# Resonance-Enhanced Excited-State Intramolecular Proton Transfer Emission by Base-Mediated Formation of α-Cyano-γ-lactone

Théo Andris, Timothée Stoerkler, Gilles Ulrich, Pascal Retailleau, Adèle Laurent, Denis Jacquemin, Julien Massue

► To cite this version:

Théo Andris, Timothée Stoerkler, Gilles Ulrich, Pascal Retailleau, Adèle Laurent, et al., Resonance-Enhanced Excited-State Intramolecular Proton Transfer Emission by Base-Mediated Formation of α-Cyano-γ-lactone. Organic Letters, 2025, 27 (48), pp.13240-13245. 10.1021/acs.orglett.5c04134. hal-05395078

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# Resonance-Enhanced Excited-State Intramolecular Proton Transfer Emission by Base-Mediated Formation of α-Cyano-γ-lactone

Théo Andris, Timothée Stoerkler, Gilles Ulrich, Pascal Retailleau, Adèle D. Laurent, Denis Jacquemin,*
and Julien Massue*

<figure><img src="image_2.png" /></figure>

**ABSTRACT:** This article describes the synthesis, structural, photophysical and theoretical properties of novel fluorescent dyes derived from 2-(2'-hydroxyphenyl)benzoxazole, functionalized by tricyanofurane or α-cyano-γ-lactone groups, prone to undergo an excited-state intramolecular proton transfer (ESIPT) process. We serendipitously found out that tricyanofurane can induce the formation of the corresponding lactone in basic media, leading to a highly fluorescent derivative, owing to the formation of a merocyanine in the excited-state.

Excited-state intramolecular proton transfer (ESIPT) fluorescence relies on the presence of a strong intramolecular hydrogen bond embedded in 5- or 6-membered rings. ESIPT has been observed in a variety of organic scaffolds,¹ including 2-(2'-hydroxyphenyl)benzazole (HBX) derivatives.² Initiation of a proton transfer in the excited enol (E*) species provides an emissive tautomeric keto (K*) form presenting a lower-lying singlet state, leading to a pronounced Stokes shift, a trademark of ESIPT fluorescence (Figure 1a). The fluorescence of HBX dyes is commonly weak in solution, due to the presence of a low-lying conical intersection (CI), whose accessibility can be significantly reduced in the solid-state, leading to fluorescent solid-state devices.³ ESIPT-based lasers,⁴ light-emitting diodes,⁵ sensors,⁶ along with numerous luminescent displays,⁷ have been reported, benefiting from redshifted intense solid-state fluorescence. The search for Dual Solution-Solid Emission (DSSE)⁸ has been recently in the spotlight owing to the expanded range of applications targeted by a single family of dyes and ESIPT compounds stand out as very attractive in the quest for DSSE.⁹ Several strategies have been reported in order to decrease the non-radiative deactivation through the CI, and hence to increase the photoluminescent quantum yield (QY). Introduction of molecular rigidity¹⁰ or insertion of electron withdrawing groups¹¹ at key positions of the HBX scaffold are attractive options to boost the QY of the K⁺ transition in solution. On our part, we recently reported another strategy consisting in combining the ESIPT process with the induction of a subsequent electronic delocalization in the excited-state, by introducing proton-sensitive groups such as azaheterocycles at key positions of the HBX core and we evidenced the protonation-mediated formation of a highly emissive merocyanine species in solution.¹² Herein, we investigate the influence of negative mesomeric substituents in order to assess the possibility to induce such resonance-stabilized merocyanine-type excited species in the absence of external stimuli. We decided to turn to the tricyanofuran (TCF) group,

whose very large electron-withdrawing ability and electrophilicity have been used for the development of both near-infrared absorbing chromophores¹³ and red-emitting fluorophores.¹⁴ In the literature, TCF derivatives are typically obtained via Knoevenagel condensation between aromatic aldehydes and the exocyclic acidic methyl group of the commercially available Me-TCF.¹⁵ As a result, the large majority of TCF-containing fluorophores incorporate a vinyl spacer,¹³,¹⁵ with very few examples detailing the synthesis of aryl-TCF moieties.¹⁶ Those latter derivatives, typically synthesized through a reaction between α-ketols and an excess of malononitrile in pyridine, remain largely underexplored.¹⁷ In a combined effort to exemplify the synthetic approach to the aryl-TCF substitution and further study the stabilization of the excited-state formed after ESIPT, we report here the introduction of an aryl-TCF substituent on an HBO scaffold. During the course of our studies, we unexpectedly found the TCF group to be unstable in basic conditions and yield the corresponding α-cyano-γ-lactone through a nucleophilic attack of hydroxide ions (Figure 1b). While reported as a stable building block, the serendipitous hydrolysis of the TCF group into a lactone surprisingly afforded a much brighter derivative than the fluorophore initially expected, with an intense emission from the K⁺ form in a large range of solvents. In each case, the nature of the transitions observed was investigated using *ab initio* calculations.

<figure><img src="image_3.png" /></figure>
<caption>**Figure 1.** (a) Schematic representation of the resonance-enhanced stabilization of the K\* state and (b) Structure of **HBO-lactone** and **HBO-TCF**.</caption>

The synthesis of **HBO-lactone** and **HBO-TCF** is presented on Scheme 1. α-Ketol derivative **1**, whose synthesis is described in the experimental section in the ESI, was condensed with malononitrile in the presence of pyridine with catalytic amounts of acetic acid to form intermediate TCF-substituted bromoaryl **2** which was subsequently involved in a Suzuki-Miyaura cross-coupling reaction with **HBO-Bpin**¹² in classical conditions (5% mol. of Pd(II) in toluene/H₂O 9:1 in the presence of an excess of potassium phosphate). After purification, a single product was obtained which was not the expected TCF-substituted HBO but the corresponding α-cyano-γ-lactone, **HBO-lactone** in 81% yield. This compound was undoubtedly characterized with X-Ray diffraction on a single crystal. The synthesis was then modified in order to obtain the initial target. Derivative **1** was first involved in Suzuki-Miyaura cross-coupling with **HBO-Bpin** to yield α-ketol-substituted HBO **3** which was then condensed with malononitrile to provide **HBO-TCF** in 54% yield.

<figure><img src="image_4.png" /><figcaption>**Scheme 1.** Synthesis of **HBO-lactone** and **HBO-TCF**</figcaption></figure>

**HBO-TCF** was found to be perfectly stable in solution, as well as in powder, excluding an intrinsic instability of the fluorophore and pointing at the Suzuki-Miyaura coupling reagents for the *in situ* hydrolysis of the TCF group. Both **HBO-lactone** and **HBO-TCF** were obtained as single crystals and their structure investigated by X-Ray diffraction (Figure 2). Structural data and description can be found in the ESI.

<figure><img src="image_5.png" /><figcaption>**Figure 2.** ORTEP diagrams of (a) **HBO-lactone** and (b) **HBO-TCF** (right). C in grey, H in white with spheres of arbitrary radius, N in blue and O in red (or atoms are displayed with conventional colors) with thermal ellipsoids size of 50%.</figcaption></figure>

In order to shed more light on the lactone formation during the Suzuki coupling between **2** and **HBO-Bpin**, we conducted

additional experiments by gradually modifying the cross-coupling standard conditions (Table 1). The removal of Pd(II) catalyst, of the coupling partner **HBO-Bpin** or the suppression of both (entries 1-3) impeded the possibility of the cross-coupling to occur but led to the formation of the lactone **2'**, as a result of the hydrolysis of the TCF group in **2**. Despite the presence of water, no reaction was observed in the absence of base (K₃PO₄) confirming the need of a basic medium to provide hydroxide ions able of undergoing the nucleophilic attack on the TCF group to yield the lactone (entry 4). The nature of the base was then examined (entries 5-7) and led to various results. While the use of NaOH 1M led to the sole observation of **HBO-lactone** in 28% yield, cesium carbonate provided a mixture of both products and cesium fluoride did not seem to be basic enough to induce the hydrolysis of **HBO-TCF**, which was the only isolated product. The amount of phosphate ion needed was also evaluated (entries 8-9). The use of one equivalent of base led to the sole observation of **HBO-TCF**, highlighting the fact that the Suzuki-Miyaura coupling occurs prior to the TCF hydrolysis. In the absence of catalyst and coupling partner, lactone **2'** was easily formed in 83% yield with a small excess of phosphate (entry 9). Finally, at 25°C, no reaction occurs and the starting material **2** was recovered (entry 10).

<figure><img src="image_6.png" /><figcaption>**Table 1.** Variations from standard experimental conditions</figcaption></figure>

<table><thead><tr><th>Entry</th><th>Variations from standard conditions</th><th>Products obtained</th></tr></thead><tbody><tr><td>1</td><td>w/o Pd</td><td>2', 74%</td></tr><tr><td>2</td><td>w/o <b>HBO-Bpin</b></td><td>2', 74%</td></tr><tr><td>3</td><td>w/o <b>HBO-Bpin</b>, w/o Pd</td><td>2', 79%</td></tr><tr><td>4</td><td>w/o <b>HBO-Bpin</b>, w/o Pd, no base</td><td>2</td></tr><tr><td>5</td><td>Cs₂CO₃ as base</td><td><b>HBO-Lactone</b>, 38% and <b>HBO-TCF</b>, 25%</td></tr><tr><td>6</td><td>CsF as base</td><td><b>HBO-TCF</b>, 54%</td></tr><tr><td>7</td><td>NaOH 1M as base</td><td><b>HBO-Lactone</b>, 22%</td></tr><tr><td>8</td><td>1 eq of K₃PO₄</td><td><b>HBO-TCF</b>, 28%</td></tr><tr><td>9</td><td>w/o <b>HBO-Bpin</b>, w/o Pd, 1.5 eq of K₃PO₄</td><td>2', 83%</td></tr><tr><td>10</td><td>25°C</td><td>2</td></tr></tbody></table>

The photophysical properties of **HBO-lactone** and **HBO-TCF** were studied in ten solvents as well as in the solid-state. The photophysical data are compiled in Table S1, while absorption and emission spectra are presented in Figures S24-25 and 3, respectively.

<figure><img src="image_7.png" /></figure>
**Figure 3.** Emission spectra in solution of (a) **HBO-Lactone** and (b) **HBO-TCF**, along with (c) and (d) respective photographs of solutions under irradiation ($\lambda_{exc}$ = 365 nm).

In solution, **HBO-lactone** exhibit a lower-lying absorption band located between 343 and 350 nm with absorption coefficient $\varepsilon$ values between 6,900 and 29,500 $M^{-1}cm^{-1}$ (Figure S24). This band is not much affected by the nature of the solvent; a common trend in the HBO family.¹² As for **HBO-TCF**, its absorption band in solution appears to be significantly redshifted as compared to **HBO-lactone** ($\lambda_{abs}$ = 394-404 nm), a feature consistent with the extra delocalization and stronger electron-withdrawing provided by the TCF group (Figure S25). After photoexcitation in the S₀-S₁ band, both dyes exhibit fluorescence by the naked eye albeit to a very different extent.

