A Dissipative Reaction Network Drives Transient Solid-Liquid and Liquid-Liquid Phase Cycling of Nanoparticles.

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 non-equilibrium 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 the pH value, and reversible phase cycling is reproducible over several cycles.

An electric molecular motor.

Macroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors1-3 that can be driven by electricity could not be more timely. Here we describe an electric molecular motor based on a [3]catenane4,5, in which two cyclobis(paraquat-p-phenylene)6 (CBPQT4+) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet7,8, whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by FOF1 ATP synthase9. The unidirectionality is powered by an oscillating10 voltage11,12 or external modulation of the redox potential13. Initially, we focused our attention on the homologous [2]catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT4+ ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a [3]catenane is free from the production of waste products and represents an important step towards surface-bound14 electric molecular motors.

A Molecular Replication Process Drives Supramolecular Polymerization.

Supramolecular polymers are materials in which the connections between monomers in the polymer main chain are non-covalent bonds. This area has seen rapid expansion in the last two decades and has been exploited in several applications. However, suitable contiguous hydrogen-bond arrays can be difficult to synthesize, placing some limitations on the deployment of supramolecular polymers. We have designed a hydrogen-bonded polymer assembled from a bifunctional monomer composed of two replicating templates separated by a rigid spacer. This design allows the autocatalytic formation of the polymer main chain through the self-templating properties of the replicators and drives the synthesis of the bifunctional monomer from its constituent components in solution. The template-directed 1,3-dipolar cycloaddition reaction between nitrone and maleimide proceeds with high diastereoselectivity, affording the bifunctional monomer. The high binding affinity between the self-complementary replicating templates that allows the bifunctional monomer to polymerize in solution is derived from the positive cooperativity associated with this binding process. The assembly of the polymer in solution has been investigated by diffusion-ordered NMR spectroscopy. Both microcrystalline and thin films of the polymeric material can be prepared readily and have been characterized by powder X-ray diffraction and scanning electron microscopy. These results demonstrate that the approach described here is a valid one for the construction of supramolecular polymers and can be extended to systems where the rigid spacer between the replicating templates is replaced by one carrying additional function.

Encoding Multiple Reactivity Modes within a Single Synthetic Replicator.

Establishing programmable 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 kick-starts 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 that of 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 programmable and adaptable replicator networks.

Single-Crystal Polycationic Polymers Obtained by Single-Crystal-to-Single-Crystal Photopolymerization.

The efficient preparation of single-crystalline ionic polymers and fundamental understanding of their structure-property relationships at the molecular level remains a challenge in chemistry and materials science. Here, we describe the single-crystal structure of a highly ordered polycationic polymer (polyelectrolyte) and its proton conductivity. The polyelectrolyte single crystals can be prepared on a gram-scale in quantitative yield, by taking advantage of an ultraviolet/sunlight-induced topochemical polymerization, from a tricationic monomer-a self-complementary building block possessing a preorganized conformation. A single-crystal-to-single-crystal photopolymerization was revealed unambiguously by in situ single-crystal X-ray diffraction analysis, which was also employed to follow the progression of molecular structure from the monomer, to a partially polymerized intermediate, and, finally, to the polymer itself. Collinear polymer chains are held together tightly by multiple Coulombic interactions involving counterions to form two-dimensional lamellar sheets (1 nm in height) with sub-nanometer pores (5 Å). The polymer is extremely stable under 254 nm light irradiation and high temperature (above 500 K). The extraordinary mechanical strength and environmental stability-in combination with its impressive proton conductivity (∼3 × 10-4 S cm-1)-endow the polymer with potential applications as a robust proton-conducting material. By marrying supramolecular chemistry with macromolecular science, the outcome represents a major step toward the controlled synthesis of single-crystalline polyelectrolyte materials with perfect tacticity.

Combining Intra- and Intermolecular Charge Transfer with Polycationic Cyclophanes To Design 2D Tessellations.

A series of donor-acceptor (D-A) naphthalene-viologen-based cyclophanes of different shapes, sizes, and symmetries have been synthesized and characterized. Solution optical studies on these cyclophanes reveal the existence of photoinduced intramolecular charge transfer (CT) at 465 nm from naphthalene (D) to viologen (A) units, resulting in a conformational change in the viologen units and the emergence of an emission at 540 nm. The D-A cyclophanes with box-like and hexagon-like shapes offer an opportunity to control the arrangement within 2D layers where D-A interactions direct the superstructures. While a box-like 2,6-disubstituted naphthalene-based tetracationic cyclophane does not form square tiling patterns, a truncated hexagon-like congener self-assembles to form a hexagonal superstructure which, in turn, adopts a hexagonal tiling pattern. Tessellation of the more rigid and highly symmetrical 2,7-disubstituted naphthalene-based cyclophanes leads to the formation of 2D square and honeycomb tiling patterns with the box-like and hexagon-like cyclophanes, respectively. Co-crystallization of the box-like cyclophanes with tetrathiafulvalene (TTF) results in the formation of D-A CT interactions between TTF and viologen units, leading to tubular superstructures. Co-crystallization of the hexagon-like cyclophane with TTF generates well-ordered and uniform tubular superstructures in which the TTF-viologen CT interactions and naphthalene-naphthalene [π···π] interactions propagate with 2D topology. In the solid state, the TTF-cyclophane co-crystals are paramagnetic and display dual intra- and intermolecular CT behavior at ∼470 and ∼1000 nm, respectively, offering multi-responsive materials with potential pathways for electron transport.

