A walk along DNA using bipedal migration of a dynamic and covalent crosslinker.

DNA has previously served as an excellent scaffold for molecular transport based on its non-covalent base pairing to assemble both stationary and mobile elements. Use of DNA can now be extended to transport systems based on reversible covalent chemistry. Autonomous and bipedal-like migration of crosslinking within helical DNA is made possible by tandem exchange of a quinone methide intermediate. In this report, net transport is illustrated to proceed over 10 base pairs. This process is driven towards its equilibrium distribution of crosslinks and consumes neither the walker nor the track irreversibly. Successful migration requires an electron-rich quinone methide to promote its regeneration and a continuous array of nucleophilic sites along its DNA track. Accordingly, net migration can be dramatically influenced by the presence of noncanonical structures within duplex DNA as demonstrated with a backbone nick and extrahelical bulge.