**HBO-lactone** displays an intense single or dual emission in solution which is largely influenced by the nature of the solvent (Figure 3). In apolar aprotic (cyclohexane, toluene), and moderate polar aprotic such as chlorinated solvents (CCl₄, CH₂Cl₂) or ethers (Et₂O, THF), the emission wavelength spans a wide range of colors, from 424 to 590 nm with large QY going from 0.45 to 0.76. No decrease of the QY is observed when increasing the polarity of the solvent, a rare feature among push-pull dyes where the emission is typically significantly quenched when increasing the dielectric constant of the solvent. Shifting to polar aprotic or polar protic solvents (acetone, DMF, DMSO, EtOH) leads to a bathochromic shift of the fluorescence ($\lambda_{em}$ = 621 to 667 nm), with a marked decrease of emission intensity (QY = 0.02 to 0.09). The presence of a small shoulder in the high energies can be assigned to the E* transition in ESIPT fluorescence while the redshifted likely corresponds to the K* transition, occurring after ESIPT. Interestingly, in DMF, a dual emission at 496/658 nm is observed, with a QY value of 0.04. Owing to its strong dissociative nature, DMF has been reported to promote deprotonation in the excited state (D*), in lieu of ESIPT.¹⁸ In this present case, while the band at 496 nm can be ascribed to the E* band, the D* band could be the one observed at 658 nm, owing to a large stabilization of the excited state. As a general observation, **HBO-lactone** clearly stands out as compared not only to unsubstituted HBO but also to the large majority of HBX-based ESIPT dyes where the K⁺ radiative transition is both intrinsically weak, due to the presence of an accessible CI process, and weakly influenced by the polarity of the solvent. This photophysical behavior is reminiscent of reported ESIPT coupled ICT dyes where large Stokes shifts and QY are also observed.¹⁹ **HBO-TCF** displays a markedly different photophysical behavior (Figure 3). Although the maximum emission wavelength also spans most of the visible spectrum ($\lambda_{em}$ = 474-714 nm), multiple emission bands are observed which are difficult to ascribe, considering that the intensity of the emission is weak (QY in the range 0.01-0.09). These bands highlight a competition between K⁺ (ESIPT) and E* or D*, though the presence of random emissive aggregates cannot be ruled out. This marks a striking difference between the photophysical properties of **HBO-lactone** and **HBO-TCF**. In order to shed additional light on the nature of the excited species in both dyes, the Lippert-Mataga and the QY vs dielectric constants plots are presented on Figure 4. Both **HBO-lactone** and **HBO-TCF** present a linear correlation between the Stokes shifts and the polarizability, evidencing a polarized excited-

state in both cases. The excited-state lifetimes for **HBO-lactone** are in the ns timescale (0.2 to 3.2 ns), which is significantly shorter than those observed for typical CT-driven push-pull derivatives where alignments of dipole require additional time. For **HBO-lactone**, the strong dependency of the QY value to the dielectric constant of the solvents further highlights a resonance-stabilized ESIPT state in apolar aprotic and moderately polar protic solvents (Figure 4c).

Theoretical calculations were also performed to obtain some additional insights into the electronic properties of the various forms of both dyes (see the ESI for details, Cyclohexane, CH₂Cl₂ and DMF were selected as solvents).

<figure><img src="image_8.png" /><figcaption>**Figure 4.** (a) Lippert-Mataga plots for **HBO-lactone** and **HBO-TCF**, (b) QY vs dielectric constant plots, and hypothesis concerning the nature of the excited species in (c) apolar aprotic and moderately polar aprotic solvents and (d) polar or protic solvents.</figcaption></figure>

For vertical absorption, theory returns wavelengths of 333 and 371 nm for **HBO-lactone** and **HBO-TCF** in CH₂Cl₂, with a respective redshift of 38 nm, slightly inferior to the one observed experimentally (55 nm). The predicted solvatochromism is limited consistent with measurements. As can be seen from the Electronic Density Difference (EDD) plots, excitation induces a strong CT in both dyes, from the phenol towards the accepting group (Figure S26). From those plots, the charge separation can be estimated to reach 4.11 and 4.30 Å for **HBO-lactone** and **HBO-TCF**, respectively, which are large values confirming CT. Figure S26 also reveals that the hydroxy group of the phenol undergoes a significant drop of electronic density; a feature favorable for ESIPT. Nevertheless, in contrast to reported HBO derivatives⁹,¹⁰,¹²,²⁰ the density of the nitrogen atom of the benzoxazole group remains mostly unchanged upon absorption, suggesting that the relative stabilization of the K⁺ form could be more limited than in less decorated HBO derivatives.

