Towards low-energy-light-driven bistable photoswitches: ortho-uoroaminoazobenzenes Kim Kuntze Tampere University Jani Viljakka Tampere University Evgenii Titov University of Potsdam Zafar Ahmed Tampere University Elina Kalenius University of Jyväskylä Peter Saalfrank University of Potsdam Arri Priimagi ( arri.priimagi@tuni. ) Tampere University https://orcid.org/0000-0002-5945-9671 Article Keywords: ortho-uoroaminoazobenzenes, photoswitches, photoresponsive molecules Posted Date: June 14th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-608595/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Towards low-energy-light-driven bistable photoswitches: ortho- fluoroaminoazobenzenes Kim Kuntze,a Jani Viljakka,a Evgenii Titov,*b Zafar Ahmed,a Elina Kalenius,c Peter Saalfrankb and Arri Priimagi*a a Prof. A. Priimagi, Smart Photonic Materials, Faculty of Engineering and Natural Sciences, Tampere University, P.O. Box 541, FI-33101, Tampere, Finland. E-mail: [email protected] b Dr. E. Titov, Theoretical Chemistry, Institute of Chemistry, University of Potsdam, Karl-Liebknecht-Straße 24-25, 14476 Potsdam, Germany. E-mail: [email protected] c Department of Chemistry, University of Jyväskylä, P.O. Box 35, 40014 Jyväskylä, Finland Thermally stable photoswitches that are driven with low-energy light are rare, yet crucial for extending the applicability of photoresponsive molecules and materials towards, e.g., living systems. Combined ortho-fluorination and -amination couples high visible-light absorptivity of o-aminoazobenzenes with the extraordinary bistability of o-fluoroazobenzenes. Herein, we report a library of easily accessible o-aminofluoroazobenzenes and establish structure–property relationships regarding spectral qualities, visible light isomerization efficiency and thermal stability of the cis-isomer with respect to the degree of o-substitution and choice of amino substituent. We rationalize the experimental results with quantum chemical calculations, revealing the nature of low-lying excited states and providing insight into thermal isomerization. The synthesized azobenzenes absorb at up to 600 nm and their thermal cis-lifetimes range from milliseconds to months. The most unique example can be driven from trans to cis with any wavelength from UV up to 595 nm, while still exhibiting a thermal cis-lifetime of 81 days. switching between two essentially bistable forms with visible Introduction light, high irradiation intensities or extremely long illumination 36,37 Photochromic molecular switches such as azobenzenes1, periods (hours for ortho-chlorinated compounds ) are diarylethenes2,3 and spiropyrans4–6 pave the way towards next- required for efficient switching because of the low molar generation pharmaceuticals7–11, catalysts12–14 and functional absorptivity of the n–π* band. This is a drawback particularly materials15–18 that can be activated or controlled with a spatially when the photoswitch is illuminated through tissue or other light- and temporally precise external stimulus – light. Azobenzene scattering or -absorbing material. ortho-Amination increases the derivatives, whose geometry, dipole moment and other physical molar absorptivity but concurrently decreases the cis-lifetime to 19 properties change drastically upon cis–trans isomerization the time scale of seconds. However, as their advantage, amino- around the N=N bond, are particularly attractive photoswitches substituted azobenzenes are resistant to glutathione that reduces due to their synthetic versatility, good fatigue resistance and high less electron-rich compounds and hampers their applicability in 38,39 isomerization quantum yields1. The photochemical properties of biological systems. In addition, compared to halogens, amino azobenzene photoswitches can be tuned with simple structural substituents such as piperazine and proline derivatives provide modifications to meet the requirements of a given application. In additional functionalization sites in the ortho positions, enabling particular, many applications benefit from switching with low- molecular structures unattainable with ortho-fluorinated or energy and low-intensity light as well as from high thermal -chlorinated compounds. Thus, it would be highly desirable to stability of the metastable cis-isomer. These attributes are crucial combine the best qualities of both o-amino- and o- for switches used in living systems19 or memories20 and often halosubstituents. times advantageous for applications in solar thermal fuel systems21,22 and soft-robotic materials23–25 as well: high-energy Recently, we have shown that combined ortho-fluorination and irradiation generally has a degrading effect on the switch and its -amination yields azobenzenes with high molar