Student Abstracts: Chemistry at LBNL

The Increasing Role of Infrared Spectromicroscopy in Forensic Science. TOMMY WILKINSON (University of Central Oklahoma, Edmond, OK 73034) DALE L. PERRY (Lawrence Berkeley National Laboratory, Berkley, CA 94720).

Synthesis of Novel Imaging Agents for Targeting EGF and ErbB-2 Receptors in Breast Cancer. LINDSY FARINA (University of Alabama, Tuscaloosa, AL 35487) DR. HENRY VANBROCKLIN (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
Radio-tracer imaging agents for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) were synthesized in an effort to develop a non-invasive method for epidermal growth factor (EGF) and ErbB-2 receptor density determination in tumor cells. These receptors are overexpressed in many types of cancer, most notably, breast cancer. N-[m-Tri-(n-butyl)stannylphenyl] maleimide was synthesized and labeled with 125I via iodo-destannylation. The resulting m-[125I]IPM ((m-[125I]-Iodophenyl) maleimide) will then be conjugated to an ErbB-2 binding single chain antibody fragment via the highly reactive free sulfhydryl (thiol, -SH) group. The second branch of imaging agents explored was dialkoxyquinazoline analogs. These quinazolines were prepared by coupling dimethoxychloroquinazoline with 3 and 4-aminopyridines in DMF at reflux. Previous lead candidate quinazolines, labeled with either 18F (a positron emitter) or 125I (a low energy gamma emitter), were used as radiotracers for the EGFR tyrosine kinase-binding assay. Development of these methodologies to produce new imaging agents may lead to more sensitive and more specific tracers for targeting tumor localization and monitoring treatment.

Application of synchrotron based XRF microprobe to the study of ink and paper. T.J. WILKINSON (San Francisco State University, San Francisco, CA 94000) DALE L. PERRY (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
Analysis of paper and ink/paper combinations is essential to forensic science and law enforcement. Current analytical methods in use are destructive, and unable to provide result for small quantities of sample. In our work, synchrotron-based x-ray fluorescence microprobe has been used to analyze the low level metal ion components in commercial paper and commercial paper/ writing ink combined materials, and produce a 'metal fingerprint.? Elemental maps for different metal ions are shown for blank paper and for ink that has been applied to and eluted on the same paper. Elemental analytical data for some of the common metal ions involved are presented, and the analyses for the metal ions in the ink/paper are discussed with respect to their origins and the processes and properties which are known for the paper.

Synthesis of Rotenone Derivatives: Mitochondrial Electron Transport Chain (ETC) Complex I Probes. LINDA XIONG (Fresno City College, Fresno, CA 93741) HENRY VANBROCKLIN (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
The overall objective of the Department of Nuclear Medicine and Functional Imaging at LBNL is to develop efficient methods to help diagnose diseases and monitor treatment. The goal of this project was to produce new rotenone derivatives, compounds known to be potent inhibitors of the mitochondrial electron transport chain, which will be labeled with carbon-11 or fluorine-18 for PET (Positron EmissionTomography) imaging. These rotenone derivatives are potential imaging agents for cardiac diseases. Commercially available rotenone was converted into different analogs using various synthetic chemistry procedures. After each successful reaction step the product was purified and fully characterized. These compounds will be further converted to imaging agents in the radiochemistry laboratory or will be used to confirm the identity of the new radiolabeled compounds. Continuing the research towards finding new radiolabeled tracers will lead to better and more efficient means of identifying disease in the human body.

Refining Refinement: Benefiting from Awareness of the Incomplete Model in Computational Crystallography. AREL L. CORDERO (University of Oregon, Eugene, OR 97403), PAUL D. ADAMS (Lawrence Berkeley National Laboratory, Berkeley, CA 94720).. AREL CORDERO (University of Oregon, Eugene, OR 97405) PAUL D. ADAMS (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
Determining the three dimensional structure (tertiary structure) of protein molecules is the primary goal of protein X-ray crystallography. Computational techniques are critical to the construction and refinement of a model that best fits the experimental data. An important component of the model is the disordered solvent region of the crystal, or bulk solvent, which is accounted for by a constant electron density level outside the protein. Unfortunately, current methods also treat residual electron density from an incomplete protein model as part of the bulk solvent. In this research, methods were tested in which these two components were treated independently in both refinement and the creation of electron density maps. Forty-three solved protein structures, with diffraction resolution ranging from 3.5 to 1.1Å (1Å = 10-10 m), were used for testing and comparing the methods. Randomly selected regions of 2.5, 5.0, 7.5, and 10% of the models were removed from each protein and the models were refined using the new and current methods. Electron density maps were calculated from the models and observed data. Correlation coefficients between the electron density maps calculated from the incomplete models and the final structure were calculated and compared. The best of the new methods for treating an incomplete model demonstrated a measurable improvement over the current method and the improvement increased as the percentage of the model missing increased. This new method will be particularly important in the early stages of iterative automated model building where very incomplete models must be refined and electron density maps calculated for the next cycle of building.

