About the Department
Abstracts for Seminars — Fall 2017
Thursday, September 21, 2017
Thomas Makris, University of South Carolina
Tuning Enzyme Metal-Oxo Reactivity for the Synthesis of Hydrocarbons
A dwindling global energy supply, environmental concerns over rising atmospheric levels of carbon dioxide (CO2), and the volatility of fuel costs have served as compelling impetus to explore renewable alternatives to petroleum-based fuels. OleT is a recently discovered cytochrome P450 that catalyzes the hydrogen peroxide-dependent metabolism of Cn chain-length fatty acids to synthesize Cn-1 1-alkenes. The decarboxylation reaction provides a route for the production of drop-in hydrocarbon fuels from an abundant natural resource. This transformation is highly unusual for a P450, which typically utilize an iron(IV)−oxo intermediate known as Compound I for the insertion of oxygen into organic substrates. We have recently revealed a basis for OleT enzymatic reprogramming using transient kinetics. The OleT ferryl species performs C-H bond abstraction, and forms a hyperstable iron(IV)-OH species (Compound II) that does not readily recombine with the incipient substrate radical. The direct observation of this intermediate, normally fleeting in hydroxylases, provides a rationale for the carbon−carbon scission reaction catalyzed by OleT. The contributions of the secondary coordination sphere and substrate-binding modes for mediating the branchpoint between conventional oxygen rebound chemistry and C-C scission will be discussed.
Gregory Poon, Georgia State University
Molecular Phenotypes of Structurally Homologous ETS Transcription Factors
ETS transcription factors comprise an evolutionarily related family of genetic regulators that are ubiquitous in animals and control a myriad of physiologically critical processes. ETS proteins are united by a highly conserved DNA-binding domain, with overlapping target DNA preferences on the one hand, but are functionally diverse and non-redundant on the other. This so-called "specificity conundrum" besets not only our understanding of ETS homologs but also the structure-activity relationships of eukaryotic transcription factors in general. Translationally, it hampers efforts to develop chemical biology for transcriptional control. Our recent work on model ETS proteins has revealed several novel molecular phenotypes that relate to their functional heterogeneity in terms of sensitivity to epigenetically modified DNA, self- regulation, and restriction by heterochromatin. Understanding the mechanistic bases of these molecular phenotypes will significantly advance our understanding of how ETS proteins evolve a conserved scaffold to achieve distinct functions and help fulfill their potential as highly desirable drug targets.
Lin X. Chen, Northwestern University
Electronic Processes, Morphologies and Structural-functional Correlations in Conjugated Oligomers and Polymers for OPV and Photocatalysis
Conjugated polymers with charge transfer characters in a large extend are responsible for the recent advancement in organic photovoltaic (OPV) applications in bulk heterojunction (BHJ) devices. In the DOE-BES supported Energy Frontier Research Center (EFRC) Argonne-Northwestern-Solar-Energy-Research (ANSER) Center, we have carried out collaborative studies on electronic processes and in-situ morphological development of these low bandgap polymers and small molecules using ultrafast optical spectroscopy, static and in-situ grazing incident X-ray scattering (GIXS). Conventional organic photovoltaic models, in which donor molecules are treated as anonymous electron sources and charge carrier diffusion channels, are challenged by near-infrared transient absorption results of low bandgap polymers indicating strong correlations between intramolecular donor dynamics in < 100 fs and corresponding device power conversion efficiencies. The other conventional model being challenged is the driving force for exciton splitting in the bulk heterojunction environment which has been described by the LUMO-LUMO energy off-set between conjugated polymer electron donor and fullerene derivative electron acceptor. Our study suggests the intramolecular charge transfer characters must be combined with local and global conformations of conjugated polymer chains to achieve the low band gap. Moreover, the morphology of the BHJ films is also investigated by in-situ GIWAS/GISAX methods including the effects of additives which suggest the interplays of the additives and the polymers in solution. The morphology of the heterojunction films has been correlated directly with the yield of the charge separation on time scales from femtosecond to microsecond. In addition, new photophysical studies are also carried out on a series of metal chelating conjugated polymers showing the capability and potential in photocatalytic hydrogen generation.
