B-Ring-extended flavonol-based photoCORM: activated by cysteine-ratiometric fluorescence sensing and accurate control of linear CO release

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Vol. 9; no. 39; pp. 8263 - 8271
• Main Authors: Sun, Ying-Ji, Yu, Chao
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 13.10.2021
• Subjects: Animals; Biocompatibility; Biphenyl; Carbon monoxide; Carbon Monoxide - chemistry; Cysteine; Cysteine - chemistry; Danio rerio; Drug Design; Flavonols; Flavonols - chemistry; Fluorescence; Fluorescent indicators; Glutathione; HeLa Cells; Homocysteine; Humans; Hydrogen-Ion Concentration; Irradiation; Larva - drug effects; Light; Light irradiation; Luminous intensity; Membrane permeability; Molecular Structure; Photochemical Processes; Radiation; Radiation dosage; Reaction products; Room temperature; Sensitivity and Specificity; Toxicity; Zebrafish
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/d1tb01093j

The first B-ring-extended (to biphenyl) flavonol-based Cys-ratiometric fluorescent probe B-bph-fla-acr (2-([1,1′-biphenyl]-4-yl)-4-oxo-4 H -chromen-3-yl acrylate) is developed. B-bph-fla-acr can ratiometrically sense and non-ratiometrically image endogenous and exogenous cysteine (Cys) in living HeLa cells and zebrafish rapidly (45 s), selectively ( vs. homocysteine and glutathione), sensitively (detection limit: 18.5 nM), and with a large Stokes shift (186 nm). Quantitatively released (from the reaction of B-bph-fla-acr with Cys) fluorophore B-bph-fla-OH (2-([1,1′-biphenyl]-4-yl)-3-hydroxy-4 H -chromen-4-one) is designed as a photoCORM (photo-triggered CO releasing molecule). Under O 2 and visible light irradiation, the amount of CO released by B-bph-fla-OH can be accurately controlled linearly by adjusting the light irradiation intensity, irradiation time, or photoCORM dose. This process is accompanied by fluorescence quenching; therefore, the location of the photoCORM and the CO release process can be monitored in real time. B-bph-fla-acr and all reaction products exhibit good membrane permeability and low toxicity for living HeLa cells. In living HeLa cells and zebrafish, B-bph-fla-acr can image endogenous and exogenous Cys, and the released B-bph-fla-OH can photo-release CO under O 2 at room temperature. This study is the first to combine a B-ring-extended flavonol-based fluorescent probe (for the effective ratiometric sensing and non-ratiometric imaging of endogenous and exogenous Cys in vitro and in vivo ) with a photoCORM (Cys-activated, visible light-triggered linear CO release under O 2 ). Our study provides important insights into the biological roles of Cys and CO, as well as a reliable method for safely supplying accurately controlled amounts of CO to living systems, thereby facilitating the development of convenient clinical diagnostic molecular tools and therapeutic prodrugs. This study is the first to combine a B-ring-extended flavonol-based ratiometric fluorescent probe (for the effective sensing and imaging of Cys in vivo ) with a photoCORM (Cys activated, visible light-triggered, accurate control of linear CO release).