ATP/azobenzene-guanidinium self-assembly into fluorescent and multi-stimuli responsive supramolecular aggregates

Building stimuli-responsive supramolecular systems is a way for chemists to achieve spatio-temporal control over complex systems as well as a promising strategy for applications ranging from sensing to drug-delivery. For its large spectrum of biological and biomedical implications, adenosine 5’-triphosphate (ATP) is a particularly interesting target for such a purpose but photoresponsive ATP-based systems, such as photocaged compounds, have mainly been relying on covalent modification of ATP. Here, we show that simply mixing unmodified ATP with AzoDiGua, an azobenzene-guanidium compound with photodependent nucleotide binding affinity, results in the spontaneous self-assembly of the two non-fluorescent compounds into photoreversible, micrometer-sized and fluorescent aggregates. Obtained in water at room temperature and physiological pH, these supramolecular structures are dynamic and respond to several chemical, physical and biological stimuli, resulting in a multi-stimuli control of the suspension turbidity and aggregate fluorescence. The presence of azobenzene allows a fast and photoreversible control of their assembly upon cycles of UV (395/25 nm) and blue (480/30 nm) irradiation of moderate power. ATP chelating properties to metal dications enable ion-triggered disassembly and fluorescence control with valence-selectivity. Finally, the supramolecular aggregates are disassembled by alkaline phosphatase in a few minutes at room temperature, resulting in enzymatic control of fluorescence through ATP hydrolysis. These results highlight the interest of using a photoswitchable nucleotide binding partner as a self-assembly brick to build highly responsive supramolecular entities involving biologically relevant target molecules without the need to covalently modify them.