Toby L. Nelson, Oklahoma State University
Design and Synthesis of Organic Semiconductors: From Eumelanin-Inspired Organic Materials to Novel Electron Acceptors
Melanin is a unique class of natural occurring pigments found in the hair, eyes, skin and the brain of mammals. Eumelanin is the black-brown variety of Melanin and understood to be a biosynthesized heterogeneous macromolecule containing 5,6-dihydroxyindole and 5,6- dihydroxyindole-2-carboxyic acid. Nature has chosen this substance with such complexity and undefined structure as the centerpiece for so many functions like coloration, radiation hardness, and neuron protector. This presentation will introduce what we call Eumelanin-inspired materials and our efforts to tune the Eumelanin-inspired indole core for applications such as sensors, OLEDs and antimicrobials.
The development of carbon-carbon cross coupling of electron-poor aromatic heterocycles remain scarce. With their low-lying frontier molecular orbitals, these molecules are inherently resistant to electrophilic reagents and are also susceptible to reduction and nucleophilic decomposition pathways when they are exposed to strong bases. From our best knowledge, benzo[1,2-b:4,5- b']dithiophene-1,1,5,5-tetraoxide (BDTT) has seen very limited utility as a building block for the synthesis of organic semiconductors despite it being an electron poor heterocycle with promise for development of electron acceptor materials. This lack of effort is likely due to the difficulties of precursor syntheses with carbon-carbon cross coupling reactions that result in low yields. Our progress toward the development of a copper catalyzed C-H direct arylation reaction for regioselective functionalization of BDTT will be presented. The utilization of the methodology for the development on new electron acceptors will also be discussed.
Tracy A. Brooks, Binghamton University
Nucleic Acid Clamp-Mediated Stabilization of MYC Promoter G-Quadruplex DNA
The prolific transcription factor MYC, with more than 30,000 binding sites across the genome, shows aberrant expression and activity in numerous disease states, including stent restenosis, polycystic kidney disease, liver fibrosis, and up to 80% of all cancers, such as non-Hodgkin’s lymphoma (NHL) and breast cancers (BC). Oncological changes in MYC regulation are connected to genomic translocations and amplifications; it is often a driver oncogene to which the cells are highly addicted. Decreased MYC expression is a validated therapeutic approach in both NHL and BC, and as — in the MYC promoter is an established approach to decreasing transcription and facilitating tumor lysis. While most MYC G4 targeted therapeutic development has focused on small molecules, we have pioneered the use of nucleic acid (NA)-based clamps to specifically stabilize the MYC G4 and modulate transcription. We will discuss the development of the lead NA clamp and its demonstration of promoter and G4 isoform specificity, induction of the physiologically relevant MYC promoter structure, and downregulation of promoter activity. Moreover, we will share our findings demonstrating entrance of the clamp into nuclei where it binds to the MYC promoter both as a function of transcription and of induction of the G4 with an ellipticine. We are developing the lead NA clamp as a nanotherapeutic for the treatment of NHL and BC, and the G4-focused NA clamp approach is being applied to other, high-value, molecular targets.
Kevin Stamplecoskie, Queen’s University
Atomically Precise Metal Clusters and Their Use in Light Harvesting
Nanomaterials synthesis has advanced rapidly over the past several decades, to the point where it is now possible to synthesize atomically precise particles, referred to as ‘clusters’. Clusters have exact numbers of atoms and stabilizing ligands. Importantly, the precise synthesis and atomic precision affords materials researchers an unprecedented ability to tune the optical and electronic properties of materials. Stable metal clusters in particular, are a rapidly growing research field. A large bank of different clusters, with variations in stabilizing ligands, the choice of metal or alloy, and/or the number of metal atoms, have been isolated. Owing to their extremely small size, even minor structural deviations can have dramatic effects on the electronic and optical properties of clusters.
The unique optical properties of clusters will be highlighted in this seminar, especially as they relate to the structure of thiol protected, atomically precise gold clusters. The distinctive properties of individual clusters have made them attractive candidates for biