Search

This work was supported by the award of a Postgraduate Studentship from Engineering and Physical Sciences Research Council (EP/K503162/1) to TK and by the University of St Andrews. The emergence of collections of simple chemical entities that create self-sustaining reaction networks, embedding replication and catalysis, is cited as a potential mechanism for the appearance on the early Earth of systems that satisfy minimal definitions of life. In this work, a functional reaction network that creates and maintains a set of privileged replicator structures through auto- and cross-catalyzed reaction cycles is created from the pairwise combinations of four reagents. We show that the addition of individual preformed templates to this network, representing instructions to synthesize a specific replicator, induces changes in the output composition of the system that represent a network-level response. Further, we establish through sets of serial transfer experiments that the catalytic connections that exist between the four replicators in this network and the system-level behavior thereby encoded impose limits on the compositional variability that can be induced by repeated exposure to instructional inputs, in the form of preformed templates, to the system. The origin of this persistence is traced through kinetic simulations to the properties and inter-relationships between the critical ternary complexes formed by the auto- and crosscatalytic templates. These results demonstrate that in an environment where there is no continuous selection pressure, the network connectivity, described by the catalytic relationships and system-level interactions between the replicators, is persistent, thereby limiting the ability of this network to adapt and evolve. Postprint

Financial support for this work was provided by the University of St Andrews and EaStCHEM, Northwestern University, and the Engineering and Physical Sciences Research Council (Grant EP/K503162/1). Establishing instructable and self-sustaining replication networks in pools of chemical reagents is a key challenge in systems chemistry. Self-replicating templates are formed from two constituent components with complementary recognition and reactive sites via a slow bimolecular pathway and a fast template-directed pathway. Here, we re-engineer one of the components of a synthetic replicator to encode an additional recognition function, permitting the assembly of a binary complex between the components that mediates replicator formation through a template-independent pathway, which achieves maximum rate acceleration at early time points in the replication process. The complementarity between recognition sites creates a key conformational equilibrium between the catalytically inert product, formed via the template-independent pathway, and the catalytically active replicator that mediates the template-directed pathway. Consequently, the rapid formation of the catalytically inert isomer “kickstarts” replication through the template-directed pathway. Through kinetic analyses, we demonstrate that the presence of the two recognition-mediated reactivity modes results in enhanced template formation in comparison to systems capable of exploiting only a single recognition-mediated pathway. Finally, kinetic simulations reveal that the conformational equilibrium and both the relative and absolute efficiencies of the recognition-mediated pathways affect the extent to which self-replicating systems can benefit from this additional template-independent reactivity mode. These results allow us to formulate the rules that govern the coupling of replication processes to alternative recognition-mediated reactivity modes. The interplay between template-directed and template-independent pathways for replicator formation has significant relevance to ongoing efforts to design instructable and adaptable replicator networks. Postprint

The financial support for this work was provided by EaStCHEM and the Engineering and Physical Sciences Research Council (Grant EP/K503162/1). The creation of reaction networks capable of exhibiting responses that are properties of entire systems represents a significant challenge for the chemical sciences. The system- level behavior of a reaction network is linked intrinsically to its topology and the functional connections between its nodes. A simple network of chemical reactions constructed from four reagents, in which each reagent reacts with exactly two others, can exhibit up-regulation of two products even when only a single chemical reaction is addressed catalytically. We implement a system with this topology using two maleimides and two nitrones of different sizes—either short or long and each bearing complementary recognition sites—that react pairwise through 1,3-dipolar cycloaddition reactions to create a network of four length-segregated replicating templates. Comprehensive 1H NMR spectroscopy experiments unravel the network topology, confirming that, in isolation, three out of four templates self-replicate, with the shortest template exhibiting the highest efficiency. The strongest template effects within the network are the mutually cross-catalytic relationships between the two templates of intermediate size. The network topology is such that the addition of different preformed templates as instructions to a mixture of all starting materials elicits system-level behavior. Instruction with a single template up-regulates the formation of two templates in a predictable manner. These results demonstrate that the rules governing system-level behavior can be unraveled through the application of wholly synthetic networks with well-defined chemistries and interactions. Postprint

