C&EN’s Year in Chemistry 2020

One topic has dominated much of the scientific literature this year, just as it has dominated news reports and family conversations: the novel coronavirus and COVID-19, the disease it causes. Cases of the pneumonia-like disease were reported in December 2019, but the coronavirus, now known as SARS-CoV-2, became the story of 2020.

Using computational methods, the COVID-19 Dispersed Volunteer Research Network recently analyzed the scientific literature for publications related to COVID-19. It found thousands. Anhvinh Doanvo, the data scientist who led the project, tells C&EN that group members analyzed the scope of coronavirus research performed this year (Patterns 2020, DOI: 10.1016/j.patter.2020.100123). They found that most publications focused on public health, outbreak reporting, clinical care, and testing for coronaviruses. A smaller number focused on basic research. But, Doanvo says, “there’s a massive amount of effort being devoted to every area in basic science” to study this virus. Here’s a look at some of 2020’s coronavirus research.

Structures

Credit: Jason McLellan/University of Texas at Austin

The SARS-CoV-2 spike protein was one of the first coronavirus structures to be solved.

After SARS-CoV-2’s genetic code was published Jan. 10, structural biologists jumped into action to understand the 3-D structures of the virus’s proteins. Their aim was to know not just how the virus works on a molecular level but also how to guide the design of drugs, vaccines, and antibody therapies. The virus’s spike protein, a segment that latches onto and infects human cells, has now been imaged multiple times. It took just a couple of weeks for Jason McLellan and coworkers at the University of Texas at Austin to determine the initial structure (Science 2020, DOI: 10.1126/science.abb2507). Since then, other teams have imaged drugs bound to the virus’s main protease and its RNA-dependent RNA polymerase (Science 2020, DOI: 10.1126/science.abb3405 and 10.1126/science.abb7498), as well as antibodies bound to the spike protein (Science 2020, DOI: 10.1126/science.abb7269). In fact, by late November, an international repository of biological structures known as the Protein Data Bank contained data for over 500 coronavirus-related structures. But the work isn’t finished. Researchers continue to screen for drug candidates and antibody therapies and solve the structures of more viral proteins (Nat. Struct. Mol. Biol. 2020, DOI: 10.1038/s41594-020-00536-8).

Masks

Credit: Shutterstock

Mixing fabrics and paying attention to fit help make the most protective mask.

As the COVID-19 pandemic began to unfold, people in Asian countries were quick to don masks to stop the virus’s spread, but people elsewhere were slower. Public health officials in Europe and the US decided they did not know enough about the way SARS-CoV-2 spread and were concerned that encouraging people to buy masks could lead to shortages for health-care workers. Within a few months, however, observational studies and lab tests presented a body of evidence indicating that masks help slow the spread of the disease (Morb. Mortal. Wkly. Rep. 2020, DOI: 10.15585/mmwr.mm6928e2 and 10.15585/mmwr.mm6931e1). The US Centers for Disease Control and Prevention now says masks reduce the number of virus-containing droplets people release when they exhale and may also minimize droplet inhalation. To help shoppers and do-it-yourself types find or sew the most effective reusable mask, scientists at the University of Chicago and Argonne National Laboratory sought to identify the best fabric to use. They showed that layers of tightly woven cotton or silk and mixtures of materials are good choices (ACS Nano 2020, DOI: 10.1021/acsnano.0c03252 and 10.1021/acsnano.0c04897). Stanford University materials scientists showed that adding disposable filters made from facial tissues inside homemade masks gives even better results (Nano Lett. 2020, DOI: 10.1021/acs.nanolett.0c02211). Just as with socks and underwear, after wearing a cloth mask, people need to wash it before wearing it again. One study found infectious virus on the outer layer of a surgical mask 7 days after it was worn (Lancet Microbe 2020, DOI: 10.1016/S2666-5247(20)30003-3).

False starts

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Keeping surfaces clean is always important but might not make as much of an impact in stopping the spread of COVID-19 as first thought.

