C&EN’s Year in Chemistry 2019

The bacteria on our insides and outsides influence nearly every aspect of our being, whether it be our birth, our behavior, or the efficacy of our medications.

In studies in mice and of human cells, one big idea reinforced in 2019 is that the metabolites produced by microbes in our guts can play a role in our health. In fact, Andrew Goodman of Yale School of Medicine and coworkers found that many common drugs are metabolized by various species of gut bacteria, raising questions as to whether this might affect how drugs work.

Microbiome research is a comparatively young field, several scientists told C&EN, and a burst of big findings released this year can be credited in part to improved analytical technology and a growing number of scientists from all fields studying our microbial inhabitants.

“There’s a critical mass now of labs that are working on the microbiome,” says Peter Turnbaugh, a microbiome scientist at the University of California, San Francisco. “We’ve had a lot of people come from chemistry and from quantitative backgrounds. They’re bringing new perspective.”

Here are some interesting microbiome findings that made news in 2019:

Neuro effects

Doctors have long noted that the most common treatment for Parkinson’s disease, levodopa, works better for some people than others. Peter Turnbaugh of the University of California, San Francisco, and Emily Balskus of Harvard University found that gut bacteria carve off bits of levodopa for their use, potentially deactivating the drug before it can reach the bloodstream and get to the brain (Science 2019, DOI: 10.1126/science.aau6323).

Motor function

A research team based in Israel reported that nicotinamide, a metabolite produced by gut bacteria, seems to protect mice from the ravages of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that leads to muscle wasting and reduced motor function. Led by Eran Elinav at the Weizmann Institute of Science, the team tested common gut microbes in mice genetically engineered to develop ALS and found that some species ameliorated symptoms, and others made them worse. Nicotinamide is known to have a role in neuronal health, and Elinav thinks this compound might be helping to reduce oxidative stress in the nervous system (Nature 2019, DOI: 10.1038/s41586-019-1443-5).

Autoimmunity

As bacteria in our bodies remodel themselves, sometimes they shed an immune-stimulating chemical called peptidoglycan. Earlier this year, researchers based in Singapore reported that large amounts of this compound circulating in mice bred to have autoimmune arthritis can exacerbate the disease. In humans, autoimmune arthritis is characterized by deformed joints and lost range of motion in various body parts. The researchers, led by Yue Wang at the Institute of Molecular and Cell Biology, found that a single injection of an antibody against peptidoglycan reduced symptoms and seemed to slow disease progression in the mice (Nat. Microbiol. 2019, DOI: 10.1038/s41564-019-0381-1).

Reproduction

Babies come into this world with the microbiomes their moms give them. Sort of. University College London’s Baby Biome Study found that babies born by C-section have different microbiomes than their counterparts who were born vaginally. One worrying finding: babies born by C-section have strains of hospital bacteria in their guts, including some with antibiotic-resistance markers (Nature 2019, DOI: 10.1038/s41586-019-1560-1). Trevor Lawley of the Wellcome Sanger Institute, who led the research group, thinks that antibiotics that women take before C-sections might kill off some species, making room for hospital species to settle in, but the overall health impact of these findings will take several years to tease out.

Gut health

It’s no surprise that the microbiome has an enormous impact on the very intestines where many of our microbes reside. Early in 2019, Balskus of Harvard and Silvia Balbo of the University of Minnesota Twin Cities discovered that colibactin, a compound secreted by intestinal Escherichia coli, alkylates the DNA of the cells lining our guts. Alkylated bases on DNA tend to fall off the biopolymer, triggering a cell’s DNA-repair mechanisms (Science 2019, DOI: 10.1126/science.aar7785). And sometimes these repair tools fail, leading to mutations that could induce diseases like colon cancer. Balskus says there is still work to be done to firmly connect colibactin to colon cancer, but screening for alkylated DNA bases might become a valuable diagnostic procedure.

Credit: Environmental Working Group/Social Science Environmental Health Research Institute/Northeastern University

A map of PFAS water contamination in the US. Blue circles represent locations where PFAS have been detected in tap water. Purple dots represent contaminated industrial or military sites as of October 2019. Red dots represent other known sites. Locations are approximate. View the full interactive map at ewg.org.

It’s not every year that water chemistry scores a spot at the movie theater. The November release of Dark Waters, a film starring Mark Ruffalo as a lawyer investigating water contamination in West Virginia, crowned a year of expanded public awareness of PFAS, the family of nonpolymer per- and polyfluoroalkyl substances that persist in the environment and are linked to health problems. Meanwhile, an ever-growing list of contaminated sites drew increased regulatory scrutiny as scientists raced to understand the chemicals and test potential treatments.

In 2019, scientists studying the persistent pollutants uncovered new information about their impact, how they cycle in the environment, and what it will take to get rid of them. Development continued on a battery of potential treatment methods, including new adsorbents that better target PFAS and destructive technologies aimed at demolishing the strong C–F bonds that make PFAS so persistent. Chris Higgins, who studies emerging contaminants at the Colorado School of Mines, says he expects this “every tool on the table” approach to continue.

“It’s such a big liability; you don’t want to put all your eggs in one basket,” he says.

After a few years in the pipeline, some technologies have cleared important milestones on the road to large-scale use. For example, a plasma reactor that uses electricity and argon gas to generate highly reactive species that can break down PFAS completed a field test in September, treating hundreds of liters of contaminated water at Wright-Patterson Air Force Base in Ohio.

“We’re starting to be able to bring some of these technologies to the table, where there was a lot of skepticism before” about whether PFAS could be treated effectively, says Michelle Crimi, who studies water remediation methods at Clarkson University.

Credit: Clarkson University

Researchers used a plasma reactor to break down PFAS molecules in contaminated water during a field test this year.

And this year, scientists reported that a microbe found in a New Jersey wetland could detoxify PFAS, potentially offering a cheaper and more sustainable approach to treating contaminated water than energy-intensive systems like the plasma reactor.

The difficulty in removing PFAS from the environment has drawn attention to how we dispose of contaminants and their fate in the environment, Crimi says. She hopes the experience will prompt society to focus more on preventing pollution in the first place. The year 2020 could shape up to be another interesting one for PFAS, as federal regulators continue to grapple with whether and how to regulate these compounds.

Higgins says he’s encouraged to see a wealth of new information brought to light about the compounds.

“It’s actually a pretty exciting time to be following all the research,” he says.

Credit: Modestino lab

In an electrochemical cell, acrylonitrile (AN) combines to make adiponitrile (ADN) at the cathode, while water and oxygen form at the anode.

Electrochemical organic synthesis leaped forward in 2019, with chemists using it to make industrial processes greener by lowering energy consumption and emissions.

Used to produce nylon 6,6, a common ingredient in textiles, adiponitrile is one of the largest-volume chemicals produced worldwide. The standard industry route for making it is inefficient and creates unwanted by-products. This year, Miguel Modestino and coworkers at New York University increased the yield of adiponitrile synthesis and the selectivity with which it’s created by pulsing the current in an electrosynthesis system and optimizing reaction conditions with a type of machine learning.

Epoxides, ubiquitous in the manufacture of consumer goods, are another important industrial chemical. Their synthesis, which produces high levels of carbon dioxide and involves hazardous conditions, was also tackled this year by electrochemistry. Karthish Manthiram and coworkers at the Massachusetts Institute of Technology showed that an electrochemical cell could make epoxides from olefins at room temperature and ambient pressure while producing minimal waste and no CO₂.

The traditional synthesis combines ethylene and oxygen at 270–290 °C and 1–3 MPa. CO_2,which forms from overoxidation, increases the carbon footprint of the process. Manthiram’s method grabs the oxygen atom from water and transfers it to an olefin in a one-compartment electrochemical cell.

In addition, this year chemists have directly used electricity to make industrial processes greener. Making syngas, a valuable mixture of carbon monoxide and hydrogen, accounts for about 3% of global CO₂ emissions. That’s in part because the reactor used to slam methane and steam together to produce syngas is heated by combustion. To reduce CO₂ emissions from this process, Peter M. Mortensen of Haldor Topsoe and coworkers developed an alternative to steam reforming using electrical heating rather than combustion. The researchers estimate that replacing the world’s reformers with their versions and powering them with renewable electricity could shave almost 1% off global CO₂ emissions.

In a way, a lot of the reactions that scientists are pursuing with electricity could have happened in the past, Manthiram says, but now people are viewing electrification with fresh eyes. Renewable electricity has become cheaper, and technologies that use or generate electricity, such as electric cars and solar cells, are prevalent, he says.

Chemists are learning that they can drive organic synthesis with electrodes in a way that they can’t with standard reagents, making it possible to coax high selectivities and new molecular structures from reactions, Manthiram says. Now and in the future, joining electrified reactions with renewable power sources such as solar cells can work toward making synthesis more sustainable.

Aluminum complex broke benzene. Benzene, a simple, aromatic, six-membered ring that’s found in crude oil, is known for its hardiness. While chemists have developed myriad ways to tinker with its C–H bonds, reactions that cleave its C–C bonds are rare. A team led by the University of Oxford’s Simon Aldridge and Jose M. Goicoechea discovered an aluminum complex that’s capable of busting open benzene’s C–C bond, converting the cyclic molecule into a linear one (shown; J. Am. Chem. Soc. 2019, DOI: 10.1021/jacs.9b05925). Unlike previous reagents used in benzene-breaking reactions, the Oxford team’s aluminum complex is stable at room temperature as long as it’s under an inert atmosphere. The reaction could be used to expand the range of molecules made from petroleum.

Click chemistry tool kit expanded. Primary amines are plentiful substrates, and this year chemists reported a reaction that turns them into azides. By doing so, the team boosted the number of compounds that can be used in the popular copper(I)-catalyzed azide-alkyne cycloaddition, or CuAAC, click reaction—in which an azide and an alkyne assemble into a triazole quickly, reliably, and without any by-products. Jiajia Dong of the Shanghai Institute of Organic Chemistry, K. Barry Sharpless of Scripps Research in California, and coworkers discovered that fluorosulfuryl azide transforms primary amines into azides (shown; Nature 2019, DOI: 10.1038/s41586-019-1589-1). The chemists generated fluorosulfuryl azide fleetingly in their flasks via the reaction of imidazolium fluorosulfuryl triflate salt and sodium azide, thereby sidestepping the risk of explosion. Dong and Sharpless’s team was able to make large libraries of novel compounds using this approach, and one has already yielded a promising compound for fighting tuberculosis.

Stereochemical control produced poly(vinyl ethers). Chemists Karl Ziegler and Giulio Natta won the 1963 Nobel Prize in Chemistry for their work making isotactic polyolefins—polymers in which most of the pendant groups have the same stereochemical configuration. But that method doesn’t work for making poly(vinyl ethers), because oxygen atoms in the monomers poison Ziegler-Natta catalysts. So poly(vinyl ethers) have remained niche products. Taking advantage of a technique that’s popular for controlling the stereochemistry of pharmaceuticals, Frank A. Leibfarth, a chemist at the University of North Carolina at Chapel Hill, and postdoc Aaron J. Teator discovered they could make isotactic poly(vinyl ethers) by using chiral anions to control the stereochemistry of the polymerization process (shown; Science 2019, DOI: 10.1126/science.aaw1703). The resulting polymers could find use in lightweight composites for making bicycles, boats, and cars.