202 research outputs found

    Light-driven eco-evolutionary dynamics in a synthetic replicator system

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    Darwinian evolution involves the inheritance and selection of variations in reproducing entities. Selection can be based on, among others, interactions with the environment. Conversely, the replicating entities can also affect their environment generating a reciprocal feedback on evolutionary dynamics. The onset of such eco-evolutionary dynamics marks a stepping stone in the transition from chemistry to biology. Yet the bottom-up creation of a molecular system that exhibits eco-evolutionary dynamics has remained elusive. Here we describe the onset of such dynamics in a minimal system containing two synthetic self-replicators. The replicators are capable of binding and activating a co-factor, enabling them to change the oxidation state of their environment through photoredox catalysis. The replicator distribution adapts to this change and, depending on light intensity, one or the other replicator becomes dominant. This study shows how behaviour analogous to eco-evolutionary dynamics-which until now has been restricted to biology-can be created using an artificial minimal replicator system.</p

    (Re-)Directing Oligomerization of a Single Building Block into Two Specific Dynamic Covalent Foldamers through pH

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    Dynamic foldamers are synthetic folded molecules which can change their conformation in response to an external stimulus and are currently at the forefront of foldamer chemistry. However, constitutionally dynamic foldamers, which can change not only their conformation but also their molecular constitution in response to their environment, are without precedent. We now report a size- and shape-switching small dynamic covalent foldamer network which responds to changes in pH. Specifically, acidic conditions direct the oligomerization of a dipeptide-based building block into a 16-subunit macrocycle with well-defined conformation and with high selectivity. At higher pH the same building block yields another cyclic foldamer with a smaller ring size (9mer). The two foldamers readily and repeatedly interconvert upon adjustment of the pH of the solution. We have previously shown that addition of a template can direct oligomerization of the same building block to yet other rings sizes (including a 12mer and a 13mer, accompanied by a minor amount of 14mer). This brings the total number of discrete foldamers that can be accessed from a single building block to five. For a single building block system to exhibit such highly diverse structure space is unique and sets this system of foldamers apart from proteins. Furthermore, the emergence of constitutional dynamicity opens up new avenues to foldamers with adaptive behavior

    Catalysis as a Robust Feature and Catalytic Promiscuity as a Recurrent Trait in Peptide Based Self-Replicators

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    Recently, the first self-replicating molecules have been described that are capable of catalyzing different reactions in addition to their own formation. These findings raise the question whether such catalytic promiscuity is a widespread characteristic, or whether it is feature restricted to a special subset of replicators. Another related issue is whether catalytic activity of these systems is sensitive to alterations in the peptide structure. Both of these questions are relevant in the context of evolution. Widespread catalytic promiscuity would be beneficial if replicators are to acquire a metabolism that involves catalysis of different chemical reactions. Furthermore, in order to enable adaptation and acquisition of new traits through mutation and selection, it is desirable that self-replicating molecules can mutate and explore structure space while retaining their catalytic activity. Here we demonstrate that catalytic promiscuity of a class of peptide based self-replicators is indeed a recurrent trait in a significant fraction of the probed structure space. Specifically, we investigated eighteen self-assembly driven self-replicators, each made from a different single building block, and six replicators that emerged from a binary building block mixture. Most of these were found to catalyze both the retro-aldol reaction of methodol, as well as the cleavage of fluorenylmethoxycarbonyl (FMOC) groups. No obvious correlation exists between the efficiencies with which replicators catalyze these two reactions, indicating that the reactions have different requirements with respect to catalyst structure. The degree of catalytic activity varied with replicator structure spanning up to three orders of magnitude. Of the binary mixtures, most gave replicators with activities in between those of the replicators made of the corresponding individual building blocks. However, in one instance, where specific interactions promote the formation of a specific two-building-block replicator mutant, this species had an activity that exceeded that of the corresponding single-building-block replicators. These observations imply that evolutionary enhancement of a specific catalytic activity of self-replicating molecules should be possible also in a regime where mutation rates are relatively high

    Tailorable and Biocompatible Supramolecular-Based Hydrogels Featuring two Dynamic Covalent Chemistries

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    Dynamic covalent chemistry (DCC) has proven to be a valuable tool in creating fascinating molecules, structures, and emergent properties in fully synthetic systems. Here we report a system that uses two dynamic covalent bonds in tandem, namely disulfides and hydrazones, for the formation of hydrogels containing biologically relevant ligands. The reversibility of disulfide bonds allows fiber formation upon oxidation of dithiol-peptide building block, while the reaction between NH−NH2 functionalized C-terminus and aldehyde cross-linkers results in a gel. The same bond-forming reaction was exploited for the “decoration” of the supramolecular assemblies by cell-adhesion-promoting sequences (RGD and LDV). Fast triggered gelation, cytocompatibility and ability to “on-demand” chemically customize fibrillar scaffold offer potential for applying these systems as a bioactive platform for cell culture and tissue engineering

