University of Vermont

College of Arts and Sciences

Department of Chemistry

UVM Chemistry News: 2005-2002
Organometallics cover page 11-2007

Prof. Geiger's Research Adorns the Cover of the American Chemical Society Journal Organometallics

William E. Geiger, Ph.D., Professor and Pomeroy Chair of Chemistry, had his publication, Organometallic Electrochemistry: Origins, Development, and Future, selected to be the cover of the November 2007 issue of the prestigious ACS journal Organometallics.

The complete citation and PDF of the article can be found at Organometallics, 26 (24), 5738-5765, 2007

The publication describes Prof. Geiger's perspective on the evolution of organotransition metal electrochemistry from its origin with ferrocene to its promise in future applications is presented. Examples are given of key findings on the relationships of electron transfer to molecular structures and to the reactions of organotransition metal complexes.

DE Matthews

Prof. Matthews Elected into the Vermont Academy of Science and Engineering (VASE)

Dwight E. Matthews, Ph.D., Professor and Chair of Chemistry and Professor of Medicine at UVM, was elected into the Vermont Academy of Science and Engineering at their annual meeting on September 18, 2007.

Four distinguished engineers and scientists were honored by the Vermont Academy of Science and Engineering (VASE) in recognition of outstanding accomplishments in their fields: Steve Arms, President of MicroStrain Inc in Williston, VT, who has been developing micro-miniature displacement, strain, force and pressure sensors for 20 years. These sensors are being utilized in numerous applications within the medical, industrial and automotive market place. Prof. Dwight Matthews, who is an internationally recognized analytical chemist with specific expertise in mass spectrometry. He has successfully bridged many areas by applying mass spectrometry to problems in clinical medicine and nutrition. Dr. Colin Osborne, Chief Engineer of Concepts NREC, White River Junction, VT, who is a world renowned leader in the field of turbomachinery design and development. He has contributed significantly within the specific area of centrifugal compressors. Prof. George Pinder, Professor of Computer Science and Director of Groundwater Remediation Design, University of Vermont, who is considered one of the top engineers in the field of numerical simulation of groundwater contamination. His work has had a real impact on environmental problems throughout North America and the world.

There are 48 members in the academy. Up to 4 members from academia, engineering and science are selected annually by VASE. UVM Emeritus Professors of Chemistry Christopher Allen, Ted Flanagan, and Martin Kuehne are also members of VASE.

VASE press release 9/18/2007

ACS expo

Prof. Leenstra Appointed Chair of the American Chemical Society (ACS) Committee on Meetings and Expositions

Willem Leenstra, Ph.D., Associate Professor of Chemistry at UVM, has been appointed by the ACS to serve as chair of the Committee on Meetings and Expositions for 2007.

The ACS organizes two national meetings & expositions every year. Each meeting attracts more than 11,000 chemists, chemical engineers, academicians, graduate and postdoctoral students, and other related professionals. During the meeting, scientists present new multidisciplinary research, hear the latest information in their areas of professional interest, and network with colleagues. Programming is planned by the 33 technical divisions of the ACS that cover all scientific fields, secretariats that focus on multidisciplinary programming, and ACS committees. Each meeting features more than 7,000 presentations organized into technical symposia that highlight important research advances. Prof. Leenstra and his ACS Committee on Meetings and Expositions oversees the planning and execution of these meetings.

DE Matthews

Prof. Matthews Leads National Institutes of Health (NIH) Study Section

Dwight E. Matthews, Ph.D., Professor and Chair of Chemistry and Professor of Medicine at UVM, has been selected by the NIH to serve as chair of the Integrative Nutrition and Metabolic Processes Study Section, part of the NIH's Center for Scientific Review.

With a two-year term that began July 2006, Matthews has a unique opportunity to contribute to the national biomedical research effort, leading a 15-member group that reviews a significant number of NIH grant applications and helps shape the future of U.S. scientific inquiry into the fundamental workings of human biology and health.

Matthews' areas of expertise include analytical chemistry and mass spectrometry, and the application of stable isotope tracers to study human metabolism. He is director of the Mass Spectrometry Facility in the College of Medicine. He was selected on the basis of his "demonstrated competence and achievement in [his] scientific discipline as evidenced by the quality of research accomplishments, publications in scientific journals, and other significant scientific activities," writes Dr. Toni Scarpa, director of the NIH's Center for Scientific Review.

Matthews received a Ph.D. in analytical chemistry from Indiana University in 1977. After teaching and researching at the Washington University School of Medicine in St. Louis and at Cornell University Medical College in New York City, he joined the University of Vermont in 1996. He was appointed Chair of the Chemistry Department in 2002, and he was named a University Scholar for 2004-05.

