“…A sought-after target for GQ-sensing includes lead ion (Pb 2+ ), − which is a highly toxic heavy metal, with the ability to induce GQ-folding with superior stability compared to other common metals, such as K + and Na + . − Typical platforms are label-free (Figure A), using either GQ-specific fluorescent light-up probes − or the GQ/hemin DNAzyme complex for signal amplification. , These platforms can provide a turn-on response to Pb 2+ -binding upon formation of parallel GQ structures, ,, which contain an exposed outer G-tetrad for strong π-stacking interactions with the free dye. A turn-off response occurs when Pb 2+ -binding promotes GQ polymorphism and transitions the parallel GQ motif (favored by K + ) into an antiparallel GQ structure, which is a poor target for planar aromatic probes because their outer G-tetrads are partially shielded by lateral or diagonal loops. ,, However, GQ-sensing of Pb 2+ using such noncovalent labels presents significant challenges in real samples with coexisting metal cations, especially K + , and other molecules that can promote nonspecific GQ binding that generate false-positive outcomes …”