Dr. Laura Hunsicker-Wang                                                                Biochemistry

Biochemistry & Bioinorganic Chemistry

Research in the Hunsicker-Wang laboratory will focus on studying enzymes that utilize or bind metal ions, called metalloproteins.  There are two major areas of interest: iron-sulfur cluster enzymes and copper chaperones. 

 

Metal ions inside of a cell can play one of two roles. They can be found at the active site of an enzyme, and play critical roles in the life of a cell.  However, if the metal ions are left free, they can do damage to critical parts of the cell.  For this reason, a system of proteins called chaperones have evolved, which bind and deliver metal ions to their respective metalloprotein.  One family of these chaperones is the coppers chaperones, which shuttle copper ions to Cu/Zn SOD, Fet3, and cytochrome oxidase.  The research in the Hunsicker-Wang lab will work toward identifying, purifying, and characterizing copper chaperones from the thermophilic eubacterium, Thermus thermophilus.  We will also explore how copper chaperones select for only copper.

 

Iron-sulfur proteins make up ~30% of all metalloproteins.  These proteins utilize iron and sulfur atoms that are organized into clusters.  These proteins are often involved in electron transfer reactions.  Specifically, the Rieske protein contains a 2Fe-2S cluster, which is ligated to the protein via 2 cysteine and 2 histidine residues.  The reduction potential of this protein depends on the organism and the type of system that it was derived from.  Previous studies have shown that the number of hydrogen bonds to the cluster, the solvent accessibility, and the type of charge residues near the cluster all affect the reduction potential.  Research on this protein will involve making site-specific mutations, purifying, crystallizing and solving the structure of the mutant enzymes. The reduction potentials of these mutants will also be evaluated.  Thus, the protein will be purified, the effect on reduction potential evaluated, and the structural consequences of the mutation determined.  Future studies will work toward evolving a new function of a larger enzyme complex, called a dioxygenase, which has a Rieske domain.  The new function would be to break down environmental pollutants, and would be accomplished by making randomized mutations to both the Rieske domain and the substrate-binding domain.

 

Dr. Bert Chandler                                             Inorganic & Materials Chemistry

Nanotechnology & Environmental Heterogeneous Catalysis

Our research combines the fields of nanotechnology and environmental heterogeneous catalysis.  We are motivated by the desire to rationally design new materials in order to solve a variety of environmental problems, particularly chemistry associated with alternate fuel sources (biomass & hydrogen) and cleaner selective oxidation chemistry.  Supported metal nanoparticles are important catalysts for these reactions and our approach is to begin developing a fundamental understanding of these catalysts, their properties, and reaction mechanisms. 

In order to study these catalytic reactions, we are developing new methods for preparing and studying well defined bimetallic nanoparticles based on Pt and Au.  We use a special class of polymers called dendrimers to prepare new bimetallic nanoparticles.  Polyamidoamine (PAMAM) dendrimers are hyperbranched polymers with chemical functionalities that allow them to bind a controlled number of metal ions.  Their architecture consists of a porous periphery and open interior, which create an ideal environment for trapping guest species.  The wide potential applications of these macromolecules include drug delivery vehicles, enzyme mimics, and nanoscale assembly. 

We use PAMAM dendrimers as nanoreactors to prepare dendrimer encapsulated metal nanoparticles (DENs) with controllable sizes (20-100 atoms) and compositions (see above). The DENs are deposited onto an oxide and activated to yield supported metal nanoparticles catalysts.  We are interested in all of the steps pictured above and projects can be tailored to student interests, background, and ability.  Representative projects include studying metal-dendrimer coordination chemistry, dendrimer properties, solution nanoparticle chemistry and interactions with probe molecules, supported nanoparticle properties, catalysis, and catalytic mechanisms.

We are also investigating ways to use proteins to template oxides in order to design new surfaces and catalytic sites (see below).  The basic idea is to use proteins such as Lysozyme or polypeptides to template small regions of oxide surrounded by an organic over-layer.  These directed sites will be used to controllably assemble catalytic sites, such as nanoparticles or the molecules like the one pictured below.  Current interests include probing the surface protein-protein interactions, polypeptide design and synthesis, and organic synthesis of acid-base bifunctional molecules for enzyme-inspired catalysts.

The research in our group is inherently interdisciplinary, involving chemistry, biochemistry, and engineering.  Most students have individual projects and opportunities to work in several of our larger areas of interest.  We collaborate with several research groups at Trinity and at major research universities.  Students who work in the group for longer periods of time may have opportunities to travel to some of these schools to use specialized equipment, carry out unique catalysis experiments, and work with other leading groups in these fields.

Dr. Steven M. Bachrach                                                           Organic Chemistry

Computational & Internet Chemistry

My research interests are divided into two broad areas: computational organic chemistry and internet chemistry. Both areas involve extensive use of computers, but interested students need not be experts in programming. Projects can be designed for the computer novice to the expert; what is needed is a strong motivation to learn and explore.

