Binding of Precursors to Replicator Assemblies Can Improve Replication Fidelity and Mediate Error Correction.

Copying information is vital for life's propagation. Current life forms maintain a low error rate in replication, using complex machinery to prevent and correct errors. However, primitive life had to deal with higher error rates, limiting its ability to evolve. Discovering mechanisms to reduce errors would alleviate this constraint. Here, we introduce a new mechanism that decreases error rates and corrects errors in synthetic self-replicating systems driven by self-assembly. Previous work showed that macrocycle replication occurs through the accumulation of precursor material on the sides of the fibrous replicator assemblies. Stochastic simulations now reveal that selective precursor binding to the fiber surface enhances replication fidelity and error correction. Centrifugation experiments show that replicator fibers can exhibit the necessary selectivity in precursor binding. Our results suggest that synthetic replicator systems are more evolvable than previously thought, encouraging further evolution-focused experiments.

Assertive community treatment for high-utilizing alcohol misuse patients: a before-and-after cohort study protocol.

BACKGROUND: The challenge posed by Alcohol-Related Frequent Attenders (ARFAs) in Emergency Departments (EDs) is growing in Singapore, marked by limited engagement with conventional addiction treatment pathways. Recognizing this gap, this study aims to explore the potential benefits of Assertive Community Treatment (ACT) - an innovative, community-centered, harm-reduction strategy-in mitigating the frequency of ED visits, curbing Emergency Medical Services (EMS) calls, and uplifting health outcomes across a quartet of Singaporean healthcare institutions. METHODS: Employing a prospective before-and-after cohort design, this investigation targeted ARFAs aged 21 years and above, fluent in English or Mandarin. Eligibility was determined by a history of at least five ED visits in the preceding year, with no fewer than two due to alcohol-related issues. The study contrasted health outcomes of patients integrated into the ACT care model versus their experiences under the exclusive provision of standard emergency care across Hospitals A, B, C and D. Following participants for half a year post-initial assessment, the evaluation metrics encompassed socio-demographic factors, ED, and EMS engagement frequencies, along with validated health assessment tools, namely Christo Inventory for Substance-misuse Services (CISS) scores, University of California, Los Angeles (UCLA) Loneliness scores, and Centre for Epidemiologic Studies Depression Scale Revised (CESD-R-10) scores. DISCUSSION: Confronted with intricate socio-economic and medical challenges, the ARFA cohort often grapples with heightened vulnerabilities in relation to alcohol misuse. Pioneering the exploration of ACT's efficacy with ARFAs in a Singaporean context, our research is anchored in a patient-centered approach, designed to comprehensively address these multifaceted clinical profiles. While challenges, like potential high attrition rates and sporadic data collection, are anticipated, the model's prospective contribution towards enhancing patient well-being and driving healthcare efficiencies in Singapore is substantial. Our findings have the potential to reshape healthcare strategies and policy recommendations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04447079. Initiated on 25 June 2020.

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

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.

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

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.

Out-of-Equilibrium Self-Replication Allows Selection for Dynamic Kinetic Stability in a System of Competing Replicators.

Among the key characteristics of living systems are their ability to self-replicate and the fact that they exist in an open system away from equilibrium. Herein, we show how the outcome of the competition between two self-replicators, differing in size and building block composition, is different depending on whether the experiments are conducted in a closed vial or in an open and out-of-equilibrium replication-destruction regime. In the closed system, the slower replicator eventually prevails over the faster competitor. In a replication-destruction regime, implemented through a flow system, the outcome of the competition is reversed and the faster replicator dominates. The interpretation of the experimental observations is supported by a mass-action-kinetics model. These results represent one of the few experimental manifestations of selection among competing self-replicators based on dynamic kinetic stability and pave the way towards Darwinian evolution of abiotic systems.

The Brπ halogen bond assisted self-assembly of an asymmetric molecule regulated by concentration.

