Different reactive oxygen species were detected by the molecular probes 1-3 that were composed of the phthalimide fluorophore as reporter and a methionine-derived thioether side-chain as receptor part. The sulfoxides that were formed as the primary oxidation products show strong fluorescence in the blue-green (430-540 nm) spectral region. Self-sensitized oxidation by singlet oxygen is in general inefficient indicating rapid electron-transfer quenching of the excited probe molecules. With hydrogen peroxide as thermal oxidant conversion to the sulfoxides is slow but can be accelerated by addition of titanium(IV) catalysts, whereas hypochlorite as oxidant behaves much more reactive even under uncatalyzed conditions. Singlet oxygen that is generated by energy transfer from the photosensitizer Rose Bengal was detected by sensor 1a with rate constants of >10 7 M -1 s -1 , a typical rate constant for the oxidation of thioethers to sulfoxides.
The fluorescence emission of the parent 2-aminobenzimidazole
(ABZ, 1), the mono- and disubstituted derivatives (2, 3), 2-aminonaphthoimidazole (4), and
4-amino dinaphthodiazepine 5 (λem =
315–400 nm) is strongly quenched in the presence of aqueous
hydrogen peroxide. The quenching process is dual: for diazepine 5, quenching is dynamic at lower H2O2 concentrations with linear reduction of the fluorescence lifetime
from 4.3 to 2.6 ns. At higher H2O2 concentrations,
a second species appears in the absorption and emission spectra with
fluorescence lifetimes of 1.3 ns, indicating the formation of a new
(ground-state) hydrogen-bonded ABZ-H2O2 complex
(static quenching). Sensors 1 and 2 show
also dual quenching that fits with a static 1:1 and 1:2 model with K
1:1 = 8(11) M–1 and K
1:2 = 21(147) M–1 for 1(2). The formation of a 1:2 complex (1:(H2O2)2) is also supported by density
functional theory (DFT) calculations and spectra simulations.
The photophysical properties of fluorescent phthalimides with thioether groups directly connected to the chromophore or separated by alkyl spacers, respectively, were studied. Intermolecular fluorescence quenching by electron transfer from dimethylsulfide to the 4,5-dimethoxy phthalimide (DMPht) model compound 6 is dynamic and fast. The fluorescence properties of 6 and the remote C 5 -spaced thioether derivative 5 are nearly identical. In compounds 1-4 with shorter spacer lengths, fluorescence quenching is strong for C 2 and C 3 -spaced 2 and 3 and less pronounced for C 1 -and C 4 -spaced compounds 1 and 4, mapping the conformational landscape of these molecules. The o-,m-,p-substituted N-(thiomethyl)benzyl DMPht 7 are almost non-fluorescent which correlates very well with the intermolecular thioanisole fluorescence quenching of 6. In contrast, the 3-and 4-thiomethyl phthalimides 8 and 9 show divergent fluorescence that is also rationalized by DFT calculation results. The fluorescence properties can be switched by oxidation of the thioethers to sulfoxides with H 2 O 2 or 1 O 2 (off! on for 1,4,7 and on!off for 9). Further functionalized molecules that were based on the model compounds are the sulfurcontaining amino acid methionine derivative 10, dipeptides 11 a,b, and S-alkylated cysteine derivatives 12 to 14 a-d with strong side-chain-dependent fluorescence.[a] Dr.
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