Light‐Controlled Destruction and Assembly: Switching between Two Differently Composed Cage‐Type Complexes

Abstract We report on two regioisomeric, diazocine ligands 1 and 2 that can both be photoswitched between the E‐ and Z‐configurations with violet and green light. The self‐assembly of the four species (1‐Z, 1‐E, 2‐Z, 2‐E) with CoII ions was investigated upon changing the coordination vectors as a function of the ligand configuration (E vs Z) and regioisomer (1 vs 2). With 1‐Z, Co2(1‐Z)3 was self‐assembled, while a mixture of ill‐defined species (oligomers) was observed with 2‐Z. Upon photoswitching with 385 nm to the E configurations, the opposite was observed with 1‐E forming oligomers and 2‐E forming Co2(2‐E)3. Light‐controlled dis/assembly was demonstrated in a ligand competition experiment with sub‐stoichiometric amounts of CoII ions; alternating irradiation with violet and green light resulted in the reversible transformation between Co2(1‐Z)3 and Co2(2‐E)3 over multiple cycles without significant fatigue by photoswitching.

Triggered and controlled assembly and disassembly are among the most fundamental processes in living systems. For instance, light-triggered cis to trans isomerisation of retinal inside rhodopsin ultimately leads to the macroscopic perception of light following several consecutive processes, including the assembly of two rhodopsins with transducin and disassembly of the heterotrimeric transducin into two of its three components. [1] Stimulus-controlled assembly and disassembly are ubiquitous steps in biological signal transduction cascades. In natural and synthetic systems, light is an almost ideal stimulus and control tool since it can be applied with high spatiotemporal resolution with different wavelengths, and it is typically waste-and by-product-free. [2] Light has been exploited to trigger the self-assembly of nanoparticles, [3] polymers [4] and gels [4a, 5] as well as to drive the folding of polymers [6] and the operation of molecular machines [7] and shuttles. [8] Despite the numerous examples of stimuli-responsive metal-organic cages and helicates, [2,9] light-responsive examples are relatively rare and include the use of photoswitchable guests and counterions [10] as well as photoinduced metal-ligand bond breakage, [11] photolabile groups [12] or photoacids [13] to trigger the self-assembly/ disassembly of cages. Photoswitchable cages [2] based on azobenzene, [14] dithienylethene, [15] overcrowded alkenes, [16] and more recently, diazocine [17] have been reported but are challenging to design; for example, incomplete photoswitching (from overlapping n-π* and π-π* bands or overlap with the metal's MLCT band) can lead to isomeric mixtures and large ligand geometry changes upon photoswitching can produce ill-defined self-assemblies. [2, 9a, 14b] Beves et al. recently reported on a photoswitchable, azobenzene-based Pd complex that switches between two different complex geometries and stoichiometries upon irradiation with two different wavelengths of visible light. [14c] Recently, diazocines (bridged azobenzenes) were developed as a new type of photoswitch with promising properties for applications, ranging from photopharmacology [18] to switchable surfaces [19] and smart materials. [20] The good separation of n-π* and π-π* bands, efficient photoswitching with visible light and the thermodynamic stability of the Z configuration (as opposed to the E configuration for azobenzenes) make diazocines appealing for the design of photoswitchable cages. However, the development of diazocine-based, photoswitchable cages is in its infancy. Clever et al. recently reported on a photoresponsive, diazocinebased Pd 2 L 4 cage. [17] Upon irradiation with two different wavelengths, the complex reversibly changes its cage volume and binds or releases a guest.
We report that violet and green light direct the outcome of self-assembly in a competition experiment with Co II ions and a mixture of the two photoswitchable regioisomeric diazocine ligands, 1 and 2 ( Figure 1). In their thermodynamically stable Z form, Co 2 (1-Z) 3 is self-assembled since 2-Z does not form discrete self-assemblies with Co II ions. Upon irradiation with violet light (385 nm) ligands 1 and 2 simultaneously switch to their metastable E form and metastable Co 2 (2-E) 3 is self-assembled since ligand 1-E forms ill-defined complexes with Co II . Irradiation with green light (520 nm) switches both ligands simultaneously back to their original Z configuration, restoring the initial Co 2 (1-Z) 3 . Thus, we report the reversible photoswitching between Co 2 (1-Z) 3 and Co 2 (2-E) 3 without fatigue over a number of cycles. To the best of our knowledge, it is the first example of a reversible light-controlled transformation between two distinct metallosupramolecular structures including different ligands via dis/assembly. Ligands 1 and 2 each consist of a diazocine-backbone and two 2-pyridyl-triazole units attached to both benzene rings ( Figure 2). They differ in the point of attachment of the two pyridyl-triazole groups (para with respect to the azo group in 1 and meta in 2), which gives rise to different coordination vectors (bite angles � 61 and 63°). An even stronger change in their bite angles is achieved upon lightinduced Z!E isomerization ( � 137 and 110°).
