Chemical tracers reveal oxygen-dependent switch in cellular pathway to fat (Nature Chemical Biology)

By Tien Nguyen, Department of Chemistry

Using tracer compounds, scientists have been able to track the cellular production of NADPH, a key coenzyme for making fat, through a pathway that has never been measured directly before.

By tracking this pathway, known as malic enzyme metabolism, which is one of a few recognized routes to make NADPH, researchers from Rabinowitz lab discovered a novel switch in the way fat cells make NADPH depending on the presence of oxygen. The findings were published in Nature Chemical Biology.

Ling Liu (left) and Joshua Rabinowitz (right)

“No one had ever shown an environmental dependent switch in any NADPH production pathway,” said Joshua Rabinowitz, Professor of Chemistry and the Lewis-Sigler Institute for Integrative Genomics at Princeton and principal investigator of the work. “No one had the tools to look,” he said.

NADPH is critical to not only fat synthesis, but also protein and DNA synthesis, and antioxidant defense, implicating it in many diseases such as cancer and diabetes. By understanding and monitoring the pathways through which NADPH is made, scientists can work towards influencing these processes using therapeutic compounds.

The Rabinowitz lab first applied their tracer method in 2014 to study the most well known NADPH production pathway, the oxidative pentose phosphate pathway (oxPPP). The method relied on compounds labeled with deuterium atoms, hydrogen’s heavier cousin, which can be deployed in the cell and measured by a technique called mass spectrometry.

In this work, the researchers extended their method to probe the lesser-known malic enzyme pathway by developing two new, orthogonal tracer compounds specific to this pathway. One tracer, a deuterated succinate compound, enters the cycle more directly but is somewhat challenging for the cell to uptake, while the other, a deuterated glucose molecule, is taken up by the cell readily but takes an extra step to enter the pathway.

The research team investigated the malic enzyme pathway under various concentrations of oxygen. Low oxygen environments, which are found in fat cells in obesity, are of particular clinical interest. They found that in a low oxygen environment, the oxidative pentose phosphate pathway produced more NADPH than the malic enzyme pathway, but in a higher oxygen environment, the pathway contributions completely flipped.

“It’s like the cells are quite clever. They choose the pathway depending on what they want to make, and what nutrients they can access,” said Ling Liu, a graduate student in the Rabinowitz lab and lead author on the work.

One advantage of this method is that it tracks NADPH made specifically in the cytosolic compartment of the cell, whereas the previous leading technique, which relied on tracer compounds with carbon-13 atoms, is unable to differentiate between malic enzyme activity in the cytosol and mitochondria.

NADPH involvement in essential cellular processes has a direct impact on diseases such as diabetes, obesity and cancer. “All of these central biomedical questions depend on an understanding of NADPH pathways, and if you can’t quantify how a metabolite is made and used, you can’t understand what’s going on,” Rabinowitz said. “Ultimately, we’re trying to understand the fundamental chemistry that’s leading to these important biological outcomes,” he said.

Read the full article or abstract:

Liu, L.; Shah, S.; Fan, J.; Park, J. O.; Wellen, K. E.; Rabinowitz, J. D. “Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage.Nat. Chem. Bio. Published online March 21, 2016.

This work was supported by the US National Institutes of Health grants R01CA163591, R01AI097382 and P30DK019525 (to the University of Pennsylvania Diabetes Research Center).

Electrons slide through the hourglass on surface of bizarre material (Nature)

An illustration of the hourglass fermion predicted to lie on the surface of crystals of potassium mercury antimony. (Bernevig et al., Princeton University)

An illustration of the hourglass fermion predicted to lie on the surface of crystals of potassium mercury antimony. (Image credit: Laura R. Park and Aris Alexandradinata)

By Staff

A team of researchers at Princeton University has predicted the existence of a new state of matter in which current flows only through a set of surface channels that resemble an hourglass. These channels are created through the action of a newly theorized particle, dubbed the “hourglass fermion,” which arises due to a special property of the material. The tuning of this property can sequentially create and destroy the hourglass fermions, suggesting a range of potential applications such as efficient transistor switching.

