Author: MIT News

Chemists glimpse the fleeting “transition state” of a reaction

by Anne Trafton | MIT News Office |

During a chemical reaction, the molecules involved in the reaction gain energy until they reach a “point of no return” known as a transition state.

Until now, no one has glimpsed this state, as it lasts for only a few femtoseconds (quadrillionths of a second). However, chemists at MIT, Argonne National Laboratory, and several other institutions have now devised a technique that allows them to determine the structure of the transition state by detailed observation of the products that result from the reaction.

“We’re looking at the consequences of the event, which have encoded in them the actual structure of the transition state,” says Robert Field, the Robert T. Haslam and Bradley Dewey Professor of Chemistry at MIT. “It’s an indirect measurement, but it’s among the most direct classes of measurement that have been possible.”

Field and his colleagues used millimeter-wave spectroscopy, which can measure the rotational-vibrational energy of reaction product molecules, to determine the structure of the products of the breakdown of vinyl cyanide caused by ultraviolet light. Using this approach, they identified two different transition states for the reaction and found evidence that additional transition states may be involved.

Field is the senior author of the study, which appears this week in the Proceedings of the National Academy of Sciences. The lead author is Kirill Prozument, a former MIT postdoc who is now at Argonne National Laboratory.

A central concept of chemistry

For any chemical reaction to occur, the reacting molecules must receive an input of energy that enables the activated molecules to reach a transition state, from which the products are formed.

“The transition state is a central concept of chemistry,” Field says. “Everything we think about in reactions really hinges on the structure of the transition state, which we cannot directly observe.”

In a paper published in 2015, Field and his colleagues used laser spectroscopy to characterize the transition state for a different type of reaction known as an isomerization, in which a molecule undergoes a change of shape.

In their new study, the researchers explored another style of reaction, using ultraviolet laser radiation to break molecules of vinyl cyanide into acetylene and other products. Then, they used millimeter-wave spectroscopy to observe the vibrational level population distribution of the reaction products a few millionths of a second after the reaction occurred.

Using this technique, the researchers were able to determine nascent populations of molecules in different levels of vibrational energy — a measure of how much the atoms of a molecule move relative to each other. Those vibrational energy levels also encode the geometry of the molecules when they were born at the transition state, specifically, how much bending excitation there is in the bond angles between hydrogen, carbon, and nitrogen atoms.

This also allowed the researchers to distinguish between two slightly different products of the reaction — hydrogen cyanide (HCN), in which a central carbon atom is bound to hydrogen and nitrogen, and hydrogen isocyanide (HNC), in which nitrogen is the central atom, bound to carbon and hydrogen.

“This is the fingerprint of what the structure was during the instant that the molecule was released,” Field says. “Previous methods of looking at reactions were blind to the vibrational populations, and they were blind to the difference between HCN and HNC.”

The researchers found both HCN and HNC, which are produced via different transition states, among the reaction products. This suggests that both of those transition states, which represent different mechanisms of reaction, are in play when vinyl cyanide is broken apart by the ultraviolet laser.

“This implies that there are two different mechanisms competing for transition states, and we’re able to separate the reaction into these different mechanisms,” Field says. “This is a completely new technique, a new way of going to the heart of what happens in a chemical reaction.”

The new technique allows scientists to explore the transition state in a way that has previously not been possible, says Arthur Suits, a professor of chemistry at the University of Missouri.

“In this work, the researchers use the powerful new technique of broadband rotational spectroscopy to monitor the nascent vibrational distributions of the products of a photodissociation reaction, thereby gaining deep insight into two different transition states,” says Suits, who was not involved in the study. “Broadband rotational spectroscopy continues to amaze us with unexpected applications such as this glimpse of the elusive transition, and other exciting advances driven by this technique are no doubt on the way.”

Additional mechanisms

The researchers’ data shows that there are additional reaction mechanisms beyond those two, but more study is needed to determine their transition state structures.

Field and Prozument are now using this technique to study the reaction products of the pyrolytic breakdown of acetone. They also hope to use it to explore how triazine, a six-membered ring of alternating carbon and nitrogen atoms, breaks down into three molecules of HCN, in particular, whether all three products form simultaneously (a “triple whammy”) or sequentially.

The research was funded by the Department of Energy, the Petroleum Research Fund, and the National Science Foundation. Other authors of the paper include Joshua Baraban PhD ’13 of Ben-Gurion University; G. Barratt Park PhD ’15 of the Max Planck Institute for Biophysical Chemistry; Rachel Shaver SM ’13; P. Bryan Changala of the University of Colorado at Boulder; John Muenter of the University of Rochester; Stephen Klippenstein of Argonne National Laboratory; and Vladimir Chernyak of Wayne State University.

Lamborghini and MIT pave the way for the electric supercar of the future

by MISTI |

“He was here to dream, and I said ‘OK, let’s dream together,’” recalls Professor Mircea Dincă of his first encounter with Automobili Lamborghini Head of Development Riccardo Parenti in February 2017. Two years later, the team is celebrating its first major collaborative victory by filing a joint patent.

The new patented material was synthesized by Dincă’s lab in the Department of Chemistry, with the support of Automobili Lamborghini’s Concept Development Department, and will serve as the technological base for a new generation of supercapacitors. By increasing the surface area exposed to electric charge in relation to mass and volume, the patent promises to increase energy density by up to 100 percent when compared to existing technology. This is a big leap, even when compared to Lamborghini’s cutting-edge supercapacitors, and, more broadly, a game-changer in high-performance motor sport.

A second collaboration, with Professor John Anastasios Hart’s team in the Department of Mechanical Engineering, pursues new design principles for high-performance battery materials that can be integrated into the vehicle structure, and is on schedule to deliver its first prototypes in the next year. Together, these collaborations are key in meeting the performance targets Lamborghini set for its Terzo Millennio car.

As Stefano Domenicali, chair and CEO of Automobili Lamborghini, puts it, “The joint research with MIT fully embodies our values and our vocation for anticipating the future: a future in which hybridization is increasingly desirable and inevitably necessary.”

Federica Sereni, consul general of Italy in Boston, Massachusetts, comments: “Italian companies, in particular those in the automotive industry, know how to combine passion, tradition, research, and innovation in a way that is unique in the world. Therefore, the match between Lamborghini and MIT is a perfect one, leading to an ideal combination between vision and a level of technological innovation that is among the most advanced in the world”.

Serenella Sferza, MIT-Italy Program co-director, concurs, praising the MIT-Italy-Lamborghini partnership as a perfect example of how, by acting as a bridge between MIT and Italy’s centers of excellence, the MIT-Italy Program opens avenues for research and innovation that include meaningful student experiences. In this case, after connecting Lamborghini to professors Dincă and Hart, Sferza also recruited mechanical engineering student Patricia Das ’17 and chemical engineering and chemistry student Angela Cai ’19, whose research at Santa Agata Bolognese cemented and advanced the Lamborghini-MIT collaboration.

“The Lamborghini-MIT Italy partnership exemplifies the range of MISTI activities and the symbiotic ways in which they feed on each other,” says Sferza. “I initially met Patricia and Angela when they applied to the MIT-Italy Global Teaching Labs program, and, based on their MIT academic background and their strong performance teaching STEM subjects at Italian high schools, later recruited them for the Lamborghini collaboration. Both earned high marks from Lamborghini, and learned a lot from the experience.”

“MIT-Italy has given me an invaluable chance to immerse myself in a research topic I am very passionate about in a professional setting with real, global applications,” shares Cai. “I have presented my findings and suggested future research direction to representatives from several departments at my host organization. When I finish my current work assignment, I plan on using the experience and connections gained here to pursue graduate study in this field.”

MIT-Italy and Lamborghini, the cornerstone partnership that paved the way for these initiatives, have extended their collaboration and plan to create additional student and research opportunities both on and off campus. In parallel with laboratory work, a campuswide motor sport hackathon is being considered.

“This has been such a fruitful partnership for us,” says Sferza. “There are few companies that exemplify the Italian talent for combining beautiful design with high-end technology in such a cool way. It is a joy to connect Lamborghini with MIT’s innovation community.”

The faculty, for their part, agree. “This collaboration presented us with the kind of challenges that we love at MIT. We like to understand that the work we’re doing in the lab can contribute to real, new, important technology and also have that work involve good science and engineering,” says Hart. “Our motto is ‘mind and hand,’ and this gets our minds to focus on a challenge and our hands to do something new and practical in the lab.”

“We were dreaming two years ago,” says Dincă. “Now, we really think this could be happening.”

Technique identifies T cells primed for certain allergies or infections

by Anne Trafton | MIT News Office |

When your immune system is exposed to a vaccine, an allergen, or an infectious microbe, subsets of T cells that can recognize a foreign intruder leap into action. Some of these T cells are primed to kill infected cells, while others serve as memory cells that circulate throughout the body, keeping watch in case the invader reappears.

MIT researchers have now devised a way to identify T cells that share a particular target, as part of a process called high-throughput single-cell RNA sequencing. This kind of profiling can reveal the unique functions of those T cells by determining which genes they turn on at a given time. In a new study, the researchers used this technique to identify T cells that produce the inflammation seen in patients with peanut allergies.

In work that is now underway, the researchers are using this method to study how patients’ T cells respond to oral immunotherapy for peanut allergies, which could help them determine whether the therapy will work for a particular patient. Such studies could also help guide researchers in developing and testing new treatments.

“Food allergies affect about 5 percent of the population, and there’s not really a clear clinical intervention other than avoidance, which can cause a lot of stress for families and for the patients themselves,” says J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research. “Understanding the underlying biology of what drives these reactions is still a really critical question.”

Love and Alex K. Shalek, who is the Pfizer-Laubach Career Development Associate Professor at MIT, an associate professor of chemistry, a core member of MIT’s Institute for Medical Engineering and Science (IMES), and an extramural member of the Koch Institute, are the senior authors of the study, which appears today in Nature Immunology. The lead authors of the paper are graduate student Ang Andy Tu and former postdoc Todd Gierahn.

Extracting information

The researchers’ new method builds on their previous work developing techniques for rapidly performing single-cell RNA sequencing on large populations of cells. By sequencing messenger RNA, scientists can discover which genes are being expressed at a given time, giving them insight into individual cells’ functions.

Performing RNA sequencing on immune cells, such as T cells, is of great interest because T cells have so many different roles in the immune response. However, previous sequencing studies could not identify populations of T cells that respond to a particular target, or antigen, which is determined by the sequence of the T cell receptor (TCR). That’s because single-cell RNA sequencing usually tags and sequences only one end of each RNA molecule, and most of the variation in T cell receptor genes is found at the opposite end of the molecule, which doesn’t get sequenced.

“For a long time, people have been describing T cells and their transcriptome with this method, but without information about what kind of T cell receptor the cells actually have,” Tu says. “When this project started, we were thinking about how we could try to recover that information from these libraries in a way that doesn’t obscure the single-cell resolution of these datasets, and doesn’t require us to dramatically change our sequencing workflow and platform.”

In a single T cell, RNA that encodes T cell receptors makes up less than 1 percent of the cell’s total RNA, so the MIT team came up with a way to amplify those specific RNA molecules and then pull them out of the total sample so that they could be fully sequenced. Each RNA molecule is tagged with a barcode to reveal which cell it came from, so the researchers could match up the T cells’ targets with their patterns of RNA expression. This allows them to determine which genes are active in populations of T cells that target specific antigens.

“To put the function of T cells into context, you have to understand what it is they’re trying to recognize,” Shalek says. “This method lets you take existing single-cell RNA sequencing libraries and pull out relevant sequences you might want to characterize. At its core, the approach is a straightforward strategy for extracting some of the information that’s hidden inside of genome-wide expression profiling data.”

