Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques

Shima Ghasemi; Monika Shamsabadi; Axel Olesund; Francisco Najera; Andreas Erbs Hillers-Bendtsen; Fredrik Edhborg; Adil S. Aslam; Wera Larsson; Zhihang Wang; Francoise M. Amombo Noa; Rebecca Jane Salthouse; Lars Öhrström; Helen Hölzel; E. Perez-Inestrosa; Kurt V. Mikkelsen; Jörg Hanrieder; Bo Albinsson; Ambra Dreos; Kasper Moth-Poulsen

doi:10.1002/chem.202400322

Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques

Shima Ghasemi, Monika Shamsabadi, Axel Olesund, Francisco Najera, Andreas Erbs Hillers-Bendtsen, Fredrik Edhborg, Adil S. Aslam, Wera Larsson, Zhihang Wang, Francoise M. Amombo Noa, Rebecca Jane Salthouse, Lars Öhrström, Helen Hölzel, E. Perez-Inestrosa, Kurt V. Mikkelsen, Jörg Hanrieder, Bo Albinsson, Ambra Dreos, Kasper Moth-Poulsen^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

This study presents the synthesis and characterization of two fluorescent norbornadiene (NBD) photoswitches, each incorporating two conjugated pyrene units. Expanding on the limited repertoire of reported photoswitchable fluorescent NBDs, we explore their properties with a focus on applications in bioimaging of amyloid beta (Aβ) plaques. While the fluorescence emission of the NBD decreases upon photoisomerization, aligning with what has been previously reported, for the first time we observed luminescence after irradiation of the quadricyclane (QC) isomer. We deduce how the observed emission is induced by photoisomerization to the excited state of the parent isomer (NBD) which is then the emitting species. Thorough characterizations including NMR, UV-Vis, fluorescence, X-ray structural analysis and density functional theory (DFT) calculations provide a comprehensive understanding of these systems. Notably, one NBD-QC system exhibits exceptional durability. Additionally, these molecules serve as effective fluorescent stains targeting Aβ plaques in situ, with observed NBD/QC switching within the plaques. Molecular docking simulations explore NBD interactions with amyloid, unveiling novel binding modes. These insights mark a crucial advancement in the comprehension and design of future photochromic NBDs for bioimaging applications and beyond, emphasizing their potential in studying and addressing protein aggregates.

Original language	English
Article number	e202400322
Journal	Chemistry - A European Journal
Volume	30
Issue number	34
Number of pages	9
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.202400322
Publication status	Published - 2024

Bibliographical note

Funding Information:
The following agencies are acknowledged for financing the presented work: Spanish Ministerio de Ciencia e Innovaci\u00F3n (grant PID2022\u2010136705NB\u2212I00; Proyectos de I+D+I Programaci\u00F3n Conjunta Internacional, Euro\u2010NanoMed 2019 (PCI2019\u2010111825\u20102); International Postdoc Grant of the Swedish Research Council VR (#2021\u201000478); Swedish Energy Agency; the G\u00F6ran Gustafsson Foundation; the Swedish Research Council; the Chalmers Foundation; Swedish Research Council Formas; the European Research Council (ERC) under grant agreement CoG, PHOTHERM \u2013 101002131; the Catalan Institute of Advanced Studies (ICREA); and the European Union's Horizon2020 Framework Programme under grant agreement no. 951801.

Funding Information:
Microscopy images were acquired at the Centre for Cellular Imaging (CCI), Core Facilities, the Sahlgrenska Academy, University of Gothenburg. Chalmers Material Analysis Laboratory, CMAL is acknowledged for crystals characterizations, and we thank the Olle Engkvist Foundation for funding the single crystal diffractometer. We are grateful for the

Publisher Copyright:
© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

Keywords

Alzheimer
imaging
Norbornadienes
photochromism
photoswitches

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Ghasemi, S., Shamsabadi, M., Olesund, A., Najera, F., Erbs Hillers-Bendtsen, A., Edhborg, F., Aslam, A. S., Larsson, W., Wang, Z., Amombo Noa, F. M., Salthouse, R. J., Öhrström, L., Hölzel, H., Perez-Inestrosa, E., Mikkelsen, K. V., Hanrieder, J., Albinsson, B., Dreos, A., & Moth-Poulsen, K. (2024). Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques. Chemistry - A European Journal, 30(34), [e202400322]. https://doi.org/10.1002/chem.202400322

Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches : Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques. / Ghasemi, Shima; Shamsabadi, Monika; Olesund, Axel; Najera, Francisco; Erbs Hillers-Bendtsen, Andreas; Edhborg, Fredrik; Aslam, Adil S.; Larsson, Wera; Wang, Zhihang; Amombo Noa, Francoise M.; Salthouse, Rebecca Jane; Öhrström, Lars; Hölzel, Helen; Perez-Inestrosa, E.; Mikkelsen, Kurt V.; Hanrieder, Jörg; Albinsson, Bo; Dreos, Ambra; Moth-Poulsen, Kasper.

