The third orthogonal dynamic covalent bond

The existence of three fully orthogonal dynamic covalent bonds is demonstrated in solution and in functional surface architectures.


S5
After addition of benzaldehyde (5.0 mL, 92 mmol), the mixture was left under stirring at rt for 1 h.
The mixture was subjected to liquid-liquid extraction with sat. aq. NaHCO3 and EtOAc. The organic phase was dried over Na2SO4, filtered and concentrated. Purification of the remaining oil by flash column chromatography (SiO2, CH2Cl2/MeOH 9:1) afforded compound 15 as a colorless solid (151 mg, quantitative). Rf (CH2Cl2/

S14
The value of ([Bf] + [B-4]) can be obtained by comparing the absorbance at 533 nm of the reverse titration (e.g., fig. S2) with the direct titration of 4 with B (e.g., fig. S1). By finding the same absorbance at 533 nm in the latter, we can find Combining eq. S4 with eq. S5, we obtain

Orthogonal dynamic covalent bonds in solution
All experiments were run using DMSO-d6 dried over molecular sieves (3 Å), at rt. In most experiments, TES (20 mM) was also included to serve as an internal standard.    Condition A: To 0.45 mL of the disulfide stock solution in an NMR tube, was added 10.0 µL of DIPEA and 50 µL of D2O. After shaking, the solution was subjected to 1 H NMR spectroscopy to monitor the evolution of the exchange processes (Figs. S16, S14 •, 3A ■).

Condition B:
To 0.45 mL of the disulfide stock solution in an NMR tube, was added 5.0 µL of stock solution B and 45 µL of DMSO-d6. After shaking, the solution was subjected to 1 H NMR spectroscopy to monitor the evolution of the exchange processes (Figs. S17, S14 ▲, 3B ■).

Condition C:
To 0.45 mL of the disulfide stock solution in an NMR tube, was added 50 µL of stock solution C. After shaking, the solution was subjected to 1 H NMR spectroscopy to monitor the evolution of the exchange processes (Figs. S15, S14 ■, 3C ■).

Condition D:
To 0.45 mL of the disulfide stock solution in an NMR tube was added 50 µL of DMSO-d6. The solution was then subjected to 1 H NMR spectroscopy to monitor the evolution of the exchange processes (Figs. S18, S14 ♦).

Non-orthogonal hydrazone exchange conditions
Classical hydrazone exchange conditions involve the use of acid and often the use of aniline as a catalyst. In an attempt to identify mild conditions in which the exchange takes place, condition B* (DMSO-d6, 11.0 mM aniline, 11.5 mM TFA) was found, resulting in hydrazone exchange.
However, the concentrations of acid needed in these conditions are excessive and result in the hydrolysis of boronate esters (Fig. S19), showing the incompatibility of aniline catalysis with boronate esters and thus the necessity of an alternative catalyst.

Non-orthogonal boronate esters
To test the orthogonality of other boronate esters, boronate ester 36 was synthesized and tested with 8 in condition B. In these conditions, significant exchange was observed, confirming the non-orthogonal character of these exchange partners in hydrazone exchange condition B.  To determine TSA yield η, the following extinction coefficients were used: S1 10: ε311 = 14.3 mM -1 cm -1 13: ε423 = 5.5 mM -1 cm -1 TSA yield η was calculated as follows: