Browsing by Author "Charles B. Boss, Committee Member"

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Characterization of the Dynamics of Beta Sheet Formation by Time-Resolved Infrared Spectroscopy and Computational Modeling
(2003-07-29) Maness, Shelia Jane; Stefan Franzen, Committee Chair; Carol A. Haney, Committee Member; Charles B. Boss, Committee Member; Morteza G. Khaledi, Committee Member
Limited solubility of beta hairpin models prevents a good understanding of their formation. However, beta sheet peptides were recently designed with improved solubility allowing spectroscopic study as models for beta hairpins in larger proteins. The dynamics of cyclic analogs of gramicidin S and two unconstrained beta sheet peptides, H1a and H3, were studied using both a static, temperature-dependent FTIR technique and nanosecond time-resolved infrared spectroscopy. Quench dynamics and density functional theory (DFT) calculations were used to complement the experimental work and to aid in the analysis of two of the cyclic peptides. The folding rates of cyclic peptides are accelerated by at least an order of magnitude over the rates of linear beta hairpin peptides suggesting that nucleation of the folding event is the rate-determining step. The kinetic data for H1a and H3 were analyzed using singular value decomposition (SVD). The H1a peptide has two observed relaxation rates corresponding to several hundreds of nanoseconds and a few microseconds while the H3 peptide fit to a two-state model with a microsecond observed lifetime. Both nucleation and propagation components of folding were measured in these studies, and the results present a complete hypothesis for the sequence of events in beta sheet formation.
Drug Partitioning and Solvation Environments in Lipid Bilayers
(2004-12-09) Carrozzino, Jennifer Marie; Edmond F. Bowden, Committee Member; Morteza G. Khaledi, Committee Chair; Charles B. Boss, Committee Member; Daniel L. Feldheim, Committee Member
The main goal of this research project was to investigate various factors influencing solute partitioning and solvation in lipid bilayer membranes using liposomes as biomembrane models and applying a combination of spectroscopic and capillary electrophoresis techniques. The first area of investigation involved using a series of polarity sensitive solvatochromic indicators to probe the dipolarity of various phospholipid and synthetic surfactant vesicles. A homologous series of probes of varying hydrophobicity allowed a systematic probing of the dipolarity in the interfacial region of the vesicles and resulted in very specific polarity information for various regions or microenvironments depending on the probes positions. This dipolarity was examined in terms of vesicle size and composition, in addition to indicator partitioning behavior. To develop Liposome Electrokinetic Chromatography (LEKC) as a method for rapidly determining liposome - water distribution coefficients, the effects of various parameters on the retention of basic drugs in liposomes were examined. This included characterizing the electrostatics of interactions between charged drugs and charged lipid membranes by examining the effect of membrane and buffer compositions. Additionally, LEKC was used to determine the effect of pH on the partitioning of basic drugs into liposomes composed of lipids which mimic the composition of natural cell membranes. Drug partitioning as a function of pH is examined in detail in terms of the fractions of charged and neutral drug forms in the aqueous and lipid phases. An increase in pH results in a smaller degree of ionization of the basic drugs and consequently leads to a lower degree of interaction with the negatively charged membranes. Finally, LEKC retention was used in QSAR studies for the evaluation of membrane permeability and intestinal absorption. LEKC retention factor data was correlated with human oral absorption in comparison with other methods such as octanol - water partitioning, total number of hydrogen bonding groups, and polar surface area. LEKC retention data was also related to Caco-2, MDCK, and human jejunal permeability in comparison with the standard model, octanol - water partitioning.
Evaluation of Immersive Technology for Chemical Education
(2006-09-03) Hasan, Zeshan; Charles B. Boss, Committee Member; Maria T. Oliver-Hoyo, Committee Chair; William L. Switzer, Committee Member
Incorporating immersive technology into education has the potential to offer robust pedagogical situations to students that they otherwise would not be able to experience. Research suggests the incorporation of immersive technology in future chemistry labs will require utilizing a 3D graphics engine designed with VC++ and OpenGL. The design requirements, prototype, and tools were outlined to aid in the construction of a platform independent 3D graphics engine for chemistry. The lack of forensic chemistry materials currently available supported the development of a new hands-on forensic activity that exposes students to the drug screening techniques used by modern forensic chemists. In the activity developed, students are introduced to the common chemical spot tests used in forensic laboratories and are familiarized with forensic applications of thin-layer chromatography. The research presented has identified five easily accessible laboratory chemicals that can mimic illicit materials in a presumptive drug testing activity such as CSTs. Students can use the non-specific nature of CSTs to rapidly screen for the presence of ?illicit? material and tentatively identify any suspected material by TLC.
The Interaction of Boronic Acid Based Self-Assembled Monolayers as a Potential Glucose Sensor
(2005-08-02) Allen, Angela M.; Christopher Gorman, Committee Chair; Charles B. Boss, Committee Member; Edmond F. Bowden, Committee Member; Kenneth W. Hanck, Committee Member
Recognition of sugars such as glucose with phenylboronic acid–terminated self assembled monolayers (SAMs) was the basis for the designing and fabricating a biosensor. Self-assembled monolayers were formed on gold surfaces as shown by infrared spectroscopy. The continuous, repeatable increase of the electrochemical impedance as the concentration of glucose was increased gave indication of binding. This binding could be attributed to the precedent formation of relatively stable esters between phenylboronic acids and sugars. This impedance change upon binding between glucose and a phenylboronic acid-terminated SAM showed promise in the development of a glucose biosensor.
