Donor-acceptor Stenhouse Adducts with Three Orthogonally Controlled Intrisic Stationary States

Photoresponsive molecules with more than two intrinsic stationary states are very Interesting. Here, we demonstrate a series of crown ether (CE) substituted donoracceptor Stenhouse adducts (DASAs) that can be switched between three stationary states under orthogonal control of light and metal ions. DASA-CE molecules are selfassembled into 1:1 head-to-tail supramolecular structures to form di-linear states due to strong van der Waals interactions between electron-donating and -withdrawing moieties. Furthermore, treatment with metal ions (Na or K) switches the di-linear back to the linear state, which is reversible after adding free crown ether. On the other hand, green light irradiation induces linear-to-cyclic isomerization of DASA-CE, while the photoisomerization from di-linear to cyclic state is inhibited. The reverse cyclic-tolinear isomerization can occur under heating in the dark. All in all, the orthogonal switching of DASA-CE between di-linear, linear and cyclic states enables the development of smart materials in environments with complex stimuli.

To achieve this, the introduction of two or more stimuli-responsive functional groups into one molecular or macromolecular system, which can be controlled in an orthogonal manner, has been reported. For example, Feringa et al demonstrated an intramolecular combination of photoswitching based on DASAs and Azo, while the isomerization of DASAs and Azo could be controlled separately 14 . Therefore, the resulting molecule could be switched between four independent states by controlling light and heat. This orthogonal control realized at the molecular level may open up applications for these materials in multi-stimuli environments. However, introducing more stimuli-responsive functional groups increases the complexity of the systems, which is not ideal for future developments. Instead, is it possible to realize intrinsically orthogonal switching between multiple (n>2) stationary states in a single molecule without introducing other stimuli-responsive groups? This is the question that needs to be answered.
Therefore, van der Waals interactions may exist between the electron-donating andwithdrawing moieties, which leads to the self-assembly of DASAs and induces the formation of a third state. However, this phenomenon has not been previously reported.
This might be the reason of mismatched molecular geometries between the two moieties.
In the current work, we synthesized a series of new DASA derivatives (DASA-CE) using crown ethers (CEs) with different sizes (15-crown-5 and 18-crown-6) as the electron-donating moiety, while Meldrum's acid and barbituric acid were selected for the electron-withdrawing moiety (Scheme 1). For the first time, linear DASA-CE selfassembles into a 1:1 head-to-tail supramolecular structure (di-linear state in Scheme 1) due to the strong van der Waals interaction between the crown ether (electron-rich) and the electron-withdrawing moiety.
Adding metal ions (Na + or K + ) switches the di-linear state back to linear state, which is reversible by introducing free crown ethers into the system. A series of DASA-CE were synthesized using 15-crown-5 and 18-crown-6 as the electron-donating moieties, and Meldrum's acid or barbituric acid as the electronwithdrawing moieties (Scheme S1, see detail in Supporting Information (SI)). The synthesized DASA-CE were termed DASA-NC5, DASA-NC6, DASA-OC5 and DASA-OC6, respectively (Scheme 1). All four compounds have similar physical properties. Therefore, DASA-NC5 will be used to represent all DASA-CE in forthcoming discussions.
The three stationary states of DASA-NC5 could be clearly observed in one single 1 H nuclear magnetic resonance (NMR) spectrum ( Figure S1). The switching between the three independent states will be discussed in detail.

