Chris Arumainayagam - Surface Science and Catalysis (email Professor Arumainayagam)

Research Interests: My area of research, investigating the interactions between molecules and solid surfaces, is a field that has developed extensively in only the past 25 years. Surface chemistry plays a crucial role in a wide range of technologically important problems, including catalysis, corrosion, semiconductors, adhesion, and lubrication. The primary focus of my research has been the application of surface science techniques to the understanding of catalysis. Reactions are studied on single crystal surfaces with well-ordered arrays of surface sites with well-defined atomic structure and chemical composition. The experiments are conducted in an ultrahigh vacuum (UHV) apparatus (pressure equal to 10-13 atmospheres) to prevent contamination from unwanted background gas adsorption.

Recently, at Wellesley College, we have pioneered a technique for studying radiation chemistry with surface science methods. Radiation chemistry involves the study of how high-energy particles (e.g., electrons, protons, a particles) and high-energy photons (e.g., x-rays and g-rays) interact with matter, inevitably causing ionization. Radiation chemistry has numerous applications, including sterilizing food, treating sewage sludge and exhaust gases, and treating cancer. My students at Wellesley and I have demonstrated that the exposure of nano-scale thin films to low-energy (< 55 eV) electrons under ultrahigh vacuum conditions followed by temperature programmed desorption (TPD) is a new method of investigating radiation chemistry.

Student Projects:

1. In conjunction with isothermal experiments, post-irradiation temperature programmed desorption experiments were used to identify eight previously known radiolysis products of methanol. The utility of the method was demonstrated by the identification of a previously unknown methanol radiolysis product: methoxymethanol (CH₃OCH₂OH). Moreover, this technique allowed study of the dependence of the radiation product yield on initial electron energy, providing additional insight into the physical processes underlying radiation chemistry of methanol.

2. Temperature programmed reaction spectroscopy (TPRS) experiments conducted at Wellesley have demonstrated a new reaction pathway for reactions of ethylene glycol (HOCH₂CH₂OH) on metal surfaces. Ethylene glycol undergoes direct intramolecular elimination on Mo(110) involving selective C-O bond scission, resulting in the evolution of gaseous ethylene (C₂H₄) at temperatures below 400 K with ~ 90 % selectivity.

3. We are currently studying the reactions of formaldehyde on clean and oxygen-modified Mo(110). Our results demonstrate that gas-phase ethylene is evolved from formaldehyde reaction, providing an unprecedented example of carbon-carbon bond formation on clean Mo(110).

4. We plan to use the post-irradiation temperature programmed desorption technique developed at Wellesley College to study the interaction of low-energy electrons with chlorocarbons such as carbon tetrachloride. This project has potential applications to electron-beam driven low-temperature plasma reactors that are currently being developed as an efficient method for on-site decomposition of hazardous organic compounds.

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William F. Coleman - inorganic chemistry, molecular spectroscopy, chemical applications of lasers, computers in chemical education (email Prof. Coleman)

Research Interests:  My principal research interests are in the spectroscopy and photochemistry of transition metal and actinide complexes. In recent years, this work has focused on attempting to understand the mechanism of energy transfer between different metal complexes, in particular our observations that the details of these energy transfer processes frequently depend on the wavelength of the initial excitation preceding energy transfer, and in multiple-photon processes in such complexes.  In the past I have also worked on developing the theory of band spreading in capillary zone electrophoresis, on developing new chemical lasers, on the role of chromium in the glucose tolerance factor, on rotational and vibrational energy transfer in small molecules.  Recently I've begun to work in the area of ab initio molecular orbital calculations.

Student Projects:  Several recent student projects have been directed at the energy transfer issue in complexes of Cr(III), Cr(VI) and the uranyl ion. Of particular interest at the moment is the question of the relationships among the absorption, emission and excitation spectra of uranyl compounds and the ways in which they affect the excited state properties of the uranyl ion, most notably energy transfer processes. Other projects have looked at multiple-photon processes in ruby and in simple uranyl salts, at developing a laser spectroscopic probe of chromium in the glucose tolerance factor and dietary supplements, at the mechanism of yellowing of artists oils in the presence of chromate based pigments, at developing computer models of complex excited state decay curves, and at molecular orbital calculations to assess the role of d orbitals in "hypervalent" compounds of second row non-metal elements. A number of students have also worked with me on the design of new experiments for use in introductory chemistry laboratory, focusing on computerized data acquisition and analysis. Six students will be engaged in research with me during Fall 1997.  Our group has a home page that is "a work in progress".  

