Construction of a pH‐Mediated Single‐Molecule Switch with a Nanopore‐DNA Complex

Abstract A molecular switch is one of the simplest examples of artificial molecular machines. Even so, the development of molecular switches is still at its very early stage. Currently, building single‐molecule switches mostly rely on the molecular junction technique, but many of their performance characteristics are device‐dependent. Here, a pH‐mediated single‐molecule switch based on the combination of an α‐hemolysin (αHL) nanopore and a hexacyclen‐modified DNA strand is developed. The single‐stranded DNA is suspended inside an αHL through biotin‐streptavidin linkage and the hexacyclen‐modified nucleobase interacts with amino acid residues at positions 111, 113, and 147 to cause current oscillations. Distinct current transitions are observed when pH is tuned back and forth in the range of 3.0–7.4, with a typical “up” level when pH > 6.5 and a “down” level when pH < 4.5. This nanopore‐DNA complex possesses membrane‐bound advantages and may find applications in single‐cell studies where pH could be readily tuned to control ON‐OFF functions.