Water-soluble triazolium covalent cages for ATP sensing

Water-soluble organic cages are attractive targets for their molecular recognition and sensing features of biologically relevant molecules. Here, we have successfully designed and synthesized a pair of water-soluble cationic cages employing click reaction as the fundamental step followed by the N-methylation of the triazole rings. The rigid and shape-persistent 3D hydrophobic cavity, positively charged surface, H-bonding triazolium rings, and excellent water solubility empower both cages to exhibit a superior affinity and selectivity for binding with adenosine-5'-triphosphate (ATP) compared to cyclophanes and other macrocyclic receptors. Both cage molecules (PCC & sdot;Cl and BCC & sdot;Cl) can bind a highly emissive dye HPTS (8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt) to form non-fluorescent complexes. The addition of ATP resulted in the stronger cage subset of ATP complexes with the retention of HPTS emission upon its displacement. The resultant indicator-displacement assay system can efficiently sense and quantify ATP in nanomolar detection limits in buffer solutions and human serum matrix. Spectroscopic and theoretical studies revealed the synergistic effect of pi & sdot;& sdot;& sdot;pi stacking interaction between the aromatic moiety of the cationic cages and the adenine moiety of ATP, as well as the electrostatic and hydrogen bonding interaction between the phosphate anion of ATP and triazole protons of cages, played the pivotal roles in the sensing process. Two water-soluble organic cages were synthesized through a three-fold click reaction, followed by N-methylation and anion exchange. The cages bind to the HPTS (8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt) dye and quench its emission. The cage subset of HPTS complexes exhibit turn-on emission to sense ATP with a nanomolar detection limit, both in water and in human serum matrix. image