For **HBO-lactone** in CH₂Cl₂, theory including CC2 corrections predicts vertical fluorescence at 451, 561, and 795 nm for the E*, K⁺, and D* transitions respectively. In that same solvent, the experimental fluorescence bands appear at 469 and 588 nm (Figure 2a and Table S2), and the band assign-
ment regarding the theoretical result is obvious: the former band corresponds to the enol form E*, and the later to the keto tautomer K'. We note that the ESIPT driving force is -0.09 eV, which is a moderate value, compatible with dual emission according to previous benchmarks.¹⁹ TD-DFT predicts excited-state dipoles of 25 and 32 D for the relaxed E* and K* forms, i.e., very large values. In cyclohexane and DMF the K* emission is respectively computed at 503 and 588 nm, indicating marked solvatofluorochromism. All these data fit experimental outcomes. For the D* species (in DMF), the 795 nm value is too redshifted as compared to the measurements at 658 nm, yet this corresponds to a 0.3 eV error, possible at this level of theory. As can be seen in Table S3, the theoretical estimates for D* are also strongly method-dependent.

For **HBO-TCF** in cyclohexane, we compute no driving force for ESIPT, and theory hints that the 514 nm emission likely comes from E* (computed at 478 nm, see Table S4). In CH₂Cl₂, the computed fluorescence wavelengths are significantly redshifted as compared to **HBO-lactone** with values at 507 and 651 nm for the E* and K* forms, whereas the driving force for ESIPT is also decreased to -0.05 eV indicating that the relative weight of the enol band could be significantly larger in **HBO-TCF** than in **HBO-lactone**. Looking at Figure 3b, one notices indeed a relatively intense band at 563 nm and another one at 674 nm, which is compatible with the calculations.

In summary, the synthesis of **HBO-lactone** and **HBO-TCF** is described herein and we have shown that the TCF group, long reported as stable can undergo hydrolysis in basic medium to provide the corresponding lactone. Both compounds were undoubtedly characterized by X-Ray diffraction. The nature of the accepting group (lactone vs TCF) triggers major differences in terms of photophysical properties and notably concerning the stabilization of the excited-species. The K⁺ transition of **HBO-lactone** is accompanied by an important QY value, up to 76%, an unprecedented value, as ESIPT is usually correlated to an important fluorescence quenching in solution. These additional examples of DSSE dyes validate our strategy of combining ESIPT process and the formation of a merocyanine as an efficient way to boost the QY value in solution. Potential applications of these dyes are currently under investigation.

## ASSOCIATED CONTENT

### Data Availability Statement

The data underlying this study are available in the published article and its online supplementary material.

### Supporting Information

The Supporting Information is available free of charge on the ACS Publications website.

Experimental data, ¹H and ¹³C NMR spectra, structural data, spectroscopic data, details of the computational procedures and methods, along with additional theoretical data.

## AUTHOR INFORMATION

### Corresponding Authors

**Julien Massue** - Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé (ICPEES), Equipe Chimie Organique

pour la Biologie, les Matériaux et l'Optique (COMBO), UMR CNRS 7515, 25 Rue Becquerel, 67087 Strasbourg Cedex 02, France. Email: massue@unistra.fr

**Denis Jacquemin** - Nantes Université, CNRS, CEISAM UMR 6230, F-44000 Nantes, France and Institut Universitaire de France (IUF), F-75005, Paris, France. Email: Denis.Jacquemin@Univ-Nantes.fr

## Authors

**Théo Andris** - Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé (ICPEES), Equipe Chimie Organique pour la Biologie, les Matériaux et l'Optique (COMBO), UMR CNRS 7515, 25 Rue Becquerel, 67087 Strasbourg Cedex 02, France.

**Timothée Stoerkler**† - Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé (ICPEES), Equipe Chimie Organique pour la Biologie, les Matériaux et l'Optique (COMBO), UMR CNRS 7515, 25 Rue Becquerel, 67087 Strasbourg Cedex 02, France.

**Gilles Ulrich** - Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé (ICPEES), Equipe Chimie Organique pour la Biologie, les Matériaux et l'Optique (COMBO), UMR CNRS 7515, 25 Rue Becquerel, 67087 Strasbourg Cedex 02, France.