Story from the Vermont Medicine Magazine, summer 2006 (page 4)

Petrucci RCMS award

Prof. Giuseppe Petrucci and Students Receive the RCM Beynon Prize in Mass Spectrometry for 2006

Shown in photo: John Monaghan, (Journal Editor of Rapid Communications in Mass Spectrometry), UVM Chemistry graduate student Brian LaFranchi and UVM Prof. Giuseppe (Joe) Petrucci, holding the award certificate

John Wiley and Sons, Ltd established the RCM Beynon Prize in 2004 to mark the 80th birthday of John Herbert Beynon, the founding Editor of Rapid Communications in Mass Spectrometry (RCM). This award, consisting of a monetary award of $1000 (US) plus a certificate for each contributing author, is awarded annually by an ad hoc sub-committee of the Editorial Board of RCM to the corresponding author(s) of a paper published in RCM that, in the opinion of the Awards Subcommittee, describes an innovative advance in mass spectrometric instrumentation or methodology that has had the greatest immediate impact in its particular sub-discipline over the previous two calendar years (i.e., published in the previous two volumes of RCM).

The winning paper of the 2006 RCM Beynon Prize published in RCM in 2004 and 2005 was awarded to Brian W. LaFranchi, James Zahardis and Giuseppe A. Petrucci. The paper was "Photoelectron resonance capture ionization mass spectrometry: a soft ionization source for mass spectrometry of particle-phase organic compounds" (Rapid Commun. Mass Spectrom. 2004, 18, 2517-2521). The prize was presented to Prof Joe Petrucci and Brian LaFranchi (James Zahardis could not be present) at the American Society for Mass Spectrometry Conference in Seattle, Washington, USA, in May 2006.

The RCM congratulates Prof. Petrucci and his students for an imaginative piece of work that well exemplifies the daring approach to methodology development that characterized the career of John Beynon, a founding father of the field of modern mass spectrometry.

chem week display

Chemists Celebrate Their Science With Prose and Shows

UVM news release date: 10-25-2005 by Kevin Foley from the View

Shown in photo: Prof. Martin Case and graduate student Karen Murphy investigate the properties of thermochromic putty and ducks at the Burlington Town Center mall. (Image: Fiona Case)

Carbon helium molybdenum nitrogen americium aluminum lawrencium astatine ununhexium? Let's put that another way: C He Mo N Am Al Lr At Uuh? Still not clear? Do we have to explain everything? Fine: Chem on a mall rat: Uuh?

"Chem on a mall rat: Uuh?" is an unlikely sentence and an unlikely sight, except perhaps for participants in National Chemistry Week, an annual outreach celebration that ran from Oct. 16-22, 2005 and put members of UVM's Department of Chemistry into the Burlington Town Center Mall (and the ECHO science center) for color-changing, smoke-generating, frozen-banana-nailing "chemistry shows."

In addition to the demonstrations, Associate Professor Willem Leenstra devised a fiendish chemical prose contest for this year's festivities, challenging participants to write by stringing together symbols from the periodic table of the elements. (In fact, this story was entirely composed using element symbols, with portions even written in periodic table pirate talk, much like this: I LiEs.)

The contest awarded on Oct. 28 $100 prizes for the longest and most creative passages. The contest was prominently featured in the Seven Days newspaper and attracted plenty of entries. "We really got some creative responses from nonchemists," Leenstra said.

UVM faculty members Martin Case and Dan Savin, as well as undergraduate and graduate chemistry students, also participated in the week's chemical demonstrations, which were conducted under the auspices of the Vermont section of the American Chemical Society. Leenstra says the events were a lot of fun, and great outreach, but he's packing away his colored dusts, flashy titrations, liquid-nitrogen-forged banana hammer and other tricks for another year and returning to his normal physical chemistry and spectroscopy research barring exceptional circumstances. "I could practically have another full-time job doing the shows," he laughs.

Angie Gatesy

Heart of Glass

UVM news release date: 09-27-2005 by Jon Reidel from the View

Angela Gatesy (left), a scientific glassblower for more than 20 years, shares her skills with senior Laura Krusheski. (Photo: Bill DiLillo)

The threat of catastrophe loomed over the first two months of Angela Gatesy's scientific glassblowing apprenticeship. She occasionally lost sleep imagining the possible consequences of a subtle mistake – like a faulty piece causing dangerous liquids to mix and explode. Alleviating her fears was the knowledge that she was being taught by Roy Clark, a renowned glassblower who had been turning out scientific apparatus at UVM for more than 30 years. The four years in the early 1980s that Gatesy spent under Clark's tutelage, who still stops by the shop today despite his 88 years, allowed her to continue the university's tradition of employing an in-house glassblower to create and repair the various glassware needed by professors in the midst of time sensitive scientific research.