In an article published in the journal Nature this week, the researchers theorize the existence of these hourglass fermions in crystals made of potassium and mercury combined with either antimony, arsenic or bismuth. The crystals are insulators in their interiors and on their top and bottom surfaces, but perfect conductors on two of their sides where the fermions create hourglass-shaped channels that enable electrons to flow.

The research was performed by Princeton University postdoctoral researcher Zhi Jun Wang and former graduate student Aris Alexandradinata, now a postdoctoral researcher at Yale University, working with Robert Cava, Princeton’s Russell Wellman Moore Professor of Chemistry, and Associate Professor of Physics B. Andrei Bernevig.

The new hourglass fermion exists – theoretically for now, until detected experimentally – in a family of materials broadly called topological insulators, which were first observed experimentally in the mid-2000s and have since become one of the most active and interesting branches of quantum physics research. The bulk, or interior, acts as an insulator, which means it prohibits the travel of electrons, but the surface of the material is conducting, allowing electrons to travel through a set of channels created by particles known as Dirac fermions.

Fermions are a family of subatomic particles that include electrons, protons and neutrons, but they also appear in nature in many lesser known forms such as the massless Dirac, Majorana and Weyl fermions. After years of searching for these particles in high-energy accelerators and other large-scale experiments, researchers found that they can detect these elusive fermions in table-top laboratory experiments on crystals. Over the past few years, researchers have used these “condensed matter” systems to first predict and then confirm the existence of Majorana and Weyl fermions in a wide array of materials.

The next frontier in condensed matter physics is the discovery of particles that can exist in the so-called “material universe” inside crystals but not in the universe at large. Such particles come about due to the properties of the materials but cannot exist outside the crystal the way other subatomic particles do. Classifying and discovering all the possible particles that can exist in the material universe is just beginning. The work reported by the Princeton team lays the foundations of one of the most interesting of these systems, according to the researchers.

In the current study, the researchers theorize that the laws of physics prohibit current from flowing in the crystal’s bulk and top and bottom surfaces, but permit electron flow in completely different ways on the side surfaces through the hourglass-shaped channels. This type of channel, known more precisely as a dispersion, was completely unknown before.

The researchers then asked whether this dispersion is a generic feature found in certain materials or just a fluke arising from a specific crystal model.

It turned out to be no fluke.

A long-standing collaboration with Cava, a material science expert, enabled Bernevig, Wang, and Alexandradinata to uncover more materials exhibiting this remarkable behavior.

“Our hourglass fermion is curiously movable but unremovable,” said Bernevig. “It is impossible to remove the hourglass channel from the surface of the crystal.”

Bernevig explained that this robust property arises from the intertwining of spatial symmetries, which are characteristics of the crystal structure, with the modern band theory of crystals. Spatial symmetries in crystals are distinguished by whether a crystal can be rotated or otherwise moved without altering its basic character.

In a paper published in Physical Review X this week to coincide with the Nature paper, the team detailed the theory behind how the crystal structure leads to the existence of the hourglass fermion.

An illustration of the complicated dispersion of the surface fermion arising from a background of mercury and bismuth atoms (blue and red). (Image credit: Mingyee Tsang and Aris Alexandradinata)

An illustration of the complicated dispersion of the surface fermion arising from a background of mercury and bismuth atoms (blue and red). (Image credit: Mingyee Tsang and Aris Alexandradinata)

“Our work demonstrates how this basic geometric property gives rise to a new topology in band insulators,” Alexandradinata said. The hourglass is a robust consequence of spatial symmetries that translate the origin by a fraction of the lattice period, he explained. “Surface bands connect one hourglass to the next in an unbreakable zigzag pattern,” he said.

The team found esoteric connections between their system and high-level mathematics. Origin-translating symmetries, also called non-symmorphic symmetries, are described by a field of mathematics called cohomology, which classifies all the possible crystal symmetries in nature. For example, cohomology gives the answer to how many crystal types exist in three spatial dimensions: 230.

In the cohomological perspective, there are 230 ways to combine origin-preserving symmetries with real-space translations, known as the “space groups.” The theoretical framework to understand the crystals in the current study requires a cohomological description with momentum-space translations.

“The hourglass theory is the first of its kind that describes time-reversal-symmetric crystals, and moreover, the crystals in our study are the first topological material class which relies on origin-translating symmetries,” added Wang.

