C&EN’s Talented 12

Welcome to the third annual Talented 12 issue. It took us months of scouring the globe to collect all 12 of the rising stars in chemistry featured in the pages that follow.

The dream team we’ve assembled is tackling some of the toughest scientific challenges facing the world today. These young scientists are battling the opioid epidemic, inventing new medicines and better ways to make them, and harnessing sunlight to make fuel and other useful chemicals.

To find our 12, we called on a panel of esteemed advisers, C&EN’s advisory board, and Talented 12 alumni to nominate prospects aged 42 or younger who are pushing the boundaries in their fields. We also accepted nominations from readers through an online form. Finally, we researched and evaluated the more than 150 candidates amassed during this process to zero in on the path-paving individuals highlighted here.

We’re certain these 12 will be scientific MVPs someday. You should collect their autographs now.

As a fourth-year graduate student, Fikile Brushett already had a faculty job lined up at Massachusetts Institute of Technology. But he wanted to do a postdoc anyway, so MIT held his spot. In grad school, he studied energy conversion in fuel cells, and he wanted to learn about the other side of the energy equation—storage—before he started his own lab..

As a fourth-year graduate student, Fikile Brushett already had a faculty job lined up at Massachusetts Institute of Technology. But he wanted to do a postdoc anyway, so MIT held his spot. In grad school, he studied energy conversion in fuel cells, and he wanted to learn about the other side of the energy equation—storage—before he started his own lab.

During his two years as a postdoc at Argonne National Laboratory, Brushett worked on electrochemical flow batteries, which are used for energy storage on the electrical grid. “I thought I would see if I liked it. If not, I could go back to working on fuel cells,” he says. “At least I’d know something about storage.”

Unlike the familiar batteries used in portable devices, which store their charge in solid electrodes, redox flow batteries store charge in electrolyte solutions that are housed in separate tanks and pumped into an electrochemical reactor to alternately charge and discharge the battery. Most flow batteries use water-based electrolyte solutions.

When Brushett moved away from water-based systems and started working on all-organic systems as a postdoc, critics said they would be too expensive to make and operate. Brushett and his colleagues responded by developing a techno-economic model to show that all-organic flow batteries are in fact economically feasible. The model tells them what material properties are required to overcome cost hurdles and points to the most promising research areas. Such modeling “can help define a design space that is obscured at first,” Brushett says.

Now at MIT, he’s using the model to guide the design of new materials. A major focus of his lab is understanding how chemical structure affects the function of redox active molecules, with the goal of expanding the toolbox for engineering batteries. In addition, his lab is developing new electrochemical reactors to improve battery performance.

He’s proud of the work his lab is doing to explore the design possibilities for flow batteries. “I hope it inspires our friends in the organic chemistry community, who are far better at molecular synthesis, to look for new materials.”

Three Key Papers

“Concentration-Dependent Dimerization of Anthraquinone Disulfonic Acid and Its Impact on Charge Storage” (Chem. Mater. 2017, DOI: 10.1021/acs.chemmater.7b00616)

“High Current Density, Long Duration Cycling of Soluble Organic Active Species for Non-Aqueous Redox Flow Batteries” (Energy Environ. Sci. 2016, DOI: 10.1039/c6ee02027e)

“An All-Organic Non-Aqueous Lithium-Ion Redox Flow Battery” (Adv. Energy Mater. 2012, DOI: 10.1002/aenm.201200322)

Research At A Glance

Credit: Yang H. Ku/C&EN

Brushett is developing batteries for storing energy from sustainable sources such as wind and sunlight. The molecules shown in this all-organic electrochemical flow battery are among the ones that his lab is creating to improve the devices’ efficiency and capacity.

While working as an undergrad in a polymer chemistry lab, Luke Connal realized that polymers are powerful—for example, they can be therapeutics, mining tools, or even counterfeit-proof currency..

Today, running his own lab at the University of Melbourne, Connal wants to harness the power of polymers to design catalysts that mimic enzymes. He thinks these catalytic materials could do jobs in industry or in commercial products that less-robust enzymes can’t.

“This is a platform that could really transform catalysis,” says Michelle Coote, one of Connal’s colleagues at Australian National University.

