I-motif Formed at Physiological pH Triggered by Spatial Confinement of Nanochannels: An Electrochemical Platform for pH Monitoring in Brain Microdialysates

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)_n spacer, 5′-COOH-(T)_n-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.