The Talented 12

Secret agent James Bond (aka 007) has saved the world so many times, he makes it look easy. What the extraordinary young scientists profiled in this issue will tell you is, in reality, it’s anything but.

Welcome to the second annual Talented 12 issue, in which we’re blowing the covers of a group of top-notch chemistry “operatives” whose mission it is to solve some of the world’s most diabolical scientific problems. This group is monitoring our food supply for contaminants, tackling unyielding diseases such as Alzheimer’s, and finding better ways to convert sunlight into electricity.

Finding these rising stars wasn’t easy (they’ve been undercover, duh). During a months-long process, we picked the brains of a panel of esteemed advisers, last year’s winners, and our editorial board for nominees who looked promising. And we accepted nominations from you, dear readers, via an online form. Then we investigated and evaluated each prospect, age 42 or younger, to see whether they had what it takes to make our elite team.

You’ll want to keep an eye on these agents. We expect them to help safeguard the planet for future generations. And unlike James Bond, they won’t need Q to outfit them with exotic gadgets for saving the world. They can build their own.

Lauren Austin admits her college experience was a little different: While hurdling the challenges inherent to a chemistry degree, she was also striving to become a world-class runner. But she wouldn’t have had it any other way. “If I had to focus on one or the other, I probably would have gone crazy,” she says.

Austin attended the University of Central Florida (UCF) so she could keep working with her high school track coach—her father. Her goal was to land a spot running the 800-meter event for the U.S. Olympic team in Beijing.

It was also at UCF that Austin met Qun Huo, a chemist who became Austin’s undergrad adviser. Working with Huo, Austin discovered a passion for nanoscience that would steer her to the labs of Georgia Institute of Technology’s Mostafa A. El-Sayed as a graduate student.

While working with El-Sayed, Austin helped develop ways to peer inside living cells to unravel complex biological interactions. She and her colleagues designed gold nanoparticles that seek out cell nuclei and, once there, enhance Raman scattering signals.

These signals reveal real-time changes in biomolecules that are characteristic of healthy, diseased, or drug-treated cells. This information could potentially guide efforts to create diagnostics, find drug targets, or understand if a drug candidate is working.

Austin possesses a rare combination of creativity, passion, and intellect, says El-Sayed, adding that these will be useful traits for bolstering the bionanotechnology portfolio of Austin’s new employer, Merck & Co. “I really hope they realize what they have in her,” he says.

Austin just started her career as a senior scientist at Merck, but is eager to bring her expertise to the pharmaceutical pipeline, for instance, by invoking nanoscience to improve drug delivery or drug screening methods.

Austin didn’t make the 2008 Olympic team, but she says that helped prepare her to persevere through the realities of science. “Ninety-nine percent of the time, something doesn’t work out,” she says. “I can handle that.”

Three Key Papers

“Observing Real-Time Molecular Event Dynamics of Apoptosis in Living Cancer Cells Using Nuclear-Targeted Plasmonically Enhanced Raman Nanoprobes” (ACS Nano 2014, DOI: 10.1021/nn500840x)

“Exploiting the Nanoparticle Plasmon Effect: Observing Drug Delivery Dynamics in Single Cells via Raman/Fluorescence Imaging Spectroscopy” (ACS Nano 2013, DOI: 10.1021/nn403351z)

“Real-Time Molecular Imaging throughout the Entire Cell Cycle by Targeted Plasmonic-Enhanced Rayleigh/Raman Spectroscopy” (Nano Lett. 2012, DOI: 10.1021/nl3027586)

Research At A Glance

Credit: ACS Nano

Austin and her grad school colleagues designed coated gold nanoparticles that congregate at cell nuclei (shown in the optical photograph). There, the particles enhance Raman scattering signals, such as those from the breakdown of DNA or proteins, that can indicate cell health or response to drug treatment.

When organic materials chemist Luis Campos was growing up, his mother, who worked at a biochemistry lab, told him he could become anything he wanted—as long as it wasn’t a couch potato.

He has not disappointed. Campos is one of the most talented young organic chemists in academia, says his postdoc adviser, materials mastermind Craig Hawker of the University of California, Santa Barbara. “He’s a trailblazer,” Hawker says.

