CO2-Responsive Adenine Nucleobase: New Insight into Manipulating the Photophysical Properties and Biological Activities of Functional Fluorescent Molecules

We report important progress in the preparation and development of gas-responsive fluorescent materials with potential as efficient anticancer treatments and fluorescent probes for biomedical imaging. An environmental stimuli-responsive multifunctional material (ESMM) composed of rhodamine 6 G containing a pH-sensitive spirolactam unit and a self-complementary multiple hydrogen-bonded adenine group was successfully synthesized through a simple and efficient two-step synthetic pathway. ESMM has extremely poor water solubility, even in a weakly acidic aqueous environment, but can easily dissolve in common organic solvents. Due to the unique polar heteroaromatic structure of the adenine group that confers chemical reactivity (or responsiveness) with CO2, hydrophobic ESMM can rapidly and completely dissolve in water on simple CO2 bubbling treatment, which is followed by formation of self-assembled spherical-like nanoparticles. The resulting nanoparticles demonstrate unique spontaneous fluorescent characteristics in water and their photophysical properties, surface charge, acid-base characteristics, and self-assembled morphology can be quickly and stably switched on and off by alternating cycles of CO2 and N2 bubbling, to thus effectively manipulate their physical performance. Importantly, in vitro cell assays clearly indicated that protonation of the adenine group by CO2 remarkably enhances the anti-hemolytic properties of ESMM and results in highly potent and selective cytotoxicity against cancer cells at low doses, but not in normal cells. In contrast, pristine ESMM did not exhibit selective cytotoxic effect on normal or cancer cells. Therefore, this newly discovered CO2-responsive system may have a great potential to improve the safety and effectiveness of chemotherapeutic drugs.