Students Learning to Manipulate Molecules at University of New England

Chemistry students at the University of New England (UNE) in Biddeford, Maine are learning how to make a better molecule -- meaningful work that has the potential to influence both medicine and the environment. But while their Professor, Dr. Amy Deveau, may end the school semester by grading them on their project, she really delights in knowing that her students are getting their “wings” to fly solo as skilled researchers adept at using scientific methods.

“Students learn to use deductive reasoning, and that going from A to B is not necessarily a straight line,” she said. “The ‘cookbook’ type approach is not something I want for my students. Research is discovery-based.” Deveau shares her enthusiasm and expertise in small molecule design, synthesis, and spectroscopic characterization in the area of medicinal chemistry, with a focus on applications to chemotherapy and pain & addiction. Her research interests combine chemistry and biology, but she turned to teaching undergraduates when she found how much she enjoys “seeing the light come on” in her students’ eyes when they learn something new and develop an independent passion for their work.

Discovery-based research with published results

Two of Deveau’s research students prepared posters selected for presentation at the Spring 2008 American Chemical Society (ACS) conference in New Orleans. Andrea Pelotte (class of 2009) and Nancy Costa (class of 2008) explained their work in the Alfond Center for Health Sciences chemistry lab, where they perform their experiments with the familiarity of budding chefs in a professional kitchen. From their hooded workbench they select compounds contained in round bottom flasks, transfer them to TLC plates, chromatography columns, or NMR tubes, then run them through a series of analyses. These analyses always end with using the Nuclear Magnetic Resonance (NMR) spectrometer that is situated in a corner room inside the lab. They are as familiar with the NMR as they are their laptop computers, and they tirelessly perform experiments to get confirmation or, more likely, new data that raises more questions that need to be answered by more experiments.

“NMR teaches you how to accept failure – nothing is easy when you’re removing oxygen here and putting on hydrogen there. You just learn to accept it and have patience. We have a love-hate relationship with the NMR. It doesn’t lie,” said Costa, who traveled to New Orleans to present her poster on research to identify the “greenest and most cost-effective method out of three proposed synthetic approaches to make ethyl(4-phenylphenyl) acetate.”

Costa and Pelotte, working both together and separately, have become adept at manipulating molecules, swapping one atom for another, hiding groups that they want to stay attached, while giving other groups of atoms permission to leave so they can be replaced. They discuss “leaving groups” and “protecting groups” -- for example, adding a benzyl to a molecule so they can hide the alcohol group temporarily – as though they could actually see these building blocks of chemistry and our world.

Their designs on the molecular level have real potential applications, and Deveau believes so strongly in their work that she and students have filed for grants to support further research.

Real world benefits for drug dependency

Pelotte’s honor’s thesis research has far-reaching health benefits and is presently supported through UNE Provost’s and College of Arts and Sciences mini-grants (note: past work on the project was supported by the American Society for Pharmacology and Experimental Therapeutics and the UNE-COM Dean's Research Fellowship). The goal of Pelotte’s research is to develop new opioid antagonists that can be used to treat narcotic addiction, and to help manage the negative side effects of opioids when they are used as pain relievers. Her team conducted research to identify analogs of the mu-opioid receptor antagonist 6ß-Naltrexol. Because the mu receptor plays a role in pain and addiction mechanisms it is a common target for drugs trying to treat these conditions.

Structures of naltrexol, naltrexamide, and morphine and that target the mu-opioid receptor.

The challenge was to design molecules that both target specifically the mu receptor and also interact with this receptor in a particular way. “There are two primary types of receptor agonists –inverse agonists and neutral antagonists,” she explained. “We are looking for compounds that are neutral antagonists.” Deveau and her collaborators believe that a neutral antagonist might help reverse a patient’s dependence on a drug like morphine while minimizing withdrawal symptoms and other undesirable side effects.

