Motion -be it the ability to change shape, rotate or translate -is an important potential asset for functional nanostructures. For translational motion, a variety of DNA-based and small-molecule walkers have been created, but observing the translational motion of individual molecules in real time remains a significant challenge. Here, we show that the movement of a small-molecule walker along a 5-foothold track can be monitored continuously within a protein nanoreactor. The walker is an organoarsenic(III) molecule with exchangeable thiol ligands, and the track a line of cysteine residues 6Å apart within an α-haemolysin protein pore that acts as the nanoreactor. Changes in the flow of ionic current through the pore reflect the individual steps of a single walker, which require the making and breaking of As-S bonds, and occur in aqueous solution at neutral pH and room temperature. The walker moves considerably faster (~0.7 s per step) than previous walkers based on covalent chemistry and is weakly processive (6 ± 1 steps per outing). It shows weak net directional movement, which can be described by a thermodynamic sink arising from the different environments of the cysteines that constitute the track.Creating nanoscale objects that can change shape1, rotate2,3 or translate4 is an important goal in nanotechnology. Examples of translational motion include chemotactic droplets5, chemically propelled objects6, and DNA walkers7, some of which offer the possibility of cargo delivery8-10. The development of small-molecule walkers is also under intense investigation11. The motion of such walkers can be random, or biased directionally through asymmetry of the track or the input of "fuel". Examples of non-covalent small-molecule walkers embrace various rotaxanes and related structures12. Walkers that employ covalent chemistry afford optimal spatial precision13, 14. For example, Leigh and co-workers observed the slow random motion of a functionally symmetric covalent walker, α-methylene-4-nitrostyrene, with a step-time of hours on a 9-foothold oligoethylenimine track15, 16. The walker lingered in a thermodynamic well at a terminal track site, thereby Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms * Correspondence and requests for materials should be addressed to G.S.P (gokce.pulcu@chem.ox.ac.uk) or H.B (hagan.bayley@chem.ox.ac.uk). Author Contributions: G.S.P. designed and performed experiments, analyzed data and wrote the paper; E.M. prepared the protein samples; L.C. synthesized the molecular walker and performed experiments; H.B. designed experiments, analyzed data and wrote the paper.Author Information: Readers are welcome to comment on the online version of the paper.The authors declare no competing financial interests. Europe PMC Funders GroupAuthor Manuscript Nat Nanotechnol. Author manuscript; available in PMC 2016 ...

Metal ion probes are used to assess the accessibility of cysteine side chains in polypeptides lining the conductive pathways of ion channels and thereby determine the conformations of channel states. Despite the widespread use of this approach, the chemistry of metal ion-thiol interactions has not been fully elucidated. Here, we investigate the modification of cysteine residues within a protein pore by the commonly used Ag(+) and Cd(2+) probes at the single-molecule level, and provide rates and stoichiometries that will be useful for the design and interpretation of accessibility experiments.

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complicating interferences, the variation of the binding strength across the different generation of UPys should arise solely from dendritic microenvironment and steric effects. These two series of compounds differ from one another in the proximity of the dendron to the central UPy unit. The first set of compounds S-Gn contains a methylene spacer between the UPy and the first branching point of the dendron, while the second L-Gn has a longer trimethylene spacer. Hence, the steric effect of the dendron should be less felt by the UPy unit in the latter series. We also examined the microenvironment of these hydrocarbon dendrons by carrying out solvatochromic studies on dendritic p-nitro-A C H T U N G T R E N N U N G aniline derivatives (S-Gn-probe) of the shorter chain S-Gn series. Based on these studies, we report that a) the polarity of the microenvironment of the three generation of hydrocarbon dendrons are nearly the same, b) all dendrons can preserve the dimerization strength (K dim* = 10 7 m À1 ) of the DDAA UPy tautomers at 25 8C, and for the dendrons L-Gn with a longer spacer, even at 50 8C, c) the % amount of DADA tautomer is different for these two series of compounds, and is also temperature dependent, d) the lower limits on K' dim* of the weaker DADA tautomers are found to be 10 5 -10 6 m À1 , and e) the proximity of the dendritic branching show that the UPy unit also exerts some effect on the binding strength. Hence the K dim* values of the (L-Gn) 2 are two times higher than those of the (S-Gn) 2 series in 10 % [D 6 ]DMSO/CDCl 3 solution. Our experimental findings show that the microenvironment polarity and the dendritic branching can have significant influence on the binding strength and profile in supramolecular hydrogen bonding.