Physical & Applied Sciences
Project: Collagen Fiber Activity in Memory Shaped & Carbon Aerogels
Presenter: Autumn Jones
Major: Physics
Classification: Senior
Faculty Mentor: Dr. Firouzeh Sabri, Physics
Abstract: Collagen fibers play a critical role in regulating and defining most tissues; therefore, it is not surprising that the role in collagen is key when studying and combining in vitro models and biomaterials. This study was aimed at a better understanding of collagen behavior in different memory shape aerogels. Collagen behavior was measured by quantifying collagen fibers length, width, orientation, and density in different aerogels with varying pore sizes. Data was collected from the collagen fibers in 6 different memory shaped aerogels. So far, the data shows that the stiff aerogel with larger pores had the highest density of collagen fibers with fibers of larger width. Current works are focused on varying the collagen density placed onto both carbon and memory shaped aerogels to determine the collagen behavior as a function of higher density in each aerogel.
Project: Experimental Validation of Structure-Based Pharmacophores: Toward a High-Throughput Screening Tool for GPCR Ligand Discovery
Presenter: Martin Guerrero
Major: Chemistry
Classification: Sophomore
Faculty Mentor: Dr. Kristine Ruddick, Chemistry
Abstract: A powerful tool in drug discovery is the pharmacophore; a model that approximates key steric and electronic features necessary for optimal ligand-target interaction and hence drug-induced biological response. Using molecular modeling techniques, our group has developed a protocol for generating structure-based pharmacophores via feature annotation of energetically optimized chemical functional group fragments. Generated pharmacophores can then be used to search compound databases containing millions of drugs to elucidate candidate active ligands for a target, the results from which can be further analyzed to identify a set of potential novel therapeutic drugs for experimental validation. This work will include background and rationale for the cell-based assay systems; we will use to validate the model and test the druglike features of computationally predicted hit list compounds. We will first test the model using the well-known dopamine D2 receptor as proof-of-principle. The D2 receptor is a well-studied G protein-coupled receptor (GPCR) that signals via the interaction between the receptor in the cell membrane and the Gαi G-protein subunit to inhibit adenylate cyclase and trigger a cellular response involving downstream effectors (2nd messengers) such as cyclic AMP (cAMP), calcium ions (Ca2+), and ERK (MAP kinase). We have found cell-based assays designed to monitor various 2nd messengers problematic due to the complex nature of engineered mammalian cell line-based host cells which contain thousands of endogenous GPCR and other receptors; thus no true null live cell-line exists. For this reason, we will screen drug candidates for the D2 receptor using the NanoLuc-based complementation assay (Promega) which is independent of cellular interference. NanoLuc is an engineered luciferase from the deep-sea shrimp, Oplophorus gracilirostris, and this technology can monitor the interaction of the receptor with specific G-proteins and has been proven effective as a high-throughput screening tool.
Project: Synthesis & Characterization of Rhodium-Aluminum & Iridium-Aluminum Heterobimetallic Complexes Bridged by 5-Hydroxyquinoline
Presenter: Michael Chaney
Major: Biomedical Engineering, Chemistry & Mathematical Sciences
Classification: Sophomore
Faculty Mentor: Dr. Timothy Brewster, Chemistry
Abstract: This project is aimed to serve as an intermediate step towards the final goal of creating a heterobimetallic complex capable of tunable catalysis. Metaphorically speaking, the eventual goal is the creation of a gear shifting mechanism to control the speed of a reaction of interest using localized redox. reactions. Recall that redox. reactions in chemistry involve adding or subtracting electrons from an element to induce a change in oxidation state, by method of oxidation or reduction. In essence, we aim to determine if the reactivity of the transition metal of interest can be modulated by adjusting the electrochemical activity, or oxidation state, of an attached redox active aluminum complex. In collaboration with the Graves' Group of Swarthmore College and the Clark Group of the University of Memphis, we aim to answer that question.
The molecule to be used towards either proving or disproving this theory will be a heterobimetallic complex consisting of Vaska's Complex and Graves' Complex, graciously provided by the Graves' Group, bridged by 5-Hydroxyquinoline. Vaska's Complex does not possess any noteworthy characteristics as a catalyst, but the complex serves as an excellent placeholder due to its consisting of either Rhodium or Iridium as its transition metal center, and its Carbonyl group. The carbonyl group is especially of interest due to its ability to be utilized as a measurement of electrochemical activity by method of Infrared Spectroscopy. If changes can be observed regarding the relative placement of the IR Spectra peak associated with the Vaska's Complex Carbonyl, a change in electrochemical activity can be inferred. The Graves' Complex will serve as the site of oxidation in this instance, with the Vaska's Complex serving as a placeholder for the catalyst portion of the complex.
The heterobimetallic complex of interest has been synthesized, but further research into the matter will be necessary for testing to commence. The first method of synthesis had poor yields, with an excess of starting materials being noted in the mass spectra. As a result, new methods are being explored to bring about the synthesis of the desired heterobimetallic complex. The presentation with regards to the Works in Symposium will explore the first methodology utilized towards the synthesis of the complex of interest, the current methods being explored, and the future of this project.