"I learned from one of the best," says Gatesy. "I felt a big responsibility taking over after Roy. He smoked a pipe right next to a big torch he used (for glassblowing). I had smoke in my face; I didn't know if I could handle it. But Roy was great. There were very few women glassblowers at the time and Roy never questioned me being a woman."

Gatesy, still one of a handful of female scientific glassblowers nationally, is a crucial part of a department that thrives on research and depends on highly specialized kinds of Pyrex glassware capable of handling particular manipulations of gasses and liquids.

"There are things that occur every day that she fixes or designs," says William Geiger, a professor of chemistry who requires students in his Advanced Chemistry Lab course to learn basic glassblowing techniques from Gatesy. "Without her we'd have to send out for glassware, which takes time and is expensive. Having her on-site allows us to immediately fix any potential problem. She's a huge asset."

Industrial arts 101: Walking into Cook A213 feels more like a 1950s era high school industrial arts shop. A red neon sign designed by Gatesy greets you with the words "Glass Shop." Beakers, tubes and other functional items intermingle with more artistic creations, such as goblets made by the occasional art student that Gatesy takes on. Her current charge is Laura Krusheski, who is trying to start a glassblowing program within the art department.

Gatesy says she mostly teaches chemistry students "glassblower appreciation," but knows that as professionals they'll need to have some skills for special circumstances, like breaking something while working over the weekend in the lab. "Every chemist should learn how to do simple manipulations with glassware," says Geiger. "One comment I can rely on from students is that they really liked the glassblowing part of the course. They'll find as they advance in their careers that they'll be designing more complex things that start with basic glassblowing skills."

Most of Gatesy's instruction and work is conducted on a large lathe, which is more delicate than a machinist or woodworking lathe, and according to Gatesy, functions more like a sewing machine. Gatesy uses Pyrex, a popular material due to its lower co-efficient of expansion compared to the older softer glass that Clark jokingly says "cracks when you look at it," to construct the multitude of contraptions professors ask her to create. Sometimes they give her a crudely drawn diagram of a prototype or verbally explain what they need. Once the glass reaches about 1000 ºC (2000 ºF), Gatesy has just a few seconds to bend the glass into the requested shape, or into one of the vacuum manifolds, pieces of distillation equipment, or round bottom flasks she also makes.

"There are two critically important factors to being a good glassblower: technical skills and personal interactions," says Geiger. "The successful glassblower is able to translate their skills into an aid for the experimentalist. In part, Angela's strength comes from how easy it is to interact with her. Not all glassblowers have this ability."

The coveted glassblower: Historically, many chemistry teachers were also skilled glassblowers. Clark learned from longtime UVM chemistry professor Phil Baker. The highly skilled scientific glassblowers were valued enough in the 1940s that they were spared from going to war, although Clark enlisted during WWII on his own anyway. "They were seen as too important to go to war," he says. "It's a much more exact science than artistic glassblowing. When you make something it's supposed to work."

Clark, who started working at UVM in 1939 as a ditch digger, was recruited to help set up labs at the university after it was discovered that he had taken chemistry courses in high school. The U.S. government started allocating large sums of money for scientific research at universities after Sputnik was launched in 1957, spurring the need for scientific glassblowers. Clark, who took over on a full-time basis after receiving training from Baker and at workshops, says a university glassblower is needed now more than ever.

"Not having a glassblower would cost the university a fortune," he says. "It's expensive to send away for glassware, especially the specially made items that Anglea makes. The amount of time that would be wasted would be costly to both the researcher and the university. Angie is worth her weight in gold," he says.

Honors Day  4/22/2005

Senior Chemistry Awards at the College of Arts & Sciences Honor's Day Program, April 22, 2005

Shown in photo: Associate Dean of the College and Associate Professor of Chemistry Joel Goldberg, Kelly Perry, Professor and Chair of Chemistry Dwight Matthews and Tom Matthews

Graduating senior Kelly Perry received the American Institute of Chemists Award given to the outstanding senior B.S. degree chemistry major.

Graduating senior Thomas Matthews received the Charles E. Braun Award given to an outstanding senior chemistry major.

Kelly graduated with a B.S. degree in chemistry in May 2005 has begun studies towards a Ph.D. degree in chemistry at Rensselaer Polytechnic Institute (RPI) fall 2005.

Tom graduate with a B.A. degree in chemistry and a B.S. degree in biochemistry in May 2005. He began studies towards a Ph.D. degree in chemistry at Duke University fall 2005. Professor Matthews is also the proud father of son, Tom.

