Self-reporting styrylthiazolium photopharmaceuticals: mitochondrial localisation as well as SAR drive biological activity

Gao, Li; Kraus, Yvonne; Stegner, Andrea Anna Therese; Wein, Thomas; Heise, Constanze; Brunn, Leonie von; Fajardo-Ruiz, Elena; Ahlfeld, Julia; Thorn‐Seshold, Oliver

doi:10.1039/d2ob00347c

“…The authors have cited additional references within the Supporting Information. [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]…”

Section: Supporting Informationmentioning

confidence: 99%

Merged Molecular Switches Excel as Optoacoustic Dyes: Azobenzene–Cyanines Are Loud and Photostable NIR Imaging Agents

Müller,

Liu,

Gujrati

et al. 2024

Angewandte Chemie

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Optoacoustic (or photoacoustic) imaging promises micron‐resolution noninvasive bioimaging with much deeper penetration (>cm) than fluorescence. However, optoacoustic imaging of enzyme activity would require loud, photostable, NIR‐absorbing molecular contrast agents: which remain unknown. Most organic molecular contrast agents are repurposed fluorophores, with severe shortcomings of photoinstability or phototoxicity under optoacoustic imaging, as consequences of their slow S1→S0 electronic relaxation. We now report that known fluorophores can be rationally modified to reach ultrafast S1→S0 rates, without much extra molecular complexity, simply by merging them with molecular switches. Here, we merge azobenzene switches to cyanine dyes to give ultrafast relaxation (<10 ps, >100‐fold faster). Without even adapting instrument settings, these azohemicyanines display outstanding improvements in signal longevity (>1000‐fold increase of photostability) and signal loudness (here: >3‐fold even at time zero). We show why this simple but unexplored design strategy can still offer stronger performance in the future, and can also increase the spatial resolution and the quantitative linearity of photoacoustic response over extended longitudinal imaging. By bringing the world of molecular switches and rotors to bear on problems facing optoacoustic agents, this practical strategy will help to unleash the full potential of optoacoustic imaging in fundamental studies and translational uses.

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“…The authors have cited additional references within the Supporting Information. [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]…”

Section: Supporting Informationmentioning

confidence: 99%

“…Synthesis, photophysics data, and NMR spectra (PDF). The authors have cited additional references within the Supporting Information [59–75] …”

Section: Supporting Informationmentioning

confidence: 99%

Merged Molecular Switches Excel as Optoacoustic Dyes: Azobenzene–Cyanines Are Loud and Photostable NIR Imaging Agents

Müller,

Liu,

Gujrati

et al. 2024

Angew Chem Int Ed

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Optoacoustic (or photoacoustic) imaging promises micron‐resolution noninvasive bioimaging with much deeper penetration (>cm) than fluorescence. However, optoacoustic imaging of enzyme activity would require loud, photostable, NIR‐absorbing molecular contrast agents: which remain unknown. Most organic molecular contrast agents are repurposed fluorophores, with severe shortcomings of photoinstability or phototoxicity under optoacoustic imaging, as consequences of their slow S1→S0 electronic relaxation. We now report that known fluorophores can be rationally modified to reach ultrafast S1→S0 rates, without much extra molecular complexity, simply by merging them with molecular switches. Here, we merge azobenzene switches to cyanine dyes to give ultrafast relaxation (<10 ps, >100‐fold faster). Without even adapting instrument settings, these azohemicyanines display outstanding improvements in signal longevity (>1000‐fold increase of photostability) and signal loudness (here: >3‐fold even at time zero). We show why this simple but unexplored design strategy can still offer stronger performance in the future, and can also increase the spatial resolution and the quantitative linearity of photoacoustic response over extended longitudinal imaging. By bringing the world of molecular switches and rotors to bear on problems facing optoacoustic agents, this practical strategy will help to unleash the full potential of optoacoustic imaging in fundamental studies and translational uses.

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“…[36][37][38][39] Notably, the Thorn-Seshold group has recently successfully applied substituted styrylbenzothiazole switches for in vivo photocontrol of the microtubule cytoskeleton, while they demonstrate the potential of a substituted styrylthiazolium switch for addressing mitochondrial targets. [40][41][42] These examples highlight the great potential of styrylbenzazole switches in photopharmacology. [10][11][12][13][14][15] Nevertheless, further applications as photoswitches, as well as broader systematic investigations of the photophysical and photochemical properties of these scaffolds, have thus far remained limited.…”

Section: Introductionmentioning

confidence: 97%

“…Another modification that has been studied is fusing the styrylbenzazole scaffold with a crown ether moiety, which is capable of binding several (metal cation) guests, accessing different characteristics of the E and the Z isomers, such as different binding properties [36–39] . Notably, the Thorn‐Seshold group has recently successfully applied substituted styrylbenzothiazole switches for in vivo photocontrol of the microtubule cytoskeleton, while they demonstrate the potential of a substituted styrylthiazolium switch for addressing mitochondrial targets [40–42] . These examples highlight the great potential of styrylbenzazole switches in photopharmacology [10–15] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Styrylbenzazole Photoswitches and Evaluation of their Photochemical Properties

Stindt,

Crespi,

Feringa

2024

Chemistry A European J

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Styrylbenzazoles form a promising yet under‐represented class of photoswitches that can perform a light‐driven E‐Z isomerization of the central alkene double bond without undergoing irreversible photocyclization, typical of the parent stilbene. In this work, we report the synthesis and photochemical study of 23 styrylbenzazole photoswitches. Their thermal stabilities, quantum yields, maximum absorption wavelengths and photostationary state (PSS) distributions can be tuned by changing the benzazole heterocycle and the substitution pattern on the aryl ring. In particular, we found that push‐pull systems show large redshifts of the maximum absorption wavelengths and the highest quantum yields, whereas ortho‐substituted styrylbenzazole photoswitches exhibit the most favorable PSS ratios. Taking advantage of both design principles, we produced 2,6‐dimethyl‐4‐(dimethylamino)‐styrylbenzothiazole, a thermally stable and efficient P‐type photoswitch which displays negative photochromism upon irradiation with visible light up to 470 nm to obtain a near‐quantitative isomerization with a very high quantum yield of 59%. Furthermore, 4‐hydroxystyrylbenzothiazole was demonstrated to be a pH‐sensitive switch which exhibits a 100 nm redshift upon deprotonation. Ortho‐methylation of this switch improved the obtained PSS ratio in its deprotonated state from E:Z=53:47 to E:Z=18:82. We anticipate that this relatively unexplored class of photoswitches will form a valuable expansion of the current family of photoswitches.

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Self-reporting styrylthiazolium photopharmaceuticals: mitochondrial localisation as well as SAR drive biological activity

Cited by 3 publications

References 48 publications

Merged Molecular Switches Excel as Optoacoustic Dyes: Azobenzene–Cyanines Are Loud and Photostable NIR Imaging Agents

Merged Molecular Switches Excel as Optoacoustic Dyes: Azobenzene–Cyanines Are Loud and Photostable NIR Imaging Agents

Merged Molecular Switches Excel as Optoacoustic Dyes: Azobenzene–Cyanines Are Loud and Photostable NIR Imaging Agents

Synthesis of Styrylbenzazole Photoswitches and Evaluation of their Photochemical Properties

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