 

Our use of computational chemistry is to solve the Schrödinger equation using ab initio techniques, the most rigorous and complete computational method. We use a number of packages to solve the physics, providing us with optimized geometries, electron distributions, molecular orbitals, and reaction energetics. The current research efforts in this area focus on anion chemistry, particularly nucleophilic substitution at heteroatoms and related elimination reactions. I am interested in determining the mechanisms of these reactions and comparing them with carbon-based chemistry. Our studies of nucleophilic substitution at sulfur suggests an addition-elimination reaction and not a standard Sn1 or Sn2. Nucleophilic substitution at sulfur is a critical step in the activity of many biochemical processes, such as control of protein folding and the action of extremely potent antitumor agents. Elimination is often a competing reaction with substitution, and we are exploring the mechanism for elimination to give thiocaronyl compounds. We are also looking into substitution and elimination reactions of organolsenium compounds, which also have biological implications. Computational chemistry provides an excellent tool for attacking these problems by allowing us to closely examine the transition state, the effect of solvent and substituents, and obtain accurate energetics. In fact, our major emphasis recently has been employing various models towards incorporating solvent in our calculations.

 

I have a long-standing interest in the mechanism of pericyclic reactions involving heteroatoms and will continue to explore new applications. Recently, we have examined the effect of solvent upon the Diels-Alder reaction of carbonyl compounds.

 

My internet projects center on creating new resources for research chemists. Current interest lies in developing an XML database of our computational chemistry results. This project involves programming with HTML, java and perl and makes use of high-performance Unix workstations.

 

 

Dr. Nancy Mills                                                                           Organic Chemistry

Synthetic Organic Chemistry; Aromaticity & Antiaromaticity

One of the most important concepts in organic chemistry is that of aromaticity. Benzene, the quintessential aromatic molecule, has a unique set of “behaviors” that indicate that something special is going on in the molecule and that special character of benzene is called aromaticity. Unfortunately, it is difficult to determine which of the ways that benzene behaves, its structure, or stability, or magnetic properties, is the best way to measure and evaluate aromaticity, this key concept in organic chemistry.

The flip side of aromaticity is antiaromaticity and people have tended not to study antiaromaticity because they assumed that the necessary species would be very difficult to make and study. Through a stroke of luck, we have identified a suite of compounds, shown below, that appear to be antiaromatic, in terms of their magnetic properties, but are still stable enough to characterize. That means that we can begin to compare the behavior of our “antiaromatic” species to that of benzene to begin to sort out which properties are truly characteristic of aromaticity. This is pretty cool because we are looking at one of the big questions in organic chemistry and doing so with the efforts of undergraduate researchers!

We are doing two kinds of projects. Part of the group is looking at species like 1 above which we have characterized by magnetic properties and are characterizing them by other properties, such as stability or by examining their structure. Other students are expanding the investigation to new species that theory says should have increased antiaromaticity, to see if theory is correct and if so, to see if there are new, unexpected behaviors in these previously unknown compounds.

As we have explored this field, it has become apparent that we could also benefit from looking at the molecules corresponding to 1 and 2 that are aromatic, and compare those molecules with model compounds that are neither aromatic nor antiaromatic. Because we will be looking at molecules that span the spectrum from antiaromatic to aromatic, we call this the “aromaticity/antiaromaticity continuum” (see below). Therefore, we need students to prepare the starting materials for the aromatic compounds and explore their conversion into these species.    

Students working in my group spend a lot of time making the molecules that are converted to 1 and 2. The vast majority of the molecules we need are ones that have never been made before. Since everyone in the group gets a molecule of his or her own, you also get the opportunity to be the first person in the world to see a particular compound, which is pretty neat. Much of the efforts of the group involve organic synthesis, purification via chromatography, and characterization by NMR and IR spectroscopy. Since we also predict behavior of these compounds before we make them or rationalize their behavior by calculations, students with a particular interest in computer science and chemistry can become involved in computational chemistry.

 

Dr. Adam R. Urbach                                                                  Organic Chemistry

 

Bio-Organic Chemistry and Molecular Recognition

 

Bioorganic chemistry uses techniques in organic chemistry, like synthesis and NMR spectroscopy, to study proteins, nucleic acids, and other biological molecules.  The major goals are to understand the structure and reactivity of biomolecules, and to create new compounds that can selectively bind to (or “recognize”) them, giving us a way to increase or inhibit their reactivity.  Drugs do this—they recognize a specific protein, bind tightly to it, and inhibit its activity.  The ultimate challenge of bioorganic chemistry is to be able to design a drug that can selectively bind to any protein we want.  Another important goal is to make compounds that act as “sensors” by binding to and revealing the presence and quantity of a specific biomolecule, either by changing color or by producing light or electricity.  Sensors are key components of medical diagnostics technology, such as a device that can measure the amount of a hormone in a patient’s blood.

