Recent Advances in the Synthesis and Application of Polymer Compartments for Catalysis

Abstract

Catalysis is one of the most important processes in nature, science, and technology, that enables the energy efficient synthesis of essential organic compounds, pharmaceutically active substances, and molecular energy sources. In nature, catalytic reactions typically occur in aqueous environments involving multiple catalytic sites. To prevent the deactivation of catalysts in water or avoid unwanted cross-reactions, catalysts are often site-isolated in nanopockets or separately stored in compartments. These concepts have inspired the design of a range of synthetic nanoreactors that allow otherwise unfeasible catalytic reactions in aqueous environments. Since the field of nanoreactors is evolving rapidly, we here summarize-from a personal perspective-prominent and recent examples for polymer nanoreactors with emphasis on their synthesis and their ability to catalyze reactions in dispersion. Examples comprise the incorporation of catalytic sites into hydrophobic nanodomains of single chain polymer nanoparticles, molecular polymer nanoparticles, and block copolymer micelles and vesicles. We focus on catalytic reactions mediated by transition metal and organocatalysts, and the separate storage of multiple catalysts for one-pot cascade reactions. Efforts devoted to the field of nanoreactors are relevant for catalytic chemistry and nanotechnology, as well as the synthesis of pharmaceutical and natural compounds. Optimized nanoreactors will aid in the development of more potent catalytic systems for green and fast reaction sequences contributing to sustainable chemistry by reducing waste of solvents, reagents, and energy.

Keywords: block copolymers; cascade reactions; catalysis; controlled polymerization techniques; nanostructures; organocatalysis; polymer architectures; self-assembly; transition metal catalysis.

Figure 1

Catalysis in compartments. (A) The enzyme catalase converting H₂O₂ to water and oxygen. (B) Block copolymer micelle with catalyst in the hydrophobic core compartment.

Figure 2

Selection of frequently used polymer compartments for catalysis.

Figure 3

Multistep cascade reaction mediated by a combination of three different supported catalysts in a one-pot reaction. Each colored box shows a different reaction path. Reproduced with permission of [50]. Copyright 2006 Wiley-VCH.

Figure 4

Example for single chain polymer nanoparticles (SCPN) catalysis. (A) SCPN with L-proline for the enantioselective aldol reaction of cyclohexanone and p-nitrobenzaldehyde. (B) Selective point folding of SCPNs promoted by triphenylphospane coordination with dichloro(1,5-cyclooctadiene)palladium. (A) reproduced with permission of [58]. Copyright 2013 Wiley-VCH. (B) reproduced with permission of [63]. Copyright 2015 Royal Society of Chemistry.

Figure 5

Core-confined acid and base catalysts for cascade reactions. (A) PSSA and VEMAP catalysts in star polymer cores performing the acid-base cascade reaction. Reference reactions are given in the table. (B) One-pot enantioselective cascade catalysis of site-isolated iminium and enamine catalysts in star polymers. (A) adapted with permission of [78]. Copyright 2005 Wiley-VCH. (B) reproduced with permission of [79]. Copyright 2008 American Chemical Society.

Figure 6

Cascade catalysis with bottlebrushes. (A) Acid and base catalysts site-isolated in two bottlebrushes. (B) Hollow brushes with base catalyst in the cross-linked shell and acid catalyst on the stabilizing corona. Adapted with permission of [83] and [84]. Copyright 2014 and 2018 Royal Society of Chemistry.

Figure 7

Polystyrene-block-polybutadiene-block-poly(tert-butyl methacrylate) (PS-b-PB-b-PT) template for organic/inorganic Pt hybrids. (A) Nanostructure fabrication process. (B) TEM of multicompartment nanofiber with Pt double helix and PS corona. (C) STEM of Pt double helix, grey scale analysis of the marked areas, and EDX analysis (yellow: S; red: Pt). (D) Scheme of PS sulfonation to PSS. (E) Scheme of the catalytic degradation of MB to Leuco MB. (F) Ln(c_t/c₀) vs. time without catalyst (black), c_cat = 10 mg·L⁻¹ (red), 12.5 mg·L⁻¹ (blue), 25 mg·L⁻¹ (yellow), and 50 mg·L⁻¹ (green); reference sample Pt/C at 100 mg·L⁻¹ (purple). Initial concentrations are: [MB] = 2.0 × 10⁻⁵ м, [NaBH₄] = 2.0 × 10⁻² м. (G) SEM image of 0.45 µm PTFE syringe filter and Pt@MCNFs-coated filter surface (H). (I) Flow set-up to catalyze MB in water using modified syringe filter at a flow rate of 1 mL·h⁻¹. Adapted with permission of [93]. Copyright 2020 American Chemical Society.

Figure 8

PAOx BCPs for micellar transition metal catalysis. (A) Bis(1,3-dimethylimidazoline-2-ylidene)palladium(II) diiodide catalyst for Heck reaction. (B) Triphenylphosphane (TPP) ligand for Pd-catalyzed Heck coupling. (C) Hydroaminomethylation using the BCP in (B) with Ir- or Ir-/Rh-catalysts. (D) Chiral (2S,4S)-4-di-phenylphosphino-2-(diphenylphosphinomethyl)pyrrolidine (PPM) ligand for asymmetric hydrogenation. (A) reproduced with permission of [101]. Copyright 2005 American Chemical Society. (B,C) reproduced with permission of [105]. Copyright 2008 Wiley-VCH. (D) reproduced with permission of [106]. Copyright 2003 Wiley-VCH.

