Intra- and Intermolecular Fluorescence Quenching of Alkylthio-Substituted Phthalimides by Photoinduced Electron Transfer: Distance, Position and Conformational Dependence

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 H2O2 or O-1(2) (off -> on for 1,4,7 and on -> off for 9). Further functionalized molecules that were based on the model compounds are the sulfur-containing 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