**Pascal Retailleau** - Service de Cristallographie Structurale, ICSN-CNRS, Université Paris-Saclay, 1 Avenue de la Terrasse, Bât. 27, 91198 Gif-sur-Yvette Cedex, France.

**Adèle D. Laurent** - Nantes Université, CNRS, CEISAM UMR 6230, F-44000 Nantes, France

## Present Address

†University of Ottawa, Department of Chemistry, D'Iorio Hall, 10 Marie Curie, Ottawa ON Canada, K1N 6N5.

## Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

## Notes

The authors declare no competing financial interest.

## ACKNOWLEDGMENT

The authors thank the CNRS for financial support and the ANR TraSIPT (ANR-24-CE07-6830) for funding a doctoral grant for T.A. T.S. acknowledges the ED222 *Sciences Chimiques* for a PhD fellowship. D.J. and A.D.L. thank the GLiCID Computing Facility (Ligerien Group for Intensive Distributed Computing, 10.60487/glicid, Pays de la Loire, France) for generous allocation of computational time.

## REFERENCES

(1) (a) Zhao, J.; Ji, S.; Chen, Y.; Guo, H.; Yang, P. Excited state intramolecular proton transfer (ESIPT): from principal photophysics to the development of new chromophores and applications in fluorescent molecular probes and luminescent materials. *Phys. Chem. Chem. Phys.*, **2012**, *14*, 8803-8817. (b) Massue, J.; Jacquemin, D.; Ulrich, G. Molecular Engineering of Excited-state Intramolecular Proton Transfer (ESIPT) Dual and Triple Emitters. *Chem. Lett.*, 2018, 47, 9, 1083-1089. (2) (a) Chen, Y.; Fang, Y.; Gu, H.; Qiang, J.; Li, H.; Fan, J.; Cao, J.; Wang, F.; Lu, S.; Chen, X. Color-Tunable and ESIPT-Inspired Solid Fluorophores Based on Benzothiazole Derivatives: Aggregation-Induced Emission, Strong Solvatochromic Effect, and White Light Emission. *ACS Appl. Mater. Interfaces*, **2020**, *12*, 49-51.
55094-55106. (b) Arachchige, K.M.; Corbin, B.; Ediriweera, P.; Vrionides, M.A.; Salmon, C.; Pang, Y.; Mani, T.; Sameera, W.M.C.; Abeywickrama, C.S. Deprotonation-Induced Large Fluorescence Turn ON in a 2,4-Bis[benzo[d]thiazol-2-yl]phenol (HBT-BT) Derivative. *J. Phys. Chem. A*, **2025**, 129, 19, 4189-4203.

(3) Padalkar, V.S.; Seki, S. Excited-state intramolecular proton-transfer (ESIPT)-inspired solid state emitters. *Chem. Soc. Rev.*, **2016**, 45, 169-202.

(4) Yan, C.-C.; Wang, X.-D.; Liao, L.-S.; Organic Lasers Harnessing Excited State Intramolecular Proton Transfer Process. *ACS Photonics*, **2020**, 7, 6, 1355-1366.

(5) Wu, K.; Zhang, T.; Wang, Z.; Wang, L.; Zhan, L.; Gong, S.; Zhong, C.; Lu, Z.-H.; Zhang, S.; Yang, C. De Novo Design of Excited-State Intramolecular Proton Transfer Emitters via a Thermally Activated Delayed Fluorescence Channel. *J. Am. Chem. Soc.* **2018**, 140, 28, 8877-8886.

(6) Li, J.; Xu, B.-S.; Zhang, X.; Zhao, L.-L.; Yi, S.-Z.; Li, B.-N. Recent Advances in Smart Sensing Based on Excited-State Intramolecular Proton-Transfer (ESIPT)-Inspired Emitters. *Asian J. Org. Chem.* **2025**, 14, e202400572.

