Search

Despite considerable technological advancements in solid-phase peptide synthesis (SPPS), commercial platforms are limited in flexibility and chemical capability. Here, the authors present a fully automated programmable platform that combines the efficiency of SPPS with the chemical flexibility of a Chemical Processing Unit (Chemputer), enabling synthesis of peptide substrates with subsequent chemical modifications.

The use of a universal chemical programming language (χDL) to encode and execute synthesis procedures for a variety of chemical reactions is reported, including reductive amination, ring formation, esterification, carbon–carbon bond formation and amide coupling. These procedures are validated and repeated in two international laboratories and on three independent robots.

Distributing a reaction workload across laboratories can solve chemical problems more efficiently, but it is challenging to develop viable hardware and software. Here, the authors present an internet-connected network of cheap robots that can perform chemical reactions and share outcomes in real time, demonstrating a digitized approach to chemical collaboration.

The polyoxoanion [P₂W₁₈O₆₂]⁶⁻ has been shown to reversibly accept up to 18 electrons upon reduction in aqueous solution. The resulting highly reduced solution can then be used either for the on-demand generation of hydrogen over a catalyst bed, or as a high-energy-density electrolyte in a redox flow battery.

The ability to discover and optimise the synthesis of inorganic nanomaterials has significant impact on various fields, from sensing to medicine. Here, the authors use a genetic algorithm to drive a robotic platform toward a pre-defined, spectroscopic goal in order to discover and optimise the conditions for several nanoparticle shapes.

For practical applications, water-oxidation catalysts should be inexpensive, active and stable. Here, Cronin and co-workers dope molybdenum into the Weakley sandwich-type polyoxometalate, showing that this dramatically lowers the overpotential for the oxygen evolution reaction while maintaining the stability against oxidation.

A wide range of porous framework materials has been assembled with a modular approach that takes advantage of prefabricated structural building units (SBUs). Now, it has been shown that functional all-inorganic frameworks can be made from a macrocyclic polyoxometalate SBU — that has a built-in aperture approximately 1 nm in diameter — linked together with redox-switchable metal ions.

Adding low concentrations of aromatic organic cations to an aqueous solution in which polyoxometalate-based crystals are immersed leads to the spontaneous growth of tubular structures with controllable diameters. Tubes can be fused together to form junctions and are shown to act as channels through which liquids can flow.

A low-cost 3D printer is used to combine chemical reactions and the reactor to produce an active ‘reactionware’ system for organic and inorganic synthesis. Active elements such as catalysts can be incorporated into the walls of printed reactors, and other printed-in components that enable electrochemical and spectroscopic analysis can also be included.

It is unclear whether strategies involving antibiotic cycling can efficiently control the emergence of antibiotic-resistant bacteria. Here, Yoshidaet al. show that the evolution of multi-drug-resistant bacteria in vitrocan be manipulated by administering pairs of antibiotics and switching between them.

To mark the occasion of Nature Chemistry turning 10 years old, we asked scientists working in different areas of chemistry to tell us what they thought the most exciting, interesting or challenging aspects related to the development of their main field of research will be — here is what they said.

Computing platforms based on chemical processes can be an alternative to digital computers in some scenarios but have limited programmability. Here the authors demonstrate a hybrid computing platform combining digital electronics and an oscillatory chemical reaction and demonstrate its computational capabilities.

Current chemical automation ontologies are disconnected from essential structured programming constructs such as variables, functions, and loops. Herein the authors present an approach to translating computer science concepts to first-class primitives within a universal high-level chemical programming language executable in the Chemputer.

While automated reaction systems typically work for the synthesis of pre-defined molecules, automated systems to discover reactivity are more challenging. Here the authors report an autonomous organic reaction search engine that allows discovery of the most reactive pathways in a multi-reagent, multistep reaction system.

Assembly theory conceptualizes objects as entities defined by their possible formation histories, allowing a unified language for describing selection, evolution and the generation of novelty.

A limitation of robotic platforms in chemistry is the lack of feedback loops to adjust the conditions in-operando. Here the authors present a dynamically programmable robotic system that uses sensors for real-time adaptation, achieving yield improvements in syntheses and discovering new molecules.

The automated synthesis of highly reactive compounds is challenging. Now a digital automated platform is developed for safer, inert-atmosphere synthesis of air-, moisture-, pressure- and temperature-sensitive compounds from across the periodic table.

An optimization algorithm is used to discover guest molecules based on knowing only the structure of the host. The molecules are represented as 3D volumes, optimized to improve host–guest interaction and converted into SMILES using a transformer model.

Small sugar molecules produced by an autocatalytic reaction cycle confined inside vesicle-based 'artificial cells' can trigger a response in living bacterial cells.

The synthesis of molecular nanostructures often requires the variation of several parameters, such as stoichiometry, pH, counter-ion etc. Here, the authors report a flow reaction array with algorithmic control which is used as a ‘search engine’ to isolate six nanoscale clusters from a massive parameter space.

