A co-registered molecular keypad lock for the generation of singlet oxygen

Abstract

A dithienylethene (DTE)-anthracene dicarboximide dyad was prepared by condensation of an amino-substituted photoswitch with 2,3-anthracenedicarboxylic anhydride. The asymmetrically substituted dyad also includes a pyridine moiety, which provides a handle for further post-synthetic modifications (e.g., the herein employed methylation). The methylated dyad can be photoswitched between the ring-open and ring-closed DTE forms in several cycles without noticeable fatigue, being the UV light-induced ring-closing much more efficient (Φ_o→c = 0.11) than the ring-opening at >550 nm light irradiation (Φ_c→o = 0.005). On the one hand, the ring-open form of the dyad shows significant blue fluorescence of the electronically-decoupled anthracene dicarboximide chromophore (λ_f = 427 nm, Φ_f = 0.19). However, this emission is quantitatively quenched by a highly efficient FRET process in the closed form of the dyad. On the other hand, the open form of the dyad also shows sufficient excited triplet-state population and subsequent sensitization of singlet-oxygen (¹O₂) formation (Φ_Δ = 0.21), which again is completely deactivated for the closed form of the DTE. The thus achieved dual light-control of ¹O₂ formation can be interpreted as a molecular keypad lock and provides an interesting additional layer of functionality of ¹O₂ photosensitizers (PSs). The concomitant observation of fluorescence enables the co-registered operation of the molecular device.

---

Introduction

The use of light to exert stimulus-controlled functions is particularly appealing due to its spatiotemporal character.¹ In this context photoswitches are especially valuable tools, enabling to toggle in a reversible manner between different states with contrasting structural and electronic properties.^2–5 This potential has been capitalized in a broad range of applications, including biological contexts, catalysis, information processing and storage, or materials science.^6–18

One particular field of interest is the external control of the action of singlet-oxygen (¹O₂) photosensitizers (PSs), with potential benefits for a more selective mode of action.^19–24 When integrating photoswitches and PSs in molecular devices, it is possible to exert reversible ON/OFF sequences of ¹O₂ generation.^25–30 This is based on the ability of one of the forms of the photoswitch to act as quencher of the excited singlet state of the PS, thereby inhibiting all follow-up processes. This includes the formation of excited triplet states by intersystem crossing (ISC) and in ultimate consequence energy transfer to triplet molecular oxygen (³O₂), leading to the formation of ¹O₂. In such setting, the formation of ¹O₂ can be controlled in a double manner: by light of wavelength λ₁ that activates the photoswitch and another photonic stimulus at λ₂ that triggers the PS itself (see Fig. 1a).^26,31 The action of the photoswitch provides an additional layer of control and potentially enhances the spatially confined selectivity of ¹O₂ formation, which may be of interest in photodynamic therapy, antibacterial treatments, or oxidative organic transformations.^28,32,33

Fig. 1 Photochemical control of singlet oxygen formation and photoisomerization of 1. (a) Schematic Jablonski diagrams demonstrating the interplay between excited state pathways in the different forms of the photoswitch. (b) Structures of the open (1o) and closed form (1c) of the herein investigated dyad.

Among the various families of photoswitches that can be potentially employed for the outlined purposes are hemithioindigos, azobenzenes, spiropyrans, and dithienylethenes (DTEs).^26,28–30 Especially the latter stand out for their robust and all-photonic modus operandi. When combined with a PS, DTEs can modulate Förster resonance energy transfer (FRET) processes upon light irradiation,^34,35 providing a dynamic way to regulate ¹O₂ formation. This was shown for intermolecular cocktail approaches, molecular dyads, and metal–organic frameworks that incorporate DTE and PS.^{31–33,36–40} A large dynamic range of ON/OFF switching, meaning that practically only one of the photoswitch forms enables ¹O₂ formation, is highly desirable. This requires a stringent molecular and photophysical design of the FRET process and the implicated energy donor–acceptor pair.

It is noteworthy that for many reported systems the control of ¹O₂ production instead occurs partially, being generally described in qualitative terms. This limitation arises from the coexistence of multiple excited-state pathways, mainly FRET and photoinduced electron transfer (PeT), whose individual contributions are difficult to disentangle. As a result, establishing predictive relationships between molecular design and the associated photochemical performance remains a worthwhile objective. Herein we address this challenge by introducing a DTE-anthracene dicarboximide dyad (1, see Fig. 1b) that showcases clear-cut binary “all-or-nothing” switching of ¹O₂ generation and the fluorescence of the PS. Although the parallel involvement of PeT is thermodynamically plausible, based on conservative estimates, the observed trend in ¹O₂ formation consistently tracks FRET, providing a framework for the rational light-induced control of photosensitization.

Furthermore, the use of multiple light-input signals and the all-photonic switching of the DTE provide a means to implement the molecular design with the function of a keypad lock, where the order of application of the light inputs matters decisively for the binary value (i.e., 0 or 1) of the functional output.^41–44 This usefully complements earlier works by the Akkaya group, who demonstrated the photosensitized formation of ¹O₂ in dependence on AND logical operations with chemical and photonic inputs.^45–48 In addition, the dyad partitions the decay of the excited singlet state between radiative “fluorescent” deactivation and triplet state population via ISC.⁴⁹ This enables the co-registration of ¹O₂ formation via the detection of fluorescence and establishes a “report-and-release” protocol.⁵⁰

Results and discussion

Design and synthesis

The design of compound 1 is based on a perfluorinated DTE core due to its higher stability compared to fluorine-free analogues.⁵¹ One arm of the DTE was functionalized with an anthracene dicarboximide unit, serving as the PS. Both functional units are connected through a benzyl spacer to ensure electronic decoupling. The other arm was substituted with a pyridine moiety to potentially allow the post-functionalization of the dyad, for instance by the S_N2 Menshutkin reaction with alkyl halides,⁵² coordination with transition metals,⁵³ or via Zincke reactions for solid-phase synthesis of peptides,⁵⁴ thereby broadening its application spectrum. In this work, the straightforward methylation was chosen to demonstrate the ease of such modifications.

DTE 1 was prepared according to the synthetic route shown in Scheme 1. The central building block DTE-I₂ was obtained by following a published procedure, starting from 2-methylthiophene.⁵⁵ Subsequent functionalization involved two sequential Pd(PPh₃)₄-catalyzed Suzuki coupling reactions. First, DTE-I₂ was reacted with one equivalent of 4-pyridinylboronic acid, providing the mono-substituted A1 in 30% yield. A second coupling reaction with one equivalent of 4-(aminomethyl)phenylboronic acid pinacol ester hydrochloride was performed in the presence of the XPhos ligand, affording the product A2 in 45% yield. The free amine group of DTE A2 was then condensed with 2,3-anthracenedicarboxylic anhydride. The resulting compound A3 was obtained in 36% yield. Finally, methylation of the pyridine moiety using methyl iodide afforded photoswitch 1 in 56% yield. For comparative studies, the model compound 2 was synthesized by direct methylation of A1 with methyl iodide. Additionally, the anthracene dicarboximide 3 was prepared by condensation of 2,3-anthracenedicarboxylic anhydride with benzylamine and used as a model chromophore in this study. The new products were characterized by ¹H, ¹³C, and ¹⁹F NMR spectroscopy, gCOSY and gHSQC experiments, and high-resolution mass spectrometry (see SI).

Scheme 1 Synthesis of 1, 2, and 3. Reagents and conditions: (i) Pd(PPh₃)₄, Na₂CO₃, 4-pyridinylboronic acid, DME, H₂O, 90 °C. (ii) Pd(PPh₃)₄, Na₂CO₃, 4-(aminomethyl)phenylboronic acid pinacol ester hydrochloride, XPhos, DME, H₂O, 90 °C.; (iii) 2,3-anthracenedicarboxylic anhydride, EtOH, reflux; (iv) methyl iodide, DCM, rt; (v) EtOH, reflux. The chemical yield for each reaction is provided below the corresponding compound number in the scheme. All DTE-containing compounds were obtained in their open form and are shown like this.

Photochemistry

The most important photochemical and photophysical data of the herein investigated compounds are compiled in Table 1. The qualitative inspection of the UV/vis absorption spectra of the open and closed forms of 1 (i.e., 1o and 1c, respectively) and the two model compounds 2 and 3 reveals the presence of both chromophores in dyad 1 (Fig. 2a). Furthermore, for 1o the absorption spectrum corresponds to the sum of the spectra of the ring-open model DTE 2o and 3 (Fig. 2a). This suggests that both chromophores are electronically decoupled by the benzyl bridge in the dyad, as was intended in the design approach. However, for 1c there is a significant deviation of the long-wavelength absorption maximum in comparison to the ring-closed model DTE 2c, which manifests in a difference of 37 nm. This is likely due to the acceptor₁–π–acceptor₂ character of 1c, where the closed DTE core serves as π-bridge.

Fig. 2 (a) UV/vis absorption spectra of 1o (magenta), 1c (green), 2o (black), 2c (red), and 3 (blue) in acetone (all at 10 µM). (b) UV/vis absorption spectra of 2o (black), 2c (red), and emission spectrum of 3 (blue dashed line) in acetone. These spectra are shown separately for a better appreciation of the spectral overlap between the anthracene dicarboximide emission and the UV/vis absorption of the DTE core for 2c, but not for 2o. This clear-cut differentiation of spectral overlap leads to the observed “all or nothing” FRET process in dependence on the isomerization state of the DTE.

