Logically Regulating Peroxidase-Like Activity of Gold Nanoclusters for Sensing Phosphate-Containing Metabolites and Alkaline Phosphatase Activity

Phosphate-containing metabolites and alkaline phosphatase (ALP) activity are useful biomarkers for many types of diseases. However, there are few straightforward, sensitive, and efficient colorimetric methods for the quantification of them only when resorting to unstable transition metal ions or specially designed organic substrates. Herein, we have demonstrated that histidine-protected gold nanoclusters (His-AuNCs) possess intrinsic peroxidase-like activity with Au atom facilitated formation of superoxide anions (O₂^•-) and their electron transfer ability. More interestingly, phosphate-containing metabolites can severely inhibit the peroxidase-like activity of His-AuNCs by blocking the generation of O₂^•- and electron transfer, and then ALP is able to restore the inhibition process through hydrolyzing the phosphate-containing metabolites. Therefore, using peroxidase-triggered chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) as an amplifier, a colorimetric on-off-on switch has been developed for sensing phosphate-containing metabolites and ALP based on the logical regulation of such deactivation and reactivation processes for the first time. According to the intrinsic mimic enzyme-catalyzed amplification and clear response mechanism, our colorimetric assay exhibits excellent sensitivity, selectivity, and sensing performance. Furthermore, on the basis of the proposed colorimetric sensors, a combinatorial "NOR+IMPLICATION" logic gate is further rationally constructed.