Our understanding of how the new coronavirus spreads and can be treated and who is most susceptible to infection has changed over the past year. Early public health advice focused on reducing transmission of the virus on surfaces and objects, known as fomites, but the importance of surface transmission was soon contested, and research began to focus on airborne transmission. Doctors have long known that viruses hitch a ride on large droplets of spittle that fall quickly to the ground. But the idea that smaller droplets could spread the disease as they waft in the air was controversial. Nevertheless, air measurements in hospitals in Wuhan, China (Nature 2020, DOI: 10.1038/s41586-020-2271-3), and outdoors in Northern Italy (Environ. Res. 2020, DOI: 10.1016/j.envres.2020.109754), among other places, implicated aerosols as a potential infection risk.

Credit: Shutterstock

As more researchers looked into the connection between blood type and COVID-19 risk, the link appeared weak.

Meanwhile, another idea that was debated in the scientific literature was whether having type O blood protected people from the severity of COVID-19. Multiple studies of patients hinted that people with type A blood had a higher chance of developing severe respiratory failure compared with people with type O blood; some of these studies were published in preprint servers and thus haven’t been peer-reviewed (medRxiv 2020, DOI: 10.1101/2020.05.31.20114991, 10.1101/2020.03.11.20031096, and 10.1101/2020.04.08.20058073; Br. J. Haematol. 2020, DOI: 10.1111/bjh.16797). But later studies found no link between blood type and disease severity (Transfusion 2020, DOI: 10.1111/trf.15946; Ann. Hematol. 2020, DOI: 10.1007/s00277-020-04169-1). The authors of one of the later studies, which followed 957 patients admitted to Massachusetts General Hospital with COVID-19, suggested the authors of the earlier studies had not compared their patients with appropriate control groups.

Credit: NASA JPL/Caltech

Scientists think they have detected phosphine, a possible sign of life, in Venus's atmosphere. It will be years before we know if the detection is real and if it came from a living organism.

With Earth’s climate rapidly changing, our own atmosphere is holding plenty of scientists’ attention. But other planets’ atmospheres revealed some surprises in 2020 and gave astrochemists a lot of work to do in the years to come.

The most exciting—and controversial—discovery came from Venus. An international group of researchers announced in September that it had detected phosphine in the planet’s atmosphere. The stinky, toxic gas has few natural sources on Earth, but one is oxygen-averse microbes, making the molecule a possible signature for life. The team reported evidence for small amounts of phosphine in Venus’s thick, hot clouds based on analysis of microwave signals collected by two telescopes.

Scientists met the announcement with excitement and some skepticism. While biological activity appears to be the best explanation so far for phosphine, researchers are still trying to replicate and verify the group’s findings. Experts discovered an error in the way data from one of the telescopes were processed; a reanalysis of the data by some of the original researchers concluded that the phosphine level was just one-fifth of the originally reported value. Other scientists independently analyzing the same data decided the chemical was not there at all.

And that’s fine, according to Sarah Rugheimer, an expert on atmospheric biosignatures at the University of Oxford. This race to confirm and understand an exciting announcement is “a great example of how science should play out,” she says. Clara Sousa-Silva, an astrochemist at the Massachusetts Institute of Technology and a member of the original research team, says new observations of Venus that could start in June will produce more data that should help answer questions.

Rugheimer also says the debates emphasize how little we know about our nearest neighbor: “It’s humbling.”

The limits of our understanding were apparent in April, as well, when Johns Hopkins University Applied Physics Laboratory scientists determined that our overall picture of how Venus’s atmosphere mixes might be flawed. New calculations of N₂ levels suggest our sister planet has almost one and a half times as much nitrogen in its atmosphere as scientists had thought. The group says Venus’s atmosphere may be divided into regions of distinct composition, contrary to the idea that the balance of gases is homogeneous up to an altitude of about 100 km. New models of atmospheric behavior could be useful as astronomers turn their attention to planets beyond our solar system.

