Click chemistry-mediated cyclic cleavage of metal ion-dependent DNAzymes for amplified and colorimetric detection of human serum copper (II)

Daxiu Li, Jiaqing Xie, Wenjiao Zhou, Bingying Jiang, Ruo Yuan, Yun Xiang

The determination of the level of Cu(2+) plays important roles in disease diagnosis and environmental monitoring. By coupling Cu(+)-catalyzed click chemistry and metal ion-dependent DNAzyme cyclic amplification, we have developed a convenient and sensitive colorimetric sensing method for the detection of Cu(2+) in human serums. The target Cu(2+) can be reduced by ascorbate to form Cu(+), which catalyzes the azide-alkyne cycloaddition between the azide- and alkyne-modified DNAs to form Mg(2+)-dependent DNAzymes. Subsequently, the Mg(2+) ions catalyze the cleavage of the hairpin DNA substrate sequences of the DNAzymes and trigger cyclic generation of a large number of free G-quadruplex sequences, which bind hemin to form the G-quadruplex/hemin artificial peroxidase to cause significant color transition of the sensing solution for sensitive colorimetric detection of Cu(2+). This method shows a dynamic range of 5 to 500 nM and a detection limit of 2 nM for Cu(2+) detection. Besides, the level of Cu(2+) in human serums can also be determined by using this sensing approach. With the advantages of simplicity and high sensitivity, such sensing method thus holds great potential for on-site determination of Cu(2+) in different samples. Graphical abstract Sensitive colorimetric detection of copper (II) by coupling click chemistry with metal ion-dependentDNAzymes.