Even the molecules and materials Campos and his team develop overachieve. For example, his lab has created light-responsive materials that generate two pairs of charge-carriers when struck by a single photon. Conventional solar cells, by contrast, generate at most one pair of charge-carriers per photon.

The two-for-one materials could translate into organic solar cells that better convert sunlight into electricity. These solar cells can be easily made by printing organic materials directly onto low-cost substrates, such as plastics, which means they can be used in ways that rigid silicon cells can only dream about: as flexible power supplies or as energy-harvesting windows, for example. But the lackluster efficiency of organic cells has stymied their widespread adoption.

The higher efficiency materials being developed by the Campos group perform a type of quantum mechanical maneuver known as singlet fission. When a photon excites an electronic singlet state, the material can split it into two triplet states.

Although Campos didn’t discover this process, he has developed materials with remarkable dispositions for achieving singlet fission, notably his so-called “push-pull” copolymers and oligoacene-based materials.

Preparing the next generation of trailblazers is as important to Campos as designing next-gen materials. Campos has prioritized his students’ development as scientists above the results they produce. As a result, his clever and energetic students have become more engaged and more comfortable exploring their creativity in the lab, he says. “The most rewarding part of the job is working with the members of my group.”

Three Key Papers

“Molecular Length Dictates the Nature of Charge Carriers in Single-Molecule Junctions of Oxidized Oligothiophenes” (Nat. Chem. 2015, DOI: 10.1038/nchem.2160)

“The Evolution of Cyclopropenium Ions into Functional Polyelectrolytes” (Nat. Commun. 2014, DOI: 10.1038/ncomms6950)

“A Design Strategy for Intramolecular Singlet Fission Mediated by Charge-Transfer States in Donor-Acceptor Organic Materials” (Nat. Mater. 2014, DOI: 10.1038/nmat4175)

Research At A Glance

Credit: Campos Research Group/infinityPV/C&EN

Organic solar cells contain electron donors and acceptors sandwiched between electrodes. These electron-shuffling groups can either exist in separate layers or within the same molecule. Campos’s group develops donors and acceptors that work together to generate two pairs of electronic charge carriers (right) from a single photon of sunlight—a boost in efficiency compared with conventional materials (left and bottom).

Figuring out how complex materials work—and then making them work better—often requires exposing the chemical secrets hidden deep inside.

Getting a close view of a material’s atomic structure helps scientists see how a drug hits its target, reveal how a lobster’s shell forms, or learn about the super-fast chemical reactions inside a cordless drill battery.

But the ability to capture that level of detail is extremely rare. Not only can Karena Chapman do it, she helps other scientists do it too. She is in charge of the high-energy X-ray beamline at Argonne National Laboratory and has spent the past decade developing its capabilities.

Researchers from around the globe bring their samples—zeolites, battery electrodes, nanoparticles, and pharmaceuticals—to the world-class synchrotron facility at Argonne to learn how, when, and where atomic bonds form and how chemical reactions proceed under real-world pressures and temperatures.

Answering those questions is worth traveling for. As a grad student doing crystallography in Australia, Chapman jumped at the chance to conduct short bouts of experiments at Argonne. The facility is in high demand, so visiting researchers who’ve managed to secure a time slot to use the beamline are under pressure to make the most of their 36 or 48 hours of access by revising their experiments on the fly. “It’s science for adrenalin junkies,” she says.

That scientific rush brought Chapman back to Argonne for a postdoc in 2005. She never left. Now a leading materials researcher, she has made discoveries about how high-power electrode materials work and ways to manipulate and improve gas-capturing metal-organic framework compounds.

In her collaborations with other scientists, Chapman dives in when an experiment needs finesse and will push the boundaries of what the beamline can do, says John Parise, professor of geosciences at Stony Brook University. “She is very clever at designing experiments and has a passion to get results. Everyone wants to come work with Karena.”

