Research Magazine 2006
illustration of ionic liquids
Room-temperature ionic liquids are one of Daniel Armstrong's three principal research areas.
We want to do things that haven't been done before, or were thought to be impossible to do before.

Separated from the mix

Daniel Armstrong's chemical innovations have changed the way pharmaceutical companies develop drugs and earned him the reputation as a molecular trailblazer

Daniel ArmstrongTiny cellular molecules mean big breakthroughs for Daniel Armstrong. It’s the kind of science that changed international policy, altered the way a major industry conducts business, prevented nasty things like birth defects and almost surely saved some lives. The kind many deemed impossible.

“We invent and develop new methods,” he said. “We invent an area, [and] everybody else jumps into it afterward.”

Dr. Armstrong’s vita is a roll call of chemistry’s highest honors, but that isn’t what motivates him. He thrives on accomplishing the extraordinary.

Armstrong is UT Arlington’s first Robert A. Welch Chair in Chemistry, a sign that the University’s College of Science has emerged as a prominent player. (Universities don’t apply for Welch chairs; the Houston-based Welch Foundation awards them based on a university’s reputation in research.) Though Welch chairs are given only to Texas universities, they’re considered prestigious positions nationally. So prestigious that Armstrong left a distinguished professorship at Iowa State University to fill UT Arlington’s Welch Chair.

Before arriving here in January, he had already made his name as the father of micelle- and cyclodextrin-based separations, a type of chemistry so innovative that he literally developed new techniques, ran new tests and found new applications. He has published more than 400 papers, compiling such a volume of influential work that the Scientific Citation Index lists him as one of the world’s most frequently cited scientists. He and his 25 investigators operate on more than $2 million in active grants.

“Dr. Armstrong is the world leader in the separation of enantiomers,” said chemistry and biochemistry Professor Zoltan Schelly, who headed the Welch Chair search committee. “This has tremendous importance.”

For UT Arlington and the world of chemistry.

A Top 10 program

Armstrong first visited UT Arlington in summer 2005 and was impressed by its faculty, growth and drive. So impressed that he uprooted most of the members of his research team and transplanted them to Arlington. And now that he’s mostly settled in, he’s not looking back.

“This has been very positive,” he said. “We want to do innovative, cutting-edge research, and that’s always been the goal regardless of where we’ve been. I will only go someplace that will benefit that general goal. If I can do better research here, and my family likes it here, it’s a no-brainer. It’s an easy decision.”

Besides, Armstrong believes UT Arlington is about to become synonymous with leading chemistry research.

“I’ve heard the president and the provost both say that they’d like to be at least a Top 100 university with Top 50 programs. But I think we can bring them a Top 10 program as early as next year. … And that’s almost amazing when you think about it. There are departments and universities that strive for decades to have something that’s Top 10. At this point, UT Arlington will come from almost nowhere, as far as the rankings go, to get to the Top 10 in just a few years. It’s really astounding. But I think we’re going to do it.”

If that happens, science Dean Paul Paulus will know why. “The addition of Daniel Armstrong and the other top scientists we have hired in the past few years will significantly enhance the research prowess of our college and our ability to provide a world-class education for both our graduate and undergraduate students.”

Those recent hires also include renowned analytical chemist Purnendu Dasgupta to be the department’s new chair. Dr. Dasgupta, who studies the chemical constituents of atmospheric gases, arrives in the spring, but his collaboration with Armstrong includes a co-authored mass spectrometry project.

Inventions and breakthroughs

In less than a year at UT Arlington, Armstrong’s research has made the cover of two prominent journals: The Journal of Physical Chemistry (March 2006) and Analytical Chemistry (May 2006). He researches principally in three fields—chiral separations, room-temperature ionic liquids and identifying cells using capillary electrophoresis—and in all three, he’s ahead of the curve.

