A reactive nitrone-based organogel that self-assembles from its constituents in chloroform

The authors thank the EPSRC for funding (DTA studentship to JER, EP/K503162/1)The reversible reaction of an aldehyde with a hydroxylamine affords a nitrone which is capable of forming a stiff gel with chloroform at concentrations as low as 0.20 wt% (6 mM). The gelator forms dynamically from its constituents and the gel assembly can be degraded in a controlled manner through a recognition-mediated reaction that targets the nitrone component of the gel network.PostprintPeer reviewe

Two synthetic replicators compete to process a dynamic reagent pool

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.Complementary building blocks, comprising a set of four aromatic aldehydes and a set of four nucleophiles—three anilines and one hydroxylamine—combine through condensation reactions to afford a dynamic covalent library (DCL) consisting of the eight starting materials and 16 condensation products. One of the aldehydes and, consequently, all of the DCL members derived from this compound bear an amidopyridine recognition site. Exposure of this DCL to two maleimides, Mp and Mm, each equipped with a carboxylic acid recognition site, results in the formation of a series of products through irreversible 1,3-dipolar cycloaddition reactions with the four nitrones present in the DCL. However, only the two cycloadducts in the product pool that incorporate both recognition sites, Tp and Tm, are self-replicators that can harness the DCL as feedstock for their own formation, facilitating their own synthesis via autocatalytic and cross-catalytic pathways. The ability of these replicators to direct their own formation from the components present in the dynamic reagent pool in response to the input of instructions in the form of preformed replicators is demonstrated through a series of quantitative 19F{1H} NMR spectroscopy experiments. Simulations establish the critical relationships between the kinetic and thermodynamic parameters of the replicators, the initial reagent concentrations, and the presence or absence of the DCL and their influence on the competition between Tp and Tm. Thus, we establish the rules that govern the behavior of the competing replicators under conditions where their formation is coupled tightly to the processing of a DCL.PostprintPeer reviewe

A recognition-mediated reaction drives amplification within a dynamic library

The authors thank EaStCHEM (Graduate Studentship to JWS) and the University of St Andrews for financial support.A single, appropriately designed, recognition event targets and transforms one of two reactive members of an exchanging pool of compounds through a recognition-mediated irreversible cycloaddition reaction, altering dramatically the final composition and kinetic behaviour of the dynamic library.Publisher PDFPeer reviewe

A synthetic replicator drives a propagating reaction-diffusion front

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.PostprintPeer reviewe

A dissipative reaction network drives transient solid-liquid and liquid-liquid phase cycling of nanoparticles

Financial support for this work was provided by the University of St Andrews and EaStCHEM, and the Leverhulme Trust [Grant RPG-2019-155].Transient states maintained by energy dissipation are an essential feature of dynamic systems where structures and functions are regulated by fluxes of energy and matter through chemical reaction networks. Perfected in biology, chemically fueled dissipative networks incorporating nanoscale components allow the unique properties of nanomaterials to be bestowed with spatiotemporal adaptability and chemical responsiveness. We report the transient dispersion of gold nanoparticles in water, powered by dissipation of a chemical fuel. A dispersed state that is generated under nonequilibrium conditions permits fully reversible solid–liquid or liquid–liquid phase transfer. The molecular basis of the out-of-equilibrium process is reversible covalent modification of nanoparticle-bound ligands by a simple inorganic activator. Activator consumption by a coupled dissipative reaction network leads to autonomous cycling between phases. The out-of-equilibrium lifetime is tunable by adjusting pH, and reversible phase cycling is reproducible over several cycles.Publisher PDFPeer reviewe

A critical cross-catalytic relationship determines the outcome of competition in a replicator network

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.PostprintPeer reviewe

Exploring the emergence of complexity using synthetic replicators

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.PostprintPeer reviewe

Cooperative binding in a phosphine oxide-based halogen bonded dimer drives supramolecular oligomerization

The authors thank the Marie Curie Initial Training Network on Replication and Adaption in Networks (ReAd) for financial support (early stage researcher funding to L.M.).Triphenylphosphine oxide forms halogen-bonded (XB) complexes with pentafluoroiodobenzene and a 1,4-diaryl-5-iodotriazole. The stability of these complexes is assessed computationally and by 31P NMR spectroscopy in d8-toluene solution, where both complexes are weakly associated. This knowledge is applied to the design and synthesis of two self-complementary phosphine oxide-iodotriazole hybrids that incorporate a phosphine oxide XB acceptor and a 1,4-diphenyl-5-iodotriazole XB donor within the same molecule. The self-complementary design of these modules facilitates their assembly in both d8-toluene and, surprisingly, d2-DCM into dimers, with significant stabilities, through the formation of halogen-bonded diads. The stability of these assemblies is a result of significant levels of cooperative binding that is present in both solvents. The connection of two of these hybrid units together, using a flexible spacer, facilitates the aggregation of these modules in d2-DCM solution, through halogen bonding, forming oligomeric assemblies.PostprintPeer reviewe

Generating system-level responses from a network of simple synthetic replicators

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.PostprintPeer reviewe

Orthogonal recognition processes drive the assembly and replication of a [2]rotaxane

The financial support for this work was provided by EPSRC (Grant EP/K503162/1 and EP/E017851/1) and the Ministry for Higher Education Malaysia.Within a small, interconnected reaction network, orthogonal recognition processes drive the assembly and replication of a [2]rotaxane. Rotaxane formation is governed by a central, hydrogen-bonding-mediated binding equilibrium between a macrocycle and a linear component, which associate to give a reactive pseudorotaxane. Both the pseudorotaxane and the linear component undergo irreversible, recognition-mediated 1,3-dipolar cycloaddition reactions with a stoppering maleimide group, forming rotaxane and thread, respectively. As a result of these orthogonal recognition-mediated processes, the rotaxane and thread can act as auto-catalytic templates for their own formation and also operate as crosscatalytic templates for each other. However, the interplay between the recognition and reaction processes in this reaction network results in the formation of undesirable pseudorotaxane complexes, causing thread formation to exceed rotaxane formation in the current experimental system. Nevertheless, in the absence of competitive macrocycle-binding sites, realization of a replicating network favoring formation of rotaxane is possible.PostprintPeer reviewe