TY - JOUR
T1 - Mitochondria-targeted COUPY photocages
T2 - synthesis and visible-light photoactivation in living cells
AU - López-Corrales, Marta
AU - Rovira, Anna
AU - Gandioso, Albert
AU - Nonell, Santi
AU - Bosch, Manel
AU - Marchán, Vicente
N1 - Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
PY - 2023/6/2
Y1 - 2023/6/2
N2 - Releasing bioactive molecules in specific subcellular locations from the corresponding caged precursors offers great potential in photopharmacology, especially when using biologically compatible visible light. By taking advantage of the intrinsic preference of COUPY coumarins for mitochondria and their long wavelength absorption in the visible region, we have synthesized and fully characterized a series of COUPY-caged model compounds to investigate how the structure of the coumarin caging group affects the rate and efficiency of the photolysis process. Uncaging studies using yellow (560 nm) and red light (620 nm) in phosphate-buffered saline medium have demonstrated that the incorporation of a methyl group in a position adjacent to the photocleavable bond is particularly important to fine-tune the photochemical properties of the caging group. Additionally, the use of a COUPY-caged version of the protonophore 2,4-dinitrophenol allowed us to confirm by confocal microscopy that photoactivation can occur within mitochondria of living HeLa cells upon irradiation with low doses of yellow light. The new photolabile protecting groups presented here complement the photochemical toolbox in therapeutic applications since they will facilitate the delivery of photocages of biologically active compounds into mitochondria.
AB - Releasing bioactive molecules in specific subcellular locations from the corresponding caged precursors offers great potential in photopharmacology, especially when using biologically compatible visible light. By taking advantage of the intrinsic preference of COUPY coumarins for mitochondria and their long wavelength absorption in the visible region, we have synthesized and fully characterized a series of COUPY-caged model compounds to investigate how the structure of the coumarin caging group affects the rate and efficiency of the photolysis process. Uncaging studies using yellow (560 nm) and red light (620 nm) in phosphate-buffered saline medium have demonstrated that the incorporation of a methyl group in a position adjacent to the photocleavable bond is particularly important to fine-tune the photochemical properties of the caging group. Additionally, the use of a COUPY-caged version of the protonophore 2,4-dinitrophenol allowed us to confirm by confocal microscopy that photoactivation can occur within mitochondria of living HeLa cells upon irradiation with low doses of yellow light. The new photolabile protecting groups presented here complement the photochemical toolbox in therapeutic applications since they will facilitate the delivery of photocages of biologically active compounds into mitochondria.
KW - Photoremovable protecting groups
KW - Photoprotecting groups
KW - Coumarin scaffold
KW - Oxidative stress
KW - Fluorophores
KW - Dysfunction
KW - Activation
KW - Mechanisms
KW - Chemistry
KW - Strategy
UR - http://www.scopus.com/inward/record.url?scp=85162205692&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:001014340700001&DestLinkType=FullRecord&DestApp=WOS_CPL
UR - http://hdl.handle.net/20.500.14342/4663
U2 - 10.1021/acs.joc.3c00387
DO - 10.1021/acs.joc.3c00387
M3 - Article
AN - SCOPUS:85162205692
SN - 0022-3263
VL - 88
SP - 7128
EP - 7140
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 11
ER -