Computational Design and Synthesis of a Deeply Red-Shifted and Bistable Azobenzene

We computationally dissected the electronic and geometrical influences of ortho-chlorinated azobenzenes on their photophysical properties. X-ray analysis provided the insight that trans-tetra-ortho-chloro azobenzene is conformationally flexible and thus subject to molecular motions. This allows the photoswitch to adopt a range of red-shifted geometries, which account for the extended n → π* band tails. On the basis of our results, we designed the di-ortho-fluoro di-ortho-chloro (dfdc) azobenzene and provided computational evidence for the superiority of this substitution pattern to tetra-ortho-chloro azobenzene. Thereafter, we synthesized dfdc azobenzene by ortho-chlorination via 2-fold C–H activation and experimentally confirmed its structural and photophysical properties through UV–vis, NMR, and X-ray analyses. The advantages include near-bistable isomers and an increased separation of the n → π* bands between the trans- and cis-conformations, which allows for the generation of unusually high levels of the cis-isomer by irradiation with green/yellow light as well as red light within the biooptical window.

1 Experimental section 1.1 Material and Methods

Equipment and Instruments
Nuclear magnetic resonance (NMR) spectroscopy: NMR-spectra were acquired with the following spectrometers: Varian INOVA 400 (400 MHz for 1 H and 101 MHz for 13 C spectroscopy), Bruker Avance III HD 400 MHz NMR spectrometer equipped with a broadband probe (400 MHz for 1 H and 101 MHz for 13 C spectroscopy), Bruker Avance III HD 400 MHz NMR spectrometer equipped with a Cryo-head

Infrared spectroscopy (IR):
IR spectra were recorded on a PerkinElmer Spectrum BX II FT-IR device equipped with an attenuated total reflection (ATR) measuring unit. For measurements, the neat substances were directly applied as a thin film on the ATR unit. The measured wavenumbers are reported with their relative intensities which were classified as: vs (very strong), s (strong), m (medium), w (weak), vw (very weak), br (broad) or combinations thereof.

Roithner
The opical power output of the LEDs was measured using a ThorLabs (https://www.thorlabs.de) Power and Energy Meter Interface PM101 equipped with the Slim Photodiode Power Sensor S130VC.
The experiments were conducted using a 50 µM and 500 M solution of the compound in DMSO.

Methods
Unless otherwise noted, all reactions were magnetically stirred under inert gas (N2) atmosphere using standard Schlenk techniques. Glassware was evacuated and dried by heating with a heat-gun (set to 550 °C). Drying over Na2SO4 or MgSO4 implies stirring with an appropriate amount of anhydrous salt for several minutes followed by filtration through a glass frit and rinsing of the filter cake with additional solvent. Electric heating plates and oil baths were used for reactions at elevated temperature. Stated reaction temperatures refer to the external bath temperature. Cannulas and syringes were used for the transfer of reagents and solvents, which were flooded with inert gas (3×) before use.

Material and Methods
Structures of all studied model compounds were optimized on PBE0-D3/def2-TZVP 4-7 level of theory. Vibrational frequency calculations were employed subsequently, to ensure obtained minima to be true minima on the obtained potential energy surface. Excitation energies were then calculated on TD-PBE0/def2-TZVP//PBE0-D3/def2-TZVP [4][5][6][7] level of theory, using previously obtained structures. Difference densities as well as molecular orbital contributions to the first two excited states were calculated using corresponding methods.
The Turbomole program package 8 was used to obtain optimized structures, vibrational frequencies, single point and excitation energies and corresponding difference densities and molecular orbitals. S10

UV-Vis Data -Initial Wavelength Screening
The initial wavelength screening was conducted using a 50 M DMSO solution azobenzene derivative. Staring from the dark-adapted or ambient light-adapted state, the UV-Vis spectra were recorded after 3 min irradiation pulses of light using the wavelengths that are depicted at the X-axis of the graph. The irradiation pulses were applied sequentially, beginning from the most red-shifted wavelengths of the graph and moving along the spectrum to the most blue-shifted wavelengths. For each recorded UV-Vis spectrum, the absorption data point that was measured at the specified wavelength (see black description box) was plotted into the graph. The data point highlighted in black is the absportion at the dark-adapted or ambient light-adapted state. Using this approach, the most red-shifted wavelength which allowed photoswitching within a timeframe of 3 min as well as wavelengths that produced high cisor trans-photostationary   Due to poor crystal quality and diffraction patterns, the desired completeness of 0.985 could not be obtained at higher diffraction angles. The completeness has been improved by allowing a higher common volume of overlapped reflections.