Enzymes achieve their catalytic prowess by folding in specific ways to orient key chemical groups. But when an enzyme loses this structure, it also loses its function, making the proteins sensitive to harsh conditions, such as high temperatures or high salt levels, that can unfold them.

Polymers are far more stable and can withstand a wider range of conditions. So Connal set to work on mimicking the active sites of enzymes—where the chemical action happens—in polymer structures.

His first target of mimicry was the so-called catalytic triad of proteases. These enzymes use the triad—an alcohol, a carboxylate, and an imidazole—to chew up the amide backbones of other proteins. Connal’s team earlier this year reported a polymer resin that breaks down esters with enzymelike kinetics using the same trio of functional groups.

Connal is collaborating with the consumer product company Unilever on the protease project, with the goal of replacing stain-fighting enzymes in laundry detergents with more stable, longer lasting polymers. With those applications in mind, he says his group’s goal is to keep the material’s synthesis concise and scalable.

Connal’s success is due in part to how he combines an engineer’s focus on performance with a synthetic chemist’s ability to efficiently make molecules, says Craig Hawker, Connal’s postdoc adviser at the University of California, Santa Barbara.

Besides using polymers to mimic enzymes, Connal also develops polymers for conductors in lithium-ion batteries and for purifying metals from ores. “Once you realize the potential of polymers,” he says, “there is so much you can do.”

Three Key Papers

“Triggered and Tunable Hydrogen Sulfide Release from Photogenerated Thiobenzaldehydes” (Chem.–Eur. J. 2017, DOI: 10.1002/chem.201701206)

“2D and 3D-Printing of Self-Healing Gels: Design and Extrusion of Self-Rolling Objects” (Mol. Syst. Des. Eng. 2017, DOI: 10.1039/c7me00023e)

“Simple Design of an Enzyme-Inspired Supported Catalyst Based on a Catalytic Triad” (Chem 2017, DOI: 10.1016/j.chempr.2017.04.004)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

Connal’s group designed a polymer with active sites that mimic the catalytic amino acids of proteases (left). Their polymer active sites contain the same three functional groups as the enzymes: an alcohol, an imidazole, and a carboxylate. These polymers one day could replace enzymes used in laundry detergents.

Growing up in New Jersey, Jillian Dempsey was surrounded by the pharmaceutical industry. It would have been natural for her to become part of it, and in fact, that was her plan. But Dempsey switched course in college when she saw how physical inorganic chemistry could curb humanity’s addiction to fossil fuels..

Dempsey and her team at the University of North Carolina, Chapel Hill, are now studying next-generation catalysts for artificial photosynthesis. Like natural photosynthesis, this process creates energy-rich compounds from water, carbon dioxide, and sunlight. Whereas plants make sugars, artificial leaves would produce fuels including hydrogen and methane.

Molecular fuels, especially hydrocarbons, dominate the shipping and transportation industries, in which sustainable but bulky technologies have struggled to make inroads. Batteries and solar panels gobble up an aircraft’s weight budget, for example, leaving no room for ticketed passengers or valuable cargo. Comparatively lightweight molecular fuels, such as methane, are much better suited for these applications. Artificial photosynthesis promises a sustainable way of making them without extracting them from deep in Earth.

But converting cheap and abundant reactants into valuable fuels requires a reshuffling of both protons and electrons through reactions known as proton-coupled electron transfers. Dempsey’s research combines electrochemical methods with time-resolved spectroscopy to reveal how well different catalysts choreograph these reactions under different conditions.

“She’s worked out ways to tell exactly how these reactions go,” says electron-transfer-chemistry expert Harry B. Gray of California Institute of Technology, who was Dempsey’s doctoral adviser. Her research, coupled with her excellence as a teacher and mentor, have established her as an emerging leader in chemistry, Gray adds. “I can’t think of anyone who does more for the chemical enterprise.”

Dempsey’s work is already helping researchers design improved catalysts, Gray says, and she’s doing that with an eye toward cost. For instance, her team is particularly interested in cobalt and nickel complexes that are cheaper than more conventional platinum catalysts.

Although it will be years before artificial photosynthesis is ready to fill fuel tanks on a commercial scale, Dempsey may already be sharing a glimpse of the chemistry that will help power the future.

