School of Chemistry and Molecular Engineering, East China Normal University, Dongchuan Road 500, Shanghai 200241, China.
Anal Chem. 2020 Mar 17;92(6):4535-4540. doi: 10.1021/acs.analchem.9b05732. Epub 2020 Feb 25.
The development of switches responding to specific pH changes was particularly useful in wide application fields. Owing to flexible switches simulated by pH, i-motif DNAs are widely used as a pH sensor. But its character of structure transition strongly dependent on acidic pH severely hampers the application of i-motif DNA in physiological media. Herein, we report the stable i-motif structure formed at a physiological pH triggered by spatial confinement of silica nanochannels. Three classic DNA chains containing 21-mer i-motif domain base-pairs and a single-stranded multiply (T) spacer, 5'-COOH-(T)-CCCTAACCCTAACCCTAACCC-3', were employed to evaluate the enhanced stability of i-motif structure. Compared to their free states in a dilute solution, the transition pH of all i-motif DNAs decorated in nanochannels remarkably shifts toward a neutral pH. Moreover, the transition midpoint can be tuned sensitively over the physiologically relevant pH range through slightly varying the length of T base spacer. Density functional theory (DFT) calculations validate that the increased proton density in a nanochannel triggers the formation of an i-motif structure under a neutral pH. Finally, this i-motif DNA based nanochannels electrode was successfully employed to monitor pH in brain microdialysates followed by cerebral ischemia. The present approach is not limited by fundamental investigation for DNA conformation but may extend toward the manipulation of i-motif based structures for artificial molecular machines and signaling systems.
对特定 pH 值变化有响应的开关的发展在广泛的应用领域特别有用。由于 pH 模拟的灵活开关，i-motif DNA 被广泛用作 pH 传感器。但其结构转换强烈依赖于酸性 pH 的特性严重阻碍了 i-motif DNA 在生理介质中的应用。在此，我们报道了由二氧化硅纳米通道的空间限制引发的在生理 pH 值下形成的稳定 i-motif 结构。使用三条含有 21 个碱基对的 i-motif 结构域和单链多（T）间隔基的经典 DNA 链，5'-COOH-(T)-CCCTAACCCTAACCCTAACCC-3'，来评估 i-motif 结构的增强稳定性。与它们在稀溶液中的自由状态相比，所有在纳米通道中修饰的 i-motif DNA 的转变 pH 值都明显向中性 pH 值移动。此外，通过稍微改变 T 碱基间隔的长度，可以敏感地调节转变中点在生理相关 pH 范围内。密度泛函理论（DFT）计算验证了纳米通道中增加的质子密度在中性 pH 值下触发 i-motif 结构的形成。最后，该基于 i-motif DNA 的纳米通道电极成功用于监测脑微透析液中的 pH 值，随后进行脑缺血。这种方法不仅受到 DNA 构象的基础研究的限制，而且可能扩展到基于 i-motif 的结构的人工分子机器和信号系统的操作。
