Photoresponsive Dissipative Macrocycles Using Visible‐Light‐Switchable Azobenzenes

Abstract

Visible light can be used to shift dynamic covalent imine assemblies out of equilibrium. We studied a fluorinated azobenzene building block that reliably undergoes geometric isomerism upon irradiation. The building block was used in combination with two different amines, ethylenediamine and R,R‐1,2‐diaminocyclohexane, to create a library of imine macrocycles. Whereas the simple amine can be used to access a polymeric state and a defined bowl‐shaped macrocycle, the chiral amine gives access to a rich network of macrocycles that undergo both isomerisation as well as interconversion between different macrocyclic species, thereby allowing for control over the number of monomers involved in the cyclo‐oligomerization; ¹H‐ and ¹⁹F‐DOSY NMR, MALDI‐MS measurements, and UV/Vis spectroscopy were used to study the processes.

The utilization of fluorinated, visible‐light‐switchable azobenzenes in combination with two different amines, ethylenediamine and R,R‐1,2‐diaminocyclohexane, enabled the creation of a library of macrocyclic compounds that include highly strained, metastable, and dissipative systems. These studies give a detailed insight into photoresponsive dissipative systems and the vast potential of using azobenzenes in dynamic covalent chemistry.

Supramolecular, or dynamic covalent interactions, enable the design and synthesis of complex supramolecular systems with well‐defined two‐ or three‐dimensional architectures. They generally approach a thermodynamic equilibrium with a stable composition of supramolecular structures. ^[1] As this dynamic covalent chemistry (DCC) allows for error correction during the formation of said supramolecular entities, the yields and selectivities are often high. ^[1f] The self‐assembled structures can have a variety of different exciting properties, and the reversible formation of metal‐free systems using boronate esters, imines, and alkynes is very well established.[ ^1c , ^1d ] Enabling these systems to become stimulus responsive can allow for the controlled assembly or disassembly of systems, or can induce geometry changes and trigger guest release, adding an additional layer of information. ^[2] For remote‐control, light has a high temporal and spatial resolution, is cheap, and generates no waste, in contrast to chemical fuels. ^[3] Azobenzenes, as one of the most commonly used photoswitches, bear several advantages, such as a distinct geometry change upon isomerisation, minimal photodegradation, and, in some cases, the ability to switch with visible light. ^[3] Creating bridged azobenzene derivatives ^[4] or implementing electron‐withdrawing substituents such as, for example, fluorine, ^[5] chlorine, ^[6b] or electron‐rich methoxy[ ^6a , ^6c ] in ortho‐position enables visible light switching and further improves photochemical properties. Replacing one or both benzenes in azobenzene with a heteroaromatic ring also alters the photochemistry, leading to long thermal half‐lives and improved photoswitching. ^[7] The incorporation of azobenzenes into different supramolecular structures was utilised to generate, among others,[ ^2b , ⁸ ] metal organic cages with switchable interior hydrophobicity ^[8g] and photoresponsive porous liquids. ^[8a] Photoswitches can also be used to synthesise photoresponsive metal organic structures ^[9] that can undergo dissipative reactions, as recently shown by the groups of Clever, ^[9a] and Beves. ^[9b] In dissipative systems, a precursor is activated, for example by converting a chemical fuel to waste ^[10a] or by light,[ ^10b , ^10c , ^10d , ^10e ] and undergoes reversible assembly. This process competes with a deactivation process, which can be either triggered by an external stimulus, such as chemical fuel, light, or heat, or the system spontaneously disassembles to recover the precursor. ^[11] The dissipative assembly or interconversion of imine systems, in contrast, has been mostly obtained by adding a fuel or a metastable acid until now. ^[12]

We present the formation of different dissipative or metastable dynamic covalent systems using photons as a stimulus, allowing control over the number of monomers involved in cyclo‐oligomerization that leads to ring contraction and extension. The ortho‐fluorinated, red light switchable 4,4′‐(diazene‐1,2‐diyl)bis(3,5‐difluorobenzaldehyde) (A), which was first synthesised by the group of Pianowski, ^[5a] was used in combination with two different amines, ethylenediamine (E) and R,R‐1,2‐diaminocyclohexane (D) to create a library of imine macrocycles. Combining the more stable azobenzene isomer E‐ A and E, an insoluble polymer is formed in higher concentrations, while the reaction of the less stable Z‐azobenzene leads to the selective formation of a Z,Z‐A²E^{2 [13]} macrocycle. In contrast, A³D³ was formed as the major product when using E‐ A with D, while using a Z‐ A enriched reaction mixture leads to the formation of several macrocycles. Intriguingly, the dissipative transformation of the macrocycle A³D³ to a mixture of different sized macrocycles can be achieved by irradiation with red light.

