A tetrazine-responsive isonitrile-caged photosensitiser for site-specific photodynamic therapy

Design and synthesis of a NAD(P)H:quinone oxidoreductase 1-activatable photosensitiser for controlled photodynamic therapy

“…Upon excitation at 610 nm, compound 2 emitted strongly at 688 nm with a fluorescence quantum yield ( Φ f ) of 0.59 relative to the unsubstituted zinc( ii ) phthalocyanine (ZnPc) ( Φ F = 0.28). 13 In contrast, the fluorescence signal of 1 could barely be observed (Fig. 2a).…”

“…S2 (ESI†), the absorption spectrum of 2 displayed two intense bands at 371 and 652 nm, which are typical for distyryl BODIPYs. 13 The longest-wavelength absorption became significantly broadened and red-shifted to 732 nm for 1 . Upon excitation at 610 nm, compound 2 emitted strongly at 688 nm with a fluorescence quantum yield ( Φ f ) of 0.59 relative to the unsubstituted zinc( ii ) phthalocyanine (ZnPc) ( Φ F = 0.28).…”

“…1 shows the molecular structure of this NQO1-activatable photosensitiser (compound 1 ) and its activation mechanism. The compound contains a distyryl boron dipyrromethene (BODIPY)-based photosensitising unit which is caged with an ester moiety 13 and a NQO1-responsive trimethylquinone unit 14 linked via a self-immolative linker. Upon interactions with NQO1 in the presence of NADPH, the quinone moiety of 1 would first undergo two-electron reduction to give a hydroquinone intermediate, followed by sequential intramolecular cyclisation into a lactone, further cyclisation into a five-membered cyclic urea and 1,6-elimination to release a p -quinone-methide and a carboxylated BODIPY (compound 2 ) as proposed previously.…”

“…Upon interactions with NQO1 in the presence of NADPH, the quinone moiety of 1 would first undergo two-electron reduction to give a hydroquinone intermediate, followed by sequential intramolecular cyclisation into a lactone, further cyclisation into a five-membered cyclic urea and 1,6-elimination to release a p -quinone-methide and a carboxylated BODIPY (compound 2 ) as proposed previously. 13,15 By converting the more electron-withdrawing ester group (with a Hammett constant σ p of 0.45) to a less electron-withdrawing carboxylate moiety ( σ p = 0.00), this compound is activated in terms of fluorescence emission and ROS generation, 16 making it a NQO1-responsive fluorescent probe and photosensitiser.…”

“…To study the activation in ROS formation inside the cells, 2′,7′-dichlorodihydrofluorescein diacetate (H 2 DCFDA) was used as the probe, which generates the highly fluorescent 2′,7′-dichlorofluorescein (DCF) upon hydrolysis and oxidation by the intracellular ROS. 13 Similarly, the three cell lines were incubated with 1 (4 μM) for 3 h with or without pre-incubation with dicoumarol (50 μM) for 1 h. The cells were then incubated with H 2 DCFDA (50 μM) for 30 min, followed by the dark or light ( λ > 610 nm, 23 mW cm −2 ) treatment for 20 min. Fig.…”