Longstanding bottleneck in crystal structure prediction solved (Science)

By Tien Nguyen, Department of Chemistry

benzene crystal
Orthographic projections of a cluster cut from the benzene crystal along the two directions (Image courtesy of Science/AAAS)

Two years after its release, the HIV-1 drug Ritonavir was pulled from the market. Scientists discovered that the drug had crystallized into a slightly different form—called a polymorph—that was less soluble and made it ineffective as a treatment.

The various patterns that atoms of a solid material can adopt, called crystal structures, can have a huge impact on its properties. Being able to accurately predict the most stable crystal structure for a material has been a longstanding challenge for scientists.

“The holy grail of this particular problem is to say, I’ve written down this chemical formula for a material, and then just from the formula be able to predict its structure—a goal since the dawn of chemistry,” said Garnet K. L. Chan, the A. Barton Hepburn Professor of Theoretical Chemistry at Princeton University. One major bottleneck towards achieving this goal has been to compute the lattice energy—the energy associated with a structure—to sufficient accuracy to distinguish between several competing polymorphs.

Chan’s group has now accomplished this task, publishing their results in the journal Science on August 8. The research team demonstrated that new techniques could be used to calculate the lattice energy of benzene, a simple yet important molecule in pharmaceutical and energy research, to sub-kilojoule per mole accuracy—a level of certainty that allows polymorphism to be resolved.

Chan credited this success to the combined application of advances in the field of quantum mechanics over the last 15 years. “Some of these advances allow you to resolve the behavior of electrons more finely, do computations on more atoms more quickly, and allow you to consider more electrons at the same time,” Chan said. “It’s a triumph of the modern field of quantum chemistry that we can now determine the behavior of Nature to this level of precision.”

The group’s next goal is to shorten the time it takes to run the desired calculations. These initial calculations consumed several months of computer time, Chan said, but with some practical modifications, future predictions should take only a few hours.

Chan’s colleagues on the work included first author Jun Yang, an electronic structure theory specialist and lecturer in chemistry, and graduate student Weifeng Hu at Princeton University. Additional collaborators were Denis Usvyat and Martin Schutz of the University of Regensburg and Devin Matthews of the University of Texas at Austin.

The work was supported by the U.S. Department of Energy under grant no. DE-SC0008624, with secondary support from grant no. DE-SC0010530. Additional funding was received from the National Science Foundation under grant no. OCI-1265278 and CHE-1265277. D.M. was supported by the U.S. Department of Energy through a Computational Science Graduate Fellowship, funded by grant no. DE-FG02-97ER25308.

Read the abstract.

Yang J., Hu, W., Usvyat, D., Matthews, D., Schutz, M., Chan, G. K. L. Ab initio determination of the crystalline benzene lattice energy to sub-kilojoule/mol accuracy. Science 2014, 345, 640.

Conservation versus innovation in the fight against antibiotic resistance (Science)

Pills (Image source: NIH)
(Image source: NIH)

“Antibiotic resistance is a problem of managing an open-access resource, such as fisheries or oil,” writes Ramanan Laxminarayan, a research scholar at Princeton University and the director of the Center for Disease Dynamics, Economics & Policy in Washington, D. C., in today’s issue of the journal Science. He goes on to say that individuals have little incentive to use antibiotics wisely, just as people have little incentive to conserve oil when it is plentiful.

As with many other natural resources, maintaining the effectiveness of antibiotics requires two approaches: conserving the existing resource and exploring new sources, Laxminarayan says. These two approaches are linked, however. “Just as incentives for finding new sources of oil reduce incentives to conserve oil,” Laxminarayan writes, “large public subsidies for new drug development discourage efforts to improve how existing antibiotics are used.” Yet new antibiotics tend to cost more than existing ones due to the expense of clinical trials and the fact that the easiest-to-find drugs may have already been discovered.

Laxminarayan’s analysis reveals that the benefits of conserving existing drugs are significant, and argues that the proposed increases in public subsidies for new antibiotics should be matched by greater spending on conservation of antibiotic effectiveness through public education, research and surveillance.

Ramanan Laxminarayan is a research scholar at the Princeton Environmental Institute. His perspective, “Antibiotic effectiveness: Balancing conservation against innovation,” appeared in the September 12, 2014 issue of Science.

Read the article.