Azobenzene A shows a high thermal half‐life, can be switched with visible light, and has a high ratio of Z‐azobenzene in the photostationary state (PSS). Because A undergoes a significant geometry change when switched, we predicted that by combining E‐ and Z‐ A with different diamines, we would be able to access different dynamic covalent entities in solution. Building block E encodes little to no precoordination, so the resulting imine should be mostly governed by the structure of the azobenzene isomer employed. As expected, the reaction of E and E‐ A only led to the formation of insoluble red oligomers (see Supporting Information, page S13). In contrast, Z‐ A and E selectively formed the small Z,Z‐A²E² macrocycle after 19 hours at room temperature under continuous irradiation with red light (660 nm) (Figure 1). The formation was observed by ¹H‐ and ¹⁹F{¹H} NMR and MALDI‐MS. Single‐crystal X‐ray analysis of Z,Z‐A²E² reveals a bowl‐like structure in which both azobenzenes are pointing upwards with the amine units pointing downwards (Figure 1c). In low concentrations (6.98 μM) the azobenzenes in Z,Z‐A²E² can be isomerised from Z to E using UV (405 nm) or blue (470 nm) light, and vice versa, using red (660 nm) or green (565 nm) light (see Supporting Information, Figures S43–S46). In higher concentrations (2.67 mM), irradiation with UV light leads to the immediate formation of a red precipitate that consists most likely of A ⁿ E ⁿ oligomers (see Supporting Information, Figure S63).

Figure 1.

a) Reaction of both azobenzene isomers Z‐ A and E‐ A with diamine E to yield the macrocycle Z,Z‐ A²E² and the oligomer A ⁿ E ⁿ , respectively, with geometries obtained from force field calculations; b) ¹⁹F{¹H} NMR spectra showing the E (pink star) to Z (turquoise circle) isomerisation of A, followed by the formation of Z,Z‐ A²E² (blue triangle) (CD₂Cl₂, 282 MHz); c) molecular structure of Z,Z‐ A²E² as seen from the top and from the side as determined by single‐crystal X‐ray diffraction measurement ^[14] (thermal ellipsoid representation with 50 % probability ellipsoids); hydrogen atoms and solvent molecules are omitted for clarity (see Supporting Information, Figures S47–S48).

Diamine D was chosen for its intrinsic precoordination known to reliably give access to trianglimines, ^[1e] which in combination with E‐ A selectively leads to the formation of E,E,E‐ A³D³ . ¹H‐ and ¹⁹F‐DOSY NMR spectra were recorded and show that the macrocycle has a solvodynamic radius of between 7.81 and 8.29 Å (see Supporting Information, Figures S22 and S24). Irradiating a solution of A with red light (660 nm) until the PSS was reached prior to the addition of D, led to a mixture of different macrocycles as confirmed by NMR and MALDI‐MS, and the formation under continuous irradiation with red light was monitored over several days (Figure 2 and Supporting Information, Figures S13–S15). After the system reached equilibrium (after 151 hours), the solution was stirred in the dark for 112 hours, during which monitoring by NMR and MALDI‐MS was continued. To assign the signals to the species, ¹⁹F‐DOSY NMR spectra were recorded, confirming the formation of macrocycles of different sizes. The signal with the largest intensity at −119.68 ppm after 19 hours can be assigned to an A²D² macrocycle, as the ¹⁹F‐DOSY shows a diffusion coefficient for this signal corresponding to a solvodynamic radius of 5.93 Å. Surprisingly, this signal broadens and shifts upfield until it merges with the signal at −119.84 ppm during the irradiation with red light and the following period in the dark. As the new signal has a similar solvodynamic radius of 6.02 Å, it can be assumed that apparently two types of Z,Z‐A²D² are formed. The peak gradually increases in intensity but declines when the irradiation is stopped. At the start of the irradiation, another species is formed, as seen by the ¹⁹F{¹H} NMR peak at −120.67 ppm, which can be assigned to an A³D³ macrocycle, according to its solvodynamic radius of 6.98 Å. After 2 days, a signal can be observed which has the same chemical shift as the E,E,E‐A³D³ macrocycle (−120.36 ppm). The increasing intensity during the irradiation and in the dark can be attributed to the thermal back isomerisation of the azobenzenes in the A²D² macrocycles and the concomitant decay to the most favoured product starting from E‐ A, A³D³ . These results are supported by MALDI‐MS measurements, which confirm the formation of A²D² as the major product at the start of the irradiation, alongside A³D³ and A⁴D⁴ . The latter seems to be formed in minor quantities, as the A⁴D⁴ species cannot be observed in the NMR‐spectra. In relation to the peaks for the larger sized macrocycles, the A²D² peak decreases significantly once and the longer the solution is kept in the absence of light.

Figure 2.

a) Reaction of Z‐ A and diamine D to yield different macrocycles, with geometries obtained from force field calculations; b) ¹⁹F{¹H} NMR spectra showing macrocycle assembly under continuous irradiation with red light (times highlighted in red) and in the dark (highlighted in black) (CD₂Cl₂, 282 MHz). The azobenzene isomers are highlighted in pink (star), the A²D² macrocycles in turquoise (circle), and the A³D³ species in blue (triangle), with geometries obtained from force field calculations.