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Michael J. Hearn - Organic Chemistry (email Professor Hearn)

Research: Synthesis of Tuberculosis Antimicrobials

Although the disease was until very recently thought to be all but eradicated in developed nations, the unexpected re-emergence of tuberculosis in neoteric, fulminant and drug-resistant strains has motivated concentrated efforts in antimycobacterial drug discovery. This discovery process has encompassed the rational redesign of existing antituberculosis compounds, as well as the unearthing of entirely new ones. The process has incorporated recent information about the chemical composition of the cell wall of Mycobacterium tuberculosis and the dormant state of the disease. We have developed general procedures for the preparation of antimycobacterials on a scale convenient for subsequent biological evaluation. These compounds are stable materials which show significant activity against Mycobacterium tuberculosis and Mycobacterium avium. Complementary spectroscopic analyses in the near-infrared (NIR) and mid-range infrared (MIR) regions offer special advantages in overseeing these preparations. For NIR, such advantages include ease of sample-handling, speed and simplicity. Estimates of pseudo-first order rate constants obtained from NIR are particularly useful in characterizing our reactions and adjusting preparative conditions. For MIR, observations of distinguishing functional group bands and selected intense fingerprint bands provide correlative evidence for completion of reaction.

Student Projects:

Preparation and Near Infrared Spectra of Pyridine Tuberculosis Antimicrobials

Preparation of Tuberculostatic 3-Acyl-1,3,4-oxadiazolines

Synthesis of New Pyridazines as Potential Antituberculosis Compounds

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David R. Haines - Synthetic bioorganic chemistry and applications of NMR to the study of bioorganic molecules (email Professor Haines)

Research Interests: A great many analogs of the natural nucleosides have been synthesized since the importance of nucleosides in the regulation of biological systems was discovered. Synthetic nucleosides have helped to elucidate mechanisms of enzyme action, and have in many instances exhibited useful pharmaceutical properties.

We have been studying several types of adenosine analogs as possible anti-tumor or anti-viral agents. Several of the compounds which we have prepared have proven to be potent antitumor agents, and tests are being conducted at the National Cancer Institute to find their ranges of activities.

Our research involves the design, synthesis and structure determinations of the compounds being tested. The structure determinations often require advanced NMR techniques for unambiguous proofs and several students have spent a significant amount of their research time perfecting and expanding on these techniques.

We are also investigating how the shapes of nucleoside analogs correlate with their biological activities. There are many instances where very slight structural changes cause major changes in the biological activity of molecules. It is reasonable that these changes may occur because the shape of the molecule has been changed. We are using NMR, including 2D NMR, to study conformations of our nucleoside analogs in the hope that patterns will be found which will allow us to better understand the requirements for biological activity.

Student Projects:

Synthesis of cyclopentenyl nucleosides as potential anti-tumor and/or anti-viral agents.

Studies of triazolo-triazoles as analogs of adenosine and inosine.

Applications of NMR to structure and conformation determinations of compounds of biological and medicinal interest.

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Sonja E. Hicks - Biochemistry, Enzyme Mechanisms (email Professor Hicks)

This laboratory is engaged in the study of the mechanism of action of mouse ribonucleotide reductase. Ribonucleotide reductase catalyzes the conversion of ribonucleotides to deoxyribonucleotides, the first committed step in the synthesis of DNA. This enzyme is controlled by intricate regulatory mechanisms and drugs targetted at the mammalian enzyme could inhibit or slow the grow of tumors while drugs targetted at the bacterial or viral reductase could inhibit their growth without affecting the host. Thus, even minor differences between reductases from various sources could be important in designing specific antitumor or antiviral drugs.

The molecular structure and cofactor requirements of reductases differ depending on the organism. Escherichia coli, mammalian and viral reductases possess an a2b2 subunit structure requiring nonheme iron. E. coli reductase has been studied extensively, and a catalytic mechanism has been proposed.