Another advantage of this technique is that it doesn’t require expensive chemicals, relies on equipment that many labs already have, and can be applied to many previously processed samples, the researchers say.

Analyzing allergies

In the Nature Immunology paper, the researchers demonstrated that they could use this technique to pick out mouse T cells that were active against human papilloma virus, after the mice had been vaccinated against the virus. They found that even though all of these T cells reacted to the virus, the cells had different TCRs and appeared to be in different stages of development — some were very activated for killing infected cells, while others were focused on growing and dividing.

The researchers then analyzed T cells taken from four patients with peanut allergies. After exposing the cells to peanut allergens, they were able to identify T cells that were active against those allergens. They also showed which subsets of T cells were the most active, and found some that were producing the inflammatory cytokines that are usually associated with allergic reactions.

“We can now start to stratify the data to reveal what are the most important cells, which we were not able to identify before with RNA sequencing alone,” Tu says.

Love’s lab is now working with researchers at Massachusetts General Hospital to use this technique to track the immune responses of people undergoing oral immunotherapy for peanut allergies — a technique that involves consuming small amounts of the allergen, allowing the immune system to build up tolerance to it.

In clinical trials, this technique has been shown to work in some but not all patients. The MIT/MGH team hopes that their study will help identify factors that could be used to predict which patients will respond best to the treatment.

“One would certainly like to have a better sense of whether an intervention is going to be successful or not, as early as possible,” Love says.

This strategy could also be used to help develop and monitor immunotherapy treatments for cancer, such as CAR-T cell therapy, which involves programming a patient’s own T cells to target a tumor. Shalek’s lab is also actively applying this technique with collaborators at the Ragon Institute of MGH, MIT and Harvard to identify T cells that are involved in fighting infections such as HIV and tuberculosis.

The research was funded by the Koch Institute Support (core) Grant from the National Institutes of Health, the Koch Institute Dana-Farber/Harvard Cancer Center Bridge Project, the Food Allergy Science Initiative at the Broad Institute of MIT and Harvard, the Arnold and Mabel Beckman Foundation, a Searle Scholar Award, a Sloan Research Fellowship in Chemistry, the Pew-Stewart Scholars program, and the National Institutes of Health.

Chemists observe “spooky” quantum tunneling

by Anne Trafton | MIT News Office |

A molecule of ammonia, NH3, typically exists as an umbrella shape, with three hydrogen atoms fanned out in a nonplanar arrangement around a central nitrogen atom. This umbrella structure is very stable and would normally be expected to require a large amount of energy to be inverted.

However, a quantum mechanical phenomenon called tunneling allows ammonia and other molecules to simultaneously inhabit geometric structures that are separated by a prohibitively high energy barrier. A team of chemists that includes Robert Field, the Robert T. Haslam and Bradley Dewey Professor of Chemistry at MIT, has examined this phenomenon by using a very large electric field to suppress the simultaneous occupation of ammonia molecules in the normal and inverted states.

“It’s a beautiful example of the tunneling phenomenon, and it reveals a wonderful strangeness of quantum mechanics,” says Field, who is one of the senior authors of the study.

Heon Kang, a professor of chemistry at Seoul National University, is also a senior author of the study, which appears this week in the Proceedings of the National Academy of Sciences. Youngwook Park and Hani Kang of Seoul National University are also authors of the paper.

Suppressing inversion

The experiments, performed at Seoul National University, were enabled by the researchers’ new method for applying a very large electric field (up to 200,000,000 volts per meter) to a sample sandwiched between two electrodes. This assembly is only a few hundred nanometers thick, and the electric field applied to it generates forces nearly as strong as the interactions between adjacent molecules.

“We can apply these huge fields, which are almost the same magnitude as the fields that two molecules experience when they approach each other,” Field says. “That means we’re using an external means to operate on an equal playing field with what the molecules can do themselves.”

This allowed the researchers to explore quantum tunneling, a phenomenon often used in undergraduate chemistry courses to demonstrate one of the “spookinesses” of quantum mechanics, Field says.

As an analogy, imagine you are hiking in a valley. To reach the next valley, you need to climb a large mountain, which requires a lot of work. Now, imagine that you could tunnel through the mountain to get to the next valley, with no real effort required. This is what quantum mechanics allows, under certain conditions. In fact, if the two valleys have exactly the same shape, you would be simultaneously located in both valleys.

In the case of ammonia, the first valley is the low-energy, stable umbrella state. For the molecule to reach the other valley — the inverted state, which has exactly the same low-energy — classically it would need to ascend into a very high-energy state. However, quantum mechanically, the isolated molecule exists with equal probability in both valleys.

Under quantum mechanics, the possible states of a molecule, such as ammonia, are described in terms of a characteristic energy level pattern.  The molecule initially exists in either the normal or inverted structure, but it can tunnel spontaneously to the other structure. The amount of time required for that tunneling to occur is encoded in the energy level pattern. If the barrier between the two structures is high, the tunneling time is long. Under certain circumstances, such as application of a strong electric field, tunneling between the regular and inverted structures can be suppressed.

For ammonia, exposure to a strong electric field lowers the energy of one structure and raises the energy of the other (inverted) structure. As a result, all of the ammonia molecules can be found in the lower energy state. The researchers demonstrated this by creating a layered argon-ammonia-argon structure at 10 kelvins. Argon is an inert gas which is solid at 10 K, but the ammonia molecules can rotate freely in the argon solid. As the electric field is increased, the energy states of the ammonia molecules change in such a way that the probabilities of finding the molecules in the normal and inverted states become increasingly far apart, and tunneling can no longer occur.

This effect is completely reversible and nondestructive: As the electric field is decreased, the ammonia molecules return to their normal state of being simultaneously in both wells.

“This manuscript describes a burgeoning frontier in our ability to tame molecules and control their underlying dynamics,” says Patrick Vaccaro, a professor of chemistry at Yale University who was not involved in the study. “The experimental approach set forth in this paper is unique, and it has enormous ramifications for future efforts to interrogate molecular structure and dynamics, with the present application affording fundamental insights into the nature of tunneling-mediated phenomena.”