In the panel below, Professor Matthews presents the closing remarks to the College of Arts & Sciences Honors Day program.

Honors Day 2005 closing remarks

Prof Matthews 4/2005
Photo by William DiLillo

Professor Matthews Named University Scholar for 2004-2005

UVM news release date: 04-29-2004 and 04-06-2005 by Kevin Foley from the View

University Scholar Dwight Matthews gets energized by challenging the "ratma" of his field. This term requires a full explanation, one that Matthews, a professor of chemistry and medicine, offered on April 7, 2005 at his University Scholar lecture titled "Measurement of Protein and Amino Acid Metabolism in Humans." The lecture is a traditional part of the University Scholar award, a program in which up to four distinguished professors are recognized for sustained excellence in research and scholarly activities.

Prof. Matthews offers a brief explanation of his whimsical term for the vast gulf between metabolism in the human body and the function of proteins and their building blocks in rapidly growing laboratory animals. "Much of the work you see on the biochemistry of metabolism refers back to E. coli bacteria, rats or mice.  E. coli isn't us. And there's no comparison between man and rat," Matthews says. "Although some men may be rats, man in general is not a rat. And we've demonstrated that quite clearly." Getting a handle on the human body's complex and complex dance of creating and breaking down proteins is important, Matthews says, because the processes are essential to life. And they're also affected by disease; AIDS, for example, wastes muscle. Understanding the subtleties of how that happens could offer insight into reversing it. This kind of understanding is difficult to come by. Matthews's primary technique for learning more about the complex interaction of hormones, amino acids and protein in the human metabolism is stable-isotope mass spectrometry. Matthews and his colleagues administer doses of purified and enriched stable isotopes in tracer amounts to human subjects. They then use the isotopes as tracers for particular compounds to understand the flows and kinetics of how particular substances (often protein, or amino acids, which form proteins) are produced, disposed and converted.

Matthews has been refining his techniques since graduate school, when he developed pioneering hybrid gas chromatography-mass spectrometry instruments that let him analyze these enriched stable isotopes with an unprecedented degree of precision. Because the isotope-enriched compounds have greater mass than normal compounds, the techniques he developed let him unravel the 20 or more amino acids that might be present in a sample of blood and discern very fine differences in enrichment. Before UVM, Matthews pursued his research on the faculty at Washington University School of Medicine in St. Louis and the Cornell University Medical College in New York city.

Make or Break Question: Stable-isotope analysis is important - and dogma, er, ratma-challenging - because it is one of the few ways to directly measure metabolism in humans. Many crucial metabolic processes happen in organs like the liver, so measuring them would demand highly invasive or dangerous techniques. Stable-isotope tracers can often reveal crucial processes through safe and comparatively noninvasive techniques like muscle biopsies. "The human piece is the most difficult and satisfying part of doing this work. You're limited by what you can and can't do," Matthews says. "With rats, you can get access to crucial tissues, or genetically 'knock-out' certain traits." The fundamental limitations of human research, Matthews says, pushes him to develop a host of "little tricks" to understand the subtleties of what goes on deep within the human body. The field has a host of stimulating complexities, from managing expensive and sometimes cantankerous instruments, to designing experiments and identifying and labeling compounds to measure specific (and often poorly understood) metabolic events, to preparing biological samples for mass spectrometry.

An example of one variety of "trick" Matthews uses lets him compare amino acid metabolism in the liver and the gut. He might give a subject a tracer both intravenously and orally, then measure and compare the dilution of the tracers in the blood. The difference lets him calculate the work done by the liver and the work done by the gut. This in vivo work still regularly challenges textbook notions of human metabolism and often directly contradicts what is known of rat physiology. In rats, for example, insulin increases protein synthesis - for humans, the opposite is usually true. Leucine, an important protein stimulator, also functions differently in animals than people. Leptin, a highly publicized hormone that regulates weight in rats, was once thought to be a key to developing obesity treatments for humans, but so far hasn't panned out. Matthews finds these disjunctions between the theoretical and the real amusing at times - and intellectually stimulating.

"The biochemistry of metabolism is fascinating. There are all these little pathways, and you can pick up a book and they'll sketch them right out for you and it will tell you exactly how an amino acid is degraded, and then you start to look at it in detail, and the book is completely wrong," Matthews says. "That's what's fun for me, when you really start understanding for the first time what's really going on in people." Now Matthews is turning some of his attention and expertise to the emerging field of "proteomics," which quantifies the expression of proteins and has many applications in clinical research.

