C&EN’s Year in Chemistry

Metallocenes circle up

Credit: Nature

This crystal structure shows a cyclocene made with strontium (large teal circles) and cyclooctatetraene (small white circles) with triisopropylsilyl groups (spindly, transparent structures). Hydrogens were omitted for clarity.

Credit: Nature

This crystal structure shows a cyclocene made with europium (large orange circles) and cyclooctatetraene (small white circles) with triisopropylsilyl groups (spindly, transparent structures). Hydrogens were omitted for clarity.

Chemists made a new type of supersize sandwich complex by coaxing 18 metallocene units to curve into a nanometer-scale ring called a cyclocene (Nature 2023, DOI: 10.1038/s41586-023-06192-4). They made these cyclocenes from metals—strontium, samarium, or europium—sandwiched between layers of cyclooctatetraenes that carry two bulky triisopropylsilyl groups. The bulky substituents force the metallocenes to bend as they stack, forming a ring.

Carbene breaks octet rule

Credit: Ying Kai Loh

This crystal structure depicts a doubly oxidized carbene dication.

Some rules are made to be broken. Carbon usually has eight valence electrons, in accordance with the so-called octet rule. A new compound—a doubly oxidized carbene dication—features a carbon atom with only four valence electrons (Nature 2023, DOI: 10.1038/s41586-023-06539-x). Researchers created a carbene with bulky substituents, oxidized the carbene, and removed an oxide anion, leaving a carbene carbon with no nonbonding electrons.

Chain-link covalent organic frameworks

Credit: Nat. Synth.

Various molecular building blocks (colored units) bond together, forming a fence-like network with interlinked components.

Researchers used catenanes—molecules that interlock like the links of a fence—to make a new type of covalent organic framework (COF) (Nat. Synth. 2023, DOI: 10.1038/s44160-022-00224-z). Each subunit in the COF is made by condensing precursors around copper(I) ions to form a network of three-ring polyhedrons. Removing the copper template ions enables the polyhedrons to move around without separating, making the resulting material soft and flexible. The COFs could be used for filtration membranes and soft robotics.

Chiral oxonium ion

The only chiral center in this compound is the oxygen atom.

Credit: Martin Smith/Jonathan Burton/Robert S. Paton

The fused triaryl ring system in a new chiral oxonium ion blocks the stereogenic oxygen from inverting, as seen in this crystal structure.

Think chirality, and carbon usually comes to mind. But other atoms can form chiral centers too. Chemists synthesized an oxonium ion—a compound with a positively charged oxygen bonded to three substituents—in which the oxygen atom is the only chiral center (Nature 2023, DOI: 10.1038/s41586-023-05719-z). The researchers locked the oxygen lone pair in place by bonding the oxygen atom to a fused triaryl ring system.

Solid-state diberyllium compound

Credit: Science

Diberyllocene is the first solid compound to contain a beryllium-beryllium bond.

Chemists created diberyllocene, the first solid-state compound to contain a beryllium-beryllium bond (Science 2023, DOI: 10.1126/science.adh4419). Each beryllium atom is bound to a cyclopentadienyl group. Beryllium, which usually exists in the +2 oxidation state, adopts the unusual +1 oxidation state in diberyllocene. The compound could be used to develop new catalysts.

Molecular motor powered by electricity

Credit: Nature

In this electric molecular motor, an oscillating voltage makes charged cyclobis (paraquat-p-phenylene) rings move around a larger loop. An isopropylphenylene group and a 2,6-dimethylpyridinium group help ensure the rings move in one direction.

Credit: Nature

In the first step of the molecular motor’s four-stage cycle, adding electrons reduces the rings and parts of the track. The rings move clockwise and bind to the track through radical-pairing interactions. Further redox steps ensure the rings make a full circuit.

Researchers invented a molecular motor powered by electricity, not chemical fuels or light, which drive most other molecular motors (Nature 2023, DOI: 10.1038/s41586-022-04910-y). The new electric motor consists of two cyclobis (paraquat-p-phenylene) rings that travel around a larger loop in response to an oscillatory voltage that drives a series of oxidation and reduction reactions. Using electricity as a power source could make it easier to integrate molecular motors with other technologies.