Three Key Papers

“Linear Free Energy Relationships in the Hydrogen Evolution Reaction: Kinetic Analysis of a Cobaloxime Catalyst” (ACS Catalysis 2016, DOI: 10.1021/acscatal.6b00667)

“Potential-Dependent Electrocatalytic Pathways: Controlling Reactivity with pKa for Mechanistic Investigation of a Nickel-Based Hydrogen Evolution Catalyst” (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b08297)

“Photo-Induced Proton-Coupled Electron Transfer Reactions of Acridine Orange: Comprehensive Spectral and Kinetics Analysis” (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja505755k)

Research At A Glance

Credit: Yang H. Ku/C&EN

Artificial photosynthesis promises to make high-energy fuels from cheap, abundant reactants. But even the simple step of splitting water to obtain hydrogen requires complex chemistry, as depicted in this cartoon. Dempsey studies the mechanisms of hydrogen-evolution catalysts, such as those shown, to improve the process.

As a full-time chemist and the father of a two-year-old, Daniel DiRocco doesn’t have much time for hobbies. If he does find a spare hour, he’s likely to spend it in the computer-controlled home brewery he built in his garage. His current goal is to master lager making. “Lager has a little more process chemistry than the ales most home brewers make,” he says..

It’s no surprise that DiRocco would favor a hobby that involves understanding complex systems. As leader of the catalysis group in process chemistry at Merck & Co., it’s his job to figure out the best reactions for making molecules on large scales so enough can be made for clinical trials or even for manufacturing on the metric-ton scale if a candidate compound is approved as a drug. The quick-and-dirty routes used to make compounds during drug discovery are rarely suitable for scaling those same molecules up, DiRocco says. Yields can be low, or the reagents used to make them can be too expensive. “If we have to make a compound on a large scale, we have to make it as quickly, efficiently, and economically as possible. Generally, that means completely redesigning how it was put together.”

In particular, DiRocco’s group specializes in bringing modern asymmetric catalysis methods and innovative new reactions to Merck’s manufacturing processes. For example, his team recently discovered a metal-free, small-molecule catalyst for making chiral nucleoside phosphoramidates—a motif that’s becoming popular in drug molecules, such as Merck’s clinical candidate MK-3682 and Gilead’s Sovaldi, both hepatitis C therapies. These molecules pose a particular challenge to make because their phosphorus atoms are chiral. While myriad methods for making chiral carbon are available, routes to chiral phosphorus are rare.

Tomislav Rovis, DiRocco’s doctoral mentor at Colorado State University, says DiRocco had the Midas touch as a graduate student. “Everything he did turned to gold. His chemical intuition was impeccable, and he had the unique ability to extract exactly the information he needed out of every reaction that he ran without getting distracted or wasting any time,” says Rovis, now at Columbia University. “It wasn’t luck but clarity of thought and a killer instinct.”

Three Key Papers

“A Multifunctional Catalyst That Stereoselectively Assembles Prodrugs” (Science 2017, DOI: 10.1126/science.aam7936)

“Late-Stage Functionalization of Biologically Active Heterocycles through Photoredox Catalysis” (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201402023)

“Catalytic Asymmetric Intermolecular Stetter Reaction of Heterocyclic Aldehydes with Nitroalkenes: Backbone Fluorination Improves Selectivity” (J. Am. Chem. Soc. 2009, DOI: 10.1021/ja904375q)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

Synthesizing molecules with a chiral phosphorus is tough. But a metal-free, small-molecule catalyst developed by DiRocco’s team makes chiral nucleoside phosphoramidates, such as Merck’s hepatitis C candidate therapy MK-3682.

Few chemists can point to Nicolas Cage as inspiration for their career, but the actor’s role as a chemical weapons expert in the 1996 film “The Rock” spurred Michael Feasel to seek a similar post. “It’s a hokey movie, but I realized that somewhere in government this job exists. So at college, I did everything to prepare myself for it,” Feasel says..

After bingeing on toxicology and chemistry courses as an undergrad, Feasel nabbed a staff job at the U.S. Army Edgewood Chemical Biological Center (ECBC). He started out by studying the health impacts of smokes and obscurants used by the military in war zones.