Out of the 230 space groups in which materials can exist in nature, 157 are non-symmorphic, meaning they can potentially host interesting electronic behavior such as the hourglass fermion.

“The exploration of the behavior of these interesting fermions, their mathematical description, and the materials where they can be observed, is poised to create an onslaught of activity in quantum, solid state and material physics,” Cava said. “We are just at the beginning.”

The study was funded by the National Science Foundation, the Office of Naval Research, the David and Lucile Packard Foundation, the W. M. Keck Foundation, and the Eric and Wendy Schmidt Transformative Technology Fund at Princeton University.

The paper, “Hourglass fermions” by Zhijun Wang, A. Alexandradinata, R. J. Cava and B. Andrei Bernevig, was published in the April 14, 2016 issue of Nature, 532,189–194, doi:10.1038/nature17410. Read the preprint.

The paper, “Topological insulators from group cohomology” by A. Alexandradinata, Zhijun Wang, and B. Andrei Bernevig, was published in the April 15, 2016 issue of Phys. Rev. X 6, 021008.

How an artificial protein rescues dying cells (PNAS)

By Tien Nguyen, Department of Chemistry

A new study from Princeton has revealed how a synthetic protein revives E. coli cells that lack a life-sustaining gene, offering insight into how life can adapt to survive and potentially be reinvented.

Michael Hecht and Katie Digianantonio

Researchers in the Hecht lab discovered the unexpected way in which a synthetic protein called SynSerB promotes the growth of cells that lack the natural SerB gene, which encodes an enzyme responsible for the last step in the production of the essential amino acid serine. The findings were published in the Proceedings of the National Academy of Sciences.

The Hecht group first discovered SynSerB’s ability to rescue serine-depleted E. Coli cells in 2011. At that time, they also discovered several other de novo proteins capable of rescuing the deletions of three other essential proteins in E. coli. “These are novel proteins that have never existed on Earth, and aren’t related to anything on Earth yet they enable life to grow where it otherwise would not,” said Michael Hecht, professor of chemistry at Princeton and corresponding author on the article.

Natural proteins are complex molecular machines constructed from a pool of twenty different amino acids. Typically they range from several dozen to several hundred amino acids in length.  In principle, there are more possible protein sequences than atoms in the universe, but through evolution Nature has selected just a small fraction to carry out the cellular functions that make life possible.

“Those proteins must be really special,” Hecht said. “The driving question was, ‘Can we do that in the laboratory? Can we come up with non-natural sequences that are that special, from an enormous number of possibilities?”

To address this question, the Hecht lab developed a library of non-natural proteins guided by a concept called binary design. The idea was to narrow down the number of possible sequences by choosing from eleven select amino acids that were divided into two groups: polar and non-polar. By using only the polar or non-polar characteristics of those amino acids, the researchers could design a plethora of novel proteins to fold into a particular shape based on their affinity to and repulsion from water. Then, by allowing the specific positions to have different amino acids, the researchers were able to produce a diverse library of about one million proteins, each 102 amino acids long.

“We had to focus on certain subsets of proteins that we knew would fold and search there first for function,” said Katie Digianantonio, a graduate student in the Hecht lab and first author on the paper. “It’s like instead of searching the whole universe for life, we’re looking in specific solar systems.”

Having found several non-natural proteins that could rescue specific cell lines, this latest work details their investigation specifically into how SynSerB promotes cell growth. The most obvious explanation, that SynSerB simply catalyzed the same reaction performed by the deleted SerB gene, was discounted by an early experiment.

To discern SynSerB’s mechanism among the multitude of complex biochemical pathways in the cell, the researchers turned to a technique called RNA sequencing. This technique allowed them to take a detailed snapshot of the serine-depleted E. Coli cells with and without their synthetic protein and compare the differences.

“Instead of guessing and checking, we wanted to look at the overall environment to see what was happening,” Digianantonio said. The RNA sequencing experiment revealed that SynSerB induced overexpression of a protein called HisB, high levels of which have been shown to promote the key reaction normally performed by the missing gene. By enlisting the help of HisB, the non-natural protein was able to induce the production of serine, which ultimately allowed the cell to survive.