Compositional Persistence in a Multicyclic Network of Synthetic Replicators.

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.

Two Synthetic Replicators Compete To Process a Dynamic Reagent Pool.

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.

An Environmentally Responsive Reciprocal Replicating Network.

A reciprocal replication system is constructed from four building blocks, A, B, C, and D, which react in a pairwise manner through either a 1,3-dipolar cycloaddition or the condensation reaction between an amine and an aldehyde to create two templates, trans-TAB and TCD. These templates are equipped with complementary recognition sites-two carboxylic acids ( trans-TAB) or two 4,6-dimethylamidopyridines (TCD)-that enable each template to direct the formation of its complementary partner through two mutually reinforcing cross-catalytic pathways, in which the templates trans-TAB or TCD preorganize the appropriate building blocks within two catalytically active ternary complexes: [C•D• trans-TAB] and [A•B•TCD]. The template-directed processes within these complexes generate a heteroduplex [ trans-TAB•TCD], which is shown to possess significant stability through kinetic simulations and fitting. As a consequence, the individual cross-catalytic pathways perform more efficiently in template-directed experiments when the concentration of the template being formed is below that of the template added as instruction. Comprehensive analysis of the system in which A, B, C, and D are mixed together directly, using a series of 1H NMR spectroscopic kinetic experiments, demonstrates that the behavior of the reciprocal system is more than the simple sum of its parts-as part of the interconnected network, the product of each reaction clearly directs the fabrication of its reciprocal partner, facilitating both higher rates of formation for both templates and improved diastereoselectivity for trans-TAB. A simple change in experimental conditions (from dry to "wet" CDCl3) demonstrates the sensitivity of the replication pathways within the network to the reaction environment, which leads to a >10-fold increase in the contribution of a new minimal self-replicator, trans-TAB*, to the replication network.

Exploring the emergence of complexity using synthetic replicators.

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.

Generating System-Level Responses from a Network of Simple Synthetic Replicators.

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.

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.

pH controlled assembly of a self-complementary halogen-bonded dimer.

Phenols and their corresponding phenoxide anions can form halogen bonds with neutral iodotriazoles. The strength of these interactions depends critically on the protonation state of the oxygen atom - the interaction of the phenoxide anion is more than an order of magnitude stronger than the corresponding phenol. The assembly of a molecule bearing both an iodotriazole and a phenoxide anion into a self-complementary dimer, stabilised by two halogen bonds between the phenoxide anions and the neutral iodotriazoles has been demonstrated. The corresponding phenol shows no halogen bond mediated assembly either in the solid or in the solution state. This assembly process can be actuated simply by a change in protonation state - treatment of the phenol with one equivalent of base results in deprotonation and assembly of the dimer. The structure of the homodimer formed by the phenoxide-bearing iodotriazole has been determined in the solid state and 19F NMR spectroscopy demonstrates that the assembled dimer persists in solution and that it has significant stability. 19F NMR spectroscopy has also been used to demonstrate that the assembly process is completely reversible.

Cooperative Binding in a Phosphine Oxide-Based Halogen Bonded Dimer Drives Supramolecular Oligomerization.

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 toluene-d8 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 toluene-d8 and, surprisingly, DCM-d2 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 DCM-d2 solution, through halogen bonding, forming oligomeric assemblies.

Exploring the self-assembly and energy transfer of dynamic supramolecular iridium-porphyrin systems.

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.

A Synthetic Replicator Drives a Propagating Reaction-Diffusion Front.

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 efficiently and with high diastereoselectivity, and this replication process brings about a dramatic change in optical 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 preformed 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 interconnected replicating networks under out-of-equilibrium conditions involving diffusion processes.

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

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.

Probing the Limits of Selectivity in a Recognition-Mediated Reaction Network Embedded within a Dynamic Covalent Library.

Two recognition-mediated reaction processes operating through reactive binary complexes drive resolution of a 24-component dynamic covalent library, assembled from individual aldehydes and nucleophiles. The effectiveness of the library resolution and selective amplification of one recognition-enabled species over another is limited by the difference in the rates of the recognition-mediated reactive processes and the strength of the recognition processes employed in the dynamic system.

Exploiting recognition-mediated assembly and reactivity in [2]rotaxane formation.

A small molecular reaction network exploits recognition-mediated reactive processes in order to drive the assembly and formation of both a self-replicating linear template (thread) and a [2]rotaxane, in which the linear template is encircled by a diamide macrocycle. Complementary recognition sites, placed at strategic positions on the reactive building blocks, drive these assembly and replication processes. Template-instructed experiments show that the thread is capable of efficient self-replication and that no cross-catalytic relationships exist between the thread and the [2]rotaxane. The rate of [2]rotaxane formation is insensitive to the addition of a preformed template, however, [2]rotaxane formation does show enhanced diastereoselectivity, most likely originating from its recognition-mediated formation through a ternary reactive complex.

Neutral iodotriazoles as scaffolds for stable halogen-bonded assemblies in solution.

The halogen bond (XB) donor properties of neutral 1,4-diaryl-5-iodo-1,2,3-triazoles are explored using a combination of computational and experimental results and are shown to be competitive in halogen bonding efficiency with the classic pentafluoroiodobenzene XB donor. The SNAr reactivity of these donors permits the facile assembly of an iodotriazole functionalised with a 3-oxypyridine XB acceptor, thus generating a molecular scaffold capable of undergoing dimerisation through the formation of two halogen bonds. The formation of this halogen-bonded dimer is demonstrated by 1H and DOSY NMR experiments and a plausible structure generated using DFT calculations.