Then, in 2012, a report by British chemical weapons specialists inspired a shift in Feasel’s focus. Solving a long-standing mystery, the British team had determined the chemical components of a spray used in 2002 by Russian special forces to resolve a hostage crisis in a Moscow theater. The aerosol, which helped end the standoff but also cost the lives of more than 120 hostages, likely contained two powerful synthetic opioids: carfentanil and remifentanil.

Carfentanil is 10,000 times as strong as morphine. It’s typically used in dart guns to subdue rhinoceroses and other game animals, Feasel says. More recently, carfentanil has also been responsible for the deaths of multiple people across the U.S. who took heroin or cocaine laced with the opioid.

But at the time of the Moscow theater standoff, chemists had never characterized how carfentanil broke down in the human body to form metabolites, molecules that would have been found in the urine and blood of victims. So as part of his day job at ECBC, Feasel started a Ph.D. to do just that, discovering unexpected human metabolites of carfentanil and trying to understand if and how they are toxic to humans.

Having completed his degree, Feasel is now developing experimental strategies to do the same for other synthetic opioids. “The fruits of his research provide critical information to combat the ongoing epidemic of opioid use,” adds Christopher Whalley, Feasel’s toxicology supervisor at ECBC.

Three Key Papers

“Metabolism of Carfentanil, an Ultra-Potent Opioid, in Human Liver Microsomes and Human Hepatocytes by High-Resolution Mass Spectrometry” (AAPS J. 2016, DOI: 10.1208/s12248-016-9963-5)

“Inhalation Toxicology of Riot Control Agents,” in Inhalation Toxicology, 3rd ed., ed. Harry Salem and Sidney A. Katz (Boca Raton, Fla.: CRC Press, 2015), 211–244, DOI: 10.1201/b16781-12

“Incapacitating agents,” in Salem and Katz, Inhalation Toxicology, 245–256, DOI: 10.1201/b16781-13

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

The synthetic opioid carfentanil is 10,000 times as strong as morphine and can easily cause overdoses. Feasel is studying how opioids such as this one break down into metabolites in the body to understand why the drugs are so potent. Identifying the metabolites could also help identify people who have overdosed.

When Renee Frontiera was growing up in Madison, Wis., her parents took her to a Christmas-themed chemistry show every year. The beloved holiday exhibition, put on by University of Wisconsin professor Bassam Shakhashiri, was what first got her excited about chemistry..

At first, she didn’t consider it as a career path. As an undergrad at Carleton College, she started out majoring in Chinese. But she took chemistry classes too, ending up with a double major.

Her undergraduate research convinced her that chemistry was what she really wanted to do, and by graduate school, Frontiera had gravitated toward spectroscopy. “I liked spectroscopy because I thought we could do really controlled studies to learn about cause and effect, how molecules work and react,” she says. “And I’ve never gone back.”

As a postdoc, she was the first person to combine ultrafast Raman spectroscopy with sensitivity-boosting surface-enhanced Raman, allowing her to measure the motions of small numbers of molecules on the femtosecond timescale.

In her own lab, Frontiera is working on a Raman version of superresolution microscopy, which enables the measurement of nanoscale features in cells and other materials. Frontiera’s combined technique could reveal chemical information about samples along with nano­meter-scale spatial resolution. Previously, achieving that level of resolution in optical microscopy required adding fluorescent tags to molecules, which can limit the type and number of molecules that scientists can observe. With her new method, Frontiera should be able to, for example, watch how a cell membrane’s structure changes over time.

“We’re coming up with new spectroscopic tools to try to understand how nanoscale environments affect chemical outcomes,” she says. In addition to cell membranes, Frontiera plans to use her new tools to study solar cells.

Frontiera has come full circle. She helps instill excitement for chemistry in kids today by performing in her own university’s chemistry outreach show, “Energy and U.” “It’s a super inspiring part of my job to be in the show,” Frontiera says. “Students leave knowing the first law of thermodynamics, which is pretty awesome for third-graders.”

Three Key Papers

“Ultrafast Surface-Enhanced Raman Probing of the Role of Hot Electrons in Plasmon-Driven Chemistry” (J. Phys. Chem. Lett. 2016, DOI: 10.1021/acs.jpclett.6b01453)

“Toward Label-Free Super-Resolution Microscopy” (ACS Photonics 2016, DOI: 10.1021/acsphotonics.5b00467)

“Surface Enhanced Femtosecond Stimulated Raman Spectroscopy” (J. Phys. Chem. Lett. 2011, DOI: 10.1021/jz200498z)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

In Frontiera’s Raman version of superresolution microscopy, she uses two laser beams (a pump and a probe) to excite a Raman signal and a third doughnut-shaped beam to turn off the signal everywhere except in the center of the doughnut. This method probes biological samples (bottom) with better spatial resolution than conventional diffraction-limited microscopy has.

Marie Heffern’s interests in the lab are as eclectic as the hobbies she pursues in her downtime. She’s proficient in three dialects of ancient Greek, she’s learning to ride a motorcycle, and she loves rock climbing almost as much as she loves being creative in the kitchen..

In fact, Heffern compares her scientific approach to her cooking style: “I like the challenge of seeing what’s left in the fridge and making a dish with whatever is there. And I don’t like following recipes.”

That resourcefulness has served her well in her attempts to understand the role of trace metals in our bodies. As a graduate student in bioinorganic chemistry, Heffern had to employ a mélange of analytical methods—spectroscopy, calorimetry, crystallography, and more—to answer a seemingly straightforward question: How does cobalt affect the function of transcription factor proteins, which turn on or off the genes involved in cancer metastasis?

After honing her skills studying how metals enable biology at a molecular level, she went bigger in her postdoc. Heffern figured out how to image copper in the body of a live mouse. Then she used the method to track the metal inside mice as they developed nonalcoholic fatty liver disease, which causes inflammation and scarring in the livers of an estimated 20% of the worldwide population. She discovered a copper deficiency in the animals’ livers as the disease progressed.

As Heffern begins her independent career at the University of California, Davis, she plans to focus on the role metals play in hormone biology, a field of research she calls metalloendocrinology. Her lab will study how peptide hormones such as insulin and oxytocin use metals to relay their vital messages to organs, as well as how trace metals in our diet interact with our genes to exacerbate obesity and hormone-related disorders.

She’s even going back to old-school literature from the 1940s for inspiration. “There are so many aspects of nutrition—and the roles metals play in it—that we thought we understood but don’t really,” she says. “Finally, we have the analytical tools to take a lot of interesting work from the past to the next level.”

Three Key Papers

“In Vivo Bioluminescence Imaging Reveals Copper Deficiency in a Murine Model of Nonalcoholic Fatty Liver Disease” (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1613628113)

“Modulation of Amyloid-β Aggregation by Histidine-Coordinating Cobalt(III) Schiff Base Complexes” (ChemBioChem. 2014, DOI: 10.1002/cbic.201402201)

“Spectroscopic Elucidation of the Inhibitory Mechanism of Cys2His2 Zinc Finger Transcription Factors by Cobalt(III) Schiff Base Complexes” (Chem.–Eur. J. 2013, DOI: 10.1002/chem.201301659)

Research At A Glance

Credit: Yang H. Ku/C&EN/Proc. Natl. Acad. Sci. USA

Heffern is studying how metals in our bodies affect hormone signaling. To track copper’s effects, she engineered mice to produce a luciferase enzyme. When researchers inject mice with the chemical CCL-1, copper in the animals’ bodies converts CCL-1 to luciferin. Then the luciferase enzyme transforms luciferin into oxyluciferin, releasing light (red = high signal).

One of the things Ashish Kulkarni loves about organic chemistry is the possibility of using his imagination to make beautiful molecules. He puts that creativity to work designing new therapies for cancer, an area that’s important to him because he’s lost close family members to the disease..

But he didn’t take a direct route to his current role as a cancer researcher.

After earning his undergraduate degree in India, Kulkarni worked in industry for three years before realizing his calling was in academia. For his Ph.D. research at the University of Cincinnati, he synthesized complex sugar molecules to use as disease diagnostics. “With glycans, I learned how to design molecules to understand biological processes,” he says.

As a postdoc at Harvard, Kulkarni put those skills to work devising nanoparticles that could act as cancer immunotherapies—drugs that prompt the immune system to home in on and attack cancer cells. Although cancer immunotherapies called checkpoint inhibitors melt away tumors in some people with cancer, they don’t work for everyone. Researchers have struggled to find a good diagnostic or biomarker to predict or track people’s responses to the treatments.

