*2.2.2. DNA as sensors and imaging agents for metal ions*

Sensing and imaging of metal ions have attracted much attention by scientists and engineers because of the important roles of metals in many fields such as environmental, biological, and medical sciences. Significant progress has been made in developing sensors and imaging agents for the detection of metal ions, mostly based on organic molecules, peptides, proteins, or cells [39–45]. Prof. Yi Li has given a significant insight to the role of DNA as sensors and imaging agents for metal Ions [46], the structure of these systems is illustrated and described in **Figure 3**. DNA does not appear to be a good candidate for sensing metal ions with high selectivity because the negatively charged phosphodiester backbones of DNA are known to be capable of binding cationic metal ions with poor selectivity for any particular metal ion. While the four DNA bases can also serve as ligands for metal ions [47–49], many of these DNA–metal ion interactions are nonspecific and weak, making the use of DNA as sensors for metal ions very challenging because selectivity and sensitivity are required for the successful detection of a specific metal ion in the presence of other potentially interfering metals in

**Figure 3.** a. General sensor design based on nucleic acid cleavage of DNAzymes for metal-ion detection. b. Fluorescent Ag<sup>+</sup> sensor based on C–Ag<sup>+</sup> –C. c. Sensors based on G-quadruplex DNA stabilized by K<sup>+</sup> . Adapted with permission from Ref. [46].

complex samples. By incorporation of signal reporters such as chromophores, fluorophores, electrochemical tags, and Raman tags, these metal-ion-specific DNA sequences have been transformed into colorimetric, fluorescent, electrochemical, and Raman sensors and imaging agents for a broad range of metal ions with high sensitivity and selectivity [50–55]. DNAzymes that is highly selective to use specific metal ions as cofactors to catalyze reactions can be obtained. In this way, DNAzymes that are dependent on bivalent metals for various chemical and biological reactions have been successfully discovered. One report of DNAzyme sensor was a fluorescent sensor for Pb2+ based on DNAzyme [56–58], which showed much higher specificity to Pb2+ over other metal ions in catalyzing the cleavage of DNA substrates with a single RNA linkage (rA) at the cleavage site.

These sensors can be further classified into different parts:


*2.2.1. G4-wires DNA as nanowire*

174 Green Electronics

sensor based on C–Ag<sup>+</sup>

Nanowires known as G4-wires [34] (or quadruplexes), consist of stacked guanine (G) tetrads (G4). These one-dimensional polymers act as prospective candidates for bio-molecular electronics because, due to the low ionization potential of guanine (the lowest among nucleicacid bases), they might be suitable to mediate charge transport by hole conduction along the helix, and have even been suggested as nano-mechanical extension-contraction machines

guanylic strands in water [36, 37] as well as lipophilic guanosine monomers in organic solvents [38], self-assemble in right-handed quadruple helices. Recent investigations has been carried out for the G4-nanowires, but the conduction properties of these nanowires are basically unknown and a direct measurement of electrical properties of G4-wires is still missing.

Sensing and imaging of metal ions have attracted much attention by scientists and engineers because of the important roles of metals in many fields such as environmental, biological, and medical sciences. Significant progress has been made in developing sensors and imaging agents for the detection of metal ions, mostly based on organic molecules, peptides, proteins, or cells [39–45]. Prof. Yi Li has given a significant insight to the role of DNA as sensors and imaging agents for metal Ions [46], the structure of these systems is illustrated and described in **Figure 3**. DNA does not appear to be a good candidate for sensing metal ions with high selectivity because the negatively charged phosphodiester backbones of DNA are known to be capable of binding cationic metal ions with poor selectivity for any particular metal ion. While the four DNA bases can also serve as ligands for metal ions [47–49], many of these DNA–metal ion interactions are nonspecific and weak, making the use of DNA as sensors for metal ions very challenging because selectivity and sensitivity are required for the successful detection of a specific metal ion in the presence of other potentially interfering metals in

**Figure 3.** a. General sensor design based on nucleic acid cleavage of DNAzymes for metal-ion detection. b. Fluorescent Ag<sup>+</sup>

–C. c. Sensors based on G-quadruplex DNA stabilized by K<sup>+</sup>

and Na<sup>+</sup>

), solutions of homo-

. Adapted with permission from Ref. [46].

[35]. In the presence of appropriate metal cations (especially K<sup>+</sup>

*2.2.2. DNA as sensors and imaging agents for metal ions*


In this category, new technologies have been developed to design sensors based on commercialized devices, compatible with portable devices, which could enable to monitor metal ions by all.

#### *2.2.3. DNA-electrochemical biosensors*

DNA biosensors are the integrated receptor-transducer devices that use DNA as biomolecular recognition element to measure specific binding processes with DNA, by electrical, thermal or optical signal transduction methods. The characteristics of DNA probes with the capacity of direct and label-free electrochemical detection find applications in rapid monitoring of pollutant agents or metals in the environment, investigation and evaluation of DNA-drug interaction mechanisms, detection of DNA base damage in clinical diagnosis, or detection of specific DNA sequences in human, viral and bacterial nucleic acids [72–75].
