Covalent adaptable networks using boronate linkages by incorporating TetraAzaADamantanes

Boronic esters prepared by condensation of boronic acids and diols have been widely used as dynamic covalent bonds in the synthesis of both discrete assemblies and polymer networks. In this study we investigate the potential of a new dynamic-covalent motif, derived from TetraAzaADamantanes (TAADs), with their adamantane-like triol structure, in boronic ester-based covalent adaptable networks (CANs). The TetraAzaADamantane-boronic ester linkage has recently been reported as a more hydrolytically stable boronic ester variant, while still having a dynamic pH response: small-molecule studies found little exchange at neutral pH, while fast exchange occurred at pH 3.8. In this work, bi- and trifunctional TetraAzaADamantane linkers were synthesised and crosslinked with boronic acids to form rubber-like materials, with a Young’s modulus of 1.75 MPa. The dynamic nature of the TetraAzaADamantane networks was confirmed by stress relaxation experiments, revealing Arrhenius-like behaviour, with a corresponding activation energy of 142 ± 10 kJ/mol. Increasing the crosslinking density of the material from 10% to 33% resulted in reduced relaxation times, as is consistent with a higher degree of crosslinking within the dynamic networks. In contrast to the reported accelerating effect of acid addition to small-molecule TetraAzaADamantane complexes, within the polymer network the addition of acid increased relaxation times, suggesting unanticipated interactions between the acid and the polymer that cannot occur in the corresponding small-molecules analogues. The obtained boronate-TetraAzaADamantane materials were thermally stable up to 150°C. This thermal stability, in combination with the intrinsically dynamic bonds inside the polymer network, allowed these materials to be reprocessed and healed after damage by hot-pressing.

Pur-A-Lyzer mega dialysis kit with a volume of 20 ml and a cut-off of 1 kDA was obtained from Merck Life Science N.V.
Common laboratory solvents were used from various suppliers. All chemicals were used without further purification.

NMR
Spectra were recorded on a 400 MHz Bruker NMR (101 MHz 13 C).

IR
Bruker TENSOR 27 Platinum FTIR spectrometer in Attenuated Total Reflection (ATR) mode, controlled by Bruker's OPUS software. Spectra were recorded from 600 to 4000 cm -1 with a resolution of 4 cm -1 and were averaged over 60 scans.

Rheology & DMA
Rheology experiments were done on an Anton Paar MCR 501 and a 702e space using 10 mm parallel plate geometries. The 501 used a N2 heat mantle, while the 702e space used a N2 driven piezzo oven for heating.
DMA was performed on the 702e space using the linear drive setup at ambient temperature with extensional clamps.

Hot-press
Samples were hot-pressed in a Specac Atlas Series Heated Platens with a WEST 6100+ Temperature Controller Unit with water cooling in a Teflon mold between Teflon sheets. Samples were hot-pressed for 1 hour at 80 °C.

TGA
TGA was measured using a Perkin Elmer Simultaneous Thermal Analyzer (STA) 6000. Samples were measured over the temperature range of 30 to 900 °C with a temperature increase of 10 °C/min.

Mass spectrometry
Mass spectrometry data were acquired using MS-ESI Thermo scientific Exactive in positive mode. The compounds were ionized without fragmentation at 0 kV spray voltage and with a capillary temperature of 150 °C.
1.7 Synthesis of TRISOXH 3 as reported by (Golovanov et al., 2018) Supplementary Scheme S1. Synthesis of TRISOXH3 In a 250 ml roundbottom flask 10.2 g (0.15 mol) of hydroxylamine hydrochloride was dissolved in 60 ml water. 60 ml of a 25% ammonium hydroxide solution in water was added. The flask was put in a water bath to provide passive cooling. Then 11.8 ml (0.15 mol) chloroacetone was added via syringe. The reaction was stirred for 1 hour, afterwhich the white precipitate was filtered off and washed with plenty of water and finally with diethyl ether. The white powder was then dried overnight at 50 °C in a vacuum oven. This resulted in a fine white powder (3.38 g; 29.7%).

