Photoswitches beyond azobenzene: a beginner's guide

Abstract

Approaching the vast, colourful world of photoswitches from a different field of study or as an undergraduate student may be overwhelming: azobenzene is undoubtedly the most famous due to its easy synthesis and the extensively studied properties. However, there are several photoswitch classes beyond azobenzene with interesting properties that can be tailored to meet one's needs. In this tutorial review, we aim to explain the important terminology and discuss the synthesis, switching mechanisms, and properties of seven interesting photoswitch classes, namely azoheteroarenes, diazocines, indigoid photoswitches, arylhydrazones, diarylethenes, fulgides, and spiropyrans.

Keywords: photoswitch properties; photoswitches; switching mechanisms; synthesis of photoswitches; tutorial review.

Figure 1

Energy diagram of a two-state photoswitch. Figure 1 was redrawn from [2].

Figure 2

Example of the absorption spectra of the isomers of a photoswitch with most efficient irradiation wavelengths to obtain the highest PSS.

Scheme 1

Photoswitch classes described in this review.

Figure 3

Azoheteroarenes.

Scheme 2

E–Z Isomerisation (top) and mechanisms of thermal Z–E isomerisation (bottom).

Scheme 3

Rotation mechanism favoured by the electron displacement in push–pull systems. Selected examples of push–pull azoheteroarenes [,,–2527].

Figure 4

A) T-shaped and twisted Z-isomers determine the thermal stability and the Z–E-PSS (selected examples) [14,29]. B) Complete vs partial conjugation predicts the thermal stability.

Figure 5

Effect of di-ortho-substitution on thermal half-life and PSS.

Figure 6

Selected thermal lifetimes of azoindoles in different solvents and concentrations. ^aConcentration of photoswitch is 50 µM. ^bConcentration of photoswitch is 75 µM [5].

Figure 7

Aryliminopyrazoles: N-pyrazoles (top) and N-phenyl (bottom).

Scheme 4

Synthesis of symmetrical heteroarenes through oxidation (A), reduction (B), and the Bayer–Mills reaction (C), also suitable for asymmetrical heteroarenes.

Scheme 5

Synthesis of diazonium salt (A); different strategies of azo-coupling: with a nucleophilic ring (B), with a lithiated ring (C), and with a precursor (D).

Scheme 6

Synthesis of arylazothiazoles 25 (A) and heteroaryltriazoles 28 (B).

Scheme 7

Synthesis of heteroarylimines 31a,b [–38].

Figure 8

Push–pull non-ionic azo dye developed by Velasco and co-workers [45].

Scheme 8

Azopyridine reported by Herges and co-workers [46].

Scheme 9

Photoinduced phase transitioning azobispyrazoles [47].

Figure 9

Diazocines.

Scheme 10

Isomers, conformers and enantiomers of diazocine.

Scheme 11

Partial overlap of the ππ* band with electron-donating substituents and effect on the PSS. Scheme 11 was adapted from [52] (© 2019 W. Moormann et al., published by Beilstein-Institut, distributed under the terms of the Creative Commons Attribution 4.0 International License, https://creativecommons.org/licenses/by/4.0).

Figure 10

Main properties of diazocines with different bridges. ^aMeasured in n-hexane [56]. ^bMeasured in THF. ^cMeasured in acetonitrile [53]. ^dMeasured in acetone [51].

Scheme 12

Synthesis of symmetric diazocines.

Scheme 13

Synthesis of asymmetric diazocines.

Scheme 14

Synthesis of O- and S-heterodiazocines.

Scheme 15

Synthesis of N-heterodiazocines.

Scheme 16

Puromycin diazocine photoswitch [60].

Figure 11

Indigoids.

Figure 12

The main representatives of the indigoid photoswitch class.

Scheme 17

Deactivation process that prevents Z-isomerisation of indigo.

Figure 13

Stable Z-indigo derivative synthesised by Wyman and Zenhäusern [67].

Figure 14

Selected examples of indigos with aliphatic and aromatic substituents [68]. Dashed box: proposed π–π interaction stabilising the diaryl-substituted derivatives.

Scheme 18

Resonance structures of indigo and thioindigo involving the phenyl ring.

Scheme 19

Possible deactivation mechanism for 4,4'-dihydroxythioindigo [76].

Scheme 20

Effect of different heteroaryl rings on the stability and the photophysical properties of hemiindigos [–62].