Scientific software development in the 21st century: Tools for solving the scientific challenges of tomorrow, today.. MARY GRIFFIN (Vassar College, Poughkeepsie, NY 12604) PROFESSOR WILLIAM A. LESTER, JR. (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
This project involved the creation of a complex ab initio quantum mechanics package for performing quantum Monte Carlo calculations of the electronic structure of atoms and molecules. Specifically, a variety of electron-electron and electron-nuclear correlation functions for electronic wave functions was added to the package. Several of the important tools of the computational chemistry and physics community are used. This paper will review some of the freely or widely available software tools for computational chemistry and how they are the loom in which the new generation of scientists weave the tapestry that is the software of tomorrow. In addition, the use of electronic correlation functions within a developing software package is explored. The purpose of implementing this part of the program is to evaluate the utility of various proposed correlation functions for use in quantum Monte Carlo simulations of large molecules. Once this is successfully completed, the correlation function parameters will be optimized and the variance of the local energy will be calculated for systems of various sizes. Since the smallest variance of the local energy indicates the most accurate trial wave function, this work will provide a benchmark against which one may determine the type of correlation function within the trial wave function that is best suited for larger systems than those treated to date with the method.

Semi-Volatile Organic Compounds in Seattle Air, Part II: Improving Productivity and Accuracy in Data Analysis for High Performance Liquid Chromatography. CLINT HOBERG (Pima Community College, Tucson, AZ 85709) LARA GUNDEL (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
Understanding human exposure to airborne polycyclic aromatic hydrocarbons (PAH) requires accurate measurements of their partitioning between the gas and particulate phases. The difficulty of measuring this partitioning efficiently and accurately has been an area of major concern. Prior methods involving GC/MS had left out many PAH due to poor sensitivity. Fluorescence detection with high performance liquid chromatography (HPLC) has greater sensitivity but the HPLC manufacturer's software produces data that can be so noisy that limits of detection suffer unless the analyst inspects and analyzes each chromatogram manually. This is a very time consuming process that limits sample throughput. The objective of this project was to adapt a commercially available software product, PeakFitÔ, for the analysis of PAH fluorescence data for automatic rather than manual processing of each chromatogram. The software used a Fourier deconvolution method as well as a Loess smoothing routine to prepare the data for further analysis. Fourier deconvolution was used because the fluorescence detectors have a zero order (true linear) response factor. We found that analysis time decreased five-fold, for a productivity increase of 5. Accuracy also improved because the software could be adapted to locate and quantify peaks that were poorly resolved. In comparison to the manual reference method PeakFit had a relative r2 value of around 0.99 for the compounds of interest, compared to r2 of about 0.5 for the same group of PAH as quantified by the HPLC software package. With these improvements LBL will be able to report Seattle PAH concentration and gas/particle partitioning data by the end of 2002.

Studies of the Surface Charge Properties of Titanium, Aluminum, and Uranium Oxides by Potentiometric Titration. CHRISTINA LEGGETT (Florida State University, Tallahassee, FL 32313) DR. HEINO NITSCHE (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
The reprocessing and separations of radioactive wastes in soils is a major concern in nuclear industry. An understanding of the surface properties of these actinide components, in the form of oxides, can facilitate removal of these actinides from soils and prevent their migration through the geosphere. Potentiometric titrations of titanium and aluminum oxide in aqueous media of different ionic strengths were conducted to determine the point of zero charge. Experiments conducted with titanium and aluminum oxide were for method development. The point of zero charge (PZC) of TiO2 in 0.001 M, 0.05M, 0.01M and 0.1M NaClO4 systems was calculated as 6.05 ± 0.147. Aluminum oxide titrations in 0.001 M and 0.01 M NaClO4 solutions yielded a PZC value of 9.27 ± 0.0353. The point of zero charge for U3O8 is 8.61. The uranium oxide data will prove to be an invaluable annex to the literature data as no data is available on this oxide.

