BETTY AND DONALD 
BAUMANN FAMILY SCHOLARSHIP
2005 - 2006 Winners
Marcel Fallet and David Moody


Marcel Fallet's Research Proposal (November, 2005):
Research director: Dr. Erin Gross

    Electrochemistry can be used as a very powerful analytical tool.  Certain reaction mechanisms, called electro-chemiluminscent (ECL) reactions, produce light in when energy is added to them.  Our research goals focus on the experimental setups ECL and capillary electrophoresis (CE).  Our focus now (and for the coming semester) is the optimization of a flow cell for ECL experiments, and the setup and optimization of a CE experiment with a high voltage power supply.
    Figures 1 and 2 below show an example of a type of quinolone and ruthenium(II)tris-(2,2’ –bipyridine) [Ru(bpy)32+] used in our research.  Our previous work consisted of using cyclic voltammetry to determine the specifics of the ECL reaction.  When an electrode produces a voltage in a solution containing a mixture of these two compounds at known concentrations, the Ru(bpy)
32+ produces light via an electron transfer between both oxidized compounds. This light can then be detected with a very sensitive instrument called a photomultiplier tube (PMT).


Figure 1: Structure of Enrofloxacin



Figure 2: Structure of Ru(bpy)
32+

Studying the reaction mechanism of this procedure by comparison with a very well studied amine (triproply-amine [TPrA]) and several cyclic voltamagrams , the oxidation of enrofloxacin was determined to be a two-electron system isolated at the piperazine ring.

    We will use these results for the optimization of our ECL experiment.  The construction of our flow cell will allow for controlled conditions in which we can vary factors such as quinolone concentration, Ru(bpy)
32+ concentration, pH, and various solvent effects (such as methanol concentration or other organic solvents).  Of these factors, pH has been the most extensively studied.  A diagram of the pH effects on this ECL experiment is shown below.

    The experimental setup includes optimization of the wave-form generator and reducing noise levels with an improved Faraday cage.  Once the flow cell is fitted with an injector tube it will be possible to inject various amounts of sample without interrupting the flow of solvent to the electrode, allowing for easier measurements.

                     Electrode

pH    Glassy carbon    Platinum
2            No                     No
7            Yes                    Yes
9            Yes                    Yes

Table 1 : Effect of pH on ECL

    In conjunction with the ECL experiment, we plan on the setup of a CE experiment that involves a high voltage power supply.  We can use CE as a separation device to separate the various types of quinolones (enrofloxacin is just one of those quinolones).  Each quinolone carries a distinct charge (depending on pH because of the pKa’s) when voltage is passed through the capillary and oxidation occurs (not oxidized in the capillary – oxidation occurs when we place the voltammetric electrode at the end for ECL), and they move along a capillary toward the ground (-) electrode, with more positive charges migrating faster.  An electrode will be coupled at the ground end of the capillary producing a constant voltage (this maximum voltage has been determined to be 1.2 volts and is optimized for the experiment).  This electrode will be surrounded by our Ru(bpy)
32+ solution and produces light when the quinolone reaches the end.  This light can then be detected by a PMT.  

    We can then test and optimize various factors such as the separation voltage and capillary diameter.  Also, solvent effects and atmospheric conditions are also important. Finally, the placement of the electrode at the end of the capillary in relation to the PMT can be analyzed to determine the best position.

    Marcel Fallet's Research Report (download as pdf file)


 



David Moody's Research Proposal (November, 2005):
Research director: Dr. Marty Hulce

     We have been working for the last four semesters and summer on an efficient synthesis of 2-methyl-3-trimethylsilyethynyl-2-cyclopenteneone. This target contains an essential feature of a class of compound called an enediyne, which has been proven to be useful as anti-cancer antibiotics by being a DNA alkylating agent that ultimately results in DNA cleavage, making these types of molecules useful in chemotherapy drugs.1-3 Building on this, a method of synthesis for the preparation of ring-enlarged exocyclic allenylketones, has been developed. Protection of 2-methyl-1,3-cyclopentaneone as its isobutyl monoenol ether was followed by reaction with trimethylsilylethynylmagnesium bromide to provide an intermediate propargylic alcohol. Acid-catalyzed dehydration with concomitant deprotection of the enol ether provided the desired 3-trimethylsilylethynyl substituted conjugated ketone. Reduction using lithium aluminum hydride gave the corresponding allyl alcohol, which was cyclopropanated using diethyl zinc with methylene iodide as a carbene source. Reoxidation leads to the desired bicyclo[3.1.0]-2-hexanone. The expected ring expansion and alleneic product was unable to be synthesized under nucleophilic addition with cyano-copper lithium reagents. Computational investigation into this suggested that the trimethylsilane interfered with the process. Consequently, this series of chemistry will be repeated with a phenyl substiuent in the hopes that the aromatic electrons will contribute to facilitating the cuprate addition. Six-membered analogs will be built up to the bicyclo[3.1.0]-2-heptanone for the same series of experiments to be performed. Further chemical studies of this will result in the addition of an alkyl nucleophile to the reoxidized product resulting in ring expansion and a unique allene substituent. Also, if a method of polymerization of these compounds can be achieved, they would result in a unique alpha helical mimic of peptide polymers.

 

1.    Smith, A. L.; Nicolaou, K. C. J. Med. Chem. 1996, 39, 2103.
2.    Jones, L. H.; Harwig, C. W.; Wentworth Jr., P.; Simeonov, A.; Wentworth, A. D.; Py, S.; Ashley, J. A.; Lerner, R. A.; Janda, K. D. J. Am. Chem. Soc. 2001, 123, 3607.
3.    Van Lanen, S. G.; Dorrestein, P. C.; Christenson, S. D.; Liu, W.; Ju, J.; Kelleher, N. L.; Shen, B. J. Am. Chem. Soc. 2005, 127, 11594.







David Moody's Research Report (download as pdf file)