(7) (a) Zhang, Y.; Yang, H.; Ma, H.; Bian, G.; Zang, Q.; Sun, J.; Zhang, C.; An, Z.; Wang, W.-Y. Excitation Wavelength Dependent Fluorescence of an ESIPT Triazole Derivative for Amine Sensing and Anti-Counterfeiting Applications. *Angew. Chem., Int. Ed.*, **2019**, 58, 8773-8778. (b) Hu, H.; Cheng, X.; Ma, Z.; Sijbesma, R.P.; Ma, Z. Polymer Mechanochromism from Force-Tuned Excited-State Intramolecular Proton Transfer. *J. Am. Chem. Soc.*, **2022**, 144, 22, 9971.

(8) Huber, A.; Dubbert, J.; Scherz, T.D.; Voskuhl, J. Design Concepts for Solution and Solid-State Emitters–A Modern View point on Classical and Non-Classical Approaches. *Chem. Eur. J.*, **2023**, 29, e2022024.

(9) Durko-Maciag, M.; Ulrich, G.; Jacquemin, D.; Mysliwiec, J.; Massue, J. Solid-state emitters presenting a modular excited-state proton transfer (ESIPT) process: recent advances in dual-state emission and lasing applications. *Phys. Chem., Chem. Phys.*, **2023**, 25, 15085.

(10) (a) Pariat, T.; Munch, M.; Durko-Maciag, M.; Mysliwiec, J.; Retailleau, P.; Vérité, P.M.; Jacquemin, D.; Massue, J.; Ulrich, G. Impact of Heteroatom Substitution on Dual-State Emissive Rigidified 2-(2'-hydroxyphenyl)benzazole Dyes: Towards Ultra-Bright ESIPT Fluorophores. *Chem. Eur. J.*, **2021**, 27, 10, 3483-3495. (b) Takagi, K.; Ito, K.; Yamada, Y.; Nakashima, T.; Fukuda, R.; Ehara, M.; Masu, H. Synthesis and Optical Properties of Excited-State Intramolecular Proton Transfer Active π-Conjugated Benzimidazole Compounds: Influence of Structural Rigidification by Ring Fusion. *J. Org. Chem.* **2017**, 82, 12173-12180.

(11) (a) Gobel, D.; Duvinage, D.; Stauch, T.; Nachtsheim, B.J. Nitrile-substituted 2-(oxazolinyl)-phenols: minimalistic excited-state intramolecular proton transfer (ESIPT)-based fluorophores. *J. Mater. Chem. C*, **2020**, 8, 9213-9225. (b) Sakurai, T.; Kobayashi, M.; Yoshida, H.; Shimizu, M. Remarkable Increase of Fluorescence Quantum Efficiency by Cyano Substitution on an ESIPT Molecule 2-(2-Hydroxyphenyl) benzothiazole: A Highly Photoluminescent Liquid Crystal Dopant. *Crystals*, **2021**, 11, 1105.

(12) (a) Stoerkler, T.; Ulrich, G.; Retailleau, P.; Achelle, S.; Laurent, A.D.; Jacquemin, D.; Massue. J. Stimuli-Induced Fluorescence Switching in Azine-Containing Fluorophores Displaying Resonance-Stabilized ESIPT Emission. *Chem. Eur. J.*, **2024**, 30, 56, e202402448.

(b) Stoerkler, T.; Ulrich, G.; Laurent, A.D.; Jacquemin, D.; Massue. J. Quinoline-Substituted Excited-State Intramolecular Proton Transfer Fluorophores as Stimuli-Sensitive Dual-State Fluorophores. *Org. Chem. Front.*, **2025**, DOI: 10.1039/D5Q000639B.

(13) (a) Valla, L.; Pitrat, D.; Mulatier, J.-C.; Le Bahers, T.; Jeanneau, E.; Ali, L.M.A.; Nguyen, C.; Gary-Bobo, M.; Andraud, C.; Bretonnière, Y. Imidazo[1,2-α]pyridine and Imidazo[1,5-α]pyridine: Electron Donor Groups in the Design of D-π-A Dyes. *J. Org. Chem.*, **2024**, 89, 8407-8419. (b) Redon, S.; Eucat, G.; Ipuy, M.; Jeanneau, E.; Gautier-Luneau, I.; Ibanez, A.; Andraud, C.; Bretonnière, Y. Tuning the solid-state emission of small push-pull dipolar dyes to the far-red through variation of the electron-acceptor group. *Dyes Pigm.*, **2018**, 156, 116-132.