LaFranchi & Petrucci
Photo by William DiLillo

Every Breath We Take

July 2004 by Lynda Majarian from the View

"When you think of air, you don't think of solids," says chemistry graduate student Brian LaFranchi. But the air we take in contains millions of solid particles, each about a hundredth of the width of a single human hair. These particles, in turn, are made up of thousands of chemical compounds that regulate global cooling and influence human health. Scientists have long studied inorganic particles, comprised mainly of sulfates and other salts. Giuseppe Petrucci, assistant professor of chemistry, believes organic particles – made up mainly of carbon and reactive oxygen compounds – deserve the same degree of consideration.

Organic particles are very reactive to atmospheric gases such as ozone and other pollutants, and these chemical reactions can greatly amplify the toxicity of these particles to humans and the environment. Car exhaust, emission from factories and power plants, diesel fuel, trees and even meat burned on the barbecue grill create "particulate pollution" that leads to increased rates of heart and lung disease, as reported last year by the Journal of the American Medical Association. Of special interest to health professionals is the emerging connection between particulate pollution and aggravated asthma in young children.

Petrucci and his team of four graduate students (including LaFranchi) are currently conducting research on the analysis and atmospheric chemical reactivity of organic particles. "We are developing a unique laser-based scientific instrument that will allow scientists, for the first time, to analyze these important particles directly," Petrucci explains. Using a custom-built particle mass spectrometer, the team samples particles from aerosols they generate in the lab. The particles are then measured and put through a detailed chemical composition analysis. Petrucci has a provisional patent for this method and is forging partnerships with both industry and other universities to utilize his technology to the fullest. "The immediate goal of our research is to develop our method as a real-time means of monitoring prevalent potentially toxic organic pollutants, he says. "The ability to take better measurements could provide the federal Environmental Protection Agency with more reliable information with which to set air quality standards, and help improve models to predict global climate change."

"We are in the process of putting together a prototype instrument to make measurements in the field this fall. We will be measuring organic particles at the Burlington waterfront, in several local neighborhoods and remote rural sites," he says. "People may be surprised to learn how quickly, depending on weather patterns, toxic particles can easily spread to the countryside." Recent epidemiological studies have identified an association between increased hospital admissions and particulate pollution. Can organic particles generated at the Burlington waterfront, for example, affect the environment across the state? A field instrument could reveal the answer.

Steven Flemer

Stevenson Flemer, Jr., Named the University of Vermont Graduate College Graduate Teaching Fellow of the Year for 2003-2004

May 2004

The Graduate College annually accepts nominations from departments offering graduate programs for outstanding graduate teaching fellows. The fellows are exemplary for their performance in and out of the classroom and laboratories. This year the Department of Chemistry was proud to nominate Steve Flemer, a graduate student in organic chemistry who works with Professor Madalengoitia.

Steve has taught a number of different laboratory sections for a variety of courses at UVM over the years he has been here. He has simply been outstanding in his level of enthusiasm and commitment to students. One former student summed it up succinctly: "Steve is awesome; Steve rocks." Steve has also worked with Prof. Strauss to prepare videos of the organic laboratory experiments. The videos prepare students for what they will be doing in the laboratory prior to their actual work in the laboratory. The videos provide a much more graphic and realistic description of the procedures to be used and familiarize students with the proper and safe techniques to conduct the laboratories. Students prefer the videos to dry words on a page - especially when Steve is the star of the video. Other teaching fellows also watch the videos to improve their own teaching skills from Steve. The Department of Chemistry is very proud that Steve was selected Graduate Teaching Fellow of the Year for 2003-04 by the Graduate College; it is indeed an honor to be selected.

Steve will be finishing his Ph.D. in chemistry this summer and would like to continue teaching. The Department of Chemistry is thrilled to be able to retain the services of Steve after he completes his degree. He will be hired as a lecturer in chemistry for the academic year, starting fall 2004, and will be teaching undergraduate chemistry -- exactly what he enjoys doing.

John Pigott & friend

There Is More To Being a Chemistry Major Than Just Chemistry

May 2004

John Pigott is just finishing his junior year at UVM with many accomplishments. Firstly, he is coming off a very difficult academic semester taking several courses in chemistry and working to complete his animal science major (as a chemistry/animal science double major), but he is also an accomplished equestrian. John describes his life as "a serious challenge in time management." However his time management skills have paid off. John shared the honor of being named outstanding sophomore in Chemistry last year and has shared the award this year being named an outstanding junior in Chemistry.

John is also out riding four days a week with the UVM Equestrian team. But he does more than ride. He has competed in the Intercollegiate Horse Show Association National Championships in May in Murfreesboro, Tenn. for the past two years. In 2003 and 2004, he competed against 400 other riders from colleges and universities nationwide in the individual open fences class competition and also won the Cacchione Cup, awarded to the competitor with the most overall points -- the first time that a rider from Northern New England has ever won the prestigious Cacchione Cup.