“Life is opportunistic. Some proteins are going to work by acting similarly to what they replaced and some will find another pathway,” Hecht said. “Either way it’s cool.”

Read the full articles here:

Digianantonio, K. M.; Hecht, M. H. “A protein constructed de novo enables cell growth by altering gene regulation.Proc. Natl. Acad. Sci. Published online before print on Feb. 16, 2016.

Fisher, M. A.; McKinley, K. L.; Bradley, L. H; Viola, S. R; Hecht, M. H. “De Novo designed proteins from a library of artificial sequences function in Escherichia Coli and enable cell growth.” PLoS One 2011, 6(1): e15364.

This research was funded by the US National Science Foundation (NSF) Grant MCB-1050510.

Study reveals mechanism behind enzyme that tags unneeded DNA (Nature Chem. Bio.)

Designer chromatin experiments

Graphical representation of designer chromatin experiments. Image courtesy of the Muir lab.

By Tien Nguyen, Department of Chemistry

Researchers have discovered the two-step process that activates an essential human enzyme, called Suv39h1, which is responsible for organizing large portions of the DNA found in every living cell.

For any particular cell, such as a skin or brain cell, much of this genetic information is extraneous and must be packed away to allow sufficient space and resources for more important genes. Failure to properly pack DNA jeopardizes the stability of chromosomes and can result in severe diseases. Suv39h1 is one of the main enzymes that chemically mark the irrelevant regions of DNA to be compacted by cellular machinery, but little is known about how it installs its tag.

Now, scientists at Princeton have used ‘designer chromatin’ templates – highly customized replicas of cellular DNA and histone proteins, the scaffolding proteins around which DNA is wrapped – to reveal new details about Suv39h1’s mechanism. The researchers investigated how Suv39h1 employs a positive feedback loop to chemically tag thousands of adjacent histones, thus signaling the cell to stow away these underlying, unnecessary DNA sequences. The work was published in in the journal Nature Chemical Biology.

“One of the things that has always fascinated me about feedback loops is that they’re super dangerous. If you make a mistake once, you end up getting reinforcement through the feedback loop,” said Manuel Müller, a postdoctoral researcher in the Muir lab and lead author on the study. “So how does Suv39h1 keep itself in check?”

Suv39h1 had been known to possess two distinct parts, but the new research revealed how they work together in order to ‘switch on’ the enzyme. One part of the enzyme, known as the chromodomain, is constantly exposed and seeks out specific chemical tags, known as a methyl groups, located at predetermined sites on histones. When the chromodomain finds these groups in the genome, it locks onto the spot and allows the other part, the enzymatic core, to install more methyl tags at adjacent histones.

“The second, anchoring step wasn’t really known before. It provides an extra level of control and allows the process to be extremely fine-tuned,” Müller said. A similar mechanism may be employed by many other enzymes operating on chromatin, given that they contain similar components of a feedback loop.

To understand how the enzyme carries out this process, the researchers synthesized complex chromatin templates that were three times larger than previously reported models. They divided the template into three blocks that could each be manipulated in various ways. For example, a block could be prepared with the chemical tag present, absent or mutated such that tagging can’t occur. “The different blocks should signal to the enzyme either start here or feel free to spread here or absolutely stop here,” said Glen Liszczak, a co-author and postdoctoral researcher in the Muir lab.

By rearranging the various domains, the research team observed where the enzyme spread its mark across the genome. They found that Suv39h1 preferred to spread across small distances, but that it could reach sequences further along if chromatin folding decreased the physical distance in space.

“We’ve learned something new about this enzyme, something that we couldn’t have without the pinpoint precision that the designer chromatin offers,” Liszczak said. “There are a lot of questions that our lab has been interested in that we can now start to answer.”

The research was funded by the Swiss National Science Foundation (postdoctoral fellowships) and the US National Institutes of Health (R01-GM107047).

Read the abstract or full article.

Müller, M. M.; Fierz, B.; Bittova, L.; Liszczak, G.; Muir, T. W. “A two-state activation mechanism controls the histone methyltransferase Suv39h1.” Nature Chem. Bio. Available online January 25, 2016.

 

Antibiotic’s killer strategy revealed (PNAS)

Marine algae

Satellite image of a E. huxleyi marine algae bloom. (Image: NASA)

By Tien Nguyen, Department of Chemistry

Using a special profiling technique, scientists at Princeton have determined the mechanism of action of a potent antibiotic, known as tropodithietic acid (TDA), leading them to uncover its hidden ability as a potential anticancer agent.

TDA is produced by marine bacteria belonging to the roseobacter family, which exist in a unique symbiosis with microscopic algae. The algae provide food for the bacteria, and the bacteria provide protection from the many pathogens of the open ocean.

“This molecule keeps everything out,” said Mohammad Seyedsayamdost, an assistant professor of chemistry at Princeton and corresponding author on the study published in the Proceedings of the National Academy of Science. “How could something so small be so broad spectrum? That’s what got us interested,” he said.

In collaboration with researchers in the laboratory of Zemer Gitai, an associate professor of molecular biology at Princeton, the team used a laboratory technique referred to as bacterial cytological profiling to investigate the mode of action of TDA. This method involves destroying bacterial cells with the antibiotic in the presence of a set of dyes, and then visually assessing the aftermath. “The key assumption is that dead cells that look the same probably died by the same mechanism,” he said.

marine algae

Scanning electron microscope image of E. huxleyi (Image credit. M. Seyedsayamdost)

The team used three dyes to evaluate 13 different features of the deceased cells, such as cell membrane thickness and nucleoid area, comprising TDA’s cytological profile. By comparing to profiles of known drugs, the researchers found a match with a class of compounds called polyethers, which possess anticancer activity.

Given their similar profiles, Seyedsayamdost and coworkers hypothesized that TDA might exhibit anticancer properties as well, and indeed observed its strong anticancer activity in a screen against 60 different cancer cell lines. “The strength of this profiling technique is that it tells you how to repurpose molecules,” Seyedsayamdost said.

The researchers were surprised by the compounds’ shared mode of action because unlike the small sized TDA, polyether compounds are quite large. But through different chemical reactions, they are both able to cause chemical disruptions in the cell membrane that render the bacterium unable to produce the energy needed to perform critical tasks, such as cell division and making proteins.

In addition to TDA’s killing mechanism, the researchers were interested in understanding the mechanism by which a bacterial strain could become resistant to the antibiotic. Particularly, they wondered how the marine roseobacter kept itself safe from the deadly antibiotic weapon that it produced.

The research team approached the task by probing the genes in roseobacter that synthesize TDA as well as the surrounding genes. They identified three nearby genes responsible for transport in and out of the cell, and upon transferring these specific genes to E. coli, were able to produce an elusive TDA resistant bacterial strain.

“We often look at natural products as black boxes,” said Seyedsayamdost, “but these molecules have evolved for millennia to fulfill a certain function. By linking the unusual structural features of TDA to its mode of action, we have begun to explain why TDA looks the way it does.”

Read the abstract:

Wilson, M. Z.; Wang, R.; Gitai, Z.; Seyedsayamdost, M. R. “Tropodithietic Acid: Mode of Action and Mechanism of Resistance.” Proc. Natl. Acad. Sci. 2016, Published online on January 22, 2016.

This work was supported by grants from the National Institutes of Health (GM 098299 and 1DPOD004389).

‘Radiolabeling’ lets scientists track the breakdown of drugs (Nature)

Graduate student Renyuan Pony Yu

Renyuan Pony Yu, a graduate student working with Princeton Professor Paul Chirik, has discovered a new way to radiolabel compounds for use in drug development.

By Tien Nguyen, Department of Chemistry

A new method for labeling molecules with radioactive elements could let chemists more easily track how drugs under development are metabolized in the body.

Chemists consider thousands of compounds in the search for a new drug, and a candidate’s metabolism is a key factor that must be evaluated carefully and quickly. Researchers at Princeton University and pharmaceutical company Merck & Co., Inc. report in the journal Nature that scientists can selectively replace hydrogen atoms in molecules with tritium atoms — a radioactive form of hydrogen that possesses two extra neutrons — to “radiolabel” compounds. This technique can be done in a single step while preserving the biological properties of the parent compound.

