Systems Chemistry: Molecular Recognition, Catalysis and Self-Replication
How the immense complexity of living organisms has arisen is one of the most intriguing questions
in contemporary science. We have started to explore experimentally how organization and function
can emerge from complex molecular networks in aqueous solution.1 We focus on networks of
molecules that can interconvert, to give mixtures that can change their composition in response to
external or internal stimuli. Molecular recognition between molecules in such mixtures leads to their
mutual stabilization, which drives the synthesis of more of the privileged structures.2
In this talk I will focus on two systems. The first is based on a single building block
that gives rise to a small but unusually rich molecular network that can be induced to
form catenanes (in the absence of any added template)2a, a self-replicator (upon
seeding), a catalyst (upon addition of its substrate), a synthetic receptor (upon adding
a single template) and an allosteric receptor (upon adding two separate templates).
The second part of the talk will focus on self-replicating
systems, where replication is driven by self-recognition of a
molecule in the dynamic network.3 Oxidation of a peptidefunctionalized dithiol building block gives rise to a mixture of
different-sized macrocycles. Stacking of the macrocycles into
fibers may result in the autocatalytic production of more of
this particular macrocycle at the expense of the other material
in the molecular network. The selection rules that dictate
which (if any) replicator will emerge from such networks are
starting to become clear.
We have observed that factors such as mechanical energy
(stirring or shaking) and the presence of cosolvents can
determine which replicator wins the competition for building
blocks.
We have also witnessed a process akin to speciation in a
system made from a mixture of two building blocks.
1
(a) R. F. Ludlow, S. Otto, Chem. Soc. Rev. 2008, 37, 101-108. (b) P. T. Corbett, J. Leclaire, L.
Vial, K. R. West, J.-L. Wietor, J. K. M. Sanders, S. Otto Chem. Rev. 2006, 106, 3652-3711. (c) J. Li,
P. Nowak, S. Otto, J. Am. Chem. Soc. 2013, 135, 9222-9239.
2
(a) K. R. West; R. F. Ludlow; P. Besenius; P. T. Corbett; P. A. G. Cormack; D. C. Sherrington; S.
Otto, J. Am. Chem. Soc. 2008, 130, 10834-10835. (b) R. F. Ludlow; S. Otto, J. Am. Chem. Soc.
2008, 130, 12218-12219.
3
J. M. A. Carnall; C. A. Waudby; A. M. Belenguer; M. C. A. Stuart, J. J.-P. Peyralans, S. Otto,
Science 2010, 327, 1502-1506.