"This championship is comparable in depth and breadth to any NCAA final, pitting the country's best collegiate riders against each other," says equestrian team coach Madeleine Austin. Some 7,000 students from more than 340 colleges and universities work their way toward the Intercollegiate Horse Show Association Nationals. About 400 equestrians compete at the national level. To qualify for national competition each year, Pigott has worked his way up through regional and then "zone" competitions. , and spends many hours each week with the team.

The balancing act for John is finding the time for his equestrian activities while simultaneously pursuing his studies in chemistry and animal science. Given his successes in all of these fields to date, it appears that he has his balance.

Photo by Sabin Gratz

Program offers $8 million grant to Vermont

May 20, 2003 Burlington Free Press – Sue Robinson. See the full newspaper story as a PDF file.

Christopher Landry, a University of Vermont chemistry associate professor, and his two partners in New York and Texas picked Vermont for their new venture largely because of a federal program that gives Vermont businesses money to get started.

"We thought, 'Here is this great opportunity in Vermont so why don't we set up there?'" Landry said. "It sounded like a great way to get off the ground." First, the group has to win the grant. Landry and his partners spent more than a month formalizing their chemical filtering business in the hopes of taking advantage of a rigorous and competitive program that has grown in money and popularity over the past year.

Funded by the National Science Foundation and other federal agencies, the Experimental Program to Stimulate Competitive Research (EPSCoR) offers grants in five sub-programs to 22 rural states. This year, Vermont has a three-year, $8 million grant, an increase from $3 million in previous years. One of EPSCoR's five projects is called the Small Business Innovative Research Phase 0. The project, created 11 years ago by a professor from St. Michael's College and another from UVM, has served as a national model, said Christopher Allen, Vermont EPSCoR project director. EPSCoR's primary mission is to offer Vermont start-ups and small businesses money to get ready for larger federal grant programs, such as the SBIR program. Under SBIR, applicants have a chance at up to $750,000.

The Phase 0 program is expanding. This year Vermont EPSCoR received 36 applications for the program, which provides $10,000 grants, compared with 23 in 2002, Allen said. He attributed the increase to the growing awareness of the program and to more laid-off workers turning to entrepreneurship. Allen is hoping to expand the grants from 10 a year to 15.

The initial $10,000 should help innovators perfect their products, do last-minute experiments, develop business plans and otherwise prepare for a more intensive federal grant process. Since 1984, 49 companies have received more than $35 million in SBIR money in Vermont. Most of those companies had their start with the Vermont program, said Paul Hale, executive director of the Vermont Technology Council, who serves on the EPSCoR board.

Landry and his partners want to use the money to tweak their product: a chemical filter aimed at helping pharmaceutical companies isolate drug-making byproducts. Their application will first be reviewed by three volunteers who are experts in the subject. The three reviewers will meet with 27 others at the end of May in a daylong session to look over each application. Only after that meeting will Landry find out whether he's on his way to free money. "I am a little on edge. My experience with grant writing has been that it is not a sure thing," said Landry, who has applied for other research grants as a professor. "This one is a bit more personal."

Discover Magazine says UVM Prof. Martin Kuehne's Drug May Bring An "End to Craving" for Addicts

Keuhne molecule 1
Keuhne molecule 2

May 2003 by

Martin Kuehne, Emeritus Professor, synthetic work of complex alkaloids has culminated with production of better versions of vinblastine and vincristine, compounds that attack leukemia. That effort, which concluded in the late 1980's, could have been a coda to a successful career. But as that drive ended, Kuehne became interested in another alkaloid, ibogaine, an unpredictable and dangerous derivative of an African bush that seemed to have powerful anti-addictive properties – and a range of dismal side-effects ranging from hallucinations to whole-body tremors. "We had succeeded nicely with the very challenging vincristine problem, and in the process we leaned a lot of chemistry which could be applied to ibogaine," Kuehne says. After several years of work, Kuehne synthesized the compound in the late 1980's and, through a process of molecular stress-testing, his group drew on the alkaloid literature to make a number of variations of ibogaine that might have the original compound's anti-addictive powers without the unwanted effects.

Kuehne then approached Stanley Glick, an expert in anti-addiction pharmacology at Albany Medical College, to begin testing the compounds on rats. In the 13 odd years since, one of Kuehne's variants, 18-methoxycoronaridine (18-MC for short), has shown a remarkable ability in lab experiments to reduce drastically and immediately rats' cravings for opiates, cocaine, nicotine and methamphetamine. It also reduces withdrawal symptoms when they stop using the drugs, and it does this without causing tremors and other dramatic side-effects.

