Lead (Pb) is a highly toxic heavy metal of great environmental and health concerns, and interestingly Pb 2+ has played important roles in nucleic acids chemistry. Since 2000, using DNA for selective detection of Pb 2+ has become a rapidly growing topic in the analytical community. Pb 2+ can serve as the most active cofactor for RNA-cleaving DNAzymes including the GR5, 17E and 8–17 DNAzymes. Recently, Pb 2+ was found to promote a porphyrin metalation DNAzyme named T30695. In addition, Pb 2+ can tightly bind to various G-quadruplex sequences inducing their unique folding and binding to other molecules such as dyes and hemin. The peroxidase-like activity of G-quadruplex/hemin complexes was also used for Pb 2+ sensing. In this article, these Pb 2+ recognition mechanisms are reviewed from fundamental chemistry to the design of fluorescent, colorimetric, and electrochemical biosensors. In addition, various signal amplification mechanisms such as rolling circle amplification, hairpin hybridization chain reaction and nuclease-assisted methods are coupled to these sensing methods to drive up sensitivity. We mainly cover recent examples published since 2015. In the end, some practical aspects of these sensors and future research opportunities are discussed. • Fundamentals of Pb 2+ recognition by DNA including DNAzymes and G-quadruplex DNA reviewed • Literature in the last five years summarized • Practical aspect of Pb 2+ detection using DNA discussed

Since 1994, deoxyribozymes or DNAzymes have been in vitro selected to catalyze various types of reactions. Metal ions play a critical role in DNAzyme catalysis, and Zn2+ is a very important one among them. Zn2+ has good biocompatibility and can be used for intracellular applications. Chemically, Zn2+ is a Lewis acid and it can bind to both the phosphate backbone and the nucleobases of DNA. Zn2+ undergoes hydrolysis even at neutral pH, and the partially hydrolyzed polynuclear complexes can affect the interactions with DNA. These features have made Zn2+ a unique cofactor for DNAzyme reactions. This review summarizes Zn2+ -dependent DNAzymes with an emphasis on RNA-/DNA-cleaving reactions. A key feature is the sharp Zn2+ concentration and pH-dependent activity for many of the DNAzymes. The applications of these DNAzymes as biosensors for Zn2+ , as therapeutic agents to cleave intracellular RNA, and as chemical biology tools to manipulate DNA are discussed. Future studies can focus on the selection of new DNAzymes with improved performance and detailed biochemical characterizations to understand the role of Zn2+ , which can facilitate practical applications of Zn2+ -dependent DNAzymes.