Confirmation of the Structure of Trans‐Cyclic Azobenzene by X‐Ray Crystallography and Spectroscopic Characterization of Cyclic Azobenzene Analogs

Abstract

The photoisomerization properties of a series of cyclic azobenzene (cAb) analogs, including non-substituted, Br-, CN-, carboxyl-, and amino cAb, were compared. While the transform of these analogs show different degrees of thermal stability, no spectral changes in the absorption wavelengths were observed for amino cAb upon exposure to purple light. The 15 N NMR chemical shifts of cAb in both cis-and trans-forms were found to show a large difference from those of aromatic azobenzene; however, the trend of difference in chemical shift is in agreement with that obtained from quantum chemical calculations. More importantly, the structure of the photoisomerization product from cis-cAb was confirmed to be, indeed, the trans-cAb by X-ray diffraction experiments. The 15 NMR data of the cAb isomers and confirmation of trans-cAb through crystal structure will be of importance for future studies in the design and applications of cAb as a photoswitch.In recent years, spatiotemporal control has been recognized as a useful approach in modulating the structures and functions of biological systems due to the possibility of introducing two regulatory domains, time and location. [1][2][3] While cyclic azobenzene (cAb, 2) was first synthesized in 1910, [4] it only attracted interest very recently with the demonstration of a color change upon exposure to purple light. [5] Compared with the linear aromatic azobenzene (Ab) system 1 (Figure 1), which has found utilities in regulating the structures and functions of peptides, proteins and nucleic acids, [1,[6][7][8][9][10][11] cAb is unique in that the yellow-red isomerization is driven by visible light, and the thermodynamically stable form is the non-planar cis-, as opposed to the co-planar trans-form in Ab, potentially offering spatiotemporal regulation complementary to that of Ab.It was recently reported by us [12] that cAb and analogs can be synthesized from 2,2'-dinitrodibenzyl 3, and transformed into the corresponding D-threoninol conjugate phosphoramidite 4 (Scheme 1) for incorporation into oligonucleotides through solid phase synthesis. We further demonstrated that photoisomerization of cAb can indeed be used to regulate DNA hybridization. [13] While work is currently in progress in our lab to demonstrate the ability of cAb to regulate processes such as DNA transcription and aptamer binding, an understanding of the influence of functional groups of cAb on its photoisomerization properties is necessary in order to design a cAb system for its desired application. More importantly, while it has been assumed in the literature that cis-cAb is transformed into the red trans-cAb upon exposure to purple light, [5] no experimental evidence has been provided to confirm the structure of the photoisomerization product. We report herein the photoisomerization and thermostability of a series of cAb analogs, and the confirmation of the trans-cAb structure by Xray crystallography.The photoisomerization properties of a few cAb analogs, non-substituted, Br-, CN-, carboxyl-and amino-cAb, were inv...

Cross-Coupling Strategy for the Synthesis of Diazocines

“…In contrast to linear azobenzene, the ( Z ) isomer of cAB is thermodynamically favored over the ( E ) isomer by 37.08 kJ/mol . The switching behavior of cAB has been examined in detail by quantummechanical simulations , and spectroscopic methods. , However, compared to linear azobenzenes, diazocines have been used to a much lesser extent (examples are a photocontrolled switch in a peptide, in polyurea, on molecular platforms, and in oligonucleotides) . The reason for this low level of exploitation of these favorable properties is that although syntheses exist, they tend to be low yielding and substrate specific.…”

Modulation of Electronic Mobility of a One‐Dimensional Coordination Polymeric Molecular Wire with Light

“…It was reported that the eight‐membered diazocine systems are thermodynamically stable in the cis conformation . We have demonstrated that the effect of ring strain responsible for the stability of cis form does not extend to the 9‐membered ring system, as our system was found to be more stable in the trans form …”

“…[48,49] It was reported that the eight-memberedd iazocine systems are thermodynamically stable in the cis conformation. [50,51] We have demonstrated thatt he effect of ring strain responsible for the stability of cis form does not extendt ot he 9-membered ring system,a so ur system was found to be more stable in the trans form. [52] The effect of metal ions on the photoisomerization of azobenzene systems weres tudied in aA g I -complex with a2 4membered cyclic azobenzene by Ta maoki( Figure 1A) [43] where the trans-complex was found to be more stable.…”

Modification of Azobenzenes by Cross-Coupling Reactions

“…69b Furthermore, the coupling of benzophenone imine with bromodiazocines was reported (Scheme 28, B). 71 The synthesis of a diazocine with turn-on fluorescence was achieved by the coupling of 3,8-dibromodiazocine with diphenylamine (Scheme 28, C). 72 Scheme 28 Buchwald-Hartwig cross-coupling reactions of diazocine derivatives 69b, 71,72 Turn-on fluorescence diazocines were prepared by a Stille cross-coupling reaction (Scheme 29, A).…”

“…71 The synthesis of a diazocine with turn-on fluorescence was achieved by the coupling of 3,8-dibromodiazocine with diphenylamine (Scheme 28, C). 72 Scheme 28 Buchwald-Hartwig cross-coupling reactions of diazocine derivatives 69b, 71,72 Turn-on fluorescence diazocines were prepared by a Stille cross-coupling reaction (Scheme 29, A). 72 Furthermore, it was possible to obtain a pyroglutamate diazocine derivative via the Stille cross-coupling reaction (Scheme 29, B).…”