Celia Henry Arnaud is a freelance writer based in College Park, Maryland.

700 million MB

Credit: Greenbaum et al./Nature

In these antibody-labeling mass spectrometry images of a cross section of a spiral artery, which delivers blood to the placenta, colors represent various cell-type markers. Human BioMolecular Atlas Program researchers are interested in how cell types fit together within tissues.

Amount of data published so far by the Human BioMolecular Atlas Program, in 1,900 datasets from almost 200 donors. The consortium combines many single-cell analytical techniques to understand the makeup of healthy human tissues in kidneys and other organs (Nature 2023, DOI: 10.1038/s41586-023-05769-3). Similar big data research consortia are cataloging molecules in the brain, cancer cells, and embryos.

12

Number of nitrogen atoms in this tricyclic environmentally friendly explosive. This compound, dubbed DTAT-K, has detonation properties comparable to those of lead azide, a commonly used explosive. But unlike the lead compound, DTAT-K is free of heavy metals that can contaminate military training grounds, and it’s safer to handle (ACS Cent. Sci. 2023, DOI: 10.1021/acscentsci.3c00219).

12

Number of nitrogen atoms in this tricyclic environmentally friendly explosive. This compound, dubbed DTAT-K, has detonation properties comparable to those of lead azide, a commonly used explosive. But unlike the lead compound, DTAT-K is free of heavy metals that can contaminate military training grounds, and it’s safer to handle (ACS Cent. Sci. 2023, DOI: 10.1021/acscentsci.3c00219).

~5 nm

Length over which a molecular wire conducted electric current. Long molecules capable of carrying electric current could lead to electronic devices even smaller, faster, and more powerful than today’s versions. But molecules longer than 1–2 nm tend to be electric insulators. This record-setting molecule, an oligoemeraldine, conducts electricity only along its edges (J. Am. Chem. Soc. 2023, DOI: 10.1021/jacs.2c12059).

Credit: Adapted from Science

Gaseous titanium tetrachloride and liquid ethylene glycol react to form a carbon-doped metal oxide nanofilm. Heating removes some of the carbon from the film and produces microscopic pores.

200–1,000 g/mol

Range of molecular weights of compounds that a porous, inorganic membrane can separate. Made via interfacial polymerization and molecular layer deposition, the holey inorganic film could be used to replace distillation and other energy-intensive separations common in industrial chemistry. Unlike polymer membranes used for desalination, the inorganic film can withstand harsh organic solvents and temperatures of up to 140 °C (Science 2023, DOI: 10.1126/science.adh2404).

200–1,000 g/mol

Credit: Adapted from Science

Gaseous titanium tetrachloride and liquid ethylene glycol react to form a carbon-doped metal oxide nanofilm. Heating removes some of the carbon from the film and produces microscopic pores.

Range of molecular weights of compounds that a porous, inorganic membrane can separate. Made via interfacial polymerization and molecular layer deposition, the holey inorganic film could be used to replace distillation and other energy-intensive separations common in industrial chemistry. Unlike polymer membranes used for desalination, the inorganic film can withstand harsh organic solvents and temperatures of up to 140 °C (Science 2023, DOI: 10.1126/science.adh2404).

<1 billion years

Period after the big bang that the universe began forming carbon dust. Researchers study cosmic dust grains, which are the building blocks of galaxies, to understand how galaxies formed and how the universe evolved. Spectroscopy observations made with the James Webb Space Telescope indicate that carbonaceous dust and carbon-based materials formed much earlier and more frequently than previously thought (Nature 2023, DOI: 10.1038/s41586-023-06413-w).

Credit: NASA GSFC/CIL/Adriana Manrique Gutierrez

The James Webb Space Telescope

<1 billion years

Credit: NASA GSFC/CIL/Adriana Manrique Gutierrez

The James Webb Space Telescope

Period after the big bang that the universe began forming carbon dust. Researchers study cosmic dust grains, which are the building blocks of galaxies, to understand how galaxies formed and how the universe evolved. Spectroscopy observations made with the James Webb Space Telescope indicate that carbonaceous dust and carbon-based materials formed much earlier and more frequently than previously thought (Nature 2023, DOI: 10.1038/s41586-023-06413-w).