Figure 9

Chemoenzymatic cascade reaction of BCP metal catalyst and enzyme-immobilized polymer beads. (A) Chemical structure of the ABC triblock terpolymer. (B) Formation of core-cross-linked core-shell NPs with Cu/bpy metal catalyst by microemulsion. (C) Two-step cascade reaction of ester cleavage and oxidation for the transformation of esters to aldehydes. Adapted with permission of [118]. Copyright 2017 Royal Society of Chemistry.

Figure 10

Site isolation of two incompatible catalysts in core and shell of ABC triblock terpolymer core-shell corona micelles. (A) Alkyne hydrogenation and asymmetric transfer hydrogenation to chiral alcohols. (B) TEMPO-catalyzed oxidation of racemic to ketones and Rh-catalyzed asymmetric transfer hydrogenation. Adapted with permission of [120] and [121]. Copyright 2015 and 2019 American Chemical Society.

Figure 11

Micellar nanoreactor with Brønsted acid in the hydrophobic domain for the catalysis of DNA-conjugated substrates in water. (A) Chemical structure of the amphiphilic BCP and self-assembly to micelles in water with reactive sites for DNA conjugation in the core. (B) Povarov reaction of 14mer DNA-benzaldehyde with p-tert-butyl-aniline and 3,4-dihydro-2H-pyran to a substituted tetrahydrochinoline. Adapted with permission of [124]. Copyright 2019 American Chemical Society.

Figure 12

L-Proline-catalyzed aldol reaction. (A) Aldol reaction of cyclohexanone (1) and 4-nitrobenzaldehayde (2) as discussed for the nanoreactors in the following. (B) Individual reaction steps exemplified on a L-proline-modified methacrylate. Reproduced with permission of [126]. Copyright 2013 American Chemical Society.

Figure 13

BCP micelles for the asymmetric aldol reaction of cyclohexanone and p-nitrobenzaldehyde in water. (A) RAFT polymerization of statistical P(S-co-ProlA) copolymers and assembly to large compound micelles in (B). (C) Catalysis with recycled catalyst system. (D) Temperature-controlled formation of micelles in water for aldol reaction of. Separation of the soluble catalytic system and insoluble aldol products in water via filtration after reaction completion. Adapted with permission of [127] and [126]. Copyright 2011 and 2013 American Chemical Society.

Figure 14

Core-shell-corona micelles with a cross-linked shell inheriting three incompatible catalysts. (A) Poly(2-oxazoline)-based core-shell-corona morphology with acid, base, and metal catalyst isolated in corona, core, and shell respectively. (B) Three-step reaction for hydrolysis-hydrogenation-acylation cascades of ketals to enantiomeric esters. Adapted and reproduced with permission of [133]. Copyright 2018 Wiley-VCH.

Figure 15

Chiral gating of substrates for asymmetric aldol reactions. (A) Templated polymerization of a cross-linked micelle. (B) Molecularly imprinted nanoparticles prepared by peptide chemistry. Adapted with permission of [135]. Copyright 2015 American Chemical Society.

Figure 16

Self-oscillating micelles. (A) PEO-b-P(NIPAAm-r-Ru(bpy)₃) BCP and redox-responsive assembly/disassembly depending on the oxidative state of Ru(bpy)₃. (B) Time-dependent scattering of the BCP solution synchronized to a BZ reaction. (C) Recorded scattering intensity over time showing oscillating formation/dissipation of BCP micelles. Adapted with permission of [136]. Copyright 2013 Royal Society of Chemistry.

Figure 17

Catalytic reactions in microcapsules. (A,B) Microcapsules with different wall thickness through interfacial cross-linking of PMPPI and TEPA. (C) PEI and nickel-based catalysts. (D) Synthesis of Pregabalin from 3-methylbutyraldehyde, nitromethane and dimethyl malonate. Adapted with permission of [144] and [146]. Copyright 2006 and 2007 American Chemical Society.

Figure 18

Enzymatic cascade reaction in a polymersome-in-polymersome system. (A) Schematic illustration of the encapsulation of the enzymes CalB and ADH in PS-b-PIAT polymersomes and subsequently encapsulated by PEO-b-PB along with PAMO and substrates in giant polymersomes. (B) Four-step cascade reaction of profluorescent 7-((4-oxopentyl)oxy)-3H-phenoxazin-3-one to the fluorescent 7-hydroxy-3H-phenoxazin-3-one. Reproduced with permission of [149]. Copyright 2014 Wiley-VCH.

Figure 19

Enzymatic cascade reaction in PMOXA-b-PDMS-b-PMOXA polymersomes. (A) Schematic illustration of the biocatalytic cycle. (B) Two-step reaction of uric acid to H₂O₂ and subsequently to water catalyzed by UOX and HRP. Reproduced with permission of [150]. Copyright 2014 American Chemical Society.

Figure 20

Multicompartment nanostructures from a series of PS-b-PB-b-PT triblock terpolymers. Reproduced with permission of [10]. Copyright 2016 Nature Publishing Group.

Figure 21

Continuous flow synthesis of ibuprofen. Reproduced with permission of [173]. Copyright 2009 Wiley-VCH.