Only recently have plasmids become available for producing the mammalian reductase M2(b₂) subunit in quantities sufficient for mechanistic studies. Last year, working in the laboratories of JoAnne Stubbe at MIT, I was able to produce milligram quantities of the M2 subunit using a pETM2 plasmid in an E. coli system. However, pure intact protein is required for quantitative mechanistic studies, and amino acid analysis indicated that the M2 subunit was being degraded from the amino terminal end during production or purification. Purification in the presence of a cocktail of protease inhibitors minimized but did not eliminate degradation. Studies are continuing to determine the nature and time of degradation and methods of preventing it.

The B2 subunit from E. coli and the M2 subunit from mouse contain 2 high spin ferric ions and a tyrosyl free radical. The tyrosyl radical in the M2 mouse subunit is much less stable than that in E. coli and is lost when iron is removed by the addition of EDTA during purification and it can be regenerated by incubation of the aposubunit with Fe 2+, O2 and dithiothreitol. This is in contrast to the E. coli reductase which contains a tightly bound iron and requires several protein factors to regenerate the tyrosyl residue.

Preliminary studies have been initiated to study the mechanism of assembly of the tyrosyl radical-dinuclear iron cluster by stopped-flow absorption spectroscopy. Apo M2 subunits are incubated with Fe 2+ and O2 under a variety of conditions to produce native M2 containing the tyrosyl radical-dinuclear iron cofactor. The course of this assembly can be followed by stopped-flow absorption spectroscopy monitoring the tyrosyl radical at 412 nm and the iron center at 320 nm and 365 nm. Colorimetic analysis of the iron content allows quantitative evaluation of the iron:radical ratio. The reassembly is rather slow, occurring over a 3 minute period and allowing visualization of possible intermediates. Optimum conditions for reassembly, the biological source of the iron and electrons, and the effect of reductase inhibitors are other questions of interest.

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Nancy H. Kolodny - Biophysical Chemistry; Applications of NMR (email Professor Kolodny)

My research involves the use of proton, sodium-23, phosphorus-31, carbon-13 and nitrogen-15 nuclear magnetic resonance (NMR) imaging and spectroscopy for the study of biologically and medically related problems. The projects range from studies of the nitrogen and phosphorus metabolism of cyanobacteria (in collaboration with Mary M. Allen of the Department of Biological Sciences), to the development of superparamagnetic contrast agents for MRI. Our medical work is in the field of ophthalmology and focuses on eye diseases such as uveal melanoma and diabetic retinopathy, and on the physiology of aqueous humor production.

NMR is extremely sensitive to the physical environment of nuclei such as hydrogen (protons), sodium or phosphorus. Pulse, or fourier transform (FT), NMR enables us to study complex molecules in solution, or the phosphate metabolites of living systems via spectroscopy, and the localized behavior of water protons or sodium ions in tissue via imaging. The various projects in which we are involved range from the molecular, through the cellular, to the tissue and finally the whole animal or human level. One- and two- dimensional NMR techniques are used for solution work. Imaging and in vivo spectroscopy depend on surface or volume coils and imaging systems such as that located at the Brigham and Women's Hospital in Boston. Solution and cyanobacteria spectroscopy is carried out at the Brigham and at Wellesley.

Student Projects:

Over the years my 350 and 370 students have been equal partners in my research projects. The type of project in which a student becomes involved depends upon her interests, but there are opportunities in every area described above.

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James H. Loehlin - Crystallography (email Professor Loehlin)

I am interested in the structures, of compounds containing primary amine and/or hydroxyl groups, in which the intermolecular arrangement allows hydrogen bonding in a linear chain. This configuration is not common but has been found in several cases. This particular structural arrangement is of interest since it allows hydrogen atoms to be produced on the opposite side of a crystal from the location of the chemical reactants causing the reaction. The hydrogen atoms are "transferred" through the crystal by a "bucket-brigade" type of mechanism analogous to the model used to explain the high electrical conductivity of dilute aqueous solutions. Two compounds in which linear hydrogen bonded chains of primary amines occur are Li(N₂H₅)SO₄ (lithium hydrazinium sulfate) and N-aminophthalimide whose structure was determined here. The former compound was the first shown to have hydrogen atom transfer of the type shown here.