Lowering the barriers

For many molecules, the barrier to tunneling is so high that tunneling would never happen during the lifespan of the universe, Field says. However, there are molecules other than ammonia that can be induced to tunnel by careful tuning of the applied electric field. His colleagues are now working on exploiting this approach with some of those molecules.

“Ammonia is special because of its high symmetry and the fact that it’s probably the first example anybody would ever discuss from a chemical point of view of tunneling,” Field says. “However, there are many examples where this could be exploited. The electric field, because it’s so large, is capable of acting on the same scale as the actual chemical interactions,” offering a powerful way of externally manipulating molecular dynamics.

The research was funded by the Samsung Science and Technology Foundation and the National Science Foundation.

School of Science appoints 14 faculty members to named professorships

by School of Science |

The School of Science has announced that 14 of its faculty members have been appointed to named professorships. The faculty members selected for these positions receive additional support to pursue their research and develop their careers.

Riccardo Comin is an assistant professor in the Department of Physics. He has been named a Class of 1947 Career Development Professor. This three-year professorship is granted in recognition of the recipient’s outstanding work in both research and teaching. Comin is interested in condensed matter physics. He uses experimental methods to synthesize new materials, as well as analysis through spectroscopy and scattering to investigate solid state physics. Specifically, the Comin lab attempts to discover and characterize electronic phases of quantum materials. Recently, his lab, in collaboration with colleagues, discovered that weaving a conductive material into a particular pattern known as the “kagome” pattern can result in quantum behavior when electricity is passed through.

Joseph Davis, assistant professor in the Department of Biology, has been named a Whitehead Career Development Professor. He looks at how cells build and deconstruct complex molecular machinery. The work of his lab group relies on biochemistry, biophysics, and structural approaches that include spectrometry and microscopy. A current project investigates the formation of the ribosome, an essential component in all cells. His work has implications for metabolic engineering, drug delivery, and materials science.

Lawrence Guth is now the Claude E. Shannon (1940) Professor of Mathematics. Guth explores harmonic analysis and combinatorics, and he is also interested in metric geometry and identifying connections between geometric inequalities and topology. The subject of metric geometry revolves around being able to estimate measurements, including length, area, volume and distance, and combinatorial geometry is essentially the estimation of the intersection of patters in simple shapes, including lines and circles.

Michael Halassa, an assistant professor in the Department of Brain and Cognitive Sciences, will hold the three-year Class of 1958 Career Development Professorship. His area of interest is brain circuitry. By investigating the networks and connections in the brain, he hopes to understand how they operate — and identify any ways in which they might deviate from normal operations, causing neurological and psychiatric disorders. Several publications from his lab discuss improvements in the treatment of the deleterious symptoms of autism spectrum disorder and schizophrenia, and his latest news provides insights on how the brain filters out distractions, particularly noise. Halassa is an associate investigator at the McGovern Institute for Brain Research and an affiliate member of the Picower Institute for Learning and Memory.

Sebastian Lourido, an assistant professor and the new Latham Family Career Development Professor in the Department of Biology for the next three years, works on treatments for infectious disease by learning about parasitic vulnerabilities. Focusing on human pathogens, Lourido and his lab are interested in what allows parasites to be so widespread and deadly, looking on a molecular level. This includes exploring how calcium regulates eukaryotic cells, which, in turn, affect processes such as muscle contraction and membrane repair, in addition to kinase responses.

Brent Minchew is named a Cecil and Ida Green Career Development Professor for a three-year term. Minchew, a faculty member in the Department of Earth, Atmospheric and Planetary Sciences, studies glaciers using remote sensing methods, such as interferometric synthetic aperture radar. His research into glaciers, including their mechanics, rheology, and interactions with their surrounding environment, extends as far as observing their responses to climate change. His group recently determined that Antarctica, in a worst-case scenario climate projection, would not contribute as much as predicted to rising sea level.

Elly Nedivi, a professor in the departments of Brain and Cognitive Sciences and Biology, has been named the inaugural William R. (1964) And Linda R. Young Professor. She works on brain plasticity, defined as the brain’s ability to adapt with experience, by identifying genes that play a role in plasticity and their neuronal and synaptic functions. In one of her lab’s recent publications, they suggest that variants of a particular gene may undermine expression or production of a protein, increasing the risk of bipolar disorder. In addition, she collaborates with others at MIT to develop new microscopy tools that allow better analysis of brain connectivity. Nedivi is also a member of the Picower Institute for Learning and Memory.

Andrei Negut has been named a Class of 1947 Career Development Professor for a three-year term. Negut, a member of the Department of Mathematics, fixates on problems in geometric representation theory. This topic requires investigation within algebraic geometry and representation theory simultaneously, with implications for mathematical physics, symplectic geometry, combinatorics and probability theory.

Matĕj Peč, the Victor P. Starr Career Development Professor in the Department of Earth, Atmospheric and Planetary Science until 2021, studies how the movement of the Earth’s tectonic plates affects rocks, mechanically and microstructurally. To investigate such a large-scale topic, he utilizes high-pressure, high-temperature experiments in a lab to simulate the driving forces associated with plate motion, and compares results with natural observations and theoretical modeling. His lab has identified a particular boundary beneath the Earth’s crust where rock properties shift from brittle, like peanut brittle, to viscous, like honey, and determined how that layer accommodates building strain between the two. In his investigations, he also considers the effect on melt generation miles underground.

Kerstin Perez has been named the three-year Class of 1948 Career Development Professor in the Department of Physics. Her research interest is dark matter. She uses novel analytical tools, such as those affixed on a balloon-borne instrument that can carry out processes similar to that of a particle collider (like the Large Hadron Collider) to detect new particle interactions in space with the help of cosmic rays. In another research project, Perez uses a satellite telescope array on Earth to search for X-ray signatures of mysterious particles. Her work requires heavy involvement with collaborative observatories, instruments, and telescopes. Perez is affiliated with the Kavli Institute for Astrophysics and Space Research.

