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Single molecule chemistry and catalysis

Covalent chemistry in nanoreactors

Protein pores can be used as nanoreactors to study covalent chemistry at the single-molecule level. We have investigated a wide variety of chemistry in this way, including the formation and cleavage of arsenic-sulfur bonds, the photochemistry of 2-nitrobenzyl protecting groups, the photoisomerization of azobenzenes, the observation of polymerization one step at a time and a hydrogen-deuterium isotope effect. New directions include the incorporation of unnatural amino acids into the a-hemolysin pore, with which to expand the range of chemistries that can be investigated, and the examination of catalysis. The nanoreactor technology is also being adapted to study complex reaction networks and molecular walkers. Recently, we have demonstrated a processive molecular hopper that steps with nanometer resolution and reverses on command. The stepping motion may prove useful for nanopore biopolymer sequencing.   

Selected papers

Lee, J. and Bayley, H. A semisynthetic protein nanoreactor for single-molecule chemistry. Proc. Natl. Acad. Sci. USA 112, 13768-13773 (2015).


Qing, Y., Ionescu, S.A., Pulcu, G.S. and Bayley, H. Directional control of a processive molecular hopper. Science 361, 908-912 (2018). doi:10.1126/science.aat3872


Qing, Y., Tamagaki-Asahina, H., Ionescu, S.A., Liu, M.D. and Bayley, H. Catalytic site-selective substrate processing within a tubular nanoreactor. Nature Nanotechnology 14, 1135-1142 (2019). doi: 10.1038/s41565-019-0579-7.



Bayley, H., Luchian, T., Shin, S.-H. and  Steffensen, M.B. Single-molecule covalent chemistry in a protein nanoreactor, pp251-277, Chapter 10 in "Single Molecules and Nanotechnology", R. Rigler and H. Vogel, eds., Springer, Heidelberg (2008).


Ying, Y.L., Hu, Z.-L., Zhang, S., Qing, Y., Fragasso, A., Maglia, G., Meller, A., Bayley, H., Dekker, C. and Long, Y.-T. Nanopore technologies: beyond DNA sequencing. Nature Nanotechnology 17, 1136-1146 (2022). DOI: 10.1038/s41565-022-01193-2

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