There are several facets to this investigation and they are all being studied. Student projects could involve one or more of the following areas.

1. For crystals containing a hydrogen bonded chain, the project involves growing suitable crystals of the compounds and then studying the resulting crystals by a variety of methods to determine whether or not proton conduction is occuring. Among the possible techniques are x-ray diffraction and a variety of spectroscopic methods. E. J. Rock and I have recently begun conductance measurements for these crystals.

2. Another possibility involves the determination of the structures of some available compounds which might show these features, whose structures have not yet been determined. Several primary amines have been found to form cocrystals with phenol, and some of these have the desired chain. Using crystallographic methods, a student experimental research project would involve growing single crystals suitable for diffraction, selection of an appropriate crystal, mounting and orienting it and then determining the unit cell geometry and space group using single crystal x-ray diffraction techniques. A complete set of diffraction intensities would be obtained then using an automated computer controlled diffractometer at a nearby university. The data would then be transferred to Wellesley's computer and the structure solved and refined.

3. Miscellaneous other crystallographic investigations are underway or could be initiated. Currently structures of a family of crystals with chiral cations and chiral anions are being investigated. The materials have been prepared by members of M. V. Merritt's research group.

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Jean A. Fuller-Stanley - Physical Organic Chemistry (email Professor Fuller-Stanley)

I am interested in using nuclear magnetic resonance (NMR) spectroscopic techniques to study the molecular structures of various systems.

Current interest is the configuration and conformation of substituted delta-lactones. Delta-lactones are usually found as part of many `natural products' of great importance to society. Compactin (lowers blood cholesterol levels), actinobolin (antitumor antibiotic which increases the hardness of human enamel, protect against certain dental disease), and the limonoids (responsible for the bitterness in citrus fruits), are but few examples of naturally occuring substance with delta-lactone rings. The conformation (shape) that these delta-lactones adopt will determine the position of the substituent groups which will affect the way that these molecules can react biologically. Thus having facile and unambiguous means of predicting the conformation will permit a better understanding of the biological mechanism.

I am also interested in using Si-29 NMR to study dp - pp backbonding in organosilicon compounds. This involves using INEPT and DEPT Selective Population Transfer sequences to measure chemical shifts and coupling constants in a variety of organosilicon compounds with very electronegative substituents.

Student Projects:

7. Carry out synthesis on dialkyl and diaryl organosilicon compounds: R₂SiXH, R = , Me, i-Pr, t-Bu, Ph: X = CF₃, NO₂, CHO, F, CH₃CO, N(CH₃)₃, etc.

Adele J. Wolfson - Biochemistry (email Prof. Wolfson)

I have two on-going research projects:

Interaction of metal ions with Endopeptidase 24.15 (EP 24.15) and its substrates: The goal of these studies is to explore how metal ions affect the way synthetic substrates and inhibitors fit into the active site of this enzyme. Endopeptidase is widely distributed throughout the body, and is thought to be involved in terminating the activity of bioactive peptides. We have found that EP 24.15 is activiated by calcium when the substrate is a synthetic one, and that the inhibitory capability of some inhibitors is also increased with calcium. Kinetics, as well as some studies of the physical and chemical properties of the enzyme and substrates, suggest that all three components: enzyme, substrate, and calcium, must be present for optimal binding. We will continue to use methods such as NMR and calorimetry to determine the strength of binding of metal to substrate or to the enzyme-substrate complex, and see if this kind of activation sheds light on other protein-ligand interactions.

Characterization of an enzyme from cyanobacteria: Cyanobacteria (sometimes called blue-green algae) contain a unique polypeptide, cyanophycin, as a nitrogen-storage molecule. Our goal is to define the role of the enzyme which breaks down cyanophycin to its component amino acids. To this end, we are developing assays for cyanophycinase activity and attempting to purify cyanophycinase.

Student Projects:

Kinetic analysis of activation of Endopeptidase 24.15 by calcium

NMR studies on the effect of metal ions on substrates and inhibitors of Endopeptidase 24.15

Development of a yellow-casein assay for cyanophycinase

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• copyright 1999 by William F. Coleman
• created May 6, 1999
• last modified May 8, 1999
• expires August 30, 2000