Tuning the push-pull dyes: Construction of polarity insensitive probes for G4 DNA

Abstract

We report here the design and synthesis of two new polarity-insensitive push-pull dyes TCP-SO3 and TCP-COOH and developed as fluorescent probes for G-quadruplex (G4) DNAs. The strategy involved in this study is to use the traditional D-π-A building block of carbazole-pyridinium (CP), while introducing of a diphenylimidazole group as a secondary donor as well as molecular rotor to form the D-D-π-A configuration, thus ascertaining the effect of the auxiliary group on the photophysics of the dyes. Additionally, N-sulfobutylpyridinium and N-(carboxyethyl) pyridinium bromide moieties are employed as electron-withdrawing anchoring groups, respectively, due to their hydrophilicity and electronic characters, thereby regulating the G4 DNA binding affinity and photophysical properties. It was found that the introduction of diphenylimidazole group to form the D-D-π-A configuration brought superior performance, in terms of polarity-insensitive property with a fluorescence-off state in various polarity solvents. Both dyes exhibited a clear-cut off-on sensing preference for G4 over non-G4 DNA structures, dye TCP-SO3 having a hydrophilic sulfonate group at electron-acceptor part displayed superior G4 DNA binding and selectivity compared to TCP-COOH with a carboxylic acid group. Detailed investigation on the relationship between the structure, photophysical properties, and G4 DNA sensing performance was described.