Crystal engineering is a powerful process for assembling complex materials but tends to require organic building blocks, which can limit stability. Here, the authors use inorganic polyoxometalates to assemble an all-inorganic metamorphic framework that can be switched between eight distinct states.

Chemical models of evolving systems are of interest to a range of researchers. Here, the authors use a liquid handling robot and an evolutionary process to explore oil droplets as a function of composition, which they claim may pave the way to explore bottom-up evolution in chemical systems.

Typically, in order to form large peptides, complex procedures or activating agents are required. Here, the authors show that simple aqueous conditions with dehydration-hydration cycles are sufficient for the oligomerization of amino acids into peptides (up to 20 amino acids long) in yields of up to 50%.

Automated systems, nowadays more commonly used in laboratory settings, are typically fixed to a narrow set of reactions and used within a complex laboratory environment. Now, a portable platform has been developed for the on-demand and on-site multistep synthesis of organic molecules, oligonucleotides and oligopeptides mapped into reactionware systems.

A robot instructed by a machine learning algorithm and coupled with real-time spectroscopic systems provides fast and accurate reaction outcome predictions and reactivity assessments, leading to the discovery of new reactions.

The transition of prebiotic chemistry to present-day chemistry lasted a very long period of time, but the current laboratory investigations of this process are mostly limited to a couple of days. Here, the authors develop a fully automated robotic prebiotic chemist designed for long-term chemical experiments exploring unconstrained multicomponent reactions, which can run autonomously and uses simple chemical inputs.

The search for life in the universe is difficult due to issues with defining signatures of living systems. Here, the authors present an approach based on the molecular assembly number and tandem mass spectrometry that allows identification of molecules produced by biological systems, and use it to identify biosignatures from a range of samples, including ones from outer space.

Automated synthesis technologies are often highly specialized, focusing only on a narrow set of reaction classes. Now, solid-phase peptide synthesis, iterative Suzuki–Miyaura cross-coupling and diazirine chemistry have all been automated using the same universal platform architecture. A convergent 12-step synthesis demonstrates the utility of the reported Chemputer system.

Using a fully automated closed-loop system, a robotic chemist synthesizes an oxygen-evolution catalyst from Martian meteorites, with implications for the production of catalysts that may underpin human survival on Mars in the future.

Unconventional computing architectures might outperform current ones, but their realization has been limited to solving simple specific problems. Here, a network of interconnected Belousov-Zhabotinski reactions, operated by independent magnetic stirrers, performs encoding/decoding operations and data storage.

Synthetic labs rely on a vast number of chemicals, which are often unstable with time and affected by price fluctuations. Here, the authors report ad hoc developed cartridge reactionware for the synthesis of four different targets in a time- and cost-saving manner.

Flash memories are essential for modern electronics; here a selenium-templated polyoxometalate is used to engineer new metal–oxide–semiconductor devices.

Using a polyoxometalate as an electron-coupled-proton buffer, the decoupling of the water oxidation and proton reduction half reactions of electrolytic water splitting is achieved. This allows O₂ and H₂ to be produced separately in both time and space. The implications of these findings for electrolyser design and low-cost hydrogen production from water are discussed.

Few studies have explored the effect of a changing environment on artificial chemical evolution. Here, the authors develop an evolutionary platform that alters the physical environment of droplet protocells, showing that a population of simple chemical species can adapt to its surroundings, in analogy to natural evolution.

Variable-temperature mass spectrometry, isotopic labelling and computational analysis have been used to characterize a metastable non-haem oxo-iron(V) intermediate generated at cryogenic temperatures, as well as to study its cis-dihydroxylation reaction with olefins. The study provides experimental evidence for the existence of this powerful and biologically important oxidant, under conditions relevant to catalysis.

The discovery and synthesis of inorganic clusters can be both time consuming and limited by a lack of reproducibility. An automated flow process coupled with multiple batch crystallization has now been successfully used to rapidly screen and scale-up the syntheses of inorganic clusters, including polyoxometalates and manganese-based single-molecule magnets.

When is an artificial cell alive? A Turing test–like method may provide the answer.

Inorganic oxide materials are used in semiconductor electronics, ion exchange, catalysis, coatings, gas sensors and as separation materials. In this Review, we explain how polyoxometalate clusters are amenable to molecular control and can be assembled into inorganic frameworks owing to the molecular nature of their building blocks.

Automation can help in performing routine tasks quickly and consistently. Algorithms facilitate the searching of current knowledge. Combining the two could lead to a chemically intelligent approach to the discovery of not only new molecules but also novel and unpredictable reactivity.

This protocol from Kitson et al. describes an approach to create bespoke 3D-printed chemical reactors known collectively as “reactionware”.

The direct glycosylation of ribose by nucleobases offers an intuitive route to nucleosides, but is known to be challenging under prebiotically plausible reaction conditions. Here, the addition of amino acids is shown to influence the product distribution, and a dynamic exchange of nucleobases between nucleosides and nucleotides is observed.