Hunting for the “Sweet Spot”: Effects of Contiguous Guanines and Strand Lengths on the Catalytic Performance of DNA-Based Peroxidase Mimetics

Abstract Guanine-rich DNA strands have the potential to activate Cu 2+ ions in peroxidase-like reactions based on the coordination of Cu 2+ with nucleobases. Comparative studies on the number of guanines elucidate a sequence dependency that contiguous guanines are crucial to intrinsic peroxidase mimicking activities of DNA-Cu(II). The optimal number of repeat units to boost the enzyme-like activity of Cu 2+ is identified via analyzing individual sequence of (T 3 G 2 ) n and (T 2 G 3 ) n . The catalytic performance of DNA-Cu(II) was found to be remarkably pH-tolerant through the H 2 O 2 -mediated oxidation of 3,3′,5,5′-tetramethylbenzidine at acidic pH, dopamine at neutral pH as well as methylene blue at alkaline pH, respectively. It is the first time to report that intrinsic peroxidase-like activities of DNA-Cu(II) are greatly associated with binding affinity and stoichiometry between Cu 2+ and DNA. (T 3 G 2 ) 4 -Cu(II) with a dominant 1:1 stoichiometry shows the K m toward H 2 O 2 of 93 mM at pH 4.0 and 8.65 mM at pH 11.0. This study paves a way to rationally design artificial metalloenzymes, and the ability to tune the enzymatic activity would be harnessed for biocatalysis, biosensing, green synthesis and nanoscience. Graphical Abstract Remarkable pH-tolerant peroxidase mimetics was constructed by direct coordination of Cu 2+ within a guanine-rich DNA scaffold, of which the enzymatic activity is greatly associated with binding affinity and stoichiometry between Cu 2+ and DNA. Intriguingly, there exist optimal guanine numbers and strand lengths to boost the catalytic performance of Cu 2+ .