Water soluble extended naphthalene diimides as pH fluorescent sensors and G-quadruplex ligandsElectronic supplementary information (ESI) available. See DOI: 10.1039/c2ob07006e

Extended naphthalene diimides (NDIs) fused to 1,4-dihydropyrazine-2,3-dione, containing two solubilizing moieties, have been synthesized. Fluorescence spectra of the new NDIs were remarkably affected by pH, as the second deprotonation of the dihydropyrazinedione moiety (p K a 6.9) switched off the emission. Binding to a G-quadruplex folded oligonucleotide and stoichiometry were evaluated by FRET melting assay and CD analysis. G-quadruplex binding was strongly enhanced shifting from pH 7.4 to pH 6.0 as a consequence of the dihydropyrazinedione moiety protonation. Cytotoxicity studies using two human telomerase-positive cell lines (HT29 and A549) revealed that the best G-quadruplex ligand was very active against the colon cell line, with an EC 50 of 300 nM. Extended naphthalene diimides (NDIs) fused to 1,4-dihydropyrazine-2,3-dione containing two solubilizing arms have been synthesized. Fluorescence spectra and G-quadruplex (G-4) binding were both remarkably affected by pH.