Bryn Mawr College

In a technological society where smaller is better (think about the new nano-ipod), there has been increasing interest in nano-circuits, that is electronics at the molecular level. The focus of this research is to study transition metal complexes and their building block, ligands, because of their potential nanotechnology application.

Transition metals, such as iridium, ruthenium, rhodium, and cobalt, have the ability to complex with organic ligands. The focus of this research is to synthesis a library of transition metal complexes and characterize their electrochemical and physical properties. Two such complexes are diagramed below, where M represents a transition metal complex and one ligand is highlighted in red.

[n]Phenacenes are compounds consisting of a particular number (n) of benzene rings fused together as shown in the following example:

[6]phenacene; n=6

These compounds are potentially useful for electrical conductivity due to their conjugation. When n is sufficiently large, electron movement may be promoted via the large pi-systems. This assumption is based on the fact that [n]phenacenes are very similar in structure to the highly conductive graphite, a small section of which is pictured below.

In the human body, indoleamine-2-3-dioxygenase (IDO) catalyses the metabolism of tryptophan (an essential amino acid). It was found that in fetal cells without tryptophan, T cells were inhibited in their multiplication stages. The suppression of T cells is essential in preventing fetal rejection from the body’s immunological responses.

It has recently been found that some tumors express the enzyme IDO. This protects the tumors from the immunological activity of T cells, thereby resulting in the undisturbed growth and reproduction of tumor (cancer) cells.
An effective way to rectify this problem is to develop some form of inhibitor for the IDO enzyme. As such, the aim of my research this summer was to aid in the synthesis of potential IDO inhibitors.

The ability to synthesize complex analogs of natural products with specific stereochemistry is important in the development of safe bioactive molecules for use as therapeutic treatments. One specific challenge is the enantioselective synthesis of stereogenic quaternary carbon centers. These quaternary carbon centers are present in bioactive molecules such as cortisone, morphine, and vitamin D3. With the successful synthesis of (+)-mesembrine through a Birch reduction-allylation reaction followed by hydrolysis and subsequently Cope rearrangement, we hope to be able synthesize (+)-lycoramine. Lycoramine is similar to galanthamine; the structures differ by only the presence of absence of one double bond. Galanthamine has been recently approved as a drug for the treatment of Alzheimer’s disease and lycoramine has been found to be nearly as potent a drug.

Allison Dudik Mentor: Dr. William Malachowski

The relatively recent discovery of carbon nano tubing, microscale tubes consisting of rings of carbon atoms, opens up new opportunities for research as to the potential uses of these tiny little conductors. One way of creating new uses for the nano tubing is by using transition metal complexes to “funtionalize” them, in other words, make it so they can respond to a chemical stimulus in a specific manner. The research done here involves synthesizing various organic ligands and reacting these compounds with transition metals, such as cobalt, to produce a complex. The resulting complex has a central metal ion that has little aromatic “appendages” which can adhere by non-covalent bonding to the carbon surface. The idea is that these ligands can “tag” the nano tubing so that it performs in the desired way, and the more soundly they adhere, the better. The research of this lab focuses mainly on creating many different variations of these complexes to see which are the most effectual in achieving this goal.

A common motif of biochemistry is the role metals play as cofactors in the active sites of enzymes. Molybdenum enzymes are found throughout biology, and fulfill important tasks such as nitrogen metabolism in plants. All molybdenum enzymes employ this metal in the same way in the form of Moco, the molybdenum cofactor. The most important piece of this complicated cofactor is a single molybdenum atom with two important components, or ligands. This unique constituent is incorporated into every molybdenum enzyme, and is known as the molybdopterin ligand.

Molybdenum (Mo) is a metallic trace element that is important for the proper functioning of most living organisms. A lack of molybdenum enzymes in humans can lead to several health problems. Molybdopterin, a dithiolene organic complex, couples with molybdenum to form the Molybdenum Cofactor (MoCo). Analyses of the formation of molybdopterin through the synthesis of models, improves the possibility of understanding how the cofactor works.

The Burgmayer Lab’s approach to the syntheses of MoCo models consists of two stages. The first stage constitutes the formation of one of the pterins; acetyl, phenyl, and difluoropheynyl, ethynyl pivulated pterins, fondly referred to as AEP, PEPP, and diFPEPP, respectively, using 2-pivaloyl-6-chloropterin (11).

The molybdopterin family of enzymes plays a vital role in many metabolic reactions involving redox reactions of sulfur and nitrogen centers in diverse substrates, including nitrogen assimilation in plants[1] and the anaerobic respiration of many bacteria[2]. In humans, deficiency in molybdopterin enzymes like sulfite oxidase causes fatal neurological damage[3]. Despite the biological importance of these enzymes, much about their structure and activity remains unknown. Their most unusual feature, a pterin-substituted dithiolene chelating the central metal ion, was conclusively determined within the past decade[4], and it is suspected that pterin redox reactions play an important role in molybdoenzyme function.

Previous research has been done that examines the accuracy of pigeon self-report. It is not clear, however, if the results of these experiments, which indicated that pigeon are accurate, actually measures self-report. It is possible that previous research was actually measuring the accuracy with which pigeons recognize what response is asked of them, not the accuracy with which they discriminate their own chosen behavior. This experiment attempts to tease apart these tasks in an effort to determine whether pigeons really can accurately report their own behavior. To obtain reinforcement (access to food), the pigeons were be required to respond to a differential reinforcement of low-rate of behavior (DRL) or a differential reinforcement of high-rate of