The financial support for this work was provided by the University of St Andrews and the Engineering and Physical Sciences Research Council (Grant EP/K503162/1). 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. Postprint

EZ-C acknowledges the University of St Andrews for financial support. IDWS acknowledges support from EPSRC (EP/J009016) and the European Research Council (grant 321305). IDWS also acknowledges support from a Royal Society Wolfson research merit award. DJ acknowledges the European Research Council (grant: 278845) and the RFI Lumomat for financial support. We present the first examples of dynamic supramolecular systems composed of cyclometalated Ir(III) complexes of the form of [Ir(C^N)2(N^N)]PF6 (where C^N is mesppy = 2-phenyl-4-mesitylpyridinato and dFmesppy = 2-(4,6-difluorophenyl)-4-mesitylpyridinato and N^N is 4,4':2',2'':4'',4'''-quaterpyridine, qpy) and zinc tetraphenylporphyrin (ZnTPP), assembled through non-covalent interactions between the distal pyridine moieties of the qpy ligand located on the iridium complex and the zinc of the ZnTPP. The assemblies have been comprehensively characterized by a series of analytical techniques (1H NMR titration experiments, 2D COSY and HETCOR NMR spectra and low temperature 1H NMR spectroscopy) and the crystal structures have been elucidated by X-ray diffraction. The optoelectronic properties of the assemblies and the electronic interaction between the iridium and porphyrin chromophoric units have been explored with detailed photophysical measurements, supported by time-dependent density functional theory (TD-DFT) calculations. Postprint

This work was supported by University of St Andrews and the award of a Postgraduate Studentship from Engineering and Physical Sciences Research Council (EP/K503162/1) to T. K. A significant number of synthetic systems capable of replicating themselves or entities that are complementary to themselves have appeared in the last 30 years. Building on an understanding of the operation of synthetic replicators in isolation, this field has progressed to examples where catalytic relationships between replicators within the same network and the extant reaction conditions play a role in driving phenomena at the level of the whole system. Systems chemistry has played a pivotal role in the attempts to understand the origin of biological complexity by exploiting the power of synthetic chemistry, in conjunction with the molecular recognition toolkit pioneered by the field of supramolecular chemistry, thereby permitting the bottom-up engineering of increasingly complex reaction networks from simple building blocks. This review describes the advances facilitated by the systems chemistry approach in relating the expression of complex and emergent behaviour in networks of replicators with the connectivity and catalytic relationships inherent within them. These systems, examined within well-stirred batch reactors, represent conceptual and practical frameworks that can then be translated to conditions that permit replicating systems to overcome the fundamental limits imposed on selection processes in networks operating under closed conditions. This shift away from traditional spatially homogeneous reactors towards dynamic and non-equilibrium conditions, such as those provided by reaction-diffusion reaction formats, constitutes a key change that mimics environments within cellular systems, which possess obvious compartmentalisation and inhomogeneity. Postprint

The authors thank EPSRC for postgraduate studentship awards to JH (EP/ E017851/1) and TK (EP/K503162/1). A simple synthetic autocatalytic replicator is capable of establishing and driving the propagation of a reaction-diffusion front within a 50 µL syringe. This replicator templates its own synthesis through a 1,3-dipolar cycloaddition reaction between a nitrone component, equipped with a 9-ethynylanthracene optical tag, and a maleimide. Kinetic studies using NMR and UV-Vis spectroscopies confirm that the replicator forms ef-ficiently and with high diastereoselectivity and this rep-lication process brings about a dramatic change in opti-cal properties of the sample – a change in the color of the fluorescence in the sample from yellow to blue. The addition of a small amount of the pre-formed replicator at a specific location within a microsyringe, filled with the reaction building blocks, results in the initiation and propagation of a reaction-diffusion front. The realization of a replicator capable of initiating a reaction-diffusion front provides a platform for the examination of inter-connected replicating networks under non-equilibrium conditions involving diffusion processes. Postprint