While current state-of-the-art techniques are quite reliable, they only work when dissolved in specific solvents, ones that aren’t always capable of dissolving the drug compound of interest. The researchers’ method, however, used an iron-based catalyst that is tolerant to a wider variety of solvents, and it labels the molecules at the opposite positions as compared to existing methods.

“The fact that you can access other positions is what makes this reaction really special,” said corresponding author Paul Chirik, the Edwards S. Sanford Professor of Chemistry at Princeton. Previous methods only incorporate radioactive tritium atoms into the molecule directly next to an atom or a group of atoms called a directing group. The new iron-catalyzed method does not require a directing group, and instead places tritium at whatever positions in the molecules are the least crowded.

“Radiolabeled compounds help medicinal chemists get a better picture of what actually happens to the drug by showing how the drug is metabolized and cleared,” said David Hesk, a collaborator at Merck and co-author on the work. By rapidly assessing the compounds’ metabolism early on, scientists can shorten the time it takes to develop and bring a drug to market. “Having another labeling reaction is very powerful because it gives radiochemists another tool in the toolbox,” he said.

This unique reactivity was actually discovered unexpectedly. Renyuan Pony Yu, a graduate student in the Chirik lab, had originally set out to use their iron catalyst for a different reaction that they were collaborating on with Merck. To study the iron catalyst’s capabilities, Yu subjected it to a technique called proton nuclear magnetic resonance spectroscopy (NMR), which allows chemists to deduce the positions of hydrogen atoms in molecules.

“We started seeing this beautiful, very systematic pattern of signals in the NMR, but we didn’t really know what they were,” said Yu, who is first author on the new study. Particularly puzzling was the fact that the pattern of signals would disappear over time.

The researchers turned to Istvan Pelczer, Director of the NMR Facility at Princeton chemistry and co-author on the work, who developed a special technique that helped them analyze the signals with much greater confidence. Using this method, they realized that the iron catalyst was reacting with the liquid solvent used to dissolve the NMR sample. The solvent’s deuterium atoms, another form of hydrogen that has one extra neutron and is not radioactive, were replacing the hydrogen atoms.

It wasn’t until Yu presented his findings to Matt Tudge, the Princeton authors’ collaborator at Merck, that the catalyst’s potential to introduce tritium atoms into radiolabeled molecules was recognized. “This is a classic example where you really need both partners,” Chirik said. “We were the catalyst experts, but they were the applications experts.”

Though tritium-labeled compounds are used mostly in metabolism studies, they can also be helpful at the very outset of a drug-discovery project to identify a biological target that the potential drugs can be tested against. The biological target could be an enzyme or protein associated with a certain disease. For example, statins are a well-known class of cholesterol-lowering drugs that target a specific enzyme in the body called HMG-CoA reductase.

To explore the scope of the reaction, Yu first optimized the reaction to incorporate deuterium atoms, which is commonly accepted as a model system for tritium. He found that the iron catalyst was surprisingly robust and successfully labeled many different types of compounds, including some from Merck’s library of past drug candidates.

“It was a very exciting project for me because I got to work with real drugs that are fully functionalized and useful,” Yu said. One of their test substrates was Claritin, which Yu bought from a local store; he extracted its active ingredient back in the lab.

Finally, Yu traveled to Merck’s campus in Rahway, where he received radioactivity training — Chirik’s laboratory isn’t equipped to handle radioactivity — and performed the reactions using tritium gas. The reactions were run in a special apparatus that looks like a steel-lined box and releases radioactive tritium gas. The apparatus can capture any unspent gas to limit the amount of radioactive waste produced.

Chemists take care to handle radioactive compounds and waste very carefully, but tritium’s radioactivity is so weak that the particles it emits cannot penetrate simple glassware. For this reason, tritium-labeled compounds can’t be used in any human imaging studies such as PET scans, which require radiolabeled compounds that emit high-energy particles.

This past summer, Yu presented the preliminary results of the iron-catalyzed reaction at the 2015 International Isotope Society Symposia to researchers in the radiolabeling and pharmaceutical community. They were very excited about the research and eager to use the catalyst in their own studies, Yu said.

But the major challenge for the researchers is that the iron catalyst is extremely air and moisture sensitive, and it can only be handled inside a glovebox, a special chamber in which oxygen and water vapor have been excluded. The Chirik group is working to develop a more stable catalyst that can be made commercially available, and have recently entered into a partnership with Green Center Canada, a company that helps bring academic research to market.