To verify that the photochemical properties of A undergo no major change upon imine formation and to get further insight into our dynamic systems, a model compound (AC² ) was synthesised starting from A and cyclohexylamine (C). While the comparison of the UV/Vis spectra of A and AC² shows a bathochromic shift for the π→π* band (314 nm to 340 nm) upon imine formation, the n→π* band remains unchanged (475 nm). As a result, the imine compounds can also be photoisomerised with green and red light (see Supporting Information, Figures S33–35) with high ratios of Z in the PSS (see Supporting Information, Figures S1–S12, Tables S1–S2). The formation of AC² was also observed closely by NMR to get a detailed insight into the kinetics of the imine formation, confirming that the reactivity of the aldehyde undergoes no significant change upon isomerisation (see Supporting Information, Figures S49–S60). Next, we investigated the photoswitching and the dissipative reaction of A³D³ . In UV/Vis concentrations (3.45–5.92 μM), A³D³ undergoes E to Z isomerisation under irradiation with red (660 nm) or green (565 nm) light (see Supporting Information, Figure S36). In higher concentrations, a dissipative reaction takes place, yielding smaller A²D² and isomerised A³D³ macrocycles, as confirmed by ¹H‐ and ¹⁹F{¹H} NMR, as well as ¹⁹F‐DOSY NMR (see Figure 3 and Supporting Information, Figures S16–S18, S24–S26). In contrast to the formation of the macrocycle mixture when employing Z‐ A, only one species of an A²D² macrocycle is initially formed (−119.84 ppm, r _s=5.64 Å). As this signal rapidly forms upon irradiation, it underlines our initial assignment that two different types of Z,Z‐ A²D² are formed from Z‐ A. Other species are simultaneously formed of which the signals at −120.37 and −120.68 ppm both can be assigned to A³D³ species. The signal at −119.32 ppm could not be correlated to a macrocycle of a specific size in this measurement. However, signals between −119.2 and −119.4 ppm observed in the ¹⁹F‐DOSY NMR for the reaction with D under continuous irradiation could be assigned to species with radii between 7.02 and 7.38 Å. Judging from these values alone, this could correlate to an open macrocyclic species even though no signals for an aldehyde were observed in the ¹H NMR spectra.

Figure 3.

a) Irradiation of A³D³ with red light (660 nm) leads to the formation of different‐sized macrocycles, with geometries obtained from force field calculations. The precursor can be regained by irradiation with UV light (405 nm); b) ¹⁹F{¹H} NMR spectra showing the transformation of A³D³ under irradiation with red light (highlighted in red) and UV light (highlighted in violet) (CD₂Cl₂, 282 MHz) with the A²D² species highlighted in pink (star), A³D³ species in turquoise (circle) and blue (triangle); c) MALDI‐mass spectrum of the reaction mixture after 17 hours of irradiation with red light (660 nm).

Upon irradiation with UV light (405 nm), the Z to E isomerisation of the azobenzene units triggers the formation of the most stable product, which is, as previously observed, the A³D³ macrocycle. Even if the MALDI‐mass spectra, which were recorded during this experiment, show the formation of larger macrocyclic species up to the size of A⁸D⁸ upon irradiation, this seems to take place in smaller amounts, as those species were not observed via NMR. To get a more detailed insight into the photoswitching of the A³D³ macrocycle, we also compared its properties to those of the reduced amine A³D³ _red (see Supporting Information, Figures S36–S42), which cannot undergo dynamic covalent exchange anymore. Preventing the dissipative formation of different macrocycles, A³D³ _red can still be isomerised with green light, but its ability to undergo E to Z isomerisation using red light is nearly zero due to the diminished π‐system. Even though A³D³ is less flexible than its amine counterpart, the photoswitchability of A³D³ _red can be an indicator that the isomerisation of A³D³ could occur without opening of the macrocycle since the steric hindrance and possible ring strain do not inhibit the photoisomerisation of the azobenzenes in the macrocycle. We concluded, based on this finding, that the isomerisation of the more rigid imine compound A³D³ could also be possible without breakage of imine bonds.

In conclusion, we have presented the first photoresponsive, dissipative, dynamic covalent macrocycle. By implementing visible light switchable azobenzenes into an imine macrocycle, we demonstrated a method to make dynamic covalent chemistry even more dynamic. In addition, we illustrated the diversity of structures accessible, containing metastable and highly strained systems when employing both structurally different isomers in the formation of supramolecular systems. We anticipate that our systems can contribute to the development of further out‐of‐equilibrium supramolecular machines and materials, where efficient control will enable the design and execution of complex novel non‐covalent syntheses, resulting in a diverse range of distinct self‐assembled structures based on the same building blocks.

Conflict of interest

The authors declare no conflict of interest.

Supporting information

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Supporting Information

Supporting Information

E. Nieland, J. Voss, A. Mix, B. M. Schmidt, Angew. Chem. Int. Ed. 2022, 61, e202212745; Angew. Chem. 2022, 134, e202212745.

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.