Mechanically Robust Hybrid Gel Beads Loaded with “Naked” Palladium Nanoparticles as Efficient, Reusable, and Sustainable Catalysts for the Suzuki–Miyaura Reaction

The increase in demand for Pd and its low abundance pose a significant threat to its future availability, rendering research into more sustainable Pd-based technologies essential. Herein, we report Pd scavenging mechanically robust hybrid gel beads composed of agarose, a polymer gelator (PG), and an active low-molecular-weight gelator (LMWG) based on 1,3:2,4-dibenzylidenesorbitol (DBS), DBS-CONHNH2. The robustness of the PG and the ability of the LMWG to reduce Pd(II) in situ to generate naked Pd(0) nanoparticles (PdNPs) combine within these gel beads to give them potential as practical catalysts for Suzuki–Miyaura cross-coupling reactions. The optimized gel beads demonstrate good reusability, green metrics, and most importantly the ability to sustain stirring, improving reaction times and energy consumption compared to previous examples. In contrast to previous reports, the leaching of palladium from these next-generation beads is almost completely eliminated. Additionally, for the first time, a detailed investigation of these Pd-loaded gel beads explains precisely how the nanoparticles are formed in situ without a stabilizing ligand. Further, detailed catalytic investigations demonstrate that catalysis occurs within the gel beads. Hence, these beads can essentially be considered as robust “nonligated” heterogeneous PdNP catalysts. Given the challenges in developing ligand-free, naked Pd nanoparticles as stable catalysts, these gel beads may have future potential for the development of easily used systems to perform chemical reactions in “kit” form.


S1.3.1 Gelation in Vials
The gelator was added in deionised water inside a vial. The vial was then heated with a heatgun until full dissolution was achieved. The solution was allowed to cool down to room temperature forming the gel.

S1.3.2 Gel Bead Production
Bead production was performed using the literature procedure previously reported by our group. 7 The gelator was suspended in deionised water inside a vial. The vial was then heated with a heat-gun until full dissolution was achieved. Using a pipette, the hot solution was dropped drop-wise into ice-cold paraffin oil with the volume of the drop determining the final size of the bead. The beads were then left for 30 minutes in the paraffin oil to ensure complete formation of the gel network, washed in 40-60 ºC petrol ether (3 x 10 mL), ethanol (3 x 10 mL) and deionised water (3 x 10 mL), by leaving the beads in each solution for 10 minutes.

S1.3.3 Proportions for the Production of Gel Beads or Gels in Vials
The proportions to produce gels in vials or in beads are the same and are reported in Table S1.

Table S1
Mass of DBS-CONHNH2, agarose and volume of water ratio for the production of gel in vials or gel beads. S1.6 Investigation into DBS-CONHNH 2 Oxidation S1.6.1 Oxidised Xerogel Dissolution into DMSO-d6

DBS-CONHNH2 / mg
Three separate 1 mL hybrid gel blocks in vials were exposed to 3 mL of slightly acidified 5 mM PdCl2 solution. After 24 hours, the gel Pd solution was removed and the gel left to dry to S6 constant mass. The xerogel was then dissolved in DMSO-d6 and filtered through a plug of Celite® twice. The NMR samples were then run normally. Successively, the sample was split into two new samples, and each one was spiked with ca. 5mg of DBS-CONHNH2 and DBS-CO2H, respectively. A 1 H NMR spectrum was then run again as normal for each sample. S1.6.2 NMR of Water-Soluble Products 1 mL of the hybrid system was exposed to 3 mL of slightly acidified aqueous 5 mM PdCl2 solution. After 24 hours, the gel Pd solution was removed and the gel left to dry to constant mass. The xerogel was added to a 0.1 M NaOD solution in D2O and sonicated for 15 minutes.

S1.7 IR Sample Preparation
Hybrid and agarose beads were prepared following the procedure described in section 7.3.2.
The DBS-CONHNH2 was prepared in vials as described in section 7.3.1. Ten hybrid beads, ten agarose beads and 1 mL of DBS-CONHNH2 were immersed in an aqueous metal ion solution concentrated enough to allow maximum uptake. These three samples together with ten hybrid beads, ten agarose beads and 1 mL of DBS-CONHNH2 without any metal were left to dry under high vacuum to constant mass. The powders were then used to record IR spectra for each system.

S1.8 Measurement of Tgel Values
Samples were prepared in vials and immersed in an oil bath. The temperature of the oil bath was increased regularly from room temperature to 100 ºC in 30 minutes. When the structure began collapsing (the gel could not support its weight), Tgel was recorded. This was performed in triplicate, and an average taken.

S1.11.1 Standard Reaction with No Stirring
The standard reaction between 4'-iodoacetophenone, a, (147.6 mg, 0.60 mmol, 1.0 eq.) and 4tolylboronic acid, 1, (97.9 mg, 0.72 mmol, 1.2 eq.) was performed exactly as described in section 1.11 with the exception of the stirring being turned completely off before addition of the beads. The conversion after an hour was determined via 1 H NMR.