Interfacial Electrochemical Investigation of Dehaloperoxidase.
(2004-04-14) Robinson, KeAndra R.; Charles B. Boss, Committee Member; Kenneth W. Hanck, Committee Member; Edmond F. Bowden, Committee Chair
The terebellid polychaete marine worm Amphitrite ornata contains an enzyme known as dehaloperoxidase (DHP). Dehaloperoxidase has unique characteristics that permit Amphitrite ornata to cohabit with other marine worms that secrete toxic haloaromatic compounds. Dehaloperoxidase has the capability to break down such compounds in the presence of hydrogen peroxide. For example, trihalophenols can be oxidized to dihaloquinones. Prior studies have described the structure, function, and mechanistic behavior of dehaloperoxidase. However, there have been no reports of the electrochemical analysis of dehaloperoxidase. The data in this thesis demonstrates the direct electrochemistry of dehaloperoxidase at bare indium tin oxide and at modified gold electrode surfaces. The gold electrodes were modified with HS(CH2)10COOH/HS(CH2)6OH mixed SAM. Not only diffusional voltammetry has been demonstrated, but also adsorption of electroactive dehaloperoxidase at the modified gold electrode surface. The successful electrochemistry of DHP is attributed to a cluster of lysines near a heme edge, analogous to cytochrome c. Using cyclic voltammetry, a formal reduction potential of the DHP FeIII/FeII heme couple in the presence of dioxygen was determined, which will provide insight into the enzymatic activity of the protein. This reduction potential was determined to be +440 mV v/s NHE. In the presence of tri-bromophenol, an organic substrate for DHP, the catalytic reduction was observed in the presence of dioxygen. In general, this thesis reports the first electrochemical investigation of dehaloperoxidase and explores its interfacial electrochemical properties at the indium tin oxide and modified gold electrode surfaces.
New Software for Chemistry Applications: Algorithms and Experiment Planners for Automated Chemistry, and an Interactive Program for Use in Photochemistry (PhotochemCAD)
(2004-11-15) Dixon, James M.; Edmond F. Bowden, Committee Member; Jonathan S. Lindsey, Committee Chair; Kenneth W. Hanck, Committee Member; Charles B. Boss, Committee Member
This dissertation is based on convergent projects that focus on helping integrate the use of computers in the chemical field. Project 1 entails development of experiment planners for automated chemistry workstations. The power of parallel workstations has become evident in their pervasive application in high-throughput screening and combinatorial chemistry. Adaptive systems make decisions automatically based on data collected from ongoing experiments. Early adaptive systems performed reactions serially and were quickly eclipsed by workstations capable of performing parallel operations but without decision-making capabilities (i.e., open-loop). Great effort has been put into developing software for automated workstations that enables parallel, adaptive experimentation. A suite of algorithms that accompany an experiment planning software package for use with automated chemistry workstations has been developed. The main objective of this research is reaction optimization, a very general problem in many areas of chemistry, but the approach is quite general. The algorithms developed for parallel, adaptive experimentation include the successive focused grid search (SFGS), multidirectional search (MDS), parallel multidirectional search (PMDS'), parallel simplex search (PSS), parallel screening each member of a set of catalysts across a range of concentration (Parascreen), and several two-tiered methods that enable broad screening followed by in-depth searches. Project 2 focuses on the growth and improvement of the PhotochemCAD software. Laboratory researchers often face the problem of organizing and managing large quantities of experimental data, as well as comparing their data with literature data. In the photochemical sciences, the core data include the spectral properties of diverse substances. One wants to know the absorption and emission properties of a compound, have pointers to the literature, and be able to perform calculations using such spectral data. A versatile software package (PhotochemCAD) has been developed that includes a database of spectral data with literature references for over 150 compounds of natural and synthetic origin. Features are available for performing diverse calculations of interest across the photochemical sciences, including Förster energy transfer, oscillator strength, multicomponent analysis, blackbody radiator, etc. This development effort has much in common with research aimed at creating versatile software programs that address the needs of experimentalists in laboratory settings.
Prediction of Peptide Maps in CZE and MEKC Systems
(2005-04-24) Shen, Yang; Edmond F. Bowden, Committee Member; Charles B. Boss, Committee Member; Morteza G. Khaledi, Committee Chair
A new Quantitative Structure-Migration Relationships(QSMR) model was developed to predict the electrophoretic mobilities of peptides in capillary zone electrophoresis(CZE). A three-step strategy was used: first, select the best charge-size term from the existing models; second, develop a muilti-linear regression(MLR) model to study the linear characteristics of peptide mobility using the best charge-size term and other descriptors; third, generate an artificial neural network(ANN) to investigate the nonlinear behavior of peptide mobility and use this ANN model to predict peptide migration behavior in CZE. To test the robustness of the QSMR model, it was applied to the data published by another research group. Very accurate predictions were achieved. To study the influence of peptide sequence on the migration of a peptide in CZE, a series of 'sequence-related' descriptors were developed. These descriptors were used to develop MLR models for peptide mobility prediction. With the 'sequence-related' descriptor, more accurate mobility could be predicted for peptides with same amino acid composition but different sequences. Group contribution approach(GCA) was used to determine the individual contribution of each amino acid residue and both N-, C- terminal to the peptide mobility in Tween20 system. Data of a relatively small number of peptides were used for this purpose. The sum of individual contributions was calculated for each peptide and used as a new descriptor in developing MLR models for the prediction of peptide mobilities in Tween20 system. Good preliminary results were achieved.