First, we investigated the photophysical properties of the diazocine ligands and their coordination behaviour independently ( Figure 2). Since the formation of multiple species could be expected in the case of incomplete photoswitching, [14b] Co II was chosen as the metal ion to reduce signal overlap by exploiting the large paramagnetic shifts in the 1 H NMR spectra. [21] The two ligands were prepared by analogous synthetic strategies (Scheme S1) from either literature-known p-diiododiazocine [22] in two steps (ligand 1) or 2-nitro-4-iodotoluene in 5 steps (ligand 2).
The photoswitching properties of ligands 1 and 2 were investigated by NMR ( Figures S41, S42, S45, and S46) and UV/Vis spectroscopy ( Figures S43, S44, S47 and S48). The ligands were converted from their thermodynamically stable Z configuration into the corresponding E form by irradiation with light of 385 nm. The photostationary state (PSS) was determined to be 76 % (E isomer) for ligand 1 and 72 % for ligand 2 ( Figures S42, S46). The thermal half-life (t 1/2 ) is 2.0 h for ligand 1 and 5.5 h for ligand 2 at 25°C ( Figures S44,  S48).
The self-assembly of the ligands (1-Z, 1-E, 2-Z, 2-E) with Co(BF 4 ) 2 (2 : 3 metal/ligand ratio) was carried out at room temperature, in particular to prevent relaxation of any metastable self-assemblies composed of 1-E and 2-E (Supporting Information Section 3). Complex formation occurs within minutes at room temperature and upon heating the solutions including ligands in their thermodynamically stable Z configurations (1-Z and 2-Z) to 50°C, no change of the NMR spectra was observed ( Figures S30,  S40). Discrete self-assemblies were isolated by precipitation with diethyl ether.
The self-assembly of ligand 1-Z with Co(BF 4 ) 2 exhibits 10 NMR signals within a chemical shift range of approximately 85 ppm (Figure 3a). All signals could be assigned using a combination of paramagnetic NMR methods (Figure 3a). [21] The fact that the complex exhibits the same number of signals as the free ligand hints at the formation of a highly symmetrical species. The ion peaks and isotope pattern in the ESI mass spectrum ( Figure S29) are consistent with the 2 : 3 Co II /ligand complex Co 2 (1-Z) 3 . According to NMR experiments, the complex is stable upon dilution to the concentrations required for ESI and UV/Vis measurements ( Figure S51).
Photoswitching of Co 2 (1-Z) 3 was investigated by irradiation with 385 nm ( Figure S52). During irradiation, the 1 H NMR signals assigned to Co 2 (1-Z) 3 decrease in intensity and new broad signals are observed (Figure 3a). Only very small signals of the original Co 2 (1-Z) 3 remain in the photostationary equilibrium (PSS), which we attribute to the incomplete photoswitching of ligand 1-Z to 1-E. The broad signals hint at a mixture of ill-defined species, suggesting the formation of polymers and oligomers. After standing of this solution at room temperature for several hours, the intensities of the 1 H NMR signals for Co 2 (1-Z) 3 increase again because 1-E thermally relaxes back to 1-Z (Fig-Figure 1. Reversible light-controlled assembly and disassembly of Co 2 -(1-Z) 3 and Co 2 (2-E) 3 . Self-assembly is directed with violet and green light. Ligands 1 and 2 are represented as blue and red "sausages". Co 2 + ions are grey spheres. Z isomers (cis azo group) have a C shape and E isomers (trans) an S shape. For an assignment to the corresponding chemical structures and DFT optimized geometries, see Figure 2. For the 2D chemical structures of 1 and 2 see Figure 3. ure S50). The thermal half-life (t 1/2 ) of ligand 1-E in the presence of Co II ions was measured to be 1.6 h (Figures S52,  S53). This half-life is 24 % shorter compared to the free ligand (2.0 h, Figures S43, S44), suggesting the thermal relaxation process is influenced by the metal ions.
Transformation of the ill-defined mixture including ligand 1-E to the discrete helicate Co 2 (1-Z) 3 was also achieved by irradiation with green light (520 nm). The conversion is complete within the detection limits of NMR spectroscopy. Photoswitching between the ill-defined mixture and Co 2 (1-Z) 3 with 385 and 520 nm is reversible without significant fatigue for 20 cycles by UV/Vis ( Figure S54) and 1 H NMR ( Figure S49) spectroscopy.