(14) (a) Lu, Z.; Liu, N.; Lord, S.J.; Bunge, S.D.; Moerner, W.E.; Twieg, R.J. Bright, Red Single-Molecule Emitters: Synthesis and Properties of Environmentally Sensitive Dicyanomethylenedihydrofuran (DCDHF) Fluorophores with Bisaromatic Conjugation. *Chem. Mater.* **2009**, 21, 797-810. (b) Ye, S.; Zhang, H.; Fei, K.; Wolstenholme, C.H.; Zhang, X. A General Strategy to Control Viscosity Sensitivity of Molecular Rotor-Based Fluorophores. *Angew. Chem. Int. Ed.* **2021**, 60, 1339-1346.

(15) Aldalbahi, A.; Periyasami, G.; Alrehaili, A. Synthesis of high molar extinction coefficient push-pull tricyanofuran-based disperse dyes: Biological activity and dyeing performance. *New J. Chem.*, **2021**, 45, 2208-2216.

(16) Bai, Y.; Wan, W.; Huang, Y.; Jin, W.; Lyu, H.; Xia, Q.; Dong, X.; Gaoc, Z.; Liu, Y. Quantitative interrogation of protein coaggregation using multi-color fluorogenic protein aggregation sensors. *Chem. Sci.*, **2021**, 14, 8468-8476.

(17) Gubler, U.; He, M.; Wright, D.; Roh, Y.; Twieg, R.; Moerner, W.E. Monolithic Photorefractive Organic Glasses with Large Coupling Gain and Strong Beam Fanning. *Adv. Mater.* **2002**, 14, 313-317.

(18) Munch, M.; Curtil, M.; Vérité, P.M.; Jacquemin, D.; Massue, J.; Ulrich, G. Ethynyl-Tolyl Extended 2-(2'-Hydroxyphenyl)benzoxazole Dyes: Solution and Solid-state Excited-State Intramolecular Proton Transfer (ESIPT) Emitters. *Eur. J. Org. Chem.*, **2019**, 1134-1144.

(19) (a) Ren, H.; Huo,F.; Zhang, Y.; Zhao, S.; Yin, C. An NIR ESIPT-based fluorescent probe with large stokes shift for specific detection of Cys and its bioimaging in cells and mice, *Sensors & Actuators: B. Chemical*, **2020**, 319, 128248. (b) Rajapakshe, B.U.; Li, Y.; Corbin, B.; Wijesinghe, K.J.; Pang, Y.; Abeywickrama, C.S. Copper-Induced Fluorescence Quenching in a Bis[2-(20-hydroxyphenyl) benzoxazole]pyridinium Derivative for Quantification of Cu2+ in Solution. *Chemosensors*, **2022**, 10, 382. (c) Zhang, P.; Xiao, Y.; Zhang, Q.; Zhang, Z.; Yub, H.; Ding, C. ESIPT-based fluorescent probe for cysteine sensing with large Stokes shift over homocysteine and glutathione and its application in living cells. *New J. Chem.*, **2019**, 43, 7620. (d) Abeywickrama, C.S.; Bertman, K.A.; Mcdonald, L.J.; Alexander, N.; Dahal, D.; Baumann, H.J.; Salmon, C.R.; Wesdemiotis, C.; Konopka, M.; Tessier, C.A.; Pang, Y. Synthesis of highly selective lysosomal markers by coupling 2-(20-hydroxyphenyl)benzothiazole (HBT) with benzothiazolium cyanine (Cy): the impact of substituents on selectivity and optical properties. *J. Mater. Chem. B*, **2019**, 7, 7502.

(20) Azarias, C.; Budzak, S.; Laurent, A. D.; Ulrich, G.; Jacquemin, D. Tuning ESIPT Fluorophores into Dual Emitters, *Chem. Sci.* **2016**, 7, 3763-3774.