Motorized Macrocycle: A Photo‐responsive Host with Switchable and Stereoselective Guest Recognition

Abstract Designing photo‐responsive host–guest systems can provide versatile supramolecular tools for constructing smart systems and materials. We designed photo‐responsive macrocyclic hosts, modulated by light‐driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first‐generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown‐ether‐like macrocycles with intrinsic motor function. The octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host–guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi‐state light‐driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli‐responsive host–guest systems and dynamic materials.


Instruments:
The molecular structures were confirmed via 1 H NMR, 13 C NMR spectroscopy and high-resolution ESI mass spectrometry. 1 H NMR and 13 C NMR spectra were measured on a Brüker AV-400 and AV-600 MHz Spectrometers. The electronic spray ionization (ESI) mass spectra were obtained on a LCT Premier XE mass spectrometer and the electron impact (EI) mass spectra were measured on a Waters mass spectrometer. The UV-vis absorption spectra were obtained on a Varian Cary 100 spectrometer (1 cm, quartz cells). CD spectra were measured in a 1 cm cuvette on Jasco V-630 spectrophotometer. The UV light source was a Shanghai Gu Cun Photoelectric ZF-7D Model with a wavelength of 310 nm.

X-ray Single Crystal Analysis:
Single crystals of the reference compound cis-R 2 were grown by solvent evaporation [7] . cis-R 2 (6 mg) was dissolved in 3 mL acetonitrile solution in a small container.
After about two weeks, white color single crystals were obtained. Suitable single crystals of cis-R 2 were selected and mounted on a Bruker D8 Venture diffractometer with a steady T = 170 K during data collection. The X-ray diffraction intensity data were collected at GaKα radiation (λ = 1.34139 Å).
Structures were interfaced through the OLEX2 [8] software. The CIF file for the crystallographic data has been deposited in the Cambridge Crystallographic Data Centre, and the CCDC number is 2063381 (cis- DFT Calculation: Computational analysis was employed to optimize the structures of the ground state minima of macrocycle-3 (i.e. stable-cis-3, unstable-trans-3, stable-trans-3, unstable-cis-3 in their respective (R, R) configurations), the guest G3, and the host-guest complexes ((P, P)-(R, R)-stable-cis-3 ⊃ G3(R) and ((P, P)-(R, R)-stable-cis-3 ⊃ G3(S)). Due to the dynamic nature of the molecules involved, all the structures were pre-screened using the CREST driver in the xTB software [9] , using the GFN force field. In this way, the most stable conformers for each structure were picked via the default series of metadynamics and dynamics runs implemented in the driver. All the geometries were consequently optimized at the GFN2-xTB level with xTB, to afford a better qualitative ordering of the conformers.
After sorting, the most stable ten conformers of each species were optimized at the PW6B95D3/def2-

SUPPORTING INFORMATION
S2 SVP level, including the implicit contribution of dichloromethane via the SMD implicit solvent method.
All DFT optimizations were conducted with the Gaussian 16, Rev B.01 software package [10] . All minima were confirmed to be such due to the absence of imaginary frequencies. In certain cases, some of the DFT calculations did not converge due to oscillations in the energy, a behavior found in ca. 50% of the conformers of the host guest-complexes (5/10 of (P, P)-(R, R)-stable-cis-3 ⊃ G3(R) and 6/10 of ((P, P)-(R, R)-stable-cis-3 ⊃ G3(S)). We could however optimize the most stable isomers found from the preliminary xTB sorting, furnishing a semi-quantitative analysis of the energies of the structures involved in the study. All the properties reported in Table S1 and S9 are Boltzmann averaged. The computational data showed a slight preference of 1.5 kcal‧mol -1 for the ((P, P)-(R, R)-stable-cis-3 ⊃ G3(S) complex over ((P, P)-(R, R)-stable-cis-3 ⊃ G3(R). All xyz coordinates for all the conformers considered are provided as separate additional file.

Binding Constants:
The binding constants were calculated using the method reported on website http://app.supramolecular.org/bindfit/.
Heating of the NMR samples (60 °C): Pressure resistant Schlenk Vessels were used, and the samples were sealed and heated before transferring into a NMR tube. The heating processes were conducted in a closed system, so no solvent lost was observed.