Bjorn Poonen, named a Distinguished Professor of Science in the Department of Mathematics, studies number theory and algebraic geometry. He, his colleagues, and his lab members generate algorithms that can solve polynomial equations with the particular requirement that the solutions be rational numbers. These types of problems can be useful in encoding data. He also helps to determine what is undeterminable, that is exploring the limits of computing.

Daniel Suess, named a Class of 1948 Career Development Professor in the Department of Chemistry, uses molecular chemistry to explain global biogeochemical cycles. In the fields of inorganic and biological chemistry, Suess and his lab look into understanding complex and challenging reactions and clustering of particular chemical elements and their catalysts. Most notably, these reactions include those that are essential to solar fuels. Suess’s efforts to investigate both biological and synthetic systems have broad aims of both improving human health and decreasing environmental impacts.

Alison Wendlandt is the new holder of the five-year Cecil and Ida Green Career Development Professorship. In the Department of Chemistry, the Wendlandt research group focuses on physical organic chemistry and organic and organometallic synthesis to develop reaction catalysts. Her team fixates on designing new catalysts, identifying processes to which these catalysts can be applied, and determining principles that can expand preexisting reactions. Her team’s efforts delve into the fields of synthetic organic chemistry, reaction kinetics, and mechanics.

Julien de Wit, a Department of Earth, Atmospheric and Planetary Sciences assistant professor, has been named a Class of 1954 Career Development Professor. He combines math and science to answer questions about big-picture planetary questions. Using data science, de Wit develops new analytical techniques for mapping exoplanetary atmospheres, studies planet-star interactions of planetary systems, and determines atmospheric and planetary properties of exoplanets from spectroscopic information. He is a member of the scientific team involved in the Search for habitable Planets EClipsing ULtra-cOOl Stars (SPECULOOS) TRANsiting Planets and Planetesimals Small Telescope (TRAPPIST), made up of an international collection of observatories. He is affiliated with the Kavli Institute.

New synthesis method yields degradable polymers

by Anne Trafton | MIT News Office |

MIT chemists have devised a way to synthesize polymers that can break down more readily in the body and in the environment.

A chemical reaction called ring-opening metathesis polymerization, or ROMP, is handy for building novel polymers for various uses such as nanofabrication, high-performance resins, and delivering drugs or imaging agents. However, one downside to this synthesis method is that the resulting polymers do not naturally break down in natural environments, such as inside the body.

The MIT research team has come up with a way to make those polymers more degradable by adding a novel type of building block to the backbone of the polymer. This new building block, or monomer, forms chemical bonds that can be broken down by weak acids, bases, and ions such as fluoride.

“We believe that this is the first general way to produce ROMP polymers with facile degradability under biologically relevant conditions,” says Jeremiah Johnson, an associate professor of chemistry at MIT and the senior author of the study. “The nice part is that it works using the standard ROMP workflow; you just need to sprinkle in the new monomer, making it very convenient.”

This building block could be incorporated into polymers for a wide variety of uses, including not only medical applications but also synthesis of industrial polymers that would break down more rapidly after use, the researchers say.

The lead author of the paper, which appears in Nature Chemistry today, is MIT postdoc Peyton Shieh. Postdoc Hung VanThanh Nguyen is also an author of the study.

Powerful polymerization

The most common building blocks of ROMP-generated polymers are molecules called norbornenes, which contain a ring structure that can be easily opened up and strung together to form polymers. Molecules such as drugs or imaging agents can be added to norbornenes before the polymerization occurs.

Johnson’s lab has used this synthesis approach to create polymers with many different structures, including linear polymers, bottlebrush polymers, and star-shaped polymers. These novel materials could be used for delivering many cancer drugs at once, or carrying imaging agents for magnetic resonance imaging (MRI) and other types of imaging.

“It’s a very robust and powerful polymerization reaction,” Johnson says. “But one of the big downsides is that the backbone of the polymers produced entirely consists of carbon-carbon bonds, and as a result, the polymers are not readily degradable. That’s always been something we’ve kept in the backs of our minds when thinking about making polymers for the biomaterials space.”

To circumvent that issue, Johnson’s lab has focused on developing small polymers, on the order of about 10 nanometers in diameter, which could be cleared from the body more easily than larger particles. Other chemists have tried to make the polymers degradable by using building blocks other than norbornenes, but these building blocks don’t polymerize as efficiently. It’s also more difficult to attach drugs or other molecules to them, and they often require harsh conditions to degrade.

“We prefer to continue to use norbornene as the molecule that enables us to polymerize these complex monomers,” Johnson says. “The dream has been to identify another type of monomer and add it as a co-monomer into a polymerization that already uses norbornene.”

The researchers came upon a possible solution through work Shieh was doing on another project. He was looking for new ways to trigger drug release from polymers, when he synthesized a ring-containing molecule that is similar to norbornene but contains an oxygen-silicon-oxygen bond. The researchers discovered that this kind of ring, called a silyl ether, can also be opened up and polymerized with the ROMP reaction, leading to polymers with oxygen-silicon-oxygen bonds that degrade more easily. Thus, instead of using it for drug release, the researchers decided to try to incorporate it into the polymer backbone to make it degradable.

They found that by simply adding the silyl-ether monomer in a 1:1 ratio with norbornene monomers, they could create similar polymer structures to what they have previously made, with the new monomer incorporated fairly uniformly throughout the backbone. But now, when exposed to a slightly acidic pH, around 6.5, the polymer chain begins to break apart.

“It’s quite simple,” Johnson says. “It’s a monomer we can add to widely used polymers to make them degradable. But as simple as that is, examples of such an approach are surprisingly rare.”

Faster breakdown

In tests in mice, the researchers found that during the first week or two, the degradable polymers showed the same distribution through the body as the original polymers, but they began to break down soon after that. After six weeks, the concentrations of the new polymers in the body were between three and 10 times less than the concentrations of the original polymers, depending on the exact chemical composition of the silyl-ether monomers that the researchers used.

The findings suggest that adding this monomer to polymers for drug delivery or imaging could help them get cleared from the body more quickly.

“We are excited about the prospect of using this technology to precisely tune the breakdown of ROMP-based polymers in biological tissues, which we believe could be leveraged to control biodistribution, drug release kinetics, and many other features,” Johnson says.

The researchers have also started working on adding the new monomers to industrial resins, such as plastics or adhesives. They believe it would be economically feasible to incorporate these monomers into the manufacturing processes of industrial polymers, to make them more degradable, and they are working with Millipore-Sigma to commercialize this family of monomers and make them available for research.

The research was funded by the National Institutes of Health, the American Cancer Society, and the National Science Foundation.

New process could make hydrogen peroxide available in remote places

by David Chandler |

Hydrogen peroxide, a useful all-purpose disinfectant, is found in most medicine cabinets in the developed world. But in remote villages in developing countries, where it could play an important role in health and sanitation, it can be hard to come by.

Now, a process developed at MIT could lead to a simple, inexpensive, portable device that could produce hydrogen peroxide continuously from just air, water, and electricity, providing a way to sterilize wounds, food-preparation surfaces, and even water supplies.

The new method is described this week in the journal Joule in a paper by MIT students Alexander Murray, Sahag Voskian, and Marcel Schreier and MIT professors T. Alan Hatton and Yogesh Surendranath.

Even at low concentrations, hydrogen peroxide is an effective antibacterial agent, and after carrying out its sterilizing function it breaks down into plain water, in contrast to other agents such as chlorine that can leave unwanted byproducts from its production and use.

Hydrogen peroxide is just water with an extra oxygen atom tacked on — it’s H2O2, instead of H2O. That extra oxygen is relatively loosely bound, making it a highly reactive chemical eager to oxidize any other molecules around it. It’s so reactive that in high concentrations it can be used as rocket fuel, and even concentrations of 35 percent require very special handling and shipping procedures. The kind used as a household disinfectant is typically only 3 percent hydrogen peroxide and 97 percent water.

Because high concentrations are hard to transport, and low concentrations, being mostly water, are uneconomical to ship, the material is often hard to get in places where it could be especially useful, such as remote communities with untreated water. (Bacteria in water supplies can be effectively controlled by adding hydrogen peroxide.) As a result, many research groups around the world have been pursuing approaches to developing some form of portable hydrogen peroxide production equipment.

Most of the hydrogen peroxide produced in the industrialized world is made in large chemical plants, where methane, or natural gas, is used to provide a source of hydrogen, which is then reacted with oxygen in a catalytic process under high heat. This process is energy-intensive and not easily scalable, requiring large equipment and a steady supply of methane, so it does not lend itself to smaller units or remote locations.

“There’s a growing community interested in portable hydrogen peroxide,” Surendranath says, “because of the appreciation that it would really meet a lot of needs, both on the industrial side as well as in terms of human health and sanitation.”

Other processes developed so far for potentially portable systems have key limitations. For example, most catalysts that promote the formation of hydrogen peroxide from hydrogen and oxygen also make a lot of water, leading to low concentrations of the desired product. Also, processes that involve electrolysis, as this new process does, often have a hard time separating the produced hydrogen peroxide from the electrolyte material used in the process, again leading to low efficiency.

Surendranath and the rest of the team solved the problem by breaking the process down into two separate steps. First, electricity (ideally from solar cells or windmills) is used to break down water into hydrogen and oxygen, and the hydrogen then reacts with a “carrier” molecule. This molecule — a compound called anthroquinone, in these initial experiments — is then introduced into a separate reaction chamber where it meets with oxygen taken from the outside air, and a pair of hydrogen atoms binds to an oxygen molecule (O2) to form the hydrogen peroxide. In the process, the carrier molecule is restored to its original state and returns to carry out the cycle all over again, so none of this material is consumed.

The process could address numerous challenges, Surendranath says, by making clean water, first-aid care for wounds, and sterile food preparation surfaces more available in places where they are presently scarce or unavailable.

“Even at fairly low concentrations, you can use it to disinfect water of microbial contaminants and other pathogens,” Surendranath says. And, he adds, “at higher concentrations, it can be used even to do what’s called advanced oxidation,” where in combination with UV light it can be used to decontaminate water of even strong industrial wastes, for example from mining operations or hydraulic fracking.

So, for example, a portable hydrogen peroxide plant might be set up adjacent to a fracking or mining site and used to clean up its effluent, then moved to another location once operations cease at the original site.

In this initial proof-of-concept unit, the concentration of hydrogen peroxide produced is still low, but further engineering of the system should lead to being able to produce more concentrated output, Surendranath says. “One of the ways to do that is to just increase the concentration of the mediator, and fortunately, our mediator has already been used in flow batteries at really high concentrations, so we think there’s a route toward being able to increase those concentrations,” he says.

“It’s kind of an amazing process,” he says, “because you take abundant things, water, air and electricity, that you can source locally, and you use it to make this important chemical that you can use to actually clean up the environment and for sanitation and water quality.”

“The ability to create a hydrogen peroxide solution in water without electrolytes, salt, base, etc., all of which are intrinsic to other electrochemical processes, is noteworthy,” says Shannon Stahl, a professor of chemistry at the University of Wisconsin, who was not involved in this work. Stahl adds that “Access to salt-free aqueous solutions of H2O2 has broad implications for practical applications.”

Stahl says that “This work represents an innovative application of ‘mediated electrolysis.’ Mediated electrochemistry provides a means to merge conventional chemical processes with electrochemistry, and this is a particularly compelling demonstration of this concept. … There are many potential applications of this concept.”