Three Key Papers

“Comprehensive Insights into the Structural and Chemical Changes in Mixed-Anion FeOF Electrodes by Using Operando PDF and NMR Spectroscopy” (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja400229v)

“Exploiting High Pressures to Generate Porosity, Polymorphism, And Lattice Expansion in the Nonporous Molecular Framework Zn(CN)₂” (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja4012707)

“Pressure-Induced Amorphization and Porosity Modification in a Metal-Organic Framework” (J. Am. Chem. Soc. 2009, DOI: 10.1021/ja908415z)

Research At A Glance

Credit: Karena Chapman/Argonne National Laboratory/C&EN

Among the many materials Chapman has studied with Argonne’s high-energy X-rays are metal-organic framework (MOF) compounds. She discovered that at increasing pressures, a particular MOF can trap radioactive I2 gas. To monitor this type of transition, she measures the X-rays scattered from the sample, plotting the data as a pair distribution function (top right). The colors in the graph indicate the probability of finding atoms separated by a given distance, and peaks correspond to observed bond lengths.

Anthony Estrada prides himself on never being outworked. A relic from his college basketball days, that fierce determination has taken on new weight as he tries to tackle the most notoriously tough area of drug discovery: neuroscience.

It was while still focused on college basketball that Estrada first discovered chemistry. After seeing his high school grades, a counselor at the University of La Verne matched him with chemistry professor Namphol Sinkaset. “I was in his office 24/7, asking to do experiments, talking about chemistry nonstop,” Estrada recalls of his undergrad adviser.

Sinkaset introduced him to famed organic chemist K.C. Nicolaou’s “Classics in Total Synthesis.” Reading the textbook, Estrada was so taken with the idea of building complex molecules that after college he joined Nicolaou’s lab at the University of California, San Diego.

Former UCSD labmates remember Estrada as “a rock star” grad student who played a critical role in cracking the synthesis of thiostrepton, an antibiotic with a whopping 10 rings, 11 peptide bonds, and 17 stereogenic centers.

Estrada then went straight to a job at Genentech, where he soon landed in the neuroscience group. It was a good fit: The knotty problem of designing molecules to overcome the biological, physical, and chemical challenges of the brain was perfect for the determined chemist.

At Genentech, Estrada worked on small molecules to block LRRK2, a protein that so far has the best-known genetic ties to Parkinson’s disease. The series of compounds is now helping elucidate the role of the protein and inform future drug discovery efforts.

Last year, Estrada jumped to Denali Therapeutics, a closely watched biotech started by an elite crew of Genentech scientists. Denali is taking fresh approaches to Alzheimer’s, Parkinson’s, and ALS—diseases that have stymied even the best drug hunters. Estrada is undaunted. The resiliency he learned in sports is keeping him focused on overcoming the industry’s earlier failures, he says: “I don’t give up.”

Three Key Papers

“Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors” (J. Med. Chem. 2014, DOI: 10.1021/jm401654j)

“Pyrimidoaminotropanes as Potent, Selective and Efficacious Small Molecule Kinase Inhibitors of the Mammalian Target of Rapamycin (mTOR)” (J. Med. Chem. 2013, DOI: 10.1021/jm400194n)

“Discovery of Highly Potent, Selective and Brain-Penetrable Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors” (J. Med. Chem. 2012, DOI: 10.1021/jm301020q)

Research At A Glance

Credit: Shutterstock/C&EN

Estrada and his colleagues at Genentech designed compounds that target the Parkinson’s disease-linked protein LRRK2. To sneak these inhibitors (some shown here) past the blood-brain barrier, the researchers had to build them so they balanced opposing needs: metabolic stability, which often requires spreading polarity across a molecule, and equal brain distribution, which favors nonpolar molecules.

Some of the best ideas are born out of a desire to improve efficiency. When Daniel Fitzpatrick started his graduate work in Steven Ley’s lab at the University of Cambridge, he was assigned a chemical synthesis project. Fitzpatrick, who had just moved halfway around the world from his native New Zealand, found much of the work repetitive.

Setting up numerous reactions for optimization and then working each one up “was taking a huge amount of time, but it didn’t require any sort of intellectual thought on my part,” he recalls. He thought, “In other areas these sorts of repetitive tasks have been relegated to machines, so I’m sure it could happen in this case too.”

Within a year of joining the lab, Fitzpatrick built a reaction setup that could be monitored remotely, and then he connected the hardware to an internet-powered control system. He was now free to monitor his reaction and change parameters anywhere he had an internet connection—at home, in the pub, or on some sandy beach thousands of kilometers away. He’s since tweaked the system so it can optimize reactions on its own, send updates via text message, or even shut itself down automatically if the reaction temperature suddenly spikes at 2 AM.

Ley says Fitzpatrick’s software and hardware control systems “have the potential to completely revamp the way work is carried out in an R&D laboratory.”

Fitzpatrick has always liked tinkering with computers, even though he’s had no formal programming training. A few years ago, after finding the software the Ley lab was using to keep track of chemicals clunky, he decided to create a better system. That led to his first start-up, which he launched at age 21: ChemInventory (cheminventory.net). The software is now used by more than 350 groups in 53 countries.

Fitzpatrick still has a year before he finishes his Ph.D., but he has yet to decide whether he’ll apply his inventiveness to industry, academia, or even another start-up.

Three Key Papers

“A Novel Internet-Based Reaction Monitoring, Control and Autonomous Self-Optimization Platform for Chemical Synthesis” (Org. Process Res. Dev. 2015, DOI: 10.1021/acs.oprd.5b00313)

“Organic Synthesis: March of the Machines” (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201410744)

“Machine-Assisted Organic Synthesis” (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201501618)

Research At A Glance

Credit: Daniel Fitzpatrick (photo)/C&EN Org. Proc Res. Dev.

Fitzpatrick has designed an automated synthesis apparatus that can be controlled via the internet, from anywhere in the world. He has used the setup to self-optimize conditions for converting an alcohol to an alkyl bromide, as well as for several other reactions.

Like a spy master who convinces an evil agent to work for the good guys, Alison Narayan wants to turn the enzymes used by cyanobacteria to produce a life-threatening paralysis poison—saxitoxin—into machines that build lifesaving drugs.

The enzymes that make saxitoxin have exquisite chemistry skills, including the enviable ability to install oxygen groups in hard-to-reach places on complex carbon molecules. That task is particularly hard for synthetic chemists but is also really important for drug development—those oxygen groups can modify a molecule’s biological activity.

Narayan isn’t the first chemist to try to make enzymes do her bidding. Protein engineers spend months, even years, rejiggering a protein to perform a single task on a single substrate. But Narayan’s plan is to coax enzymes into doing sophisticated chemistry on a wide variety of substrates. To accomplish that, she wants to mine microbial genomes for enzymes with interesting chemistry skills, engineer the enzymes to work across more kinds of substrates, and eventually incorporate the enzymes into traditional syntheses to more efficiently build complex molecules.

During her postdoc at the University of Michigan with David H. Sherman, Narayan proved the idea works. She engineered a cytochrome P450 enzyme to install hydroxyl groups on hard-to-access parts of menthol and other carbon rings, which are not the enzyme’s natural substrate.

Now with her own group, Narayan has her eye on saxitoxin. The deadly molecule indiscriminately attacks all nine types of voltage-gated sodium channels, membrane proteins essential for producing electrical signals in brain, heart, and muscle cells. Making saxitoxin specific to just one type of voltage-gated sodium channel could lead to a nonaddictive painkiller, new chemotherapies, or drugs for neurodegenerative diseases. Narayan’s current challenge is to tweak the enzymes that make saxitoxin so they install oxygens in slightly different locations on the poisonous scaffold.

Narayan says there’s a treasure trove of enzymes to be mined from the newly sequenced genomes of many microorganisms—enzymes that can decorate carbon molecules in ways a synthetic organic chemist can only dream of.

Three Key Papers

“Enzymatic Hydroxylation of an Unactivated Methylene C–H Bond Guided by Molecular Dynamics Simulations” (Nat. Chem. 2015, DOI: 10.1038/nchem.2285)

“Directing Group-Controlled Regioselectivity in an Enzymatic C–H Bond Oxygenation” (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja5016052)

“Indolizinones as Synthetic Scaffolds: Fundamental Reactivity and the Relay of Stereochemical Information” (Org. Biomol. Chem. 2012, DOI: 10.1039/clob06423a)

Research At A Glance

Credit: Gonzalo Jiménez-Osés/Nature Chemistry/C&EN

As a postdoc, Narayan modified the active site of a P450 enzyme so that it could add hydroxyl groups to unnatural substrates. To do so, she tweaked the amino acids in the active site to make it roomier and inserted a chemical arm to orient unnatural substrates, such as menthol, for catalysis.

We’ve all been there: eating something that we think is delicious in the moment, only to be taken down by a full-on intestinal apocalypse an hour or two later. It wasn’t obvious that a pathogen lurked in the food we chowed, just like it’s not obvious when other contaminants such as pesticides and nanoparticles end up on dinner plates.

Regulators, researchers, and the general public are increasingly concerned about these kinds of food pollutants. But it’s not like you can avoid the risk by simply not eating, quips Lili He, a food chemist at the University of Massachusetts, Amherst.

Drawn to using chemistry to study something as fundamental to everyday life as food, He set out during her Ph.D. to find promising analytical technologies to monitor and analyze food contaminants. She struck gold with surface-enhanced Raman spectroscopy (SERS), a technique that uses laser light to detect signals from individual molecules inside a complex sample by observing their vibrational and rotational motions. The method uses metallic nanoparticles to boost weak signals—up to 10,000 times—allowing He to identify minuscule amounts of problematic chemicals among food’s messy mixture of molecules

Since starting her own labs, He has pioneered a SERS technique for studying the depth at which pesticides can penetrate spinach leaves. Regulators worry that washing the leaves might not be enough to get rid of pesticides, potentially exposing consumers to harmful levels of the chemicals.

He is also developing SERS methods to measure and monitor dangerous bacteria and unwanted nanomaterials in food. Both the U.S. Department of Agriculture and the Food & Drug Administration have put calls out for techniques that can identify nanoparticles that enter food from pesticides, packaging, and food additives, and He wants to prove that SERS is the right choice.

In the long term, He imagines helping to build a miniaturized SERS cell phone add-on that would allow people to look for unwanted pesticides, microbes, or nanomaterials in food. This could put the power to do food safety checks in the hands of concerned consumers.

Three Key Papers

“Real-Time and In Situ Monitoring of Pesticide Penetration in Edible Leaves by Surface-Enhanced Raman Scattering Mapping” (Anal. Chem. 2016, DOI: 10.1021/acs.analchem.6b00320)

“Analysis of Silver Nanoparticles in Antimicrobial Products Using Surface-Enhanced Raman Spectroscopy (SERS)” (Environ. Sci. Technol. 2015, DOI: 10.1021/acs.est.5b00370)

“Surface-Enhanced Raman Spectroscopy for the Chemical Analysis of Food” (Compr. Rev. Food Sci. Food Saf. 2014, DOI: 10.1111/1541-4337.12062)

Research At A Glance

Credit: Anal. Chem./C&EN

Lili He has shown that surface-enhanced Raman spectroscopy (SERS) can be used to monitor food contamination. As shown here, she observes that SERS, which can amplify molecular signals with nanoparticles, tracks the depth of penetration of pesticides such as thiabendazole in spinach, a concern because many people assume pesticides are removed by washing.

Whether you’ve eaten a chunk of bread, a spoonful of honey, or a bite of steak, your endocrine system magically adapts to the various levels of sugar flooding your bloodstream. Except, of course, when the magic fails. Type 2 diabetes occurs when our bodies stop being able to properly use insulin, the peptide tasked with lowering blood sugar after meals.

Juan Pablo Maianti hopes to restore that balance. He’s devoted the past several years to exploring the biology and chemistry of insulin-degrading enzyme (IDE), which, since its discovery in 1949, has been bandied about as a potentially important diabetes drug target.

While a graduate student in David Liu’s lab at Harvard University, Maianti developed the first true IDE inhibitor and then led mouse studies of the compound that upended 60 years of conventional wisdom about IDE. As hoped, the animal studies showed his IDE inhibitor slowed insulin breakdown, thereby lowering blood sugar; however, the studies also revealed that IDE acts on two other hormones, amylin and glucagon.

Because glucagon raises glucose levels while insulin lowers them, Maianti was faced with a daunting new task: With just three months until his thesis defense, he needed to come up with substrate-selective IDE inhibitors—that is, compounds that would slow insulin degradation while allowing glucagon breakdown to proceed as usual. He did it.

Designing complex compounds is an impressive feat. But what has made Maianti “arguably the most talented student I’ve had,” Liu says, is his ability to also orchestrate all of the other aspects of a drug discovery campaign—from chemical synthesis through animal studies.

Maianti is now trying to turn his substrate-selective inhibitors into drugs. Together with Liu and former Harvard colleague Alan Saghatelian, he’s founded a stealth biotech firm that is raising money while Maianti works to tweak and test compounds.

“I didn’t really think I would end up creating a new company,” Maianti says. “But once this opportunity was in front of me, I realized that even if I lived 30 different alternative lives, this wouldn’t come up again.”

Three Key Papers

“Anti-diabetic Activity of Insulin-Degrading Enzyme Inhibitors Mediated by Multiple Hormones” (Nature 2014, DOI: 10.1038/nature13297)

“Toxicity Modulation, Resistance Enzyme Evasion, and A-site X-ray Structure of Broad-Spectrum Antibacterial Neomycin Analogs” (ACS Chem. Biol. 2014, DOI: 10.1021/cb5003416)

“Structural and Kinetic Study of Self-Assembling Macrocyclic Dimer Natural Product Aminoglycoside 66-40C and Unnatural Variants” (Chem. Sci. 2012, DOI: 10.1039/C1SC00538C)

Research At A Glance

Credit: Juan Pablo Maianti/C&EN

Maianti and his collaborators not only designed the first compounds that block insulin-degrading enzyme, a prized diabetes target, they also made those inhibitors selective: The compounds slow the breakdown of insulin in mice but don’t interfere with the enzyme’s breakdown of another important hormone, glucagon.

As a synthetic organic chemist, Bill Morandi is in the business of making molecules. But Morandi admits he’s not interested in the long, slow game of constructing complex natural products or pharmaceuticals. He prefers a faster pace. This, after all, is a man who used to play table tennis competitively.

To achieve speedy results in the lab, Morandi invents new chemical reactions. In particular, Morandi and his research group at the Max Planck Institute for Kohlenforschung want to give chemists new ways to add or remove valuable functional groups from molecules. Such reactions, he explains, can transform compounds that might otherwise be wasted into valuable feedstocks. For example, he has found ways to add complexity to simple compounds derived from petroleum and strip down complicated ones derived from biomass.

“Functional groups really determine what a molecule will do and what kind of properties it will have,” Morandi explains. Being able to selectively add these groups or take them away lets chemists make valuable molecules from more mundane ones.

With this aim in mind, Morandi’s team developed a reaction that selectively plucks off one alcohol group from a molecule that bears two adjacent alcohol groups. They also figured out a way to add hydrogen cyanide across a double bond without actually using the dangerous chemical, providing a safer alternative for this workhorse reaction. And Morandi doesn’t just focus on safer reactions; he also emphasizes sustainability: All his lab’s transformations developed to date use inexpensive earth-abundant catalysts.

Morandi’s novel catalytic reactions transform widely available chemicals into more precious compounds, notes Benjamin List, a colleague of Morandi’s at Max Planck. List says: “It may well be this kind of research in catalysis that will ultimately provide answers to the challenges of our time, such as energy, health, and transportation.”

Three Key Papers

“Catalytic Reversible Alkene-Nitrile Interconversion through Controllable Transfer Hydrocyanation” (Science 2016, DOI: 10.1126/science.aae0427)

“Boron-Catalyzed Regioselective Deoxygenation of Terminal 1,2-Diols to 2-Alkanols Enabled by the Strategic Formation of a Cyclic Siloxane Intermediate” (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/anie.201503172)

“Direct Catalytic Synthesis of Unprotected 2-Amino-1-Phenylethanols from Alkenes by Using Iron(II) Phthalocyanine” (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201507630)

Research At A Glance

Credit: Yang H. Ku/C&EN

Morandi and his team invent new reactions with an emphasis on sustainability. As depicted in this comic, the team developed a reaction that uses a nickel catalyst to shift hydrogen cyanide between two molecules, allowing them to avoid the dangerous chemical.

Renã Robinson is not one of those people who knew as a child that she wanted to be a chemist. She majored in chemistry because it seemed like a straightforward path to becoming a cardiac surgeon—a reaction to losing her father to heart complications while she was in middle school. But an internship convinced her that she didn’t want to hold that level of responsibility for someone’s life literally in her hands.

So she wound up in graduate school instead. While at Indiana University, she focused on examining the protein makeup of fruit flies to understand how they age. In David Clemmer’s group, she was a pioneer in combining two techniques—ion mobility and time-of-flight mass spectrometry—for the large-scale analysis and identification of proteins. Because commercial instruments with this combination of methods weren’t yet available, these experiments “were anything but routine,” Clemmer says.

As a grad student, Robinson didn’t see a lot of people who looked like her, a fact that helped persuade her to go into academia. There, she thought she could address the lack of African American—especially female—role models. “That gave me more purpose and more motivation,” she says.

Now with her own lab at the University of Pittsburgh, Robinson continues to study aging and related neurodegenerative diseases. She’s particularly interested in finding out how the brain and other parts of the body interact in Alzheimer’s, with the ultimate goal of identifying new therapeutic targets.

To do that, she develops proteomics methods that enable her team to identify proteins that have been modified by oxygen or other reactive species. Within the next five years, she hopes to resolve a chicken-or-egg question in Alzheimer’s: whether changes outside the brain, such as oxidative stress or metabolism changes, precede or are a response to changes in the brain. That information could help alter our perception of Alzheimer’s as just a brain disease and lead to new ways to monitor or treat it.

Three Key Papers

“Global cPILOT Analysis of the APP/PS-1 Mouse Liver Proteome” (Proteomics: Clin. Appl. 2015, DOI: 10.1002/prca.201400149)

“Proteomics Reveals Age-Related Differences in the Host Immune Response to Sepsis” (J. Proteome Res. 2014, DOI: 10.1021/pr400814s)

“Examining the Proteome of Drosophila across Organism Lifespan” (J. Proteome Res. 2007, DOI: 10.1021/pr070224h)

Research At A Glance

Credit: Courtesy of Renã Robinson/C&EN

Robinson wants to understand how proteins in the body respond to Alzheimer’s or warn of the disease’s onset. To achieve this, she uses isotopic labeling to tag proteins extracted from various tissues and then carries out proteomics analysis on them. Although her ultimate goal is to work with human tissue, the example mass spectrum shown here displays peaks from mice with Alzheimer’s symptoms and healthy animals.

Many scientists say that as a kid they always wanted to be a scientist. That wasn’t the case for UCLA’s Alex Spokoyny. “Growing up in Russia in a family where my mom was a biologist and my dad was a physicist, there was always pressure to be a scientist,” Spokoyny says.

Although he liked analyzing things, he was also a natural contrarian who would argue with his parents. Still, Spokoyny eventually compromised with his mom and dad, agreeing to attend a science high school in Russia. While there, a funny thing happened: He got hooked on chemistry.

“There’s a Russian saying: ‘Sometimes the appetite comes during the meal.’ It was really the experimental side of chemistry that captured my interest.”

Spokoyny has been hungry ever since. From his undergraduate days through his postdoc, Spokoyny has studied a vast array of chemical systems, including boron-based clusters with therapeutic potential, metal-organic framework compounds that separate gases, and methods to modify proteins.

He’s now integrating that collective wisdom into something distinctly his own—what he calls “organomimetic” chemistry. “We still have limited chemical building blocks for making compounds,” Spokoyny says. The goal of his lab is to develop boron-based inorganic clusters as three-dimensional alternatives to conventional “flat” organic molecules.

Decorating the clusters with various functional groups to manipulate their properties allows researchers to do new and interesting chemistry. For example, adding aryl ether groups and then activating the clusters with light enables them to jump-start polymerizations without expensive metal-based catalysts. The possibilities for organomimetic chemistry are vast, Spokoyny says, and could include a more versatile approach to converting sunlight into electricity and the development of highly selective cancer therapies.

“Alex is one of the most accomplished, mature, visionary young scientists I’ve ever met,” says Northwestern University’s Chad A. Mirkin, one of Spokoyny’s former advisers. “He has a better understanding of chemical reactions and how to harness them than most full professors.”

Three Key Papers

“Visible-Light Induced Olefin Activation using 3D Aromatic Boron-Rich Cluster Photooxidants” (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b03568)

“A Perfluoroaryl-Cysteine S_NAr Chemistry Approach to Unprotected Peptide Stapling” (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja400119t)

“A Coordination Chemistry Dichotomy for Icosahedral Carborane-Based Ligands” (Nat. Chem. 2011, DOI: 10.1038/nchem.1088)

Research At A Glance

Credit: Courtesy of Alex Spokoyny

Spokoyny’s group has built light-activated functionalized carboranes to serve as metal-free catalysts. One of these catalysts, shown here, can activate tricky olefins such as isobutylene to make highly branched polymers.

On his first day as a graduate student in Jim Heath’s group at Caltech, Ke Xu was handed a paper that was about to be submitted for publication. “I got a long note the next morning saying the theory part was not quite right,” Heath remembers. At first, Heath thought, “What chutzpah!” But then he realized that Xu was right.

Xu’s name was added to the paper and the chemist has been on the fast track ever since. In the three years since starting his own lab at the University of California, Berkeley, he has already made important contributions to the field of superresolution microscopy, advances that allow him to generate Technicolor images of the structural details of cells.

One of Xu’s contributions was to combine fluorescence spectroscopy with superresolution microscopy so that researchers can distinguish between assorted components in a cell at the same time. To use the technique, Xu tags the components with dyes or proteins that have slightly different fluorescence spectra. That allows him to see multiple components in a cell simultaneously at a previously unachievable resolution. “We can easily do multicolor imaging for four colors at the same time,” Xu says.

In another contribution to the field, Xu’s group figured out a way to do superresolution fluorescence imaging and electron microscopy on the exact same cells without drying them. Previously, researchers would have had to go through a difficult, error-prone dehydration process to make samples compatible with electron microscopy before they could capture cellular details with both methods, which can make images difficult to correlate and conclusions tough to nail down.

Xu plans to use the methods he’s developed to probe the internal structure and dynamics of cells at nanometer resolution. The combination should help him understand the inner workings of cells.

“Since he’s gotten to Berkeley, he’s done two beautiful experiments that have pushed the field forward,” Heath says. “And this is not an empty field. This is a crowded field.”

Three Key Papers

“Ultrahigh-Throughput Single-Molecule Spectroscopy and Spectrally Resolved Super-Resolution Microscopy” (Nat. Meth. 2015, DOI: 10.1038/nmeth.3528)

“Graphene-Enabled Electron Microscopy and Correlated Super-Resolution Microscopy of Wet Cells” (Nat. Commun. 2015, DOI: 10.1038/ncomms838)

“Actin, Spectrin and Associated Proteins Form a Periodic Cytoskeletal Structure in Axons” (Science 2012, DOI: 10.1126/science.1232251)

Research At A Glance

Credit: Ke Xu

Using a technique he developed—combined fluorescence spectroscopy/superresolution imaging—Xu collects the light emitted by various dye molecules tagging a cell. This light gets passed through a prism, which separates fluorescence into its spectral components, revealing the cell’s structural and chemical details. (The parts shown in these mammalian cells include peroxisomes, yellow, and mitochondria, violet.)

Our 2016 selection process

Finding this year’s rising stars in chemistry wasn’t easy (they’ve been undercover, duh). During a months-long process, we picked the brains of a panel of esteemed advisers, last year’s winners, and our editorial board for nominees who looked promising. And we accepted nominations from you, dear readers, via an online form. Then we investigated and evaluated each prospect, age 42 or younger, to see whether they had what it takes to make our elite team.

Our Advisers:

Carolyn Bertozzi, Stanford University; Alexis Borisy, Third Rock Ventures; Kelly Chibale, University of Cape Town; Judy Giordan, ecosVC; Kristala Jones Prather, Massachusetts Institute of Technology; Benjamin List, Max Planck Institute for Kohlenforschung; Denis Malyshev, stealth biotech; Dean Toste, University of California, Berkeley; Peidong Yang, UC Berkeley; and Tehshik Yoon, University of Wisconsin, Madison