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.


Recent work includes the incorporation of unnatural amino acids into the α-hemolysin pore, with which to expand the range of chemistries that can be investigated. The nanoreactor technology has also been adapted to study complex reaction networks.


In this earlier work, mainly with small molecules, it was assumed that the chemistry was not affected by the nanoreactor, which is broadly true. Recently, we have investigated reactions that are affected by the surroundings including confinement within a nanoreactor and the chiral environment within a protein.


Examples include a processive molecular hopper that steps with nanometer resolution and reverses on command. Based on this, the chemical ratcheting of biopolymers for sequencing applications is being explored. Another recent success is site selectivity and regioselectivity produced by the alignment of reactants within a nanoreactor. A long-term goal is vectorial catalysis in which a substrate enters through one entrance of the pore and the products exits at the opposite end.

Selected papers

Qing, Y., Pulcu, G.S., Bell, N. and Bayley, H. Bioorthogonal cycloadditions with sub-millisecond intermediates. Angewandte Chemie Int. Ed. 57, 1218 (2018). DOI: 10.1002/anie.201710262

Qing, Y., Ionescu, S.A., Pulcu, G.S. and Bayley, H. Directional control of a processive molecular hopper. Science 361, 908 (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 (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). DOI:10.1007/978-3-540-73924-1_10