Meet the 2019-20 MLK Visiting Professors and Scholars

by Beatriz Cantada | Institute Community and Equity Office |

Founded in 1990, the Martin Luther King Jr. (MLK) Visiting Professors and Scholars Program honors the life and legacy of Martin Luther King by increasing the presence of, and recognizing the contributions of, underrepresented minority scholars at MIT. MLK Visiting Professors and Scholars enhance their scholarship through intellectual engagement with the MIT community and enrich the cultural, academic, and professional experience of students. The program hosts between four and eight scholars each year with financial and institutional support from the Office of the Provost and oversight from the Institute Community and Equity Office. Six scholars are visiting MIT this academic year as part of the program.

Kasso Okoudjou is returning for a second year as an MLK Visiting Professor in the Department of Mathematics. Originally from Benin, he moved to the United States in 1998 and earned a PhD in mathematics from Georgia Tech. Okoudjou joins MIT from the University of Maryland College Park, where he is a professor. His research interests include applied and pure harmonic analysis, especially time-frequency and time-scale analysis; frame theory; and analysis and differential equations on fractals. He is interested in broadening the participation of underrepresented minorities in (undergraduate) research in the mathematical sciences.

Matthew Schumaker joins MIT for another year in the Music and Theater Arts Section within the School of Humanities, Arts, and Social Sciences. Schumaker received his doctorate in music composition from the University of California at Berkeley. At MIT, he teaches a new course, 21M.380 (Composing for Solo Instrument and Live Electronics), a hands-on music technology composition seminar combining instrumental writing with real-time computer music. Additionally, The Radius Ensemble in Cambridge, Massachusetts has commissioned Schumaker to write a new piece of music that helps translate into music the vibrant, curved gestures and slashed markings in the abstract landscapes of celebrated Ethiopian-born painter Julie Mehretu.

Jamie Macbeth is visiting from Smith College, where he is an assistant professor in computer science. He received his PhD in computer science from University of California at Los Angeles. Although this is his first year as an MLK Visiting Scholar, he is not new to MIT, since he has been a visiting scientist since 2017. He is hosted by the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL). Macbeth’s research is focused on building and studying intelligent computing systems that demonstrate a human-like capability for in-depth understanding and production of natural language, and thus can achieve richer interactions with human users. He is especially keen on building systems that decompose the meaning of language into complex conceptual structures that reflect humans’ embodied cognition, memory, imagery and knowledge about social situations.

Ben McDonald has been a postdoc in the Department of Chemistry since 2018 and is now an MLK Visiting Scholar. McDonald received his PhD in synthetic organic chemistry from Northwestern University. His research focused on the total synthesis of flavonolignan natural products and the development of reverse-polarity carbon-carbon bond forming reactions. As a member of the department’s Chemistry Alliance for Inclusion and Diversity, he is focused on advancing diversity, equity and inclusion efforts. One of the initiatives he seeks to establish is a summer research program, which recruits talented future scientists from underrepresented backgrounds.

Tina Opie is an associate professor in the Management Division at Babson College. Opie obtained her PhD in management (with a concentration in organizational behavior) from New York University’s Stern School of Business. As an MLK Visiting Scholar in MIT Sloan School of Management, along with access to MIT’s Behavioral Research Lab, she is conducting research to develop the construct of Shared Sisterhood. “Shared Sisterhood examines how high-quality relationships (e.g., relationships characterized by trust, emotional vulnerability) between black, white, and Latinx women at work facilitate workplace inclusion and equity.” Though her work has a specific focus, people of all genders and racioethnic backgrounds can be “sisters” and can contribute to fostering a more inclusive work environment. Opie established Opie Consulting Group, a diversity-and-inclusion consultancy that incorporates Shared Sisterhood in creating inclusive workplaces.

Rhonda Williams, an MLK Visiting Professor hosted by the Department of History, joins MIT from Vanderbilt University, where she was recently appointed the John L. Seigenthaler Chair in American History. She is the founder of the Social Justice Institute at Case Western Reserve University. Her essay titled “Black Women Who Educate for Justice and Put Their Time, Lives, and Spirits on the Line” was recently published in “Black Women And Social Justice Education: Legacies and Lessons” (2019, SUNY Press). On Oct. 25, Williams will deliver a social justice-related performance-lecture called “The Things That Divide Us: Meditations” at MIT. In spring 2020, she will facilitate a social justice workshop for students, faculty and staff.

For more information about our scholars and the program, visit mlkscholars.mit.edu.

Diagnosing cellular nanomechanics

by Singapore-MIT Alliance for Research and Technology |

Researchers at Singapore-MIT Alliance for Research and Technology (SMART) and MIT’s Laser Biomedical Research Center (LBRC) have developed a new way to study cells, paving the way for a better understanding of how cancers spread and become killers.

The new technology is explained in a paper published recently in Nature Communications. A new confocal reflectance interferometric microscope provides 1.5 microns depth resolution and better than 200 picometers height measurement sensitivity for high-speed characterization of nanometer-scale nucleic envelope and plasma membrane fluctuations in biological cells. It enables researchers to use these fluctuations to understand key biological questions, such as the role of nuclear stiffness in cancer metastasis and genetic diseases.

“Current methods for nuclear mechanics are invasive, as they either require mechanical manipulation, such as stretching, or require injecting fluorescent probes that ‘light up’ the nucleus to observe its shape. Both these approaches would undesirably change cells’ intrinsic properties, limiting study of cellular mechanisms, disease diagnosis, and cell-based therapies,” say Vijay Raj Singh, SMART research scientist, and Zahid Yaqoob, LBRC principal investigator. “With the confocal reflectance interferometric microscope, we can study nuclear mechanics of biological cells without affecting their native properties.”

While the scientists can study about a hundred cells in a few minutes, they believe that the system can be upgraded in the future to improve the throughput to tens of thousands of cells.