The two-dimensional (2D) self-assembly behavior of an asymmetric thienophenanthrene derivative (M1) has been theoretically predicted and further probed via STM. The barely exploited Brπ halogen bonds play an assisting role in the structural formation, and a strong cooperative effect from the C-HBr bonds is shown. Such π-type halogen bond assisted self-assembly reveals self-adaption properties, which is of great interest for flexible light-emitting devices and self-healing materials.

Ordering self-assembly structures via intermolecular BrS interactions.

Recent research studies have shown that the halogenated benzo[1,2-b:4,5-b']dithiophene (DTBDT) unit as a polymer donor exhibits high charge carrier mobility due to the well-ordered molecular packing and high crystallinity, which is meaningful for achieving highly efficient organic solar cells (OSCs). However, it is difficult to acquire the accurate packing information of polymer materials. Herein, we investigated the self-assembled behaviors of two DTBDT derivatives, 4,8-bis(4-octadecylthiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene (H-DTBDT) and 4,8-bis(5-bromo-4-octadecylthiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene (Br-DTBDT), to elucidate the effect of introducing a bromine atom on molecular packing structures by STM at the 1-phenyloctane/HOPG interface. It is observed that the H-DTBDT molecules exhibit a random arrangement along each lamella, while the Br-DTBDT molecules self-assemble into a highly ordered lamellar structure. Density functional theory (DFT) analysis combined with the topological properties of the electron density at the bond critical points revealed that the existence of weak intermolecular interactions of BrS facilitates the regular packing motif of Br-DTBDT molecules. The results helped us to understand that the BrS bond generally acted as the auxiliary force and can play the primary role in the construction of supramolecular nanostructures.

Chiral polymorphism in the self-assemblies of achiral molecules induced by multiple hydrogen bonds.

Owing to a wide range of applications within the areas such as chiral sensors, enantiomeric resolution, and asymmetric catalysis, understanding chiral adsorption phenomena at the interface is thereby of great importance. In particular, the role of multiple hydrogen bonds in inducing chiral diversiform morphologies has never been systematically investigated. Herein, by delicate control of the volume ratio of 1-octanoic acid and 1-octanol as the mixed solvent, a series of self-assembled nanostructures of 2-hydroxyl-7-pentadecyloxy-fluorenone (HPF) were sequentially fabricated, including the achiral densely-packed pattern, the chiral "6-2" pattern, the chiral alternate pattern, and the chiral double-rosette pattern. Eventually, those patterns would evolve into an achiral and thermodynamically favored zigzag pattern. Based on DFT calculations, we demonstrate that the stabilities of diversiform morphologies originate from different hydrogen bonding and molecular packing densities. In addition, quantum theory of atoms in molecule (QTAIM) analysis is further applied to interpret the nature of these hydrogen bonds.

Cooperating dipole-dipole and van der Waals interactions driven 2D self-assembly of fluorenone derivatives: ester chain length effect.

Two-dimensional supramolecular assemblies of a series of 2,7-bis(10-n-alkoxycarbonyl-decyloxy)-9-fluorenone derivatives (BAF-Cn, n = 1, 3-6) consisting of polar fluorenone moieties and ester alkoxy chains were investigated by scanning tunneling microscopy on highly oriented pyrolytic graphite surfaces. The chain-length effect was observed in the self-assembly of BAF-Cn. Self-assembly of BAF-C1 was composed of a linear I pattern, where the side chains adopted a fully interdigitated arrangement. As the length of side chains increased, the coexistence of a linear I pattern and a cyclic pattern for the self-assembly of BAF-C3 was observed. Upon increasing the length of the alkoxy chain even further (n = 4-6), another linear II structure was observed in the BAF-Cn monolayer, in which the side chains in adjacent rows were arranged in a tail-to-tail configuration. It is reasonable to conclude that not only the van der Waals forces but also the dipole-dipole interactions from both the fluorenone cores and the ester alkoxy chains play critical roles in the self-assemblies of BAF-Cn. Our work provides detailed insights into the effect of intermolecular dipole-dipole and van der Waals interactions on the monolayer morphology of fluorenone derivatives.