Chiral separations involve sorting molecules within a compound based on their “handedness” (the root cheir means “hand” in Greek). Like your left hand and right hand, chiral molecules are non-superimposable mirror images; because these molecules are so similar, the only way to identify which is which—“left-handed” vs. “right-handed”—is by introducing them to a third chiral molecule that can tell them apart.

For example, when humans take medicines made from chiral compounds, their bodies are able to distinguish the molecules. One set of molecules can be beneficial; the other might cause side effects. The classic case is the sedative thalidomide, once given for morning sickness and administered as an equal mixture of right- and left-handed forms. While one of the handed forms proved an effective medicine, the other caused disfiguring birth defects.

In the 1980s, Armstrong began looking for reasons why specific chiral molecules, like those in the human body, could differentiate between other chiral molecules, like those in drugs. Twelve years later, his discoveries led to new Food and Drug Administration policies and changed the way pharmaceutical companies develop drugs.

“We invented a way to separate the left-handed and right-handed molecules. This was the practical application of the basic research we were doing.”

Armstrong patented chromatographic columns filled with a very fine powder to which he bonded chiral selectors (the molecules that do the separations). Mixtures of chiral compounds go in one side, and the separated chiral molecules come out the other. Pharmaceutical companies began using variations of these columns after the FDA mandated that new drugs contain only one handed form of chiral molecule.

This is only part of the Armstrong big picture. He also conducts research using room-temperature ionic liquids. Ionic liquids are composed of positively and negatively charged molecules (salts). Specifically, Armstrong is interested in salts that remain liquid at room temperature and the potential applications for these strange substances.

Most liquids—water, gasoline, alcohol—contain molecules that are not charged but neutral and evaporate or burn off. Not so with these special salts.

“What’s unusual about this ionic liquid is that it’s charged, and the charges trap each other, and it has no detectable vapor pressure. It doesn’t evaporate,” Armstrong said. “You can’t smell it. You can light a match near it, and it’s never going to ignite because there’s no vapor. It produces no air pollution. So because of the interesting physical properties … a lot of people are starting to use these for all different types of applications.”

Organic chemists have begun performing synthesis and reactions in ionic liquids rather than in the dangerous flammable solvents they’ve used for years. These liquids could be used as transformer fluid, to extract pollutants, or in laboratory work in mass spectrometry or chiral separations.

The third phase of Armstrong’s research uses capillary electrophoresis to identify cells. A breakthrough here could mean improved speed and accuracy in diagnosing and treating some common diseases.

Consider a visit to the doctor for a sore throat. Currently, proper diagnosis means a doctor swabs your throat, takes the sample to a Petri dish and grows a colony.

“The trouble is, it can take a day to grow the colony, and that’s actually a pretty fast test,” Armstrong said. “Many pure cultures can take days or weeks. We wanted to do it in minutes or seconds, so we started developing separation-based methods.”

He wanted to isolate bacteria, fungi and viruses from other cells in the sample, then separate them. On paper, the result looks like an EKG reading, with the peaks representing the individual cells. In 2000, Armstrong achieved his first successful result, separating four bacteria and one fungus in less than 10 minutes. He later found that he could not only separate them, he could identify them and even tell what percent were alive or dead.

“So we published it,” he said, “and everyone thought, ‘That’s fantastic! But we aren’t sure we believe it. Nobody can do that.’ ”

But Armstrong did do it. Now he’s refining the technique and believes it could be useful not only in treating diseases but in preventing bioterrorism and helping pharmaceutical companies determine whether products are sterile. Today, tests for sterility take two weeks; Armstrong’s technique can show an absence of cells in five minutes.

All things are possible

While Armstrong can’t be certain how his research will turn out, he has the same goal for every project.

“We want to do things that haven’t been done before, or were thought to be impossible to do before. We want to provide people with the means to do it. We like to explain things that were not understood before, and by being able to explain them, you can enhance them, make them better, faster, more accurate.”

In other words, Daniel Armstrong is a trailblazer. And it doesn’t take his list of chemistry’s top honors to tell you that.

— Danny Woodward