241

Atomic mass number, or total number of protons and neutrons, in uranium-241, a newly detected isotope of uranium. By firing a beam of uranium-238 ions at a platinum-198 target, researchers induced multinucleon transfer reactions, which formed the neutron-rich isotope containing 92 protons and 149 neutrons (Phys. Rev. Lett. 2023, DOI: 10.1103/PhysRevLett.130.132502). With a predicted half-life of 40 min, uranium-241 should stick around long enough to enable scientists to probe its chemical and physical properties.

Credit: Frank von Delft group/Centre for Medicines Discovery, University of Oxford

Searching for coronavirus antivirals, researchers invited the scientific community to find compounds (such as the collection of superimposed ball-and-stick structures) capable of binding to SARS-CoV-2’s main protease (large space-filling structure).

212, 47, and 25

Number of scientists, organizations, and countries, respectively, that have contributed to an open-source science project that identified several potential antiviral drugs that target SARS-CoV-2’s main protease (Science 2023, DOI: 10.1126/science.abo7201). One of the potential drugs identified by the COVID Moonshot Consortium is in preclinical development. The consortium’s goal is to develop a safe, globally accessible, affordable antiviral pill for COVID-19.

212, 47, and 25

Credit: Frank von Delft group/Centre for Medicines Discovery, University of Oxford

Searching for coronavirus antivirals, researchers invited the scientific community to find compounds (such as the collection of superimposed ball-and-stick structures) capable of binding to SARS-CoV-2’s main protease (large space-filling structure).

Number of scientists, organizations, and countries, respectively, that have contributed to an open-source science project that identified several potential antiviral drugs that target SARS-CoV-2’s main protease (Science 2023, DOI: 10.1126/science.abo7201). One of the potential drugs identified by the COVID Moonshot Consortium is in preclinical development. The consortium’s goal is to develop a safe, globally accessible, affordable antiviral pill for COVID-19.

12 °C

Credit: ACS Photonics

This waterproof, breathable material, which may find its way into clothing and other fabrics, cools the surface it sits on by radiating heat into space. Its layered structure resembles that of skin.

Amount of cooling relative to ambient temperature provided to wearers of a breathable material with skin-like structure. Materials that provide radiative cooling—typically by reflecting heat-carrying infrared rays away from a surface—are used increasingly to reduce air-conditioning requirements in office buildings. Applying that concept to clothing, researchers made a porous layered material based on interlaced cotton-polyester fibers and treated it with poly (vinyl difluoride) and microparticles of titanium dioxide, barium sulfate, and silicon dioxide. The components and the material’s structure work together to scatter and reflect sunlight and provide cooling (ACS Photonics 2023, DOI: 10.1021/acsphotonics.3c00241).

Antifreeze for octopus brains

Adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine to inosine in RNA. Because inosine mimics guanosine, this type of editing can affect which amino acid is incorporated into a protein.

Credit: Tom Kleindinst/Woods Hole Oceanographic Institution

Octopuses don’t wear shirts. Even so, they seem to have quite a few tricks up their sleeves. By sequencing RNA from the nervous systems of captive octopuses and running temperature-controlled studies, researchers revealed one of those secrets: these cephalopods edit their messenger RNA in response to temperature changes and thereby rewrite their protein sequences on the fly. These modifications can alter the function of important nervous system proteins and protect the animals from brain freeze (Cell 2023, DOI: 10.1016/j.cell.2023.05.004).

Death cap mushroom antidote

Fungi fans beware: the death cap mushroom doesn’t just sound deadly; it is deadly. Also known asAmanita phalloides, the species contains α-amanitin, a toxin that triggers irreparable liver and kidney damage, and the mushroom caused 788 deaths in China from 2010 to 2020, according to a study of China’s Foodborne Disease Outbreak Surveillance System. Few treatments are available, and the way they work isn’t well understood. Aiming to find more treatments, researchers used a CRISPR technique and found that a protein called STT3B is required for α-amanitin toxicity. They screened a library of more than 3,000 compounds approved by the US Food and Drug Administration and determined that indocyanine green—a dye used to determine heart and liver function—could block STT3B binding. Laboratory tests showed that indocyanine green prevented α-amanitin toxicity in cells and liver organoids. The compound also helped mice survive α-amanitin poisoning if administered soon after exposure to the toxin (Nat. Commun. 2023, DOI: 10.1038/s41467-023-37714-3).