In the meantime, the Chirik group has found that the iron catalyst can replace hydrogen atoms with other groups besides deuterium and tritium atoms and is extending this chemistry into many other projects in the lab.

“This project is always going to be a special one for me because it’s kind of a pivot point for the type of chemistry that our group can do,” Chirik said, “and there’s this really cool application.”

Read the abstract.

Yu, R. P.; Hesk, D.; Rivera, N.; Pelczer, I.; Chirik, P. J. “Iron-Catalyzed Tritiation of Pharmaceuticals.” Nature, 2016, DOI: 10.1038/nature16464.

This work was supported by Merck & Co. and Princeton University’s Intellectual Property Accelerator Fund.

Scientists predict cool new phase of superionic ice (Nature Communications)

by Tien Nguyen, Department of Chemistry

Uranus as viewed by Voyager 2 in 1986 (NASA/JPL-Caltech)

Uranus (NASA/JPL-Caltech)

Scientists have predicted a new phase of superionic ice, a special form of ice that could exist on Uranus and Neptune, in a theoretical study performed by a team of researchers at Princeton University.

“Superionic ice is this in-between state of matter that we can’t really relate to anything we know of — that’s why it’s interesting,” Salvatore Torquato, a Professor of Chemistry who jointly led the work with Roberto Car, the Ralph W. ‘31 Dornte Professor in Chemistry. Unlike water or regular ice, superionic ice is made up of water molecules that have dissociated into charged atoms called ions, with the oxygen ions locked in a solid lattice and the hydrogen ions moving like the molecules in a liquid.

Published on August 28 in Nature Communications, the research revealed an entirely new type of superionic ice that the investigators call the P21/c-SI phase, which occurs at pressures even higher than those found in the interior of the giant ice planets of our solar system. Two other phases of superionic ice thought to exist on the planets are body-centered cubic superionic ice (BCC-SI) and close-packed superionic ice (CP-SI).

Each phase has a unique arrangement of oxygen ions that gives rise to distinct properties. For example, each of the phases allows hydrogen ions to flow in a characteristic way. The effects of this ionic conductivity may someday be observed by planetary scientists in search of superionic ice. “These unique properties could essentially be used as signatures of superionic ice,” said Torquato. “Now that you know what to look for, you have a better chance of finding it.”

Salvatore Torquato (left) and Roberto Car (right)

Salvatore Torquato (left) and Roberto Car (right)

Unlike Earth, which has two magnetic poles (north and south), ice giants can have many local magnetic poles, which leading theories suggest may be due to superionic ice and ionic water in the mantle of these planets. In ionic water both oxygen and hydrogen ions show liquid-like behavior. Scientists have proposed that heat emanating outward from the planet’s core may pass through an inner layer of superionic ice, and through convection, create vortices on the outer layer of ionic water that give rise to local magnetic fields.

By using theoretical simulations, the researchers were able to model states of superionic ice that would be difficult to study experimentally. They simulated pressures that were beyond the highest possible pressures attainable in the laboratory with instruments called diamond anvil cells. Extreme pressure can be achieved through shockwave experiments but these rely on creating an explosion and are difficult to interpret, Professor Car explained.

The researchers calculated the ionic conductivity of each phase of superionic ice and found unusual behavior at the transition where the low temperature crystal, in which both oxygen and hydrogen ions are locked together, transforms into superionic ice. In known superionic materials, generally the conductivity can change either abruptly (type I) or gradually (type II), but the type of change will be specific to the material. However, superionic ice breaks from convention, as the conductivity changes abruptly with temperature across the crystal to close-packed superionic transition, and continuously at the crystal to P21/c-SI transition.

As a foundational study, the research team investigated superionic ice treating the ions as if they were classical particles, but in future studies they plan to take quantum effects into account to further understand the properties of the material.

Read the article here:

Sun, J.; Clark, B. K.; Torquato, S.; Car, R. “The phase diagram of high pressure superionic ice.Nature Communications, Published online August 28, 2015.

This work was supported by the National Science Foundation (DMS-1065894) and the US Department of Energy (DE-SC0008626 and DE-SC0005180).