That’s what scientists at the University of California, Berkeley, and elsewhere did in June. They used spectral data from exoplanets and computer models to simplify a puzzle for astronomers trying to understand the composition of these distant worlds’ atmospheres. They found that silicate aerosols dominate hotter planets’ hazes, and hydrocarbon aerosols dominate colder planets’ hazes. Other species, like iron, play only minor roles. That finding will help telescope-wielding observers remove signals from these species and see past the hazes to learn what exoplanet atmospheres are made of.

Credit: Associated Press

The August Complex fire, the largest in California history, burns near the Mendocino National Forest Sept. 16, 2020.

This year was the largest wildfire season on record in California. About 4% of the state burned, killing an estimated 33 people and exposing millions to hazardous air pollution. The August Complex fire, formed when 38 separate fires converged in the northern part of the state, blazed until Nov. 12, burning about 4,180 km² of forest and brush. That’s nearly twice the area burned by what was previously the largest fire ever recorded in the state, 2018’s Mendocino Complex.

The scientific consensus is strong: wildfires in the western US are driven by human-induced climate change. The same is true in Australia, where the 2019–20 fire season consumed 21% of the country’s temperate and broadleaf forests. It’s a vicious circle: these fires, fueled by climate change, in turn release tremendous volumes of carbon dioxide.

However, CO₂ emissions from human activity showed a surprising trend this year, albeit for tragic reasons. Travel and business restrictions that were designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19, led to a dramatic decrease in global CO₂ emissions in the first half of the year relative to the same time in 2019—about 8.8%, or the equivalent of 1,551 million metric tons of the greenhouse gas. Much of the drop was thanks to fewer cars on the road. This accidental, real-world experiment shows that CO₂ emissions will fall dramatically if people drive less in the future—or switch to electric cars in greater numbers.

One promising way to keep CO₂ out of the atmosphere is to incentivize its capture and reuse as a chemical feedstock. Unfortunately, existing methods are energy intensive. Chemists and engineers are trying to change that—and they made promising advances in 2020.

Early this year, chemists at the University of Lyon reported a carbon-capture formula that relies on a promising synergy. They developed a polyamine that reacts with CO₂ to generate a material that can be used to scavenge valuable metals from dead batteries, potentially making two environmentally friendly processes less expensive.

Meanwhile, a metal-organic framework tailor made by materials scientists at the University of California, Berkeley, was the first material to meet the US Department of Energy’s targets for CO₂ capture, soaking up 90% of the gas from simulated power plant flue emissions. Treatment with low-pressure steam refreshes the capture material and releases the greenhouse gas.

Rotary reactor synthesizes molecules as it spins

A whirling reactor lets chemists run small-scale transformations with multiple steps and separate the products of those reactions without using complicated fluidics and mixers. Bartosz Grzybowski and coworkers from Ulsan National Institute of Science and Technology and the Polish Academy of Sciences designed the system, a circular container that whips around at speeds of up to 5,400 revolutions per minute (Nature 2020, DOI: 10.1038/s41586-020-2768-9). Centripetal force from that rapid rotation organizes solutions into discrete layers according to density. The densest layers form the outer rings, while the least dense layers make up the spinning core. By picking reagents and products that are soluble in different layers, the chemists can make their compounds travel through the layers as each reaction occurs. The layers don’t mix, even when they are a scant 150 µm across—about twice the width of a human hair.

Smart stir bar measures while it mixes

Credit: Dmitry Isakov

This smart stir bar (52 mm long) is made of sensor boards housed inside a 3-D printed capsule.

Putting a new spin on an old lab tool, researchers have made a magnetic stir bar that measures temperature, conductivity, color, opaqueness, stirring rate, and viscosity while simultaneously mixing a solution. The whirling wonder can collect physical property data continuously for more than 100 h and transmits the information wirelessly via Bluetooth so chemists can get real-time information on their stirring solutions (ACS Sens. 2020, DOI: 10.1021/acssensors.0c00720). A team led by Nikolay Cherkasov and Dmitry Isakov at the University of Warwick invented the smart stirrer, which is made of stackable sensor boards tucked inside a 3-D printed capsule. The stirrer’s software platform is available for free online, and its materials and components cost less than $20. Isakov tells C&EN the team plans to add other functionality to the stirrer, including the ability to measure pH and dynamic conductivity.