“Today, many disease mechanisms are not fully understood because we lack a way to look at how cells’ nucleus changes when it undergoes stress,” says Peter So, SMART BioSyM principal investigator, MIT professor, and LBRC director. “For example, people often do not die from the primary cancer, but from the secondary cancers that form after the cancer cells metastasize from the primary site — and doctors do not know why cancer becomes aggressive and when it happens. Nuclear mechanics plays a vital role in cancer metastasis as the cancer cells must ‘squeeze’ through the blood vessel walls into the bloodstream, and again when they enter a new location. This is why the ability to study nuclear mechanics is so important to our understanding of cancer formation, diagnostics, and treatment.”

With the new interferometric microscope, scientists at LBRC are studying cancer cells when they undergo mechanical stress, especially during extravasation process, paving the way for new cancer treatments. Further, the scientists are also able to use the same technology to study the effect of “lamin mutations” on nuclear mechanics, which result in rare genetic diseases such as Progeria, which leads to fast aging in young children.

The confocal reflectance interferometric microscope also has applications in other sectors. For example, this technology has the potential for studying cellular mechanics within intact living tissues. With the new technology, the scientists could shed new light on biological processes within the body’s major organs such as liver, allowing safer and more accurate cell therapies. Cell therapy is a major focus area for Singapore, with the government recently announcing a S$80 million (US $58 million) boost to the manufacturing of living cells as medicine.

About BioSyM

BioSystems and Micromechanics (BioSyM) Inter-Disciplinary Research Group brings together a multidisciplinary team of faculties and researchers from MIT and the universities and research institutes of Singapore. BioSyM’s research deals with the development of new technologies to address critical medical and biological questions applicable to a variety of diseases with an aim to provide novel solutions to the health care industry and to the broader research infrastructure in Singapore. The guiding tenet of BioSyM is that accelerated progress in biology and medicine will critically depend upon the development of modern analytical methods and tools that provide a deep understanding of the interactions between mechanics and biology at multiple length scales — from molecules to cells to tissues — that impact maintenance or disruption of human health.

About Singapore-MIT Alliance for Research and Technology (SMART)

Singapore-MIT Alliance for Research and Technology (SMART) is MIT’s research enterprise in Singapore, established in partnership with the National Research Foundation of Singapore (NRF) since 2007. SMART is the first entity in the Campus for Research Excellence and Technological Enterprise (CREATE) developed by NRF. SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore. Cutting-edge research projects in areas of interest to both Singapore and MIT are undertaken at SMART. SMART currently comprises an Innovation Centre and six Interdisciplinary Research Groups: Antimicrobial Resistance, BioSystems and Micromechanics, Critical Analytics for Manufacturing Personalized-Medicine, Disruptive & Sustainable Technologies for Agricultural Precision, Future Urban Mobility, and Low Energy Electronic Systems.

SMART research is funded by the National Research Foundation Singapore under the CREATE program.

About the Laser Biomedical Research Center (LBRC)

Established in 1985, the Laser Biomedical Research Center is a National Research Resource Center supported by the National Institute of Biomedical Imaging and Bioengineering, a Biomedical Technology Resource Center of the National Institutes of Health. The LBRC’s mission is to develop the basic scientific understanding and new techniques required for advancing the clinical applications of lasers and spectroscopy. Researchers at the LBRC develop laser-based microscopy and spectroscopy techniques for medical applications, such as the spectral diagnosis of various diseases and investigation of biophysical and biochemical properties of cells and tissues. A unique feature of the LBRC is its ability to form strong clinical collaborations with outside investigators in areas of common interest that further the center’s mandated research objectives.

Troy Van Voorhis named head of the Department of Chemistry

by Julia C. Keller |

Troy Van Voorhis, the Robert T. Haslam and Bradley Dewey Professor of Chemistry, has been named head of the Department of Chemistry, effective Oct. 1.

“I am delighted that Troy Van Voorhis will lead the chemistry department,” says Michael Sipser, dean of the MIT School of Science and the Donner Professor of Mathematics. “Troy has been a core member of the department, known for his outstanding research in physical chemistry as well as for his contributions to education and the department’s climate. I look forward to working with Troy on Science Council.”

Van Voorhis has served as associate head of chemistry since 2015, working with then-department head Timothy Jamison and, most recently, with Professor Stephen Buchwald, who has served as interim department head since July 2019.

In addition to his service to the department, Van Voorhis recently co-chaired the Working Group on Curricula and Degrees for the MIT Stephen A. Schwarzman College of Computing. He has also contributed to discussions on opportunities for the School of Science in the college.

Van Voorhis says, “I look forward to working with the department in my new role and will continue to support the growth of our chemistry community’s research, education, and outreach programs.”

“Troy is an excellent choice to head up chemistry and provide leadership for the members of our department. He has a strong record of scientific accomplishment and devotion to education and to MIT students,” says Buchwald, the Camille Dreyfus Professor of Chemistry.

“I am grateful to Steve for his service to the department as interim head. I thank Mei Hong for chairing the search committee, as well as the committee members for their efforts,” says Sipser. “I am deeply indebted to Tim Jamison for his outstanding leadership during the previous four years. Tim, who has recently become associate provost, leaves the Department of Chemistry in excellent shape.”

Van Voorhis’ research lies at the nexus of chemistry and computation, and his work has impact on renewable energy and quantum computing. His lab is focused on developing new methods that provide an accurate description of electron dynamics in molecules and materials. Over the years, his research has led to advances in light emitting diodes, solar cells, and other devices and technologies crucial to addressing 21st-century energy concerns.

Van Voorhis received his bachelor’s degree in chemistry and mathematics from Rice University and his PhD in chemistry from the University of California at Berkeley in 2001. Following a postdoctoral fellowship at Harvard University, he joined the faculty of MIT in 2003 and was promoted to professor of chemistry in 2012.

He has received many honors and awards, including being named an Alfred P. Sloan research fellow, a fellow of the David and Lucille Packard Foundation, and a recipient of a National Science Foundation CAREER award. He has also received the MIT School of Science’s award for excellence in graduate teaching.