 

Students in the Urbach laboratory design, synthesize, and study compounds that can recognize and bind tightly to specific peptides in aqueous solution.  Peptides (small proteins) are short, linear chains of amino acids, and since there are 20 common amino acids, even small peptides can have a wide variety of structures and properties.  We have recently discovered that the big donut-shaped molecule we call Q8 (see figure below) can bind tightly and specifically to certain peptides, and what’s exceptionally cool is that this happens in water!  This might seem like a given since all biological chemistry happens in water, but the fact is that the vast majority of synthetic compounds don’t even dissolve in water, and it is particularly rare to find one that can dissolve in water and bind tightly to specific peptides.  What’s more, when certain peptides bind to Q8, the sample turns orange, and so we can use this system to sense the presence of a peptide and tell us (by the intensity of color) how much peptide is present.  Current projects in the group are expanding this new technology to target larger and more complex peptides using several different approaches.  There are many aspects to this work, and individual projects are geared to the student’s interest.

 

Students in the group learn a variety of techniques, even in their first year (see caption below).  These can include:  1) organic and solid-phase synthesis to make peptides and other small molecules; 2) NMR, mass spectrometry, and X-ray crystallography to characterize molecular structure; 3) microcalorimetry, stopped-flow spectroscopy, and capillary electrophoresis to measure the thermodynamics and kinetics of binding; and 4) UV-visible and fluorescence spectroscopy to study electronic properties.  This combination of methods and approaches offers students a breadth of technique and depth of study that is excellent training for future work in a wide range of areas.

 

This image, generated from X-ray diffraction data, shows a high-resolution snapshot of the synthetic compound Q8 (stick structure) wrapped around two copies of a short peptide.  The image is rendered in stereoscopic mode, so if you cross your eyes and focus on the middle of your vision, you may see the structure in three dimensions.  A student in the Urbach group discovered this very unique complex and characterized its structure and binding properties in her first year of college.

 

Dr. Chris Pursell                                                                         Physical Chemistry

Atmospheric Surface Chemistry; Guest-Host Binding; Fuel Film Evaporation

1.         Atmospheric Surface Chemistry - Our research group has been examining chemical reactions in ice and on ice surfaces.  The motivation is to help develop a better understanding of the heterogeneous reactions that occur in the atmosphere and lead to the seasonal loss of ozone over the poles.  In the laboratory we simulate the surface of these atmospheric ice particles, known as Polar Stratospheric Clouds or PSCs, using thin films of pure water ice and mixtures of water with nitric acid.  The interaction of reactive species with the ice surface is monitored using infrared transmission spectroscopy.  The overall goal is to provide detailed experimental information that will help us better understand the chemical reactivity of the ice surface and ice-like surfaces.  Results from these studies will lead to a better understanding of the heterogeneous chemistry that occurs on atmospheric ice particles.  An example of one of our recent studies involved examining the isotopic exchange of D₂O on H₂O ice.  Using infrared spectroscopy we were able to monitor the formation of HOD in time and get kinetics information.

Very recently we have extended our studies of ice and have begun to study the physical and chemical properties of the molecular cousins of ice, namely solid ammonia and solid hydrogen sulfide.  These studies involving using infrared spectroscopy, very low temperatures (10-180 K), and a vacuum environment.  We have already discovered some very fascinating spectroscopic differences between these “cousins” and ice.  We hope to now study chemical reactions of these solids in order to compare and contrast their chemical and physical behavior.

 

2.         Guest-Host Binding - We recently began to study the binding of iodine species with cyclodextrine.  This is called guest-host chemistry.  The cyclodextrine is a large, basket-shaped molecule made from sugar molecules.  The iodine species (I^-, I₂ and I₃^-) fit inside the cyclodextrine and form a fairly stable complex.  This is an equilibrium process and we are interested in measuring the equilibrium constant (called the binding constant) and in determining the heat for this process.  Besides using UV-Vis spectroscopy to study the binding, we are interested in using a new instrument in the department that can measure the heat associated with the binding processes.

 

3.         Fuel Film Evaporation - This is a joint project with Dr. Kelly-Zion in the Engineering Science department.  Thin films of fuel can be deposited in the interior of an automobile engines, especially under cold, initial operation.  These fuel films lead to reduced performance and increased pollution.  We are studying the evaporation process of model films that represent these automobile fuel films.  These studies include (1) using infrared spectroscopy to watch the individual components evaporate, (2) using light interference from a laser to measure the film thickness during evaporation, and (3) using laser light interaction with the film’s surface and capturing the image with a digital camera (this give information about turbulence).

 

Note:  Dr. Pursell is on academic leave for the 2005-2006 academic year, but will be taking students in the summer.  Interested students should contact Dr. Oxley (susan.oxley@trinity.edu)