Kulkarni’s nanoparticle therapies could help address that quandary by simultaneously activating the immune system and lighting up if the treatment is working. “Disease develops in our body if there is an imbalance in the immune system,” Kulkarni says. “I’m developing dual-function nanoparticles that can allow us not only to create a balance in the immune system but also to monitor whether the drug is working in real time.”

One such nanoparticle is made of a polymeric backbone attached to a known checkpoint inhibitor and to a reporter molecule that’s released by an enzyme involved in the cell death pathway. With such a self-reporting treatment, doctors could quickly figure out whether patients are responding to the therapy.

The next phase of Kulkarni’s career launches this fall, when he sets up shop at the University of Massachusetts, Amherst. His lab there will focus on further developing the “immunotheranostic” nanoparticles and translating them to clinical use. Eventually, he hopes to start a company to bring his nanoparticles to people with cancer.

Three Key Papers

“Combining Immune Checkpoint Inhibitors and Kinase-Inhibiting Supramolecular Therapeutics for Enhanced Anticancer Efficacy” (ACS Nano 2016, DOI: 10.1021/acsnano.6b01600)

“Algorithm for Designing Nanoscale Supramolecular Therapeutics with Increased Anticancer Efficacy” (ACS Nano 2016, DOI: 10.1021/acsnano.6b00241)

“Reporter Nanoparticle That Monitors Its Anticancer Efficacy in Real Time” (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1603455113)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

Kulkarni’s dual-action nanoparticles contain a drug and a reporter that activates only when it has been cleaved by an enzyme involved in cancer cell death, a signal that the therapy is working.

Legend has it that the morning Corinna Schindler defended her doctoral thesis, she told Erick Carreira, her mentor at the Swiss Federal Institute of Technology (ETH), Zurich, that she planned to do a few more experiments in the afternoon, postdefense. “I thought she was joking,” he remembers. “She was serious!” While most newly minted Ph.D.s would be exhausted or ready to spend the afternoon celebrating, Schindler had some ideas she wanted to follow up on..

“Corinna ranks as one of the most ambitious, dedicated, and hardworking students I have ever encountered, with a sharp intellect to match,” Carreira says. “She is fearless in taking on all sorts of challenges in science.”

Schindler’s lab at the University of Michigan focuses on developing new reactions to make molecules that are important in materials science and medicine. “What is really interesting and exciting to us is that we can use reagents that are environmentally benign, cheap, easy to handle, and abundant, so there’s little impact on the environment,” Schindler explains. The goal, she says, is to replace reagents based on precious metals that will eventually run out.

Last year, Schindler’s group reported a carbonyl-olefin metathesis reaction that’s catalyzed by iron. Previous examples of this type of reaction required an equal ratio of carbonyl compounds to molybdenum reagents (which can be expensive and environmentally harmful). Many had tried to create a catalytic version of the reaction, but Schindler was the first to succeed. Next, Schindler hopes to use the reactions her lab has been developing to make complex molecules that could be used as treatments for cancer or inflammatory disorders.

As a mentor, Schindler tries to instill in her students that it’s important to think unconventionally. “Many young students can be very creative but are also worried about making suggestions because they feel like they don’t know everything yet,” she says. “It’s not necessary that you know every aspect of organic chemistry to come up with creative solutions to problems.”

Three Key Papers

“Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis Reaction” (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.7b05641)

“Polycyclic Aromatic Hydrocarbons via Iron(III)-Catalyzed Carbonyl-Olefin Metathesis” (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.7b01114)

“Iron(III)-Catalysed Carbonyl-Olefin Metathesis”(Nature 2016, DOI: 10.1038/nature17432)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

Schindler focuses on replacing precious-metal-based reagents with more abundant, environmentally friendly ones. She developed this iron-catalyzed carbonyl-olefin metathesis reaction to avoid the use of molybdenum reagents.

Before he began grad school, Staff Sheehan had already started two technology companies using programming skills he taught himself as a teenager. So it’s not a surprise that Sheehan, now 28, is using his academic training in electrochemistry as an entrepreneur..