In: Chemistry - A European Journal, Vol. 30, No. 34, e202400322, 2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Ghasemi, S, Shamsabadi, M, Olesund, A, Najera, F, Erbs Hillers-Bendtsen, A, Edhborg, F, Aslam, AS, Larsson, W, Wang, Z, Amombo Noa, FM, Salthouse, RJ, Öhrström, L, Hölzel, H, Perez-Inestrosa, E, Mikkelsen, KV, Hanrieder, J, Albinsson, B, Dreos, A & Moth-Poulsen, K 2024, 'Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques', Chemistry - A European Journal, vol. 30, no. 34, e202400322. https://doi.org/10.1002/chem.202400322

Ghasemi, Shima ; Shamsabadi, Monika ; Olesund, Axel ; Najera, Francisco ; Erbs Hillers-Bendtsen, Andreas ; Edhborg, Fredrik ; Aslam, Adil S. ; Larsson, Wera ; Wang, Zhihang ; Amombo Noa, Francoise M. ; Salthouse, Rebecca Jane ; Öhrström, Lars ; Hölzel, Helen ; Perez-Inestrosa, E. ; Mikkelsen, Kurt V. ; Hanrieder, Jörg ; Albinsson, Bo ; Dreos, Ambra ; Moth-Poulsen, Kasper. / Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches : Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques. In: Chemistry - A European Journal. 2024 ; Vol. 30, No. 34.

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title = "Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques",

abstract = "This study presents the synthesis and characterization of two fluorescent norbornadiene (NBD) photoswitches, each incorporating two conjugated pyrene units. Expanding on the limited repertoire of reported photoswitchable fluorescent NBDs, we explore their properties with a focus on applications in bioimaging of amyloid beta (Aβ) plaques. While the fluorescence emission of the NBD decreases upon photoisomerization, aligning with what has been previously reported, for the first time we observed luminescence after irradiation of the quadricyclane (QC) isomer. We deduce how the observed emission is induced by photoisomerization to the excited state of the parent isomer (NBD) which is then the emitting species. Thorough characterizations including NMR, UV-Vis, fluorescence, X-ray structural analysis and density functional theory (DFT) calculations provide a comprehensive understanding of these systems. Notably, one NBD-QC system exhibits exceptional durability. Additionally, these molecules serve as effective fluorescent stains targeting Aβ plaques in situ, with observed NBD/QC switching within the plaques. Molecular docking simulations explore NBD interactions with amyloid, unveiling novel binding modes. These insights mark a crucial advancement in the comprehension and design of future photochromic NBDs for bioimaging applications and beyond, emphasizing their potential in studying and addressing protein aggregates.",

keywords = "Alzheimer, imaging, Norbornadienes, photochromism, photoswitches",

author = "Shima Ghasemi and Monika Shamsabadi and Axel Olesund and Francisco Najera and {Erbs Hillers-Bendtsen}, Andreas and Fredrik Edhborg and Aslam, {Adil S.} and Wera Larsson and Zhihang Wang and {Amombo Noa}, {Francoise M.} and Salthouse, {Rebecca Jane} and Lars {\"O}hrstr{\"o}m and Helen H{\"o}lzel and E. Perez-Inestrosa and Mikkelsen, {Kurt V.} and J{\"o}rg Hanrieder and Bo Albinsson and Ambra Dreos and Kasper Moth-Poulsen",

note = "Funding Information: The following agencies are acknowledged for financing the presented work: Spanish Ministerio de Ciencia e Innovaci\u00F3n (grant PID2022\u2010136705NB\u2212I00; Proyectos de I+D+I Programaci\u00F3n Conjunta Internacional, Euro\u2010NanoMed 2019 (PCI2019\u2010111825\u20102); International Postdoc Grant of the Swedish Research Council VR (#2021\u201000478); Swedish Energy Agency; the G\u00F6ran Gustafsson Foundation; the Swedish Research Council; the Chalmers Foundation; Swedish Research Council Formas; the European Research Council (ERC) under grant agreement CoG, PHOTHERM \u2013 101002131; the Catalan Institute of Advanced Studies (ICREA); and the European Union's Horizon2020 Framework Programme under grant agreement no. 951801. Funding Information: Microscopy images were acquired at the Centre for Cellular Imaging (CCI), Core Facilities, the Sahlgrenska Academy, University of Gothenburg. Chalmers Material Analysis Laboratory, CMAL is acknowledged for crystals characterizations, and we thank the Olle Engkvist Foundation for funding the single crystal diffractometer. We are grateful for the Publisher Copyright: {\textcopyright} 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.",

year = "2024",

doi = "10.1002/chem.202400322",

language = "English",

volume = "30",

journal = "Chemistry: A European Journal",

issn = "0947-6539",

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TY - JOUR

T1 - Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches

T2 - Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques

AU - Ghasemi, Shima

AU - Shamsabadi, Monika

AU - Olesund, Axel

AU - Najera, Francisco

AU - Erbs Hillers-Bendtsen, Andreas

AU - Edhborg, Fredrik

AU - Aslam, Adil S.