    Enantioselective Self-Replicators

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    Self-replicating molecules provide a simple approach for investigating fundamental processes in scenarios of the emergence of life. Although homochirality is an important aspect of life and of how it emerged, the effects of chirality on self-replicators have received only little attention so far. Here, we report several self-assembled self-replicators with enantioselectivity that emerge spontaneously and grow only from enantiopure material. These require a relatively small number of chiral units in the replicators (down to eight) and in the precursors (down to a single chiral unit), compared to the only other enantioselective replicator reported previously. One replicator was found to incorporate material of its own handedness with high fidelity when provided with a racemic mixture of precursors, thus sorting (L)- and (D)-precursors into (L)- and (D)-replicators. Systematic studies reveal that the presence or absence of enantioselectivity depends on structural features (ring size of the replicator) that appear to impose constraints on its supramolecular organization. This work reveals new aspects of the little researched interplay between chirality and self-replication and represents another step toward the de novo synthesis of life.</p

    Departure from Randomness: Evolution of Self-Replicators that can Self-Sort through Steric Zipper Formation

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    Darwinian evolution of synthetic self-replicating entities is likely to have an important role in the emergence of life from inanimate chemical matter. Darwinian evolution of self-replicators requires that these (i) have structural space accessible to them; (ii) occupy only part of this space at any one time, and (iii) navigate this space through a process of mutation and selection. We now report a system of self-replicating hexameric macrocycles that emerges upon mixing two building blocks. It occupies a subset of possible building block sequences. Specific interactions between the building blocks, most likely through steric zipper formation involving the interdigitation of a phenylalanine residue of one building block between two leucine residues of the other building block, results in the preferential formation of a hexamer with a sequence in which the two building blocks alternate. When this system was exposed to two different replication-destruction regimes, different replicator mutant distributions were selected for. When the destruction process was non-selective (mediated by outflow in an open system) the fastest replicating sequences dominated, overriding the preference for zipper formation observed in a closed vial. However, when destruction was mediated chemically (and therefore potentially selective) the replicator mutant that combined adequate resistance to reduction with adequate replication speed and was capable of steric zipper formation, became dominant. These results constitute a rudimentary form of Darwinian evolution where replicators adapt to a changing selection pressure through mutation and selection

    Stochastic Emergence of Two Distinct Self-Replicators from a Dynamic Combinatorial Library

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    [Image: see text] Unraveling how chemistry can give rise to biology is one of the greatest challenges of contemporary science. Achieving life-like properties in chemical systems is therefore a popular topic of research. Synthetic chemical systems are usually deterministic: the outcome is determined by the experimental conditions. In contrast, many phenomena that occur in nature are not deterministic but caused by random fluctuations (stochastic). Here, we report on how, from a mixture of two synthetic molecules, two different self-replicators emerge in a stochastic fashion. Under the same experimental conditions, the two self-replicators are formed in various ratios over several repeats of the experiment. We show that this variation is caused by a stochastic nucleation process and that this stochasticity is more pronounced close to a phase boundary. While stochastic nucleation processes are common in crystal growth and chiral symmetry breaking, it is unprecedented for systems of synthetic self-replicators

    Systems Chemistry across Multiple Length Scales: Macroscopic Flow via Dissipative Co-Assemblies Featuring Transient Amides

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    Fueled chemical systems have considerable functional potential that is still largely unexplored. Here, we report a new approach to transient amide bond formation and use it to harness chemical energy and convert it to mechanical motion by integrating dissipative self-assembly and the Marangoni effect in a source-sink system. Droplets are formed through dissipative self-assembly following the reaction of octylamine with 2,3-dimethylmaleic anhydride. The resulting amides are hydrolytically labile making the droplets transient, which allows them to act as a source of octylamine. A sink for octylamine was created by placing a drop of oleic acid on the air-water interface. This source – sink system sets up a gradient in surface tension, which gives rise to a macroscopic Marangoni flow that can transport the droplets in solution with tunable speed. Carbodiimides can fuel this motion by converting diacid waste back to anhydride. This study shows how fueling at the molecular level can, via assembly at the supramolecular level, lead to liquid flow at the macroscopic level

    Selection of diverse polymorphic structures from a small dynamic molecular network controlled by the environment

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    The complex interplay between systems and their environment plays an important role in processes ranging from self-assembly to evolution. Polymorphism, where, from the same ingredients different products can be formed, is likely to be an important enabler for evolutionary adaptation. Environmental pressures may induce polymorphic behaviour, where different pressures result in different structural organisation. Here we show that by combining covalent and non-covalent bond formation three distinct polymorphs can emerge from the same small dynamic molecular network: vesicular aggregates, self-replicating fibres and nanoribbons, depending on the nature of the solvent environment. Additionally, a particular set of conditions allows the transient co-existence of both vesicles and fibres