absorptivity at 40 surroundings26,27 and, on the other hand, constant illumination is visible wavelengths and tunable cis-lifetimes. Starting from not always possible. mono- or di-ortho-fluorinated precursors, we selectively substituted one or both of the fluorines with pyrrolidine via a The observed absorption of azobenzene in the UV-visible range high-yielding nucleophilic aromatic substitution reaction, is a combination of two transitions, the symmetry-allowed π–π* producing azobenzenes with a relatively long (3 days) or and the symmetry-forbidden n–π*. While many substitution extremely short (1 s) cis-lifetime depending on the substitution patterns red-shift the π–π* band significantly19,28,29, this is pattern. However, the studied library of molecules did not accompanied by a drastic drop in the thermal stability of the cis- include tetra-ortho-substituted azobenzenes that have widely isomer30, rendering these azobenzenes unsuitable for shown the best isomerization efficiencies and cis-lifetimes 31,34 applications in photobiology where constant irradiation is not among different classes of ortho-substituted azobenzenes. possible and near-bistable systems are therefore required. ortho- The study also gave no information on how the choice of amine Substitution with suitable moieties, in turn, decouples the n–π* affects the photochemical properties of the ortho-functionalized absorption bands of the cis and trans isomers, red-shifting it for azobenzenes. Furthermore, even though the molar absorptivity the trans-form while simultaneously prolonging the cis- in the visible region was high, efficient trans–cis isomerization lifetime.31,32 However, while ortho-methoxylated33, was only achieved at relatively short wavelengths (365–405 nm). -fluorinated31,34 and chlorinated35–37 compounds enable efficient OMe OMe Hence, there is a need for systematic studies in order to better R1 R1 understand and utilize this class of azobenzenes. N N N N 1 3 R3 Herein, we present a library of 41 ortho- MeO MeO aminofluoroazobenzenes acquired by substituting one or more of OMe 4 OMe 1 1 R the fluorine atoms in mono-, di- and tetra-ortho-fluorinated R R N N azobenzenes with different secondary amines. Through a N N 2 4 R3 systematic survey of the photochemical properties of each MeO R2 MeO R2 compound, we explore the effects of (i) degree of substitution x and (ii) choice of amine, searching for the optimal molecular 1-F: R1 = F structures that can be isomerized efficiently with low-energy 2-F: R1, R2 = F H H light while maintaining long cis-lifetimes. The observed 3-F: R1, R3 = F N N structure-property relationships are further rationalized with 4-F: R1, R2, R3, R4 = F 1-x: R1 = x density functional theory (DFT) and time-dependent DFT (TD- pyr pip 1 2 DFT) calculations which provide electronic insight into low- 2-x1: R = x, R = F mono- & 3-x : R1 = x, R3 = F lying excited states and shed light on thermal isomerization. 1 disubs. H H 1 2 N N 2-x2: R , R = x Additionally, we show that commercial and inexpensive L- 1 3 OH 3-x2: R , R = x proline derivatives can be used to create azobenzenes with 1 2 3 4 dma prol 4-x1: R = x, R , R , R = F similar photoswitching properties as the pyrrolidine-substituted 1 3 2 4 4-x2-sym: R , R = x, R , R = F O O tetra- H H ones, while enhancing water solubility and providing easy 4-x : R1, R2 = x, R3, R4 = F N N 2-asym subs. 1 2 3 4 OMe synthetic access to ortho-linkage to, e.g., bioactive molecules or 4-x3: R , R , R = x, R = F NH2 4-x : R1, R2, R3, R4 = x pres pram polymer networks. 4 Figure 1. Substitution patterns of studied azobenzene derivatives and the abbreviations used for different secondary amines. (pyr = pyrrolidine, pip = piperidine, dma = Results and discussion dimethylamine, prol = L-prolinol, pres = L-proline methyl ester, pram = L-prolinamide) Synthesis Starting from the ortho-mono- and difluorinated azobenzene The series 1-x, 2-x1, 3-x1, 3-x2, 4-x1 and 4-x2-sym were stable precursors 1–3-F and utilizing previously reported synthetic enough to be isolated and studied regardless of the chosen amine, procedures40, we complemented the mono- and di-ortho- but 2-pyr2 and 4-pyr2-asym degraded over time. Of the three substituted series with piperidino- and dimethylamino- amines, piperidine produced the most stable products, substituted azobenzenes (Fig. 1); pyrrolidino-substituted demonstrated by the fact that the only stable products of higher equivalents were published previously40. The degree of degree of substitution were 4-pip3 and 4-pip4; for pyrrolidine substitution can be easily controlled for the difluorinated and dimethylamine, no stable products were acquired when more precursors 2-F and 3-F, yielding series 2-x1 and 2-x2, and 3-x1 than two fluorines