Sheehan has selected an audacious target for his start-up, Catalytic Innovations. He is building an electrochemical cell to make fuels and chemicals using only water, carbon dioxide, and energy from the sun. Although some so-called solar fuel devices have shown promise in the lab, the idea has proved difficult to commercialize.

If he manages to make it work, Sheehan would be making good on a vague ambition that has stuck with him since high school. “I was studying climate change and decided I wanted to make a ‘box’ to solve the problem,” Sheehan says. He has been steadily making progress toward a climate-friendly device that transforms water and CO2 ever since.

As a freshman at Boston College, Sheehan quickly got to work in Dunwei Wang’s lab, where he researched new materials for energy conversion and storage. He continued to build his energy knowledge while a graduate student in Charles Schmuttenmaer’s group at Yale University. While in grad school, Sheehan first made gold-coated nanoparticles to improve the performance of dye-sensitized solar cells, then moved on to artificial photosynthesis, which called for making new catalysts.

Catalysts are the secret sauce of an efficient solar fuel cell. They help break the molecular bonds of water and CO2 and reassemble the atoms into useful fuels and chemicals, such as ethanol. At Yale, Sheehan developed water-splitting catalysts with chemistry professor Gary Brudvig and Paul Anastas, director of Yale’s Center for Green Chemistry & Green Engineering.

Catalyst-driven electrochemistry is also used in metal refining and petrochemical production. So Sheehan summoned his Yale training to help Catalytic Innovations make catalysts for industry. The firm sells its iridium catalysts through Strem Chemicals.

Anastas has joined Sheehan at the start-up. “It is in Staff’s veins to take science and turn it into commercial reality,” Anastas says. “He’s really just that good.”

Three Key Papers

“Commercializing Solar Fuels within Today’s Markets” (Chem. 2017, DOI: 10.1016/j.chempr.2017.06.003)

“A Molecular Catalyst for Water Oxidation That Binds to Metal Oxide Surfaces” (Nat. Commun. 2015, DOI:10.1038/ncomms7469)

“Selective Electrochemical Oxidation of Lactic Acid Using Iridium-Based Catalysts” (Ind. Eng. Chem. Res. 2017, DOI: 10.1021/acs.iecr.6b05073)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

Sheehan is harnessing energy from the sun to make fuel and other chemicals. His electrochemical cell uses electrons generated by solar cells plus two types of catalysts to power dual chemical reactions that produce the fuel ethanol.

Bozhi Tian has a thing for the unusual. The University of Chicago chemistry professor turns common reagents into unconventional materials, twists ordinary lab procedures into uncommon ones, and finds ways of using his creations in nontraditional applications..

He does those out-of-the-ordinary things to advance the field of bioelectronics: Tian’s goal is to devise new semiconductor tools and methods to thoroughly understand and control the electrical circuitry and signaling pathways of cells.

Before Tian became hooked on science, he was passionate about art. He still is. The interest came from his father, a professional calligrapher who has written more than a dozen educational books on the art of Chinese calligraphy, Tian says.

Tian first tried his hand at calligraphy at age three. By the time he was six, he had moved on to drawing and painting and even considered following that passion and becoming an architect.

At 14, though, he “became fascinated with science, and chemistry in particular,” he says. He vividly remembers being wowed by lab demonstrations, especially ones involving fruit-juice indicators and beautiful color changes. It was also at that time he realized he could earn top grades in school if he applied himself. And so he did, hoping one day to combine science with his interest in three-dimensional shapes like the ones found in architecture.

That’s what Tian has been doing since his grad school days, when he worked with Charles M. Lieber at Harvard University. For example, at that time he designed and built flexible, 3-D, nanosized field-effect transistor bioprobes. The kinked devices, which were designed to slip inside individual cells, provide a direct way of using digital electronics to probe the electrical activity in cells that causes neurons to fire and hearts to beat.

More recently, he devised a novel lithography process to make spiny, vertebrae-shaped silicon nanowires that cling to cells more securely than do the conventional, cylindrical nanowires used to probe nerve cells, improving measurement reproducibility.

“Bozhi is the real definition of an interdisciplinary scientist,” says fellow Chicago chemistry professor Andrei Tokmakoff. He adds that Tian is also fearless, thoughtful, and soft-spoken, which is unusual in the materials business, where there can be a lot of bluster.