The substance has never been tested on humans – though a venture capital group is now trying to raise money for a trial involving clinicians at Columbia and New York Universities – but it nevertheless was the primary subject matter for a May story in Discover magazine, which billed it as "the end of craving." Kuehne says a single dose of the drug, in many cases, is enough to break the addictive spiral in animals. The compound's pharmacological effects are still being explored, but it seems to have little direct effect on dopamine, a brain chemical targeted by most other anti-addiction drugs. Instead, Glick's research shows that 18-MC operates on an entirely different pathway, the habenulo-interpeduncular, one little investigated by pharmacologists working on chemical answers to addictions. The compound's action is highly specific; unlike ibogaine, which blocks the action of multiple brain receptors, 18-MC targets only one crucial neuron, which contributes to its relatively few side effects.

Is 18-MC potentially, as Discover speculated, a miracle drug for addicts?

Prof. Kuehne cannot be sure, but he's optimistic. If the expensive and intricate process of getting a clinical trial off the ground succeeds, he thinks there is "good reason" to believe it would succeed. But the road has been long and difficult, and Kuehne is painfully aware of the hundreds of potential financial, regulatory and scientific problems that can stop a promising compound from becoming a marketable drug. UVM's patent on his vinblastine/vincristine variants, work that was at once fantastically difficult and highly successful in the lab, has not proven commercially viable. He is hopeful about 18-MC's potential, and he is coming to work every day, despite retirement. "I'm still here working, because I really want to see this come to fruition," he says. "I have thought for many years that this would be beneficial to mankind."

UVM Prof. Chris Landry is building super ceramic materials to neutralize chemical weapons safely

Prof. Landry

May 2003 by

Surface area is to porous ceramics what mojo is to blues singers – a crucial commodity, the more plentiful the better. Chris Landry, Associate Professor of Chemistry, is putting this mojo to work in the worldwide fight against chemical weapons: He's developing ceramic materials that can easily and safely neutralize mustard gas stockpiles. "There are huge existing stores of chemical weapons throughout the world. It poses environmental challenges, even a risk of terrorism. We have to get rid of this stuff," Landry says.

The conventional method for disposing of unconventional materials is incineration. But even the best disposal furnaces leak traces of the chemicals into the environment. For mustard gas, this probably isn't dangerous; but nerve gas is harmful at miniscule parts-per-billion concentrations. Burning weapons also produces nasty atmosphere-thickening greenhouse gases. And if that weren't enough, there's another problem: No one wants to live in a townhouse anywhere remotely close to a chemical weapons barbecue.

A better approach?

One possible answer, Landry thinks, lies in a deceptively humble pegboard and beaker concoction in his first-floor Cook laboratory. The machine lets Landry and his team bubble "half-mustard" (a variant of mustard gas that "tastes" compositionally similar, but is less killing) into a tube with ceramic pellets made in the laboratory. Adding a metal catalyst swiftly breaks down the active ingredients of harmless half-mustard (and, presumably, those of dangerous real mustard gas) into benign byproduct chemicals found naturally. A production model of the equipment, Landry says, could be small and simple enough for soldiers to use in the field.

In Landry's laboratory, byproducts of the reaction are shunted into a gas chromatograph that analyzes the components of the gas and typically determines that the reaction consumes about 99% of half-mustard's active ingredients in lab conditions. The exhaust is then grabbed safely by the lab's fume hood.

Three years into the research and with the process working beautifully with the ersatz chemical, Landry is hoping in the near future to put his ceramics – and his recent additional grant of $500,000 in funding from the Department of Defense – to work in neutralizing the real thing. "It's tremendously exciting," Landry says. "We're at the point now where we're working to convince a government lab to try the process with real mustard gas so we can test effectiveness under controlled, safe conditions."

Ceramic superstars

Mustard gas isn't the only potential target for Landry's specially tailored ceramic super-surfaces. Other chemical weapons substances may prove amenable to variations of the basic neutralization approach. Perhaps at some point in the future, the ceramics may prove to be an effective and economical way to reduce greenhouse gases produced by industry. "This kind of process is in industrial use right now scrubbing the exhaust from coal plants. That's where we borrowed the idea," Landry says. "But the industrial scrubbers are not nearly as effective as what we're working with here."