Table 1 Photophysical and photochemical properties of the compounds 1–3 in air-equilibrated acetone solutions

	λabs (nm) [ε(M^−1 cm^−1)]	Φo→c ^a	Φc→o ^b	λf (nm)	Φf ^c	τf (ns)^d	ΦΔ (^1O2)^e
a Determined by actinometry with potassium trioxalatoferrate(III) trihydrate (K3Fe(C2O4)3 × 3 H2O); 20% error; ref. 56 and 57.b Determined by actinometry with 1,2-bis(2,4-dimethyl-5-phenyl-3-thienyl)-3,3,4,4,5,5-hexafluoro-1-cyclopentene; 20% error; ref. 58 and 59.c Fluorescence quantum yield (excitation of the anthracene dicarboximide chromophore at 403 nm), determined with an integrating sphere; 10% error.d Fluorescence lifetime, measured by time-correlated single-photon-counting; 5% error. In parentheses the relative weight of each lifetime component is given, when multi-exponential decay was observed.e Efficiency of ^1O2 formation (25% error) determined with Rose Bengal as standard; ref. 60.f The minor fluorescence that is detected for 1c is ascribed to a residual amount of 1o in the photostationary state.g No formation of ^1O2 was observed.h The molar absorption coefficient ε for the closed form 2c is corrected for the presence of a minor amount of 2o (4%) in the photostationary state.
1o	350 [29 900]	0.11		427, 444	0.19	3.23 (89%)	0.21
	403 [7100]					6.00 (11%)
1c	350 [20 500]		0.005		^f		^g
	405 [18 500]
	653 [18 300]
2o	348 [27 600]	0.70
2c	385 [10 500]^h		0.011
	616 [14 800]^h
3	381 [5800]			431, 454	0.35	7.17 (100%)	0.58
	403 [6600]

---

The colorless 1o presents UV/vis absorption maxima at 350 and 403 nm. Upon irradiation at 365 nm (ca. 80% of the light is absorbed by the DTE core), a 6π electrocyclization reaction occurs, yielding the blue-colored 1c with absorption maxima at 350, 405, and 653 nm (Fig. 3a). Furthermore, an isosbestic point at 375 nm was observed, suggesting a clean photochemical transformation without significant formation of secondary byproducts. The selective irradiation of 1c with visible light (>550 nm) regenerates 1o (Fig. 3b). Both photoswitching processes proceed with virtually quantitative transformation (100% pure isomer in the respective photostationary states), as determined by ¹H NMR spectroscopy (see the SI). DTE 1 can be switched multiple times by alternating UV- and visible-light irradiation, exhibiting high fatigue resistance (Fig. 3d).

Fig. 3 UV/vis absorption spectra (top) and corresponding kinetic plots (insets) of DTE 1 (10 µM) in acetone. (a) ring closure by irradiation at 365 nm, (b) ring opening by irradiation at >550 nm; (c) emission spectra for excitation at 375 nm (black 1o, red 1c); (d) vis absorption (at 653 nm) and emission (at 444 nm) in repeated switching cycles (green – vis absorption, blue – emission).

The photocyclization quantum yield (Φ_o→c) of 1o at 365 nm excitation was determined using the ferrioxalate actinometer,^56,57 yielding a value of 0.11. The cycloreversion quantum yield (Φ_c→o) for irradiation at 580 nm is much smaller, with a value of 0.005, as determined with the DTE derivative 1,2-bis(2,4-dimethyl-5-phenyl-3-thienyl)-3,3,4,4,5,5-hexafluoro-1-cyclopentene.^58,59 It is noteworthy that compared with the model DTE 2o (Φ_o→c = 0.70), the photocyclization quantum yield is much lower for 1o. We assign this tentatively to the occurrence of competing excited-state processes of the DTE moiety in 1o, such as PeT involving the strongly electron-accepting anthracene dicarboximide or the methylpyridinium; see SI.⁶¹ In line with this assumption is the observation that in the more polar acetonitrile Φ_o→c drops even further to 0.07.

