Chemistry Seminars

Tim Sorey Chemistry Department Central Washington University

Tue, 30 Oct 2007 21:21:02 -0700

A research-based guided-inquiry approach for student problem solving in General Chemistry Laboratory is introduced that shows how to integrate chemical content, research design, and skills and tools of mathematics and computer-based measurement technology. Students work as research groups who cooperate to solve application problems by (a) designing and conducting hands-on experiments, (b) discussing, evaluating, and logically organizing data, (c) preparing, writing, and orally presenting their work to peers that (d) contributes to knowledge and skills required for future lab exercises. Analysis of recent assessment data suggests that this approach also increases graded performance in lecture will be presents, along with examples from Fall Quarter 2007 at Central Washington University.

Jared Shaw, University of California, Davis

Tue, 16 Oct 2007 20:58:24 -0700

New synthetic methods have been developed for the synthesis of libraries of small molecules for use in screening experiments for chemical biology. In one such screen, an inhibitor of gene transcription was discovered. As part of the library synthesis, a new four-component reaction (4CR) was discovered that is being applied to the synthesis of natural products. The synthesis of natural products and other molecules that inhibit bacterial cell division as a new mechanism for fighting infections from resistant bacteria will also be discussed.

Markus Raschke, Chemistry Department, The University of Washington

Tue, 2 Oct 2007 22:12:19 -0700

The natural time- and length-scales of the elementary excitations in matter define a new regime of ultrafast vibrational and electron dynamics as the dimensions of the medium shrink into the 1 to 100 nm range. To achieve the required femtosecond temporal and nanometer spatial resolution we take advantage of the optical antenna properties of nanoscopic metal tips. They provide the necessary local field enhancement and spatial confinement for so called scattering-type near-field optical microscopy. Here, I will discuss our recent results on the vibrational dynamics of block-copolymer nanostructures, single molecule Raman spectroscopy, and the spatially resolved optical response of plasmonic nanocrystals.

John Harrelson, Pacific University School of Pharmacy

Tue, 25 Sep 2007 21:13:11 -0700

During its lifetime, an organism is exposed to a myriad of exogenous chemicals (xenobiotics), including drugs. Survival of the species requires an efficient method to eliminate these foreign molecules from the organism. In humans, this process involves the oxidative biotransformation (i.e., drug metabolism) of xenobiotics to metabolites that are water soluble and more easily eliminated in the urine. Interestingly, although drug metabolism reactions are usually considered detoxifying, these same reactions are also involved in toxic processes. That is, drug metabolizing enzymes can bioactivate drugs or carcinogens to reactive metabolites that bind to endogenous macromolecules (e.g., proteins and DNA), which can lead to drug-induced toxicity or carcinogenesis. For example, in overdose situations, acetaminophen (Tylenol) is metabolized to a toxic metabolite that leads to liver injury.

The enzymes responsible for the oxidation of a majority of drugs and environmental chemicals are the cytochromes P450 (CYP or P450). Due to this important role in drug elimination, the modulation of CYP activity can lead to a variety of clinical outcomes with respect to drug therapy: drug-drug interactions, decreased or increased duration of action, drug toxicity and other adverse effects. One method of modulation is the binding of multiple ligands (i.e., substrates) to a single CYP enzyme. It is now well known that the binding of multiple substrates or other types of effector molecules (e.g., cytochrome b5 or metal ions) can alter binding affinities, product formation rates, product selectivity, and lead to non-Michaelis-Menten kinetics (i.e., allosterism or cooperativity). However, the mechanistic characterization of multiple-ligand binding is incomplete. Furthermore, the contribution of ligand dynamics (i.e., the motion of a substrate within an enzyme active site) to P450 allosterism has not been considered in detail.

This seminar will discuss a new method to investigate mechanisms of multiple ligand binding in CYP enzymes. Specifically, new mechanistic information from isotope effect experiments that assess substrate dynamics in CYP2A6 will be reported. CYP2A6 is the primary P450 enzyme involved in nicotine metabolism. It is also involved in the bioactivation of some tobacco carcinogens. The future application of this technique to study other drug metabolizing CYPs will also be discussed briefly.

David Tyler, University of Oregon Chemistry Department

Tue, 11 Sep 2007 08:59:21 -0700

Chemists are interested in transition metal complexes with N2 ligands because of the possibility of reacting these molecules with H2 to make ammonia in a low-energy, low-waste, and environmentally clean process. Until now, the synthesis of ammonia by this route has been futile, but we recently found an Fe-nitrogen complex that reacts with hydrogen to form ammonia.

This talk will describe our discovery as well as our success in making the reaction “greener” by devising a way to carry out the reaction in aqueous solution. In particular, the talk will describe the synthesis of the fascinating trans-Fe(L2)(H)(N2)+ complex (L2 = a chelating phosphine). In a reaction analogous to the Haber-Bosch method for making ammonia from H2 and N2, this molecule undergoes a series of reactions with N2 and H2 in water to form ammonia. A number of intermediates have been identified in the reaction, and the relationship of these species to the active sites of nitrogenase and hydrogenase enzymes will be discussed. The hydrogenase-like reactivity of one of the intermediates was explored in detail, giving important information about the role of hydrogen bonding in stabilizing a coordinated H2 ligand.

Pacific Chemistry alumnus, Justin Crossland, is a member of Professor Tyler’s research group, and this seminar includes results from Justin’s work.

Chemistry Seminars

Tim Sorey Chemistry Department Central Washington University

Jared Shaw, University of California, Davis

Markus Raschke, Chemistry Department, The University of Washington

John Harrelson, Pacific University School of Pharmacy

David Tyler, University of Oregon Chemistry Department

John Harrelson, Pacific University School of Pharmacy