Other threads of Landry's research, which involves a team of four graduate students and an undergraduate, involve investigating the appropriateness of the materials for use in chromatography, which might allow for the incredibly fine separations of desired chemicals necessary in pharmaceutical development. Another strand looks at using the materials for delivering certain drugs more effectively and precisely. "The key is the extremely high surface area of the materials we work with," Landry says. "A gram of rock you pull out of the ground might have 30 meters-squared of surface area. The stuff from our lab has 11,000 m2/ g. It gives you that much more surface that you can use."

New large pore zeolites developed at UVM lead to advanced separations technology

Macroporous zeolitic frameworks like those shown at left offer an array of new material properties.  Formation of host-guest complexes and the large surface area of molecularly porous structures greatly improves the ability of the zeolite to assist in the separation of complex mixtures.  The Landry group is pursuing the commercialization of these macroporous zeolitic compounds for use in chromatographic applications like high pressure liquid chromatography (HPLC) separation of complex pharmaceutical intermediates.

Prof. Krapcho's anticancer compounds developed at UVM begin clinical trials

Krapcho drug molecules

December 2002

A. Paul Krapcho, Ph.D., is a research-active emeritus professor in the Department of Chemistry who has been synthesizing organic compounds for several decades at the University of Vermont. His purpose has been to produce anti-cancer agents. Prof. Krapcho has seen several of his compounds progress into testing stages during his career. Although Prof. Krapcho is no longer taking new graduate students, he remains active in his research laboratory synthesizing new compounds for specific targets. Prof. Krapcho embodies organic chemistry at the University of Vermont, and his successes today of compounds in clinical trials reflect work performed several years before. It takes time for a prospective compound to advance from synthesis in the laboratory to clinical testing for efficacy. Today, other young faculty in Chemistry at the University of Vermont are following in Prof. Krapcho's path. For example, Prof. Gregory Friestad has gotten his career off to a very good start with respect to synthesis of several key classes of compounds.

The following text was abstracted from a Novuspharma press release with respect to the drug that was designed by Prof Krapcho:

Novuspharma SpA of Bresso, Milan, Italy ( announced on December 2nd, 2002 plans to begin a phase I trial of pixantrone (BBR 2778) in patients with multiple sclerosis (MS) in early 2003. Novuspharma is an Italian biopharmaceutical company primarily focused on developing new cancer therapeutics. The trial is expected to recruit 15-20 patients in Europe. The main goal of this study is to define the dose of pixantrone to be used in longer-term clinical trials and to obtain preliminary activity data. Patients will receive four infusions of pixantrone every three weeks. The effect of pixantrone on patients' brain lesions will be assessed by magnetic resonance imaging (MRI) at the start of the trial and at two, four and six months thereafter. Additional endpoints will include general safety and tolerability and number of pixantrone infusions required to induce significant lymphopenia (a reduction in the white blood cell count, pixantrone's primary mechanism of action in this indication). Pixantrone is also currently in phase III studies for the treatment of non-Hodgkin's lymphoma.

A summary of pre-clinical data for pixantrone has shown in a rat model of chronic MS that pixantrone was effective at preventing disease relapses and reducing white blood cell counts and suggested it was possibly more efficacious than mitoxantrone. Currently mitoxantrone, an immunosuppressant drug, offers the only treatment option for many patients with rapidly progressing forms of MS. However, its use is limited to 2-3 years due to its cumulative cardiotoxicity. This study also suggested an almost complete absence of cardiotoxicity compared to mitoxantrone. In addition, new data for pixantrone in a chronic model in mice demonstrated that pixantrone was highly efficacious at preventing disease development, as well as being better tolerated than mitoxantrone. Mitoxantrone is currently the only treatment option

Multiple sclerosis (MS) is a neurological disorder affecting approximately 1.5 million individuals worldwide. The disease normally starts in early to middle adulthood and is second only to trauma as the leading cause of neurological disability. The disease derives its name from the multiple areas of scarring that are found in the brains of affected subjects. Symptoms include weakness of the limbs, spasticity, bladder and gut dysfunction and disturbances of gait, vision and speech. MS is highly unpredictable and can vary from a benign illness to a rapidly evolving and incapacitating disease. The two commonest forms of MS are relapsing-remitting disease, which affects around 45% of patients and secondary progressive disease, which affects around 40% of patients. The majority of patients with relapsing-remitting disease progress to the secondary progressive form, although the time to progression is very variable.

Pixantrone (BBR 2778) is a DNA intercalator with improved efficacy and safety that Novuspharma is developing for non-Hodgkin's lymphoma (NHL). NHL is caused by the abnormal proliferation of lymphocytes (immune system cells) and 160,000 patients are estimated to be suffering from the disease in the US alone, projected to grow to 250,000 by 2007. Pixantrone has produced encouraging results to date, both from preclinical studies and from clinical trials

Last modified April 23 2010 07:46 AM

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