PPPL scientists take key step toward solving a major astrophysical mystery

By John Greenwald, Princeton Plasma Physics Laboratory

Magnetic reconnection in the Earth and sun’s atmospheres can trigger geomagnetic storms that disrupt cell phone service, damage satellites and blackout power grids. Understanding how reconnection transforms magnetic energy into explosive particle energy has been a major unsolved problem in plasma astrophysics.

Scientists at the Princeton Plasma Physics Laboratory (PPPL) and Princeton University have taken a key step toward a solution, as described in a paper published this week in the journal Nature Communications. In research conducted on the Magnetic Reconnection Experiment (MRX) at PPPL, the scientists not only identified how the mysterious transformation takes place, but measured experimentally the amount of magnetic energy that turns into particle energy. The work is supported by the U. S. Department of Energy as well as the NSF-funded Center for Magnetic Self-Organization.

Fast-camera image of plasma during magnetic reconnection with rendering of the field lines, shown in white, based on measurements made during the experiment. The converging horizontal lines represent the field lines prior to reconnection. The outgoing vertical lines represent the field lines after reconnection. Image courtesy of Jongsoo Yoo.
Fast-camera image of plasma during magnetic reconnection with rendering of the field lines, shown in white, based on measurements made during the experiment. The converging horizontal lines represent the field lines prior to reconnection. The outgoing vertical lines represent the field lines after reconnection. Image courtesy of Jongsoo Yoo.

Magnetic field lines represent the direction, and indicate the shape, of magnetic fields. In magnetic reconnection, the magnetic field lines in plasma snap apart and violently reconnect. The MRX, built in 1995, allows researchers to study the process in a controlled laboratory environment.

The new research shows that reconnection converts about 50 percent of the magnetic energy, with one-third of the conversion heating the electrons and two-thirds accelerating the ions — or atomic nuclei — in the plasma. In large bodies like the sun, such converted energy can equal the power of millions of tons of TNT.

“This is a major milestone for our research,” said Masaaki Yamada, a research physicist, the principal investigator for the MRX and first author of the Nature Communications paper. “We can now see the entire picture of how much of the energy goes to the electrons and how much to the ions in a proto-typical reconnection layer.”

The findings also suggested the process by which the energy conversion occurs. Reconnection first propels and energizes the electrons, according to the researchers, and this creates an electrically charged field that “becomes the primary energy source for the ions,” said Jongsoo Yoo, an associate research physicist at PPPL and co-author of the paper.

The other contributors to the paper were Hantao Ji, professor of astrophysical sciences at Princeton; Russell Kulsrud, professor of astrophysical sciences, emeritus, at Princeton; and doctoral candidates in astrophysical sciences Jonathan Jara-Almonte and Clayton Myers.

If confirmed by data from space explorations, the PPPL results could help resolve decades-long questions and create practical benefits. These could include a better understanding of geomagnetic storms that could lead to advanced warning of the disturbances and an improved ability to cope with them. Researchers could shut down sensitive instruments on communications satellites, for example, to protect the instruments from harm.

Next year NASA plans to launch a four-satellite mission to study reconnection in the magnetosphere — the magnetic field that surrounds the Earth. The PPPL team plans to collaborate with the venture, called the Magnetospheric Multiscale (MMS) Mission, by providing MRX data to it. The MMS probes could help to confirm the laboratory’s findings.

PPPL, on Princeton University’s Forrestal Campus in Plainsboro, New Jersey, is devoted to creating new knowledge about the physics of plasmas — ultra-hot, charged gases — and to developing practical solutions for the creation of fusion energy. Fusion takes place when atomic nuclei fuse and release a burst of energy. This compares with the fission reactions in today’s nuclear power plants, which operate by splitting atoms apart.

Results of PPPL research have ranged from a portable nuclear materials detector for anti-terrorist use to universally employed computer codes for analyzing and predicting the outcome of fusion experiments. The laboratory is managed by the University for the U.S. Department of Energy’s Office of Science, which is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time.

Read the abstract.

Yamada, M; Yoo J.; Jara-Almonte, J.; Ji, H.; Kulsrud, R.M.; Myers, C.E. Conversion of magnetic energy in the magnetic reconnection layer of a laboratory plasma. Nature Communications. Article published online Sept. 10, 2014. DOI: NCOMMS5774