Figure 15

Thermal half-lives of red-shifted hemithioindigos in toluene [79]. ^aMeasured in toluene-d₈.

Scheme 21

Structures of pyrrole [81] and imidazole hemithioindigo [64].

Figure 16

Examples of fully substituted double bond hemithioindigo (left), oxidised hemithioindigos (centre), and a sulphoxide hemithioindigo as a molecular motor (right).

Scheme 22

Structure of iminothioindoxyl 72 (top) and acylated phenyliminoindolinone photoswitch 73 (bottom). The steric hindrance in 73-Z makes it the least stable isomer and is responsible for the negative photochromism.

Scheme 23

(top) Transition states of iminothioindoxyl 72. The planar transition state is associated with a longer thermal half-life [90]. (bottom) Transition state for thermal back-isomerisation of phenyliminoindolinone 73. The partial negative charge in 73’ is stabilised by resonance with electron-withdrawing groups –R [63].

Scheme 24

Baeyer–Drewsen synthesis of indigo (top) and N-functionalisation strategies (bottom).

Scheme 25

Synthesis of hemiindigo.

Scheme 26

Synthesis of hemithioindigo and iminothioindoxyl.

Scheme 27

Synthesis of double-bond-substituted hemithioindigos.

Scheme 28

Synthesis of phenyliminoindolinone.

Scheme 29

Hemithioindigo molecular motor [85].

Figure 17

Arylhydrazones.

Scheme 30

Switching of arylhydrazones. Note: The definitions of stator and rotor are arbitrary.

Scheme 31

Photo- and acidochromism of pyridine-based phenylhydrazones.

Scheme 32

A) E–Z thermal inversion of a thermally stable push–pull hydrazone [109]. B) Rotation mechanism favoured by electron donation from the stator. C) Rotation mechanism favoured by electron withdrawal from the rotor. The effect of the rotor is milder because of the nonplanar structure.

Scheme 33

Effect of planarisation on the half-life.

Scheme 34

The longest thermally stable hydrazone switches reported so far (left). Modulation of thermal half-life through ring size (right).

Figure 18

Dependency of t_1/2 on concentration and hypothesised aggregation-induced isomerisation.

Figure 19

Structure–property relationship of acylhydrazones.

Scheme 35

Synthesis of arylhydrazones.

Scheme 36

Synthesis of acylhydrazones.

Scheme 37

Photoswitchable fluorophore by Aprahamian et al. [115].

Scheme 38

The four-state photoswitch synthesised by the Cigáň group [116].

Figure 20

Diarylethenes.

Scheme 39

Isomerisation and oxidation pathway of E-stilbene to phenanthrene.

Scheme 40

Strategies adapted to avoid E–Z isomerisation and oxidation.

Scheme 41

Molecular orbitals and mechanism of electrocyclisation for a 6π system.

Figure 21

Aromatic stabilisation energy correlated with the thermal stability of the diarylethenes [127,129].

Figure 22

Half-lives of diarylethenes with increasing electron-withdrawing groups [–129].

Scheme 42

Photochemical degradation pathway promoted by electron-donating groups [130].

Figure 23

The diarylethenes studied by Hanazawa et al. [134]. Increased rigidity leads to bathochromic shift.

Scheme 43

The dithienylethene synthesised by Nakatani's group [135].

Scheme 44

Synthesis of perfluoroalkylated diarylethenes.

Scheme 45

Synthesis of 139 and 142 via McMurry coupling.

Scheme 46

Synthesis of symmetrical derivatives 145 via Suzuki–Miyaura coupling.

Scheme 47

Synthesis of acyclic 148, malonic anhydride 149, and maleimide derivatives 154.

Figure 24

Gramicidin S (top left) and two of the modified diarylethene derivatives: first generation (bottom left) and second generation (bottom right). Top right: the difference in absorption of the closed isomers of the new photoswitchable derivatives. The upper right part of Figure 24 was adapted from [143], O. Babii et al., “Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent Photodynamic Cancer Therapy”, Angew. Chem., Int. Ed., with permission from John Wiley and Sons. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This content is not subject to CC BY 4.0.

Scheme 48

Pyridoxal 5'-phosphate and its reaction with an amino acid (top). The analogous dithienylethene derivative (bottom).

Figure 25

Fulgides.

Scheme 49

The three isomers of fulgides.