Doubly antiaromatic molecule

Credit: Leo Gross/IBM Research-Zurich

This rendered atomic force microscopy image shows C₁₆'s circular shape.

Chemistry students learn early on that some organic compounds—benzene, for example—are unusually stable and described as aromatic, a property tied to the compound’s having 4n + 2 π electrons. A few compounds possess two such systems of π electrons and are said to be doubly aromatic. Less well known is a group of rather unstable compounds that have 4n π electrons and are antiaromatic. This year, scientists used a scanning probe microscope tip to assemble a 16-carbon ring known as cyclo[16]carbon and showed that it is doubly antiaromatic (Nature 2023, DOI: 10.1038/s41586-023-06566-8). The compound’s instability could make it useful for creating other exotic carbon compounds.

Rethinking Mars’s core

Credit: Copyright IPGP-CNES

Seismic information collected by NASA’s InSight lander (colored lines) suggests that Mars’s iron core is surrounded by a layer of molten silicate.

Analyses conducted this year of seismic data recorded by NASA’s InSight lander led two research groups to revise their understanding of the core of Mars. By studying the way pressure and shear waves moved through the interior of Mars, two teams of seismologists concluded that Mars’s liquid iron core is 30% smaller than previously thought and is surrounded by a 150 km ​thick layer of molten silicate that had not been previously observed (Nature 2023, DOI: 10.1038/s41586-023-06586-4 and DOI: 10.1038/s41586-023-06601-8).

A metal-only fullerene

Using solution-phase chemistry, researchers coaxed metal atoms into forming a cage-shaped molecule that retains its structure without the need for stabilizing ligands (Science 2023, DOI: 10.1126/science.adj6491). The unexpectedly stable all-metal fullerene, which could serve as a guide for other nanostructures, consists of 12 gold atoms and 20 antimony atoms that surround a single potassium ion. X-ray crystallography shows that the molecule, [K@Au₁₂ Sb₂₀ ]⁵⁻, is a dodecahedral cage of Sb atoms combined with an icosahedron of Au atoms. Although the compound has only 32 atoms (and one potassium ion), it’s roughly the same size as its famous all-carbon fullerene cousin, C₆₀.

Credit: Adapted from Science

This fullerene is made entirely of metal atoms.

Leonardo da Vinci: Artist and chemist

Credit: J. Am. Chem. Soc.

X-ray analysis of the Mona Lisa (left) reveals a thick, lead-rich primer layer (right).

Leonardo da Vinci is known worldwide as one of the greatest artists of the Renaissance era. His skills as a chemist, however, are just starting to come to light. Earlier work showed that Leonardo often tinkered with an oil-based mixture of two lead carbonate salts—PbCO₃ and Pb₃(CO₃)₂(OH)₂—when preparing white primers. This year, researchers used X-ray and infrared methods to analyze the primers in the Mona Lisa and The Last Supper and found that the famous artist also experimented with another lead compound—plumbonacrite, Pb₅(CO₃)₃O(OH)₂ (J. Am. Chem. Soc. 2023, DOI: 10.1021/jacs.3c07000). Plumbonacrite was probably the by-product of a reaction between the oil and lead(II) oxide. This reaction made the paint thick and smooth.

Credit: Madeline Monroe/C&EN/Shutterstock

Athina Anastasaki, materials chemist, Swiss Federal Institute of Technology (ETH), Zurich

Credit: Courtesy of Athina Anastasaki

Athina Anastasaki

“With increased focus from academic and industry researchers on developing a sustainable and circular polymer economy, many of the highly selective strategies used in organic chemistry may find applications in chemical recycling. Developing new methods to selectively break down waste polymeric materials into desirable raw materials could realize the true potential of plastic waste as a feedstock. Advances in the fields of mechanochemistry, photochemistry, and organometallic catalysis show particular promise in achieving this objective. Effectively utilizing the large amounts of polyethylene and polypropylene in waste streams in an economically viable manner is the ultimate goal of these efforts.”