DASA-NC5 shows abnormally low absorbance in visible light region compared
with the well-studied diethylamine-substituted DASAs (DASA-N) when dissolved in tetrahydrofuran (THF) (Figure 1a). However, the addition of NaBF4 sharply increases the absorbance in the visible light region, which makes the DASA-NC5 solution strongly colored (Figure 1a). The absorbance of DASA-NC5 in the visible light region is closely and directly related to the concentration of added Na + ions, which reaches equilibrium when the Na + concentration approaches 1:1 with the DASA-NC5 ( Figure   S2). In addition, the absorbance in UV light region, which correlates to the electronwithdrawing moiety, shows a ~20 nm red shift after the introduction of Na + ion. On the other hand, DASA-N does not show obvious absorbance change after adding NaBF4 ( Figure S3). This indicates that the linear DASA-NC5 forms a centrosymmetric molecular system. The coplanarity of the centrosymmetric molecular structure is obviously reduced, leading to the "hypochromic effect" 29 , which limits the absorbance of the entirely conjugated molecule in visible light region of linear DASA-NC5. The centrosymmetric self-assembly of DASA-NC5 is supposed to be a 1:1 head-to-tail supramolecular structure (di-linear state), which will be discussed in detail later in this article (Scheme 1).
After introducing NaBF4 into the system, the metal ions could coordinate with the 15-crown-5 group in the electron-donating moiety, and further induce the disassembly of the centrosymmetric structure (di-linear-to-linear transition). The di-linear-to-linear transition of DASA-NC5 does not occur in all solvents. In protic solvents (i.e. ethanol), the addition of Na + does not increase the absorbance of DASA-NC5 in visible light region, which is different to that in tetrahydrofuran (THF) and dichloromethane ( Figure   S4 and S5). These might be attributed to the interaction between Na + ion and 15-crown-5 in protonic solvents [30][31] . DASA-OC5, DASA-NC6 and DASA-OC6 also show metal-ion induced di-linear-to-linear transition in THF (Figure S6-S9). DASA-CE with 15-crown-5 substituted electron-donating moieties are responsive to Na + ions, while 18-crown-6 substituted DASAs are sensitive to K + ions (see detail in SI). The absorbance variation in the visible light region caused by the addition of Na + ion was investigated on concentrations of DASA-NC5 between 0.12 and 0.015 mM (Figure 1b, red). The absorbance in the visible light region increases more upon adding Na + ions to higher concentrations of DASA-NC5 in THF, indicating more di-linear states are formed under higher concentrations. Similar changes could be noticed for the absorbance in the UV light region (Figure 1b, blue).
The di-linear-to-linear transition of DASA-NC5 was further monitored by 1 H NMR spectroscopy (Figure 1c). Two states of DASA-NC5 could be clearly identified before the addition of Na + ions (Figure 1c, red). The signals of the di-linear state is broader than those of the linear state (e.g. Hb` is broader than Hb), which is attributed to molecular aggregation. Approximately 75% of DASA-NC5 are in the di-linear state.
After the introduction of Na + ions, all of the di-linear DASA-NC5 switches to the linear state (Figure 1c, blue). These are in good accordance with the results of the UV/vis spectroscopy investigation.  (Figure S10-S13), which is in good accordance with the "push-pull" nature of DASAs. Linear DASA-NC5 shows a partially planar molecular structure, and the 15crown-5 shows a slightly larger cavity than the electron-withdrawing moiety, which is ideal for the 1:1 head-to-tail self-assembly (Figure 2b) (Figure 2c, black). No correlations of d-a and d-b exist, due to the long distance between the protons (Figure 2c, blue). In contrast, a clear correlation of d`-a` is observed for the di-linear state, indicating the formation of the head-to-tail supramolecular structure (Figure 2c, red). The transition of DASA-NC5 between linear and di-linear states is reversible.
After adding competing host molecules, the coordinated metal ions are removed from linear DASA-NC5, which further induces the linear-to-di-linear transition (Figure 3a). DASA-NC5 is mostly in the linear state after introducing Na + ions. Adding 15-crown- Figure 3) sharply decreases the absorbance in visible light region. However, the absorbance can not reach the pristine value of the di-linear state when the 15-crown-5 concentration is 1:1 with the Na + ions (Figure 3b). Increasing the amount of 15crown-5 can further decrease the absorbance of DASA-NC5, indicating that the formation of the di-linear state is promoted. This could be explained by the competition of the Na + ion between the free 15-crown-5 and DASA-NC5 (see details in SI). The absorbance in the UV light region shows similar behavior (Figure 3b, inset). The reversible transition between the linear and di-linear state was demonstrated by repeatedly treating the system with equal amounts (in molar ratio) of NaBF4 and 15crown-5 (Figure 3c). The di-linear-to-linear transition of DASA-NC5 is approximately 100% for each cycle. However, the yield of the reverse linear-to-dilinear transition decreases sharply as the cycle numbers increase, which could also be explained by the Na + ion competition (see detail in SI). introducing Na + ions (Figure 4b, black). The slightly decreased absorbance in the visible light region is due to the residual linear state in the system. After the NaBF4 addition, the absorbance in visible light region decreases sharply under green light irradiation, which is reversible after heating in the dark (Figure 4b, red and Figure   S18). Therefore, the photoisomerization of the di-linear state is restricted. The lightinduced isomerization of linear and di-linear states are further demonstrated by 1 H NMR spectra (Figure 4c). The signals of the linear and di-linear state could be clearly identified in the same spectrum (Figure 4c, black). After green light irradiation, the signals of the linear state disappear, while the new generated signals for the cyclic state are formed, indicating the light induced linear-to-cyclic isomerization. In contrast, the signals of the di-linear state do not change after light irradiation, indicating the photoisomerization of di-linear state is restricted. These are attributed to the formed stable head-to-tail supramolecular strucutre. In summary, we synthesized a series of crown ether-substituted DASA derivatives.

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The switching of the DASA-CE between di-linear, linear and cyclic states under orthogonal control of light and metal ions was realized. Taking DASA-NC5 as an example, in aprotic solvents (e.g. THF, dichloromethane), DASA-CE exist mainly in the di-linear state, which is a 1:1 head-to-tail supramolecular structure self-assembled through the van der Waals interaction between the electron-donating and -withdrawing moieties. The addition of Na + induces di-linear-to-linear transition, while the reverse linear-to-di-linear transition occurs after adding free 15-crown-5. Similar to the reported DASAs, linear DASA-NC5 isomerizes to cyclic DASA-NC5 after 530 nm green light irradiation, and switches back to the linear state under heating. However, the photoisomerization of the di-linear state is inhibited. We have successfully achieved switching of multiple (n>2) stationary states in a single molecule, which is benefical for the future development of smart materials used in environments with complex stimuli. This also leads to more intelligent photoresponsive materials, including multidrug release systems and interpenetrating polymer hydrogels.