Tuning Azoheteroarene Photoswitch Performance through Heteroaryl Design

Abstract

Photoswitchable compounds, which can be reversibly switched between two isomers by light, continue to attract significant attention for a wide array of applications. Azoheteroarenes represent a relatively new but understudied type of photoswitch, where one of the aryl rings from the conventional azobenzene class has been replaced with a five-membered heteroaromatic ring. Initial studies have suggested the azoheteroarenes-the arylazopyrazoles in particular-to have excellent photoswitching properties (quantitative switching and long Z isomer half-life). Here we present a systematic computational and experimental study to elucidate the origin of the long thermal half-lives and excellent addressability of the arylazopyrazoles, and apply this understanding to determine important structure-property relationships for a wide array of comparable azoheteroaryl photoswitches. We identify compounds with Z isomer half-lives ranging from seconds to hours, to days and to years, and variable absorption characteristics, all through tuning of the heteraromatic ring. Conformation perhaps plays the largest role in determining such properties: the compounds with the longest isomerization half-lives adopt a T-shaped ground state Z isomer conformation and proceed through a T-shaped isomerization pathway, whereas the most complete photoswitching is achieved for compounds that have a twisted (rather than T-shaped) Z isomer conformation. By balancing these factors, we report a new azopyrazole 3pzH, which can be quantitatively switched to its Z isomer (>98%) with 355 nm irradiation, near-quantitatively (97%) switched back to the E isomer with 532 nm irradiation, and has a very long half-life for thermal isomerization (t = 74 d at 25 °C). Given the large tunability of their properties, the predictive nature of their performance, and the other functional opportunities afforded by usage of a heteroaromatic system, we believe the azoheteroaryl photoswitches to have huge potential in a wide range of optically addressable applications.

Arylazoindazole Photoswitches: Facile Synthesis and Functionalization via SNAr Substitution

“…9 Fuchter et al recently reported arylazopyrrole and arylazopyrazole photoswitches, which in some cases show long thermal half-lives and quantitative Z → E photoswitching. 10 Related arylazopyrazoles were used by Ravoo et al in switchable supramolecular host–guest systems. 11 Although several methods have been reported for the synthesis of (substituted) azobenzenes, 12 high-yielding entries into new classes of azoheterocycles are desirable.…”

Visible‐Light Photoswitching by Azobenzazoles

“…Calculated geometries (see Supporting Information, Sections S16.1–16.3 for computational details and Table S23) show for each of 1 – 3 that the Z isomer has a twisted (nonplanar) conformation in the ground state. Fuchter and co‐workers have previously shown that substituents (or atoms with lone pairs) in the ortho position to an azo group can lead to such twisted configurations, which do not benefit from stabilizing dispersive interactions in the Z isomer. This suggests that the related unsymmetrical compounds in which one side of the azo bond is replaced with a phenyl ring could have considerably longer half‐lives, although potentially at the expense of the visible‐light photoswitching.…”

Optical Control of the GTP Affinity of K‐Ras(G12C) by a Photoswitchable Inhibitor

“…Irradiation for a period of 30–60 s is sufficient to convert the trans form to the cis form, and λ =395 nm light seemed more effective on both compounds because isomerization under λ =395 nm irradiation was faster than with λ =365 nm light (Figures S1 and S2), thus λ =395 nm was set as irradiation wavelength for the photoisomerization of the compounds. The spectrum of the cis isomer was estimated based on the trans spectrum and cis ‐rich photostationary states (PSS, Figures B and D).…”