Connor W. Coley, computational chemist, Massachusetts Institute of Technology

Credit: Courtesy of Connor Coley

Connor Coley

“We’ll continue to see increased accessibility and routine adoption of [artificial intelligence] techniques in chemistry, in particular Bayesian optimization for identifying reaction conditions and the use of neural network potentials as surrogates for quantum mechanical modeling. There will be newer proofs-of-concept tackling more ambitious tasks like anticipating the selectivity of C–H activation and proposing novel transformations entirely. A recognition that AI is a pervasive part of the molecular discovery toolkit might obsolesce terms like ‘AI-discovered drug,’ which often only reinforce prior support or distaste for AI techniques. Greater focus will be placed on molecular evaluation than design. For example, we may see a new wave of structure-based drug-design techniques for binding affinity prediction that build on the extensive advances in deep learning for protein structure prediction and ligand binding-pose prediction.”

Roxanne Kieltyka, supramolecular chemist, Leiden University

Credit: Courtesy of Roxanne Kieltyka

Roxanne Kieltyka

“As knowledge of living systems and tools to modify them continue to increase, we, as chemists, are provided with new opportunities to create soft materials that can interact with them and steer their function for applications spanning healthcare to the environment. This is made possible by the rapidly growing number of methods to control the synthesis of polymers with advanced properties and functions, their characterization, and fabrication using 3D printing technologies. Reversible covalent or non-covalent bonding chemistries that confer dynamic properties to these materials can unlock complex mechanical characteristics and even architectures found in cells and native tissues. For example, hydrogel designs that mimic the materials of life can influence a wide range of cell behaviors to impact how we understand, diagnose, and treat diseases. I expect that in 2024 we will see exciting examples of how far we can push these dynamic materials to emulate and leverage biological matter in ways that challenge what it means to be synthetic.”

Stafford Sheehan, chief technology officer, Air Company

Credit: Courtesy of Stafford Sheehan

Stafford Sheehan

“Breakthroughs in green chemistry will set the tone in a sustainable revolution for decarbonization. Technologies that sustainably produce molecules that are traditionally made by fossil fuels are at the forefront. In 2024, we’ll see further investment and advances in low-carbon hydrogen production, sustainable fuels, industrial electrification, and more, with a deeper understanding of next-generation catalysts and novel processing methods. These latest advancements will enhance the efficiency and impact of the energy industry, enabling humanity to grow without the resource and emissions limitations that come with using fossil fuels.”

Michael Snyder, genomicist and geneticist, Stanford University

Credit: Courtesy of Michael Snyder

Michael Snyder

“2024 will continue the era of ‘big data,’ both in collection and analysis. The cost of genome sequencing will likely reach $100 (for reagents and supplies) and the scaling of other omics, particularly proteomics and metabolomics, will rise considerably. One area of particular emphasis—single-cell spatial omics, which presently is confined primarily to RNA and protein—will also continue to rise. Machine learning and artificial intelligence, which exploded in 2023, will become even more commonplace in 2024 and applied to large heterogeneous data types. These activities will lead to a greater depth of understanding of biological systems and human disease.”

Charlotte Vogt, spectroscopist, Technion—Israel Institute of Technology

Credit: Courtesy of Charlotte Vogt

Charlotte Vogt

“Catalysts, vital for a third of the global [gross domestic product], are often highly complex—yet we still generally rely on trial-and-error for their synthesis. Rational design of catalysts has been a goal for many years, and the wide availability now of lab automation and artificial intelligence brings that goal ever closer. Lab work that took us months a few years ago, we can now do in less than a day. I hope that in 2024, we will make leaps in our understanding due to the broader accessibility of such tools. This, alongside creativity and cross-​disciplinary thinking, which could be sparked by the ease of gathering information with these tools, is absolutely necessary to drive novel processes facilitating the remediation of anthropogenic climate change, such as mass-scale (tens of [giga–metric tons per year]) carbon capture and storage, for which current solutions like direct air capture cannot effectively contribute.”

Note: All responses were sent via email.