Three Key Papers

“Atomic Gold-Enabled Three-Dimensional Lithography for Silicon Mesostructures” (Science 2015, DOI: 10.1126/science.1257278)

“Three-Dimensional, Flexible Nanoscale Field-Effect Transistors as Localized Bioprobes” (Science 2010, DOI: 10.1126/science.1192033)

“Coaxial Silicon Nanowires as Solar Cells and Nanoelectronic Power Sources” (Nature 2007, DOI: 10.1038/nature06181)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock

Tian makes novel semiconductor materials to probe and control electronic processes in cells. For example, particles that he makes of a spongy, biocompatible form of silicon adhere to neuron membranes. When a laser pulse heats up a particle, it induces a capacitance change in the membrane, causing the neuron to fire.

The field of psychiatric drug discovery needs a jump start. Not everyone responds to the available therapies, and those who do often have to deal with unmanageable side effects. Moreover, current drugs are all based on old biology: For example, the last time a truly novel drug for schizophrenia or bipolar disorder made it to market, Florence (Flo) Wagner hadn’t even been born..

She thinks it’s time for a reboot.

At the Stanley Center for Psychiatric Research at the Broad Institute of MIT & Harvard, where she is director of medicinal chemistry, Wagner and her colleagues take innovative approaches to go after some psychiatric targets that have stumped pharma. “Industry wouldn’t have touched a couple of the projects we’ve worked on,” says Edward Scolnick, chief scientist at the Stanley Center and a former president at Merck Research Laboratories. “But Flo is very confident in her abilities.”

These targets have long eluded drug developers because they are extremely similar to related proteins that chemists want to avoid hitting. To design highly selective molecules, Wagner’s team starts with high-throughput screens of compounds in which the scientists look for compounds that are selective for their target relative to related proteins. The more typical approach is to search for molecules that are potent at hitting the target.

Recently, Wagner and her colleagues developed molecules that can selectively inhibit each of the two forms of an enzyme called glycogen synthase kinase 3 (GSK3), a possible target of the bipolar disorder treatment lithium. Previous inhibitors out of industry hit both forms of GSK3 and caused serious side effects in human studies. Wagner and her colleagues showed that selectively inhibiting either of the two forms avoided that toxicity in cells. The chemists now openly share these compounds with other scientists looking to understand the biology of GSK3 in other diseases.

Meanwhile, other Stanley Center scientists are studying the biological mechanisms underlying psychiatric disorders, efforts that will provide novel drug targets. “There won’t be a lack of targets to work on,” Wagner says. “With patients awaiting new treatments, we feel a duty to show that these novel targets could lead to effective therapies.”

Three Key Papers

“Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-Wide Selectivity and Their Functional Effects”(ACS Chem. Biol. 2016, DOI: 10.1021/acschembio.6b00306)

“An Isochemogenic Set of Inhibitors To Define the Therapeutic Potential of Histone Deacetylases in β-Cell Protection” (ACS Chem. Biol. 2016, DOI: 10.1021/acschembio.5b00640)

“Kinetically Selective Inhibitors of Histone Deacetylase 2 (HDAC2) as Cognition Enhancers” (Chem. Sci. 2015, DOI: 10.1039/C4SC02130D)

Research At A Glance

Credit: Yang H. Ku/C&EN/Shutterstock/Wikimedia Commons

GSK3 is a possible target for bipolar disorder and other psychiatric disorders. Wagner’s team designed a molecule (BRD-1652) that selectively inhibits GSK3 and doesn’t interact with other related enzymes, such as CDK2 and CDK9, outside the brain.

Our advisers:

Frances H. Arnold, California Institute of Technology; James J. De Yoreo, University of Washington and Pacific Northwest National Laboratory; Anthony Estrada, Denali Therapeutics; Paula T. Hammond, Massachusetts Institute of Technology; Sarah E. Reisman, Caltech; Tobias Ritter, Max Planck Institute for Kohlenforschung; Daniel Siegwart, University of Texas Southwestern Medical Center; Alex Spokoyny, University of California, Los Angeles; Karen L. Wooley, Texas A&M University; Vivian W.-W. Yam, University of Hong Kong.