G-quadruplex fluorescence sensing by core-extended naphthalene diimides

Area of Science:

• Chemical Biology
• Molecular Biology
• Supramolecular Chemistry

Background:

• Fluorescent sensing of G-quadruplex nucleic acids (G4s) is crucial for understanding their biological roles.
• Naphthalene diimides (NDIs) are potent G4 binders but often suffer from fluorescence quenching upon binding.
• Aggregating core-extended naphthalene diimides (c_ex-NDIs) emerge as promising G4 fluorescent probes.

Purpose of the Study:

• To synthesize and characterize a library of c_ex-NDIs for G4 fluorescent sensing.
• To investigate the sensing mechanism, selectivity, and binding modes of c_ex-NDIs with different G4 topologies.
• To explore the potential of c_ex-NDIs as red-NIR emitting probes for G4 detection.

Main Methods:

• Organic synthesis of eighteen c_ex-NDIs.
• Spectroscopic analysis (absorption, emission) and titrations.
• Fluorescent intercalator displacement (FID) and circular dichroism (CD) assays.

Main Results:

• c_ex-NDIs exhibit aggregation-dependent optical properties, with quenched fluorescence in aqueous solution.
• Upon binding to anti-parallel and hybrid G4s, c_ex-NDIs disaggregate, leading to a fluorescence "light-up".
• Binding to parallel G4s results in a fluorescence "light-off", with distinct binding modes (groove vs. end-stacking) inferred for different G4 types.

Conclusions:

• The G4 sensing mechanism of c_ex-NDIs relies on induced disaggregation.
• The emission response is dependent on G4 topology, correlating with groove or end-stacking binding modes.
• c_ex-NDIs are versatile fluorescent probes emitting in the red-NIR region, complementing existing G4 detection methods.