Synthesis of bis(bromoacetoxy)ethane
Supplementary Scheme S2. Synthesis of bis(bromoacetoxy)ethane 0.85 ml (9.7 mmol) bromoacetyl bromide was dissolved in 10 ml DCM in a 250 ml round bottom flask and cooled down to 0°C. To this a mixture of 0.25g (4.0 mmol) ethylene glycol and 0.71 ml (8.8 mmol) pyridine in 2 ml DCM was slowly added over 30 minutes at 0°C. After complete addition, the ice bath was removed and the reaction mixture was stirred for 1.5h at room temperature. To the reaction 3 ml 6M HCl was added followed by 3 ml DCM. The two layers were separated and the aqueous layer was extracted with DCM. The organic layers were combined and extracted with 25 ml water, 3x 25 ml Na2CO3 (aq), and 40 ml brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure to obtain a pale yellow liquid. Yield: 1.13g (90%).

Supplementary Scheme S4. Synthesis of bis(TAADacetoxy)ethane
A mixture of 0.42 g (1.8 mmol) TRISOXH3 and 0.25 g (0.83 mmol) 1,2-bis(Bromoacetoxy)ethane in 5 ml DMF in a 25 ml round bottom flask was stirred at 65°C. After 4h the reaction mixture was gently added to 200 ml acetone, a white precipitate formed and acetone was decanted off. Next, the precipitate was washed 2x with 200 ml acetone, whereafter the precipitate was filtered off and the white solid was dried in a vacuum oven at 50 °C. Yield: 0.49 g (78%).

Preparation of boronic acid-TAAD networks
Here the method of preparing a general 10% crosslinked boronic acid-TAAD network is described. The 20% and 33% crosslinked networks were prepared similarly, but with different ratios of the TAAD linkers. The experiments with the PTSA additions were performed by preparing 33% crosslinked networks and adding a certain wt% of PTSA.
To make the networks 3 solutions were prepared, which were then combined and cast in a mold. First 41.3 mg (0.045 mmol) Bis-TAAD was dissolved in 0.1 methanol. Secondly, 6.8 mg (0.005 mmol) Tris-TAAD was dissolved in 0.1 ml methanol. Thirdly, 119.1 mg (0.0525 mmol) PBA-PPG-PBA was dissolved in 0.1 ml methanol. All three solutions were vortexed to get homogenous solution. The solutions were then combined and vortexed to get efficient mixing of all components. The solution was then quickly cast distributed over 3 circular silicon molds (h= 1 mm, r=10 mm). the materials were then left to dry in the fumehood for 2 days. After drying the materials were hot-pressed between Teflon plates in a Teflon mold (h = 1 mm, r = 10 mm) at 80 °C for 1 hour.

Self-healing properties
To prepare samples for DMA studies, the networks were prepared as normal, but instead of hotpressing for 1 hour at 80 °C in circular Teflon molds a rectangular Teflon mold (10 x 5 x 1 mm) was used instead.
Self-healing properties of the networks were tested by DMA by applying a linearly increasing extensional stress to the clamped material (10 x 5 x 0.9 mm) till breakage. After breakage occured the material was cut into pieces and hot-pressed again in a rectangular Teflon mold (10 x 5 x 1 mm) for 1 h at 80 °C.

Exchange equilibrium study
For the kinetic study of the boronic acid-TAAD exchange 0.028 mmol (15 mg) of N-methylacetate-Ophenylboronate-TAAD and 0.028 mmol of p-tolylboronic acid/4-bromophenylboronic acid/4-(trifluoromethyl)phenylboronic acid/methylboronic acid were dissolved in 500 μl d4-MeOD/D2O 50/50. The solution was left standing for 3 days. After 3 days an 1 H-NMR spectrums was recorded to calculate the conversion without catalyst. Then 25 μl AcOH stock solution, prepared by adding 5.6 μl AcOH to 50 μl D2O, was added and the mixture was shaken well. The exchange was then followed in time by measuring 1 H-NMR spectra every 12 minutes for 5 hours. Analysis was perfomed with the Mestrenova Reaction Monitoring software.  Figure S36. Representative 1 H-NMR data of the exchange reaction between Nmethylacetate-O-phenylboronate-TAAD and p-tolylboronic acid after a 3 day stability test. The peak at 7.72 ppm belongs to the product, while the peak at 7.62 ppm belongs to the starting complex. In both cases the signal corresponds to the aromatic protons ortho to the boronic acid. By integration of the peaks the progress of the exchange reaction could be monitored as function of time (see Supplementary Figure S35).