Professor Deveau further explained: “The signaling in the brain with opioid receptors is complex. Over time, higher doses of drugs are needed to cause the same medical benefit.” However this is a Catch 22. “Patients also become increasingly dependent on a drug at higher doses. Higher doses of mu receptor agonists like morphine can depress a patient’s airway and cause other negative effects on the body, such as gastro-intestinal distress.”

Screening the compounds

When designing their project Professor Deveau employed two promising mu receptor antagonists 6ß-naltrexol and 6ß-naltrexamide, as structural blueprints. Starting from naltrexol, she and students then modified its structure in the lab; six carbamate and sulfonate derivates were synthesized that do not contain a protic group at carbon 6. Additionally, they characterized these derivatives using 1H and 13C NMR, IR, and mass spectrometry. Presently they are screening these six compounds in in vitro and in vivo models for pain and addiction to characterize the efficacy, potency, and receptor subtype selectivity. Although the testing is still ongoing, Deveau and her students are very encouraged by their preliminary results. To see the poster presented at ACS 2008, click here.

Research inspires further learning

Pelotte has decided to combine her interests in biochemistry and medical biology, and majors in both. A resident of Maine, she plans to continue working on her special research project over the summer and into the following year.

“Most of the real work gets done in the summer,” Deveau explained. “Students learn that they can’t always leave an experiment until after the next class; they have to deal with most experiments immediately when they finish.”

Costa, who graduated in 2008 with a B.S. in Medical Biology, is a Long Island native who plans to return in the fall of 2009 as a medical student in UNE’s College of Osteopathic Medicine. Her research concluded with her paper on green chemistry for the undergraduate laboratory. This paper details ongoing work in the area of chemical pedagogy and efforts to make organic chemistry lab experiments at UNE more environmentally-friendly. She collaborated with Pelotte and two organic chemistry instructors at UNE as well as Dr. Deveau.

Going green

This research compared three green approaches for suzuki couplings, powerful chemical reactions that create bonds between two different carbon atoms and are commonly employed in academic and industrial research. Costa and collaborators then involved chemistry students who ran the three different reactions using Bmim[PF6]/Water, Acetone/Water, and Water with TBAB. Reaction progress was monitored using thin layer chromatography and spectra were obtained on the ECX-300 NMR in the lab, or on the ECA-400 at JEOL, 80 miles south of the University of New England in Danvers, MA.

“We got mixed results depending on student technique,” she said. “While some students achieved one hundred percent conversion, some had starting material left.” They are using NMR to determine the percent of starting material remaining, but so far have identified acetone and water as the most cost-effective method. Currently, the cost per experiment is around $2.00 and there is the added issue of disposing of any remaining starting material. “Although the ionic liquid was the most expensive, it is important to note that the solvent with the catalyst can be recycled, thus reducing experimental costs and environmental impact.” To see the poster presented at ACS 2008, click here.

UNE program designed for meaningful research

Designing experiments, working with microscale concentrations, and manipulating molecules take on real meaning in Deveau’s laboratory, where students learn the vocabulary and science of chemistry, but also learn to be researchers who pilot their own programs with her help. “We’re not dealing with post-docs who have ten years of chemistry training. Thus, it is particularly important to design a program so students can complete meaning portions of their research project in relatively short amounts of time. I do my best to teach students to be independent thinkers and train them so they can jump off and have wings.”

Deveau has been teaching at UNE for the past six years, and has seen the Chemistry & Physics department grow from six to fifteen full time professors. The Chemistry & Physics department is housed within UNE’s primarily undergraduate college, the College of Arts and Sciences (CAS). UNE has long been recognized as a leading educator of healthcare professionals through its College of Osteopathic Medicine (COM), College of Health Professions (CHP), and its newly established College of Pharmacy (CoP).

UNE’s University Campus in Biddeford, Maine is located on the Atlantic Ocean and is home to CAS, COM, and a nationally-known marine science education and research center. The Westbrook College Campus in Portland, Maine houses the CHP and CoP and is designated a national historic district. This campus is quintessential New England, with a central green surrounded by classic brick buildings.

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