AU - Larsson, Wera

AU - Wang, Zhihang

AU - Amombo Noa, Francoise M.

AU - Salthouse, Rebecca Jane

AU - Öhrström, Lars

AU - Hölzel, Helen

AU - Perez-Inestrosa, E.

AU - Mikkelsen, Kurt V.

AU - Hanrieder, Jörg

AU - Albinsson, Bo

AU - Dreos, Ambra

AU - Moth-Poulsen, Kasper

N1 - Funding Information: The following agencies are acknowledged for financing the presented work: Spanish Ministerio de Ciencia e Innovaci\u00F3n (grant PID2022\u2010136705NB\u2212I00; Proyectos de I+D+I Programaci\u00F3n Conjunta Internacional, Euro\u2010NanoMed 2019 (PCI2019\u2010111825\u20102); International Postdoc Grant of the Swedish Research Council VR (#2021\u201000478); Swedish Energy Agency; the G\u00F6ran Gustafsson Foundation; the Swedish Research Council; the Chalmers Foundation; Swedish Research Council Formas; the European Research Council (ERC) under grant agreement CoG, PHOTHERM \u2013 101002131; the Catalan Institute of Advanced Studies (ICREA); and the European Union's Horizon2020 Framework Programme under grant agreement no. 951801. Funding Information: Microscopy images were acquired at the Centre for Cellular Imaging (CCI), Core Facilities, the Sahlgrenska Academy, University of Gothenburg. Chalmers Material Analysis Laboratory, CMAL is acknowledged for crystals characterizations, and we thank the Olle Engkvist Foundation for funding the single crystal diffractometer. We are grateful for the Publisher Copyright: © 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

PY - 2024

Y1 - 2024

N2 - This study presents the synthesis and characterization of two fluorescent norbornadiene (NBD) photoswitches, each incorporating two conjugated pyrene units. Expanding on the limited repertoire of reported photoswitchable fluorescent NBDs, we explore their properties with a focus on applications in bioimaging of amyloid beta (Aβ) plaques. While the fluorescence emission of the NBD decreases upon photoisomerization, aligning with what has been previously reported, for the first time we observed luminescence after irradiation of the quadricyclane (QC) isomer. We deduce how the observed emission is induced by photoisomerization to the excited state of the parent isomer (NBD) which is then the emitting species. Thorough characterizations including NMR, UV-Vis, fluorescence, X-ray structural analysis and density functional theory (DFT) calculations provide a comprehensive understanding of these systems. Notably, one NBD-QC system exhibits exceptional durability. Additionally, these molecules serve as effective fluorescent stains targeting Aβ plaques in situ, with observed NBD/QC switching within the plaques. Molecular docking simulations explore NBD interactions with amyloid, unveiling novel binding modes. These insights mark a crucial advancement in the comprehension and design of future photochromic NBDs for bioimaging applications and beyond, emphasizing their potential in studying and addressing protein aggregates.

AB - This study presents the synthesis and characterization of two fluorescent norbornadiene (NBD) photoswitches, each incorporating two conjugated pyrene units. Expanding on the limited repertoire of reported photoswitchable fluorescent NBDs, we explore their properties with a focus on applications in bioimaging of amyloid beta (Aβ) plaques. While the fluorescence emission of the NBD decreases upon photoisomerization, aligning with what has been previously reported, for the first time we observed luminescence after irradiation of the quadricyclane (QC) isomer. We deduce how the observed emission is induced by photoisomerization to the excited state of the parent isomer (NBD) which is then the emitting species. Thorough characterizations including NMR, UV-Vis, fluorescence, X-ray structural analysis and density functional theory (DFT) calculations provide a comprehensive understanding of these systems. Notably, one NBD-QC system exhibits exceptional durability. Additionally, these molecules serve as effective fluorescent stains targeting Aβ plaques in situ, with observed NBD/QC switching within the plaques. Molecular docking simulations explore NBD interactions with amyloid, unveiling novel binding modes. These insights mark a crucial advancement in the comprehension and design of future photochromic NBDs for bioimaging applications and beyond, emphasizing their potential in studying and addressing protein aggregates.

KW - Alzheimer

KW - imaging

KW - Norbornadienes

KW - photochromism

KW - photoswitches

U2 - 10.1002/chem.202400322

DO - 10.1002/chem.202400322

M3 - Journal article

C2 - 38629212

AN - SCOPUS:85193803619

VL - 30

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 34

M1 - e202400322

ER -