Scheme 50

Thermal and photochemical side products of unsubstituted fulgide [150].

Figure 26

Maximum absorption λ_c of the closed isomer compared with the nature of the aromatic ring and the substitution pattern (selected examples). λ_c was determined on poly(methyl methacrylate) film.

Scheme 51

Possible rearrangement of the excited state of 5-dimethylaminoindolylfulgide [153].

Figure 27

Quantum yields of ring closure (Φ_E→C) and E–Z isomerisation (Φ_E→Z) correlated with the increasing steric bulkiness of substituent R.

Scheme 52

Active (E_α) and inactive (E_β) conformers (left) and the bicyclic sterically blocked fulgide 169 (right).

Scheme 53

Quantum yield of ring-opening (Φ_C→E) and E–Z isomerisation (Φ_E→Z) for different substitution patterns.

Scheme 54

Stobbe condensation pathway for the synthesis of fulgides 179, fulgimides 181 and fulgenates 178.

Scheme 55

Alternative synthesis of fulgides through Pd-catalysed carbonylation.

Scheme 56

Optimised synthesis of fulgimides [166].

Scheme 57

Photoswitchable FRET with a fulgimide photoswitch [167].

Scheme 58

Three-state fulgimide strategy by Slanina's group.

Figure 28

Spiropyrans.

Scheme 59

Photochemical (left) and thermal (right) ring-opening mechanisms for an exemplary spiropyran with arbitrary substituents R and R’. The blue arrows indicate a photochemical cleavage of the C_spiro–O bond, while the red arrows represent a thermal 6π-electrocyclic ring-opening [169].

Figure 29

Eight possible isomers of the open merocyanine according to the E/Z configurations of the bonds highlighted in blue (α, β, and γ). The orientation of the centrally located double bond (β) is used for classification into the two groups cisoid-merocyanines (β → Z configuration) and transoid-merocyanines (β → E configuration). The abbreviations of the isomers are composed of a sequence of the orientations of the bonds α, β, and γ (e.g. TCT = trans–cisoid–trans) [170].

Scheme 60

pH-Controlled photoisomerisation between the closed spiropyran 191-SP and the open E-merocyanine 191-E-MC as well as the protonated E-merocyanine 191-E-MCH⁺ and the Z-merocyanine 191-Z-MCH⁺. Both E-merocyanines are present in the most stable trans–transoid–cis (TTC) configuration, and the Z-merocyanine shows the cis–cisoid–cis (CCC) geometry (R = H, NO₂). Note that 191-Z-MCH⁺ can only switch back to 191-SP upon deprotonation, which enables pure E/Z-photoisomerisation when the medium is strongly acidic [175].

Scheme 61

Behaviour of spiropyran in water buffer according to Andréasson and co-workers [180]. 192-SP in an aqueous medium can only convert to 192-MC when it is not protonated. Box: effect of the R¹ group on the pK_a of the phenol group. The higher the pK_a, the more shifted the equilibrium towards the protonated 192-MCH⁺.

Scheme 62

(left box) Proposed mechanism of basic hydrolysis of MC [184]. (right box) Introduction of electron-donating groups to decrease the electrophilicity of the double bond [–185].

Scheme 63

Photochemical interconversion of naphthopyran 194 (top) and spirooxazine 195 (bottom) photoswitches from the closed to the open forms and thermal or light-induced ring closure. TC = transoid–cis, TT = transoid–trans isomers of the open naphthopyran species [–189].

Scheme 64

Synthesis of spiropyrans and spirooxazines 198 and the dicondensation by-product 199.

Scheme 65

Alternative synthesis of spiropyrans and spirooxazines with indolenylium salt 200.

Scheme 66

Synthesis of 4’-substituted spiropyrans 203 by condensation of an acylated methylene indoline 201 with a phenol derivative 202 (e.g., resorcin). R¹–R⁶ are arbitrary alkyl, aryl, or heteroaryl substituents [190].

Scheme 67

Synthesis of spironaphthopyrans 210 by acid-catalysed condensation of naphthols and diarylpropargyl alcohols [191].

Scheme 68

Photoswitchable surface wettability [194].

Figure 30

Some guiding principles for the choice of the most suitable photoswitch. Note that this guide is very general, and the properties can be tailored by choosing the right substitution pattern, concentration and medium, as discussed throughout the review. ^aTakes into account the effect of the substituent and the number of different positions that can bear substituents.