Fluorescence properties and energy transfer

The excitation of the anthracene dicarboximide chromophore produces an intense blue emission with two maxima at 427 and 444 nm (see Fig. 3c) and an emission quantum yield of Φ_f = 0.19 (see Table 1 for all fluorescence properties). Due to the electronic decoupling between both chromophoric moieties, the emission of 1o originates exclusively from the anthracene dicarboximide. The corresponding excitation spectrum, monitoring the blue emission, shows solely the features of the anthracene dicarboximide chromophore, including its typical fine structure. In addition, the model anthracene dicarboximide 3 yields quite identical fluorescence emission (Table 1 and Fig. 2b) and excitation spectra. Interestingly, the fluorescence quantum yield of 3 (Φ_f = 0.35) is nearly twice the value of the one observed for 1o. The trend of the quantum yields is paralleled by the fluorescence lifetimes [3.23 ns for 1o versus 7.17 ns for 3], pointing to very comparable radiative rate constants of the individual fluorophore 3 and when integrated in the dyad 1o. Hence, the inherent radiative properties are conserved in 1o and differences in fluorescence relate to the occurrence of additional non-radiative deactivation (e.g., PeT) in the dyad.

As noted for the reduced photocyclization quantum yield of 1o (see above), the observed fluorescence quenching [comparing 1o and 3; Q = (1 − Φ_f(1o)/Φ_f(3)) × 100%] hints on the occurrence of competing intramolecular excited state pathways, i.e., PeT from the DTE core to the excited singlet-state anthracene dicarboximide; see SI. As a matter of fact, while the fluorescence quenching Q amounts to 46% in acetone, it is further accentuated in the more polar solvent acetonitrile (Q = 60%).

The closed form 1c shows further quenching and exhibits only very residual fluorescence, which moreover is attributed to a very minor content of 1o in the photostationary state. In fact, the quantitative fluorescence quenching in 1c is related to a highly efficient Förster resonance energy transfer (FRET) from the excited singlet anthracene dicarboximide to the ring-closed DTE core.⁶² The occurrence of FRET in 1c is experimentally substantiated by the fact that the fluorescence of the anthracene dicarboximide donor and the absorption of the ring-closed DTE acceptor overlap to a considerable degree (J_{dipole–dipole} = 1.0 × 10⁻¹¹ cm⁶ mol⁻¹). The calculation of the critical FRET radius R₀ (see SI), which is the donor–acceptor distance for which 50% FRET efficiency is expected, yielded a value of 41 Å. The actual donor–acceptor distance (R) was approximated by simple MM2 force-field modeling of the molecular structure of 1c, yielding a value of about 14 Å. Based on these data the theoretically expected Φ_FRET amounts to practically 1, coinciding with the experimental observation of virtually quantitative fluorescence quenching. It is noteworthy that for 1o no FRET quenching applies due to the absence of absorbance of the DTE core (model 2o) at wavelengths longer than 400 nm (Fig. 2b), yielding a zero spectral overlap with the anthracene dicarboximide fluorescence spectrum.

Generation of ¹O₂

The fluorescence quantum yield of the anthracene dicarboximide moiety in 1o points to the fact that a significant part (ca. 81%) of the excited singlet state decays non-radiatively. One quenching pathway is the abovementioned possibility of PeT. Akin to other anthracene derivatives, we infer the parallel involvement of the formation of excited triplet states via ISC. The excited triplet state may then be quenched by oxygen and lead to the energy-transfer sensitized formation of ¹O₂. Indeed, upon excitation of 1o at 419 nm, addressing selectivity the anthracene dicarboximide part, the typical near-infrared (NIR) phosphorescence of ¹O₂ with a maximum at 1275 nm was detected (Fig. 4). This provides unambiguous evidence for the capacity of 1o to act as PS. The overall quantum yield for ¹O₂ formation was determined as Φ_Δ = 0.21. Performing the same experiment with the previously ring-closed dyad, that is, with 1c, showed no sign of ¹O₂ phosphorescence (Fig. 4). Upon visible-light irradiation, the system reverted to the open form 1o with full recovery of ¹O₂ generation capability. This process can be repeated without notable fatigue, as herein demonstrated for five cycles (inset of Fig. 4). The incapacity of 1c to act as PS is reasoned with the quenching of the excited singlet state of the anthracene dicarboximide by FRET (see above),⁶² which consequently disables the population of the excited triplet state and ultimately the observation of ¹O₂ formation. The quantum yield for ¹O₂ formation of 1o is lower than that of model 3 (Φ_Δ = 0.58). Due to the plausible competition of PeT with the other S₁ deactivation channels (among them ISC and T₁ population) of the anthracene dicarboximide moiety in 1o, less T₁ state is formed, which directly translates into reduced ¹O₂ formation as compared to 3.

Fig. 4 ¹O₂ phosphorescence spectra upon excitation of 1o (black line) or 1c (red line) at 419 nm; [1] = 10 µM. The inset shows the corresponding variations of emission intensity of singlet oxygen upon five photoswitching cycles, toggling between 1o and 1c by alternating irradiation at 365 nm and at >550 nm.

