A Critical Cross-Catalytic Relationship Determines the Outcome of Competition in a Replicator Network

A network of two synthetic replicators
exhibits a critical unidirectional
cross-catalytic relationship that directs competing replication processes.
In this network, nitrone N bearing a 6-methylamidopyridine
recognition site can participate in 1,3-dipolar cycloaddition reactions
with two maleimides that differ in the relative position of their
carboxylic acid recognition site: either para (Mp) or meta (Mm) relative to the maleimide ring.
These cycloaddition reactions create replicators trans-Tp and trans-Tm. In isolation, trans-Tp templates its own formation
with an efficiency that is markedly greater than that of trans-Tm. Kinetic fitting and simulations
reveal that this efficiency arises from a higher template-mediated
rate constant for the cycloaddition and lower stability of the trans-Tp template duplex,
compared to trans-Tm. By contrast, in a situation where Mp and Mm compete
for a limited quantity of N, the normally less efficient trans-Tm outcompetes trans-Tp. Through a
series of comprehensive kinetic 19F­{1H} NMR
spectroscopy experiments, this system-level outcome is traced to a
critical cross-catalytic pathway, whereby the presence of trans-Tp templates
the formation of trans-Tm, but not vice versa. Replicator trans-Tm also reduces the efficiency
of its competitor trans-Tp by sequestering trans-Tp in a heteroduplex that is more stable than
homoduplex [Tp·Tp]. The addition of different templates as
instructions reveals that, while the outcome of competition between
replicators can be altered selectively, it is limited by the reaction
environment employed. These results represent a conceptual and practical
framework for the examination of selectivity in replication networks
operating outside well-stirred batch reactor conditions.