Robot rapidly runs reactions

Optimizing a chemical transformation by repeating the reaction with small adjustments to reagents, solvents, and catalysts can be drudgery. So University of Liverpool researchers led by Benjamin Burger and Andrew I. Cooper decided to build a robot to do the laboratory grunt work. They outfitted a robot designed to work in warehouses and factories with specialized grippers and sample trays so it could operate liquid and solid chemical dispensers and laboratory instruments. In 8 days, the robotic technician performed 688 experiments, with the goal of optimizing a photocatalytic process that generates hydrogen gas from water (Nature 2020, DOI: 10.1038/s41586-020-2442-2). It used artificial intelligence to adjust the concentration of 10 chemicals, finally arriving at a mixture that produced six times as much hydrogen as the starting mixture. Cooper tells C&EN he’s been inundated with requests about the robot. “Running labs with social distancing was a key interest—something we couldn’t have foreseen,” Cooper says, because the work was done before the COVID-19 outbreak. The researchers have formed a spinout company, Mobotics, to commercialize the robot.

Taming racemic mixtures

Making carbon-carbon bonds is important in organic chemistry, but controlling stereochemistry, crucial when synthesizing pharmaceuticals, can be challenging. This year, Gregory Fu and colleagues at the California Institute of Technology met this challenge by devising a method for selectively making one stereoisomer from a racemic mixture of alkyls (Science 2020, DOI: 10.1126/science.aaz3855). Using a chiral nickel catalyst and a mixture of electrophiles and nucleophiles, Fu and his team selectively synthesized a product containing two chiral centers in up to 82% yield and 95% stereoselectivity. The group purposefully used a bidentate ligand, isoquinoline-oxazoline, so that the free spots on the Ni can bind with the oxygen on the amide nucleophiles (shown in blue), and the electrophiles (shown in red) can couple to give one stereoisomeric compound out of the four potential products. The reaction is compatible with 19 functional groups, making it applicable to many systems and potentially an important tool in synthesis.

Changing reaction times changes products

Because different enantiomers can undergo distinct reactions, controlling the yield of the right one is important in organic and pharmaceutical synthesis. This year, Shu-Li You and coworkers at the Shanghai Institute of Organic Chemistry found an unprecedented method: varying the reaction times. By combining an iridium cyclooctadiene compound and a chiral olefin to create a chiral catalyst in solution, the team selectively made either enantiomer of some chiral amines (Nat. Chem. 2020, DOI: 10.1038/s41557-020-0489-1). After 6 min, S isomers formed with 84–99% enantiomeric purity. Letting the reaction run for 10 h, however, yielded the R isomer with 74–99% enantiomeric purity (shown). This difference results from the selectivity of the catalyst, You says. Early in the reaction, the catalyst makes the S isomer quickly. Over time, this isomer decomposes, and the stabler R isomer forms.

Conjuring anilines from air

Akin to scientific magicians, chemists pulled dinitrogen from thin air this year and coupled it with benzene to make aniline derivatives (shown) (Nature 2020, DOI: 10.1038/s41586-020-2565-5). N₂ is famous for its strong and stable bond, so to make it react, chemists need to use metals to add electrons. However, electrophiles in solution tend to react with these metals, preventing the nucleophilic nitrogen from doing so and keeping it from forming the desired organic compound. So Patrick L. Holland and coworkers at Yale University made the nitrogen electrophilic. To perform this switcheroo, the chemists used diketiminate-supported iron to activate one of benzene’s C–H bonds and form a complex with N₂. A trimethylsilyl ion in solution then joins the Fe-bound and partially reduced N₂. This makes the compound electrophilic and susceptible to attack by the nearby benzene. After the aryl group joins, the N₂-derived aniline pops off the metal.