Light-driven conformational switch of i-motif DNA.

With the advantages of conformational polymorphism and programmable sequence recognition, DNA has now become a powerful tool in nanostructure fabrication and nanodevice design. In most reported cases, DNA-based nanodevices are associated with a conformational switch driven by external fuels, such as DNA/RNA strands, acids/bases, enzymes, or chemical oscillators, in contact mode. These driving methods are still far different from the electrical/ optical signal that silicon-based microelectronic devices can process and, as a result, limit the integration and further applications of the DNA devices. Thus, the regulation of DNA conformation by a noncontact stimulator, like photo/electrical signals, has become an important challenge in DNA-nanodevice design. Only a few attempts have been reported, for example, the introduction of azobenzene substitution into DNA strands to serve as a UV-sensitive artificial base pair and influence the strand melting point or remote electronic control over the hybridization behavior of DNAmolecules by inductive coupling of a radio-frequency magnetic field to a metal nanocrystal covalently linked to DNA. Recently, a strategy involving temporary masking of the Watson–Crick base pairing with a photolabile protecting group, called “caging”, has been developed. However, a photoinduced conformational switch of natural DNA has not been achieved. Herein, we present our approach for achieving a light-induced naturalDNA conformational switch between close-packed quadruplex and random-coil structures with a reversible photoirradiated pH-jump system. The mechanism of our light-driven DNA conformational switch system is illustrated in Figure 1. It comprises three main components: 1) a 21mer DNA X : 5’-CCCTAACCC TAACCCTAACCC-3’; 2) a light-induced hydroxide ion emitter, molecular malachite green carbinol base (MGCB); 3) a surfactant, cetyltrimethylammonium bromide (CTAB), that is used to improve the solubility of MGCB. It is well known that DNA strands with stretches of cytosine bases can form closely packed four-stranded structures called the “i motif” through protonated cytosine–cytosine (C:C) basepair formation under slightly acidic conditions. In our design, the initial solution containing DNA X, MGCB, and CTAB shows a slightly acidic pH value that facilitates the formation of the i-motif structure by DNA X. In the presence of 302-nm UV light, MGCB gives out OH ions, as well as showing an obvious color change, and this leads to an increase in the pH value. Thus, the i-motif structure will deform into random coils with deprotonation of the C:C base pairs. After the light is turned off, the malachite green (MG) cation will recombine with the OH ions and return to the MGCB form to complete the cycle. Consequently, the pH value decreases and the DNA X switches back to the i-motif conformation again. Accordingly, the conformational switch of DNA X could be cycled by turning the UV light on and off alternately. To verify that the designed system does work, circular dichroism (CD) spectroscopy has been employed to study the conformational changes of DNA during the cycling. As shown in Figure 2, when the system is in its initial state where the pH value is around 6.0, DNA X shows a positive peak near 285 nm, a crossover at around 270 nm, and a negative peak near 260 nm, thereby indicating a typical i-motif conformation. Control experiments showed that MGCB and CTAB have no obvious CD signal in the measured range whether Figure 1. Working mechanism of the light-induced conformational switch of DNA X. Inner cycle: The DNA conformational switch between the i-motif and random-coil structures. Outer cycle: The light-induced malachite green based pH jump. The conformational switch of DNA X was associated with the on and off phases of UV light through the translation of photoinduced hydroxide-group release by MGCB.