Abstract. RACHELLE MAJESKE (Crafton Hills College, Yucaipa, CA 92374) LARA GUNDEL (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
The objective of this project was to devise sample preparation methods for analysis of airborne PAH in samples of particulate matter collected in Seattle in 2001. Existing methods for hexane extracts were improved to isolate non-polar PAH from extracts in a mixture of hexane, dichloromethane and methanol. These contained both non-polar and polar organic compounds. The new method also had to increase productivity in the lab while minimizing analytical errors. Sample extract cleanup (removal of interferences) and solvent change steps were accomplished using a single silica solid phase extraction column instead of two. Changing solvent from hexane to acetonitrile for compatibility with reversed phase HPLC was carried out during evaporation, by taking advantage of the different boiling points of these two solvents. By eliminating certain steps and shortening others, the processing time was reduced by a factor of three. The new procedure was validated in quadruplicate by processing a mixture of standard PAH as a surrogate for extracts of PM. Recoveries averaged 91.6 +/- 2.6%, confirming the efficacy of this new method.

SYNCHOTRON STRUCTURAL APPROACHES TO THE CHEMISTRY OF METAL ION-IMIDAZOLES. MARIO ORTEGA (UCDavis, Davis, CA 95616) DALE L. PERRY (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
Synchrotron Structural Approaches to the Chemistry of Metal Ion Imidazoles, Mario Ortega (Mario Ortega University of California, Davis. Davis, CA 95616) Dr. Dale L. Perry (Lawrence Berkeley National Laboratory, Berkeley CA 94720) In the chemical world there are thousands upon thousands of bioinorganic compounds which have been identified, but have not been significantly analyzed for their important relevant properties and possible uses. The process of creating new drugs, materials, and semiconductors relies on the reactions of two or more substances to create a more complex one. Understanding the importance of this concept and utilizing are what enable breakthroughs to be made in many of these fields. During my time at LBNL I synthesized several imidazole compounds and the structural data was analyzed through the X-ray Crystallography beam line 11.3.1 of the Advanced Light Source. With the aid of this instrument I was able to see the atomic structure of my crystals and adjust my synthesis accordingly to attempt to eliminate impurities and attain the imidazolate structure. The imidazole structure would not crystallize, leaving me with crystal structure data of imidazole compounds. Imidazole and related compounds constitute the backbone of histadine and many peptides involved in human biological processes. With the data of these types accumulated here, some previously unexplained biological chemistry and related phenomena may one day be known.

Urea reactions with rare- earth metal ions . JACK SARKANY (Las Positas College, Livermore, ca 94577) DALE L. PERRY (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
Urea is a basic important biological organic compound. Urea is essential in all of the ecosystems in the world. Detection of this compound is essential in the way we analyze samples. Instead of separating the sample, a simple detection of urea can be made possible with relative ease, and in a safe manner. Metal oxides help in making complexes with urea and other metal ions. With a metal base, the sample can be mixed with a rare-earth metal ion and then splashed onto a sample; being able to be seen with IR analysis. This simpler IR spectrum can be compared to the original rare-earth metal ion, and prove or disprove the appearance of urea or not.

EXPERIMENTAL DESIGN, SYNTHESIS AND CHARACTERIZATION OF CYCLOBUTENE FOR PHOTOFRAGMENT TRANSLATIONAL SPECTROSCOPY STUDIES AT 193 NM.. ABRAHAM SPENCE (University of Rochester, Rochester, NY 14627) DANIEL M. NEUMARK (Lawrence Berkeley National Laboratory, Berkley, CA 94720).
Over several decades, research has brought much attention to the photochemistry of unsaturated hydrocarbons, which has led to many astounding advancements in our understanding of these processes. Such developments include the elucidation of the photodissociation dynamics of a given molecule, more specifically, hydrocarbons existing with at least one degree of unsaturation. Photofragment Translational Spectroscopy (PTS) has previously been used to investigate the dissociation dynamics of such molecules as 1,2-butadiene and 1,3-butadiene with great success. Among such a vast amount of information, further studies have developed concerning molecules, which behave similarly to those previously investigated. Cyclobutene, a high energy unsaturated hydrocarbon, has become a valid candidate due to its potential similarities in transition states and intermediates formed during its dissociation when compared to many of those previously investigated. In order to be utilized in PTS studies, a high purity synthesis was developed to successfully yield the gas phase product. Furthermore, a single synthesis must yield a sufficient amount of product to complete the entire study due to the large hindrance that impurity exhibits. Due to this fact, the reaction between bromocyclobutane and potassium hydroxide in ethanol must be carried out in high yield utilizing a custom designed vacuum apparatus. Characterization must then be performed to ensure cyclobutene, the desired product, was synthesized in high purity. Subsequently, PTS studies will then be used to investigate the dissociation dynamics of cyclobutene leading to a thorough comparison of the results to that of previous studies.