Ligand 2 behaves exactly the opposite of ligand 1 in the presence of Co II ions. While ligand 1-Z formed the helicate Co 2 (1-Z) 3 , 2-Z yields a ill-defined mixture (oligomers) (Figure 2b); in contrast to oligomer formation with 1-E, the regioisomer 2-E forms the helicate Co 2 (2-E) 3 (Figure 3 and Figure S38). Co 2 (2-E) 3 is stable to isolation by precipitation (Supporting Information Section 3.2) and dilution (Figure S57). Co 2 (2-E) 3 is metastable in solution. The ill-defined mixture is restored due to thermal relaxation of the ligand 2-E back to 2-Z ( Figure S56). The half-life was determined to be 9.2 h (Figures S58, S59). This is 67 % longer than the half-life for the free ligand (5.5 h, Figures S47, S48). The formation of ill-defined species shortens the half-life of 1-E and the formation of a defined triple helicate increases the half-life of ligand 2-E.
As in case of the ligand 1/Co II system, photoswitching between an ill-defined mixture and a discrete helicate was observed, however, in the reverse direction. Irradiation of ligand 2 in the presence of Co II ions (3 : 2 ratio) with 385 nm yields the discrete helicate Co 2 (2-E) 3 and with 520 nm light an ill-defined mixture is formed (Figure 3b). No fatigue was observed over 20 cycles by UV/Vis ( Figure S60) and 1 H NMR ( Figure S55) spectroscopies.
Hence, ligands 1-Z and 2-E form Co 2 L 3 self-assemblies, while ligands 1-E and 2-Z form ill-defined mixtures. Despite numerous attempts, single crystals of Co 2 (1-Z) 3 or Co 2 (2-E) 3 could not be obtained. To gain more insight into the influence of the structures of the regioisomers and their configurations on the outcome of the self-assembly, theoretical calculations were performed. In principle, complexes Co 2 (1-Z) 3 and Co 2 (2-E) 3 can exist as helicates or mesohelicates (mesocates). The energies of the four conceivable structures were calculated at the ωB97X-D3/def2-TZVP level of theory using ORCA 5.0.1 (Supporting Information Section 7). [23] In both cases, the helicate was lower in energy (1.2 and 1.8 kcal mol À 1 ) than the mesocate, and thus, we conclude that Co 2 (1-Z) 3 and Co 2 (2-E) 3 are helicates (Table S4). Helicate structures were also calculated for ligands 1-E and 2-Z and the ligand strain energies in all four helicates were compared (Table S6). Of the ligands in the Z configuration (1-Z and 2-Z), Co 2 (1-Z) 3 has a lower ligand strain energy than Co 2 (2-Z) 3 , and with the ligands in the E configuration, the ligand strain energy for Co 2 (2-E) 3 is lower than Co 2 (1-E) 3 . Ligand 1 is more susceptible to form a helicate in its Z configuration and ligand 2 prefers to form the helicate in its E configuration. This is in agreement with  the experimental findings because Co 2 (2-Z) 3 and Co 2 (1-E) 3 were experimentally not observed (Figure 4).
Having demonstrated that discrete self-assemblies are obtained with regioisomeric ligands of the opposite configuration, we envisaged a system where light could be exploited to switch between Co 2 (1-Z) 3 and Co 2 (2-E) 3 , i.e. between helicates of different compositions (Figure 1). In the initial mixture with 1-Z and 2-Z, Co 2 (1-Z) 3 forms as the major self-assembled species, as observed by 1 H NMR spectroscopy (Figures 5a and S65). Upon irradiation with 385 nm the signals of Co 2 (1-Z) 3 disappear and the signals of Co 2 (2-E) 3 grow in. Irradiation with 520 nm induces disassembly of Co 2 (2-E) 3 and restores the assembly of Co 2 (1-Z) 3 (Figures 5a and S65). Alternating irradiation with 385 nm and 520 nm demonstrated that the transformation between the two helicates is reversible over at least 20 cycles without significant fatigue (Figure 5b).
In conclusion, we report on a self-assembly system including two photoswitchable, diazocine-based ligands (1 and 2) and Co II ions. Both ligands switch to the E configuration upon irradiation with violet light (385 nm) and back to the Z isomer with green light (520 nm). Among the four possible species 1-Z, 1-E, 2-Z and 2-E, only 1-Z and 2-E form discrete cage-type complexes (helicates) with Co II ions: Co 2 (1-Z) 3 and Co 2 (2-E) 3 . Upon irradiation with 385 nm, Co 2 (1-Z) 3 disintegrates and Co 2 (2-E) 3 assembles. Irradiation with 520 nm disassembles Co 2 (2-E) 3 and Co 2 (1-Z) 3 is simultaneously rebuilt. Switching between the two helicates of different composition exhibits no fatigue or sideproducts over at least 20 switching cycles (Figure 1 and Figure 5b). Reorganization of multicomponent protein complexes triggered by external stimuli is an ubiquitous phenomenon in signal transduction pathways in nature. Our system might serve as a simple non-biological example and pave the way to the development of more sophisticated systems for artificial signal transduction cascades.