Molecular keypad lock

The photoswitching of 1 and the resulting modulation of its capability to photosensitize the formation of ¹O₂ can be interpreted in the context of molecular logic operations.^42–44 Starting with the dyad in its closed form 1c and choosing photonic signals as inputs In (In₁: irradiation at >550 nm; In₂: irradiation at 419 nm), the following Boolean logic can be realized (Table 2). No light irradiation (In₁ = In₂ = 0) leaves the dyad in the 1c state and no ¹O₂ formation is observed (Out₁ = 0). The irradiation at >550 nm (In₁ = 1) leads to ring opening (1o), but in the absence of the excitation of the anthracene dicarboximide (In₂ = 0) the output signal remains in the binary 0 state. Because of the described FRET, the same lack of ¹O₂ formation is observed for the excitation of the anthracene dicarboximide (In₂ = 1) of 1c, in the absence of irradiation at >550 nm (In₁ = 0). Only if both photonic input signals are activated (In₁ = In₂ = 1) ¹O₂ could be in principle generated. However, this is only the case (Out₁ = 1) if the inputs are applied in the sequential order In₁ first (1c → 1o) and then In₂. If this input order is reversed (In₂ before In₁) only the formation of 1o results, but no ¹O₂ is generated (Out₁ = 0). In addition, the same observations relate to the generation of fluorescence (see Table 2), which is only observed for 1o. This constitutes a case of a co-registered logic gate operation.⁵⁰

Table 2 Commented truth table for the all-photonic molecular keypad operation of 1c

In1 (>550 nm)	In2 (419 nm)	Out1 (^1O2)	Out2 (fluo)	Chemical observation
a Although the excitation at 419 nm may also directly address the ring-closed DTE chromophore, the quantum yield of the ring opening is effectively too small to yield sufficient amounts of 1o.
0	0	0	0	No photoprocesses
1	0	0	0	Only 1c → 1o
0	1^a	0	0	Quenching of ^1O2 formation in 1c
1 (2^nd)	1 (1^st)	0	0	Quenching of ^1O2 formation in 1c and subsequent 1c → 1o
1 (1^st)	1 (2^nd)	1	1	First 1c → 1o and subsequent unquenched photosensitized ^1O2 formation by 1o

---

This overall logic behavior is coincident with a 2-input priority AND gate (2-PAND), a simple representation of a keypad lock.⁴⁴ It is noteworthy, that the input and output signals are all of photonic nature. In addition, the reversibility and high fatigue resistance of the photoswitching enable the recyclable operation of this molecular keypad lock. Furthermore, by application of 365 nm light the dyad can be conveniently reset to the initial state (1o → 1c).

Conclusion

The meticulous photophysical design of the dithienylethene (DTE)-anthracene dicarboximide dyad 1 enabled the clear-cut and robust photoswitching of “all-or-nothing” ¹O₂ formation. This was enabled by the exclusive occurrence of FRET for the closed form of the photoswitch, while the open form showed zero spectral overlap between DTE absorption and anthracene dicarboximide PS emission. The dual light control of singlet-oxygen formation provides an additional layer of functionality to the action of PSs, potentially leading to increased selectivity. Further, it was shown that the dyad can be operated in a way so that a specific order of light inputs is required to observe singlet oxygen and fluorescence as outputs, akin to the function of a molecular co-registered 2-input priority AND gate or keypad lock.

Author contributions

J. C.-W.: investigation, formal analysis, validation, writing – original draft, writing – review & editing; J. A. G.-D.: investigation, writing – review & editing; U. P.: conceptualization, resources, funding acquisition, supervision, writing – review & editing.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information is available. See DOI: https://doi.org/10.1039/d6qo00295a.

Acknowledgements

This work was supported by the Spanish Ministry of Science, Innovation, and Universities (MCIU/AEI/10.13039/501100011033) and the European Regional Development Fund ERDF (grants PID2020-119992GB-I00 and PID2023-152556NB-I00). J. C.-W. was contracted through the EIC PATHFINDER project 101098934 – 4for2 (EISMEA – European Innovation Council and SMEs Executive Agency).