S1.11.2 Standard Reaction Using No Pd-Loaded Beads
The standard reaction between 4'-iodoacetophenone, a, (147.6 mg, 0.60 mmol, 1.0 eq.) and 4tolylboronic acid, 1, (97.9 mg, 0.72 mmol, 1.2 eq.) was performed exactly as described in section 1.11 with the exception of no addition of Pd-loaded beads. The conversion after an hour was determined via 1 H NMR.
The conversion after an hour was determined via 1 H NMR. S1.11.4 Reaction using Agarose-only Beads The standard reaction between 4'-iodoacetophenone, a, (147.6 mg, 0.60 mmol, 1.0 eq.) and 4tolylboronic acid, 1, (97.9 mg, 0.72 mmol, 1.2 eq.) acid was performed exactly as described in section 1.11, with the exception of six Pd-loaded agarose beads being added instead of 6 hybrid beads. Conversion was monitored via 1 H NMR.
S9 S1.11.6 Mercury Poisoning The control reaction between 4'-iodoacetophenone, a, (147.6, 0.60 mmol, 1.0 eq.) and 4-methoxyphenylboronic acid, 3, (109.4 mg, 0.72 mmol, 1.2 eq.) was carried out as described in section 1.11, with the catalyst loading doubled to twelve 5 µL Pd-loaded hybrid gel beads were added to the mixture. Aliquots taken at 1 hour and 4 hours from the reaction media were analysed by 1 H NMR to determine the conversion of 4-tolylboronic acid (in respect to internal standard) to the expected immobilised product. To ensure that no boronic acid degradation occurred under these conditions, a reaction mixture containing the same reagents, but no beads, lead to no decrease in boronic acid integral with respect to the internal standard.

S1.11.8 Leaching Experiment
The reaction between 4'-iodoacetophenone and 4-tolylboronic acid was allowed to react for 3 hours using the same procedure as described in section 1.11. The product was then extracted and the aqueous layer was made up to 15 mL by the addition of a 25% aqueous EtOH solution.
4'-iodoacetophenone, a, (0.60 mmol) and 4-methoxyphenylboronic (0.72 mmol) acid, 3, were added and the reaction mixture heated at 50 ºC for 3 hours. The reaction mixture was then extracted using CH2Cl2, dried over MgSO4 and 1 H NMR was used to determine the conversion.     Figure S3. 5 µL agarose beads before and after being exposed to Pd II solution (left), and 5 µL hybrid beads before and after being exposed to Pd II solution.

S2 Suzuki-Miyaura Product Characterisation
S5 SEM and TEM Figure S4. SEM image of a full hybrid bead after being exposed to Pd II solution Figure S5. SEM image of the surface of a hybrid bead after being exposed to Pd II solution S21 Figure S6. SEM image of the inside of a hybrid bead after being exposed to Pd II solution Figure S7. SEM image of a full agarose bead after being exposed to Pd II solution Figure S8. SEM image of the surface of an agarose bead after being exposed to Pd II solution S22 Figure S9. SEM image of the inside of an agarose bead after being exposed to Pd II solution Figure S10. TEM image of a hybrid bead after being exposed to Pd II solution showing NPs S23 Figure S11. TEM image of a hybrid bead after being exposed to Pd II solution showing NPs Figure S12. TEM image of a hybrid bead after being exposed to Pd II solution showing NPs Figure S13. TEM image of an agarose bead after being exposed to Pd II solution showing some evidence of NPs formation together with larger Pd-aggregates Figure S14. TEM image of an agarose bead after being exposed to Pd II solution showing some evidence of NPs S25 Figure S15. TEM image of an agarose bead after being exposed to Pd II solution showing large Pd-aggregates   Figure S22. FTIR spectrum of dried DBS-CONHNH2 prepared using the standard procedure.

S5.1 NP Size and Frequency
S32 Figure S23. FTIR spectrum of dried DBS-CONHNH2 prepared from the standard procedure, with Pd. Figure S24. FTIR spectrum of dried agarose beads prepared from the standard procedure. Figure S25. FTIR spectrum of dried agarose beads prepared from the standard procedure with Pd S34 Figure S26. FTIR spectrum of dried hybrid beads prepared from the standard procedure.
S35 Figure S27. FTIR spectrum of dried hybrid beads prepared from the standard procedure with Pd.

S14 XRD Data
All thermal ellipsoids are shown at 50% probability. Carbon atoms are shown in black, oxygen in red, nitrogen in blue, fluorine in dark green, chlorine light green and hydrogen in white.
1a Figure S89. Crystal Structure of 1a Data collected, solved and refined by Adrian C. Whitwood. CCDC: 2206299; 1a was crystallized by slow evaporation of hexane.  Figure S90. Crystal Structure of 1d Data collected, solved and refined by Adrian C. Whitwood. CCDC: 2206300; 1d was crystallized by slow evaporation of hexane.  Figure S91. Crystal Structure of 1e Data collected, solved and refined by Adrian C. Whitwood. CCDC: 2206301; 1e was crystallized by slow evaporation of warm MeCN.

Refinement Special details:
The hydrogens of the methyl group were disordered and modelled using a 2 position riding model (AFIX 127) in a refined ratio of 0.601:0.399 (19).  Figure S92. Crystal Structure of 8n2 Data collected, solved and refined by Adrian C. Whitwood. CCDC: 2206302; 8n2 was crystallized by slow evaporation of MeCN.