Synthesis of stable-trans-2 and stable-cis-2
To a solution of a mixture stable-trans-1 and stable-cis-1 (774 mg, 1.34 mmol) (see ref. 1 for synthetic procedure) in 100 ml THF, was added 1.40 g TBAF. The mixture was stirred at room temperature for 30 min and subsequently poured into 200 mL water and extracted with ethyl acetate (EA, 3 ×50 mL). The organic layer was dried over Na2SO4 and concentrated under vacuum. The residue was purified by silica gel column chromatography using PE/EA (5/1) as the eluent affording 178 mg (76% based on stable-trans-1) of stable-trans-2 as a creamy-white solid and 100 mg (43% based on stable-cis-

S5
A mixuture of stable-trans-3 (350 mg, 1.0 mmol), LY1 (682.7 mg, 1.0 mmol), Cs2CO3 (2.0 g, 6.0 mmol) in 400 mL acetonitrile was heated at 80˚C under argon atmosphere for 14 h. After cooling to room temperature, the solvent was removed under vacuum. The residue was poured into 50 mL water followed by extraction with ethyl acetate (EA, 3 ×30 mL). The combined organic phase was dried and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using DCM/MeOH (400/1) as eluent affording 82 mg (12%) stable-trans-3 as a white solid. 1

Synthesis of stable-cis-3
A mixture of stable-cis-2 (227 mg, 0.65 mmol), LY1 (443 mg, 0.65 mmol), Cs2CO3 (1.3 g, 4.0 mmol) in 300 mL acetonitrile was heated at 80˚C under argon atmosphere for 14 h. After cooling to room temperature, the solvent was removed under vacuum. The residue was poured into 100 mL water and extracted with ethyl acetate (EA, 2 × 30 mL). The combined organic phase was dried and the solvent removed under vacuum. The residue was purified by silica gel column chromatography using DCM/MeOH (30/1) as eluent affording 242 mg (54%) stable-cis-3 as a clear oil. 1  A mixture of stable-cis-2 (50 mg, 0.14 mmol), LY4 (33 mg, 0.14 mmol), K2CO3 (48.3 mg, 0.35 mmol) in 60 mL acetonitrile was heated at 80˚C under argon atmosphere for 24 h. After cooling to room temperature, the solvent was removed under vacuum. The residue was poured into 25 mL water and extracted with ethyl acetate (EA, 3 × 20 mL). The combined organic phase was dried with Na2SO4 and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using PE/EA (10/1) as eluent affording 45 mg (68%) stable-cis-R 1 as a white solid. 1

Synthesis of Reference Compound stable-trans-R 1
A mixture of stable-cis-2 (50 mg, 0.14 mmol), LY4 (33 mg, 0.14 mmol), K2CO3 (48.3 mg, 0.35 mmol) in 60 mL acetonitrile was heated at 80˚C under argon atmosphere for 24 h. After cooling to room temperature, the solvent was removed under vacuum. The residue was poured into 25 mL water and extracted with ethyl acetate (EA, 3 × 20 mL). The combined organic phase was dried with Na2SO4 and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using PE/EA (10/1) as eluent affording 47 mg (70%) stable-trans-R 1 as a white solid. 1

Synthesis of Reference Compound stable-cis-R 2
A mixture of stable-cis-2 (80 mg, 0.23 mmol), LY3 (105 mg, 0.23 mmol), Cs2CO3 (225 mg, 0.69 mmol) in 100 mL acetonitrile was heated at 80˚C under argon atmosphere for 24 h. After cooling to room temperature, the solvent was removed under vacuum. The residue was poured into 25 mL water and extracted with ethyl acetate (EA, 3 × 25 mL). The combined organic phase was dried with Na2SO4 and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using PE/EA (3/1) as eluent affording 30 mg (28%) stable-cis-R 2 as a white solid. 1

Synthesis of Reference Compound stable-cis-R 3
A mixture of stable-cis-2 (50 mg, 0.14 mmol), LY2 (85 mg, 0.14 mmol), Cs2CO3 (140 mg, 0.43 mmol) in 60 mL acetonitrile was heated at 80˚C under argon atmosphere for 24 h. After cooling to room temperature, the solvent was removed under vacuum. The residue was poured into 25 mL water and extracted with ethyl acetate (EA, 3 × 25 mL). The combined organic phase was dried with Na2SO4 and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using CH2Cl2/CH3OH (50/1) as eluent affording 45 mg (54%) stable-cis-R 3 as a clear oil. 1

Synthesis of Reference Compound stable-trans-R 3
A mixture of stable-trans-2 (191 mg, 0.55 mmol), LY2 (324 mg, 0.55 mmol), Cs2CO3 (536 mg, 1.65 mmol) in 260 mL acetonitrile was heated at 80˚C under argon atmosphere for 36 h. After cooling to room temperature, the solvent was removed under vacuum. The residue was poured into 25 mL water and extracted with ethyl acetate (EA, 3 × 25 mL). The combined organic phase was dried with Na2SO4 and the solvent was removed under vacuum. The residue was purified by silica gel column chromatography using CH2Cl2/CH3OH (40/1) as eluent affording 49 mg (15%) stable-trans-R 3 as a clear oil. 1

UV-vis and NMR Studies of the Reference Compounds
Scheme S2. Photochemical and thermal isomerization steps of the reference compound R 1 .