References

1. C. Brieke, F. Rohrbach, A. Gottschalk, G. Mayer and A. Heckel, Light–controlled tools, Angew. Chem., Int. Ed., 2012, 51, 8446–8476.
2. B. L. Feringa and W. R. Browne, Molecular switches, John Wiley & Sons, New York, USA, 2011.
3. A. Goulet-Hanssens, F. Eisenreich and S. Hecht, Enlightening materials with photoswitches, Adv. Mater., 2020, 32, 1905966.
4. M. M. Russew and S. Hecht, Photoswitches: from molecules to materials, Adv. Mater., 2010, 22, 3348–3360.
5. J. Volarić, W. Szymanski, N. A. Simeth and B. L. Feringa, Molecular photoswitches in aqueous environments, Chem. Soc. Rev., 2021, 50, 12377–12449.
6. Y. Yokoyama, Fulgides for memories and switches, Chem. Rev., 2000, 100, 1717–1740.
7. H. D. Bandara and S. C. Burdette, Photoisomerization in different classes of azobenzene, Chem. Soc. Rev., 2012, 41, 1809–1825.
8. M. Irie, T. Fukaminato, K. Matsuda and S. Kobatake, Photochromism of diarylethene molecules and crystals: memories, switches, and actuators, Chem. Rev., 2014, 114, 12174–12277.
9. R. Klajn, Spiropyran-based dynamic materials, Chem. Soc. Rev., 2014, 43, 148–184.
10. M. M. Lerch, S. J. Wezenberg, W. Szymanski and B. L. Feringa, Unraveling the photoswitching mechanism in donor–acceptor Stenhouse adducts, J. Am. Chem. Soc., 2016, 138, 6344–6347.
11. C. Petermayer and H. Dube, Indigoid photoswitches: visible light responsive molecular tools, Acc. Chem. Res., 2018, 51, 1153–1163.
12. F. G. Blandón-Cumbreras, M. Villabona, J. Osmólska, E. F. Petrusevich, D. B. Guzmán Ríos, R. Zaleśny, J. Olesiak-Bańska, J. Hernando and U. Pischel, Photoswitching of the two-photon absorption of donor-acceptor substituted dithienylethenes, ChemistryEurope, 2025, 3, e202500072.
13. M. Villabona, S. Wiedbrauk, F. Feist, G. Guirado, J. Hernando and C. Barner-Kowollik, Dual-wavelength gated oxo-diels-alder photoligation, Org. Lett., 2021, 23, 2405–2410.
14. G. Cabré, A. Garrido-Charles, M. Moreno, M. Bosch, M. Porta-de-la-Riva, M. Krieg, M. Gascón-Moya, N. Camarero, R. Gelabert and J. M. Lluch, Rationally designed azobenzene photoswitches for efficient two-photon neuronal excitation, Nat. Commun., 2019, 10, 907.
15. R. Castagna, G. Maleeva, D. Pirovano, C. Matera and P. Gorostiza, Donor–acceptor stenhouse adduct displaying reversible photoswitching in water and neuronal activity, J. Am. Chem. Soc., 2022, 144, 15595–15602.
16. Z. Wang, H. Hölzel and K. Moth-Poulsen, Status and challenges for molecular solar thermal energy storage system based devices, Chem. Soc. Rev., 2022, 51, 7313–7326.
17. E. Siemes, O. Nevskyi, D. Sysoiev, S. K. Turnhoff, A. Oppermann, T. Huhn, W. Richtering and D. Wöll, Nanoscopic visualization of cross–linking density in polymer networks with diarylethene photoswitches, Angew. Chem., Int. Ed., 2018, 57, 12280–12284.
18. F. Li, M. Li, Y. Shi, X. Bian, N. Lv, S. Guo, Y. Wang, W. Zhao and W.-H. Zhu, Single-visible-light performed STORM imaging with activatable photoswitches, Chem. Sci., 2025, 16, 14270–14277.
19. X. J. Jiang, J. T. Lau, Q. Wang, D. K. Ng and P. C. Lo, pH–and thiol–responsive BODIPY–based photosensitizers for targeted photodynamic therapy, Chem. – Eur. J., 2016, 22, 8273–8281.
20. A. M. Polgar and Z. M. Hudson, Thermally activated delayed fluorescence materials as organic photosensitizers, Chem. Commun., 2021, 57, 10675–10688.
21. M. Liu and C. Li, Recent advances in activatable organic photosensitizers for specific photodynamic therapy, ChemPlusChem, 2020, 85, 948–957.
22. X. Li, S. Kolemen, J. Yoon and E. U. Akkaya, , Activatable photosensitizers: agents for selective photodynamic therapy, Adv. Funct. Mater., 2017, 27, 1604053.
23. Y. Wang, G. Wei, X. Zhang, F. Xu, X. Xiong and S. Zhou, A step-by-step multiple stimuli-responsive nanoplatform for enhancing combined chemo-photodynamic therapy, Adv. Mater., 2017, 29, 1605357.
24. E. Nestoros, A. Sharma, E. Kim, J. S. Kim and M. Vendrell, Smart molecular designs and applications of activatable organic photosensitizers, Nat. Rev. Chem., 2025, 9, 46–60.
25. Y. Xu, Y. Tang and Q. Li, Visible–and near–infrared light–driven molecular photoswitches for biological applications, Adv. Funct. Mater., 2024, 22, 2416359.
26. S. K. Bag, A. Pal, S. Jana and A. Thakur, Recent advances on diarylethene–based photoswitching materials: applications in bioimaging, controlled singlet oxygen generation for photodynamic therapy and catalysis, Chem. – Asian J., 2024, 19, 202400238.
27. M. J. Fuchter, On the promise of photopharmacology using photoswitches: a medicinal chemist's perspective, J. Med. Chem., 2020, 63, 11436–11447.
28. W. Piao, K. Hanaoka, T. Fujisawa, S. Takeuchi, T. Komatsu, T. Ueno, T. Terai, T. Tahara, T. Nagano and Y. Urano, Development of an azo-based photosensitizer activated under mild hypoxia for photodynamic therapy, J. Am. Chem. Soc., 2017, 139, 13713–13719.
29. J. Ji, X. Li, T. Wu and F. Feng, Spiropyran in nanoassemblies as a photosensitizer for photoswitchable ROS generation in living cells, Chem. Sci., 2018, 9, 5816–5821.
30. J. Wang, J. Wei, Y. Leng, Y. Dai, C. Xie, Z. Zhang, M. Zhu and X. Peng, Rational design of high-performance hemithioindigo-based photoswitchable AIE photosensitizer and enabling reversible control singlet oxygen generation, Biosensors, 2023, 13, 324–335.
31. N. Sun, Y. Jin, H. Wang, B. Yu, R. Wang, H. Wu, W. Zhou and J. Jiang, Photoresponsive covalent organic frameworks with diarylethene switch for tunable singlet oxygen generation, Chem. Mater., 2022, 34, 1956–1964.
32. Z. Li, S. Chen, Y. Huang, H. Zhou, S. Yang, H. Zhang, M. Wang, H. Guo and J. Yin, Photoswitchable AIE photosensitizer for reversible control of singlet oxygen generation in specific bacterial discrimination and photocontrolled photodynamic killing of bacteria, Chem. Eng. J., 2022, 450, 138087.
33. S. K. Bag, B. Mondal, M. Karmakar, S. Das, A. Patra and A. Thakur, Controlled photooxidation via singlet oxygen generation by triplet harvesting in a heavy atom free pure organic dithienylethene–naphthalene diimide, Chem. – Eur. J., 2024, 30, 202401562.
34. T. Fukaminato, T. Sasaki, T. Kawai, N. Tamai and M. Irie, Digital photoswitching of fluorescence based on the photochromism of diarylethene derivatives at a single-molecule level, J. Am. Chem. Soc., 2004, 126, 14843–14849.
35. F. M. Raymo and M. Tomasulo, Electron and energy transfer modulation with photochromic switches, Chem. Soc. Rev., 2005, 34, 327–336.
36. J. Park, D. Feng, S. Yuan and H. C. Zhou, Photochromic metal-organic frameworks: reversible control of singlet oxygen generation, Angew. Chem., Int. Ed., 2015, 52, 11364–11368.
37. J. Ma, X. Cui, F. Wang, X. Wu, J. Zhao and X. Li, Photoswitching of the triplet excited state of diiodobodipy-dithienylethene triads and application in photo-controllable triplet-triplet annihilation upconversion, J. Org. Chem., 2014, 79, 10855–10866.
38. G. Liu, X. Xu, Y. Chen, X. Wu, H. Wu and Y. Liu, A highly efficient supramolecular photoswitch for singlet oxygen generation in water, Chem. Commun., 2016, 52, 7966–7969.
39. L. Hou, X. Zhang, T. C. Pijper, W. R. Browne and B. L. Feringa, Reversible photochemical control of singlet oxygen generation using diarylethene photochromic switches, J. Am. Chem. Soc., 2014, 136, 910–913.
40. T. M. Khang, P. Q. Nhien, T. T. K. Cuc, C. C. Weng, C. H. Wu, J. I. Wu, B. T. B. Hue, Y. K. Li and H. C. Lin, Dual and sequential locked/unlocked photochromic effects on FRET controlled singlet oxygen processes by contracted/extended forms of diarylethene–based [1] rotaxane nanoparticles, Small, 2023, 19, 2205597.
41. U. Pischel, Chemical approaches to molecular logic elements for addition and subtraction, Angew. Chem., Int. Ed., 2007, 46, 4026–4040.
42. J. Andréasson and U. Pischel, Molecules with a sense of logic: a progress report, Chem. Soc. Rev., 2015, 44, 1053–1069.
43. J. Andréasson and U. Pischel, Smart molecules at work-mimicking advanced logic operations, Chem. Soc. Rev., 2010, 39, 174–188.
44. J. Andréasson and U. Pischel, Molecules for security measures: from keypad locks to advanced communication protocols, Chem. Soc. Rev., 2018, 47, 2266–2279.
45. S. Ozlem and E. U. Akkaya, Thinking outside the silicon box: molecular and logic as an additional layer of selectivity in singlet oxygen generation for photodynamic therapy, J. Am. Chem. Soc., 2009, 131, 48–49.
46. S. Erbas-Cakmak and E. U. Akkaya, Cascading of molecular logic gates for advanced functions: a self–reporting, activatable photosensitizer, Angew. Chem., Int. Ed., 2013, 52, 11364–11368.
47. S. Erbas-Cakmak, F. P. Cakmak, S. D. Topel, T. B. Uyar and E. U. Akkaya, Selective photosensitization through an AND logic response: optimization of the pH and glutathione response of activatable photosensitizers, Chem. Commun., 2015, 51, 12258–12261.
48. I. S. Turan, G. Gunaydin, S. Ayan and E. U. Akkaya, Molecular demultiplexer as a terminator automaton, Nat. Commun., 2018, 9, 805.
49. R. Campos-González, P. Vázquez-Domínguez, P. Remón, F. Nájera, D. Collado, E. Pérez-Inestrosa, F. Boscá, A. Ros and U. Pischel, Bis-borylated arylisoquinoline-derived dyes with a central aromatic core: towards efficient fluorescent singlet-oxygen photosensitizers, Org. Chem. Front., 2022, 9, 4250–4259.
50. G. Ur, J. Axthelm, P. Hoffmann, N. Taye, S. Glaeser, H. Goerls, S. L. Hopkins, W. Plass, U. Neugebauer and S. Bonnet, Co-registered molecular logic gate with a CO-releasing molecule triggered by light and peroxide, J. Am. Chem. Soc., 2017, 139, 4991–4994.
51. M. Herder, B. M. Schmidt, L. Grubert, M. Pätzel, J. Schwarz and S. Hecht, Improving the fatigue resistance of diarylethene switches, J. Am. Chem. Soc., 2015, 137, 2738–2747.
52. N. Menschutkin, Beiträge zur Kenntnis der Affinitätskoeffizienten der Alkylhaloide und der organischen Amine, Z. Phys. Chem., 1890, 5, 589–600.
53. S. Pal, Pyridine: a useful ligand in transition metal complexes, Pyridine, 2018, 57, 57–74.
54. P. Corton, P. Novo, V. Lopez-Sobrado, M. D. Garcia, C. Peinador and E. Pazos, Solid-phase Zincke reaction for the synthesis of peptide-4,4′-bipyridinium conjugates, Synthesis, 2020, 537–543.
55. N. Sun, C. Wang, H. Wang, X. Gao and J. Jiang, Photonic switching porous organic polymers toward reversible control of heterogeneous photocatalysis, ACS Appl. Mater. Interfaces, 2020, 12, 56491–56498.
56. C. Hatchard and C. A. Parker, A new sensitive chemical actinometer-II. Potassium ferrioxalate as a standard chemical actinometer, Proc. R. Soc. London, Ser. A, 1956, 235, 518–536.
57. H. Kuhn, S. Braslavsky and R. Schmidt, Chemical actinometry, Pure Appl. Chem., 1989, 61, 187–210.
58. T. Sumi, Y. Takagi, A. Yagi, M. Morimoto and M. Irie, Photoirradiation wavelength dependence of cycloreversion quantum yields of diarylethenes, Chem. Commun., 2014, 50, 3928–3930.
59. M. Roseau, V. De Waele, X. Trivelli, F. X. Cantrelle, M. Penhoat and L. Chausset-Boissarie, Azobenzene: a visible–light chemical actinometer for the characterization of fluidic photosystems, Helv. Chim. Acta, 2021, 104, 2100071.
60. R. W. Redmond and J. N. Gamlin, A compilation of singlet oxygen yields from biologically relevant molecules, Photochem. Photobiol., 1999, 70, 391–475.
61. J. Chen-Wu, D. B. Guzmán-Ríos, P. Remón, J. A. González-Delgado, A. J. Martínez-Martínez, F. Nájera, J. F. Arteaga and U. Pischel, Photofunctional scope of fluorescent dithienylethene conjugates with aza–heteroaromatic cations, Adv. Mater., 2023, 35, 2300536.
62. It can not be excluded that also PeT from the ring-closed DTE core to the excited singlet-state anthracene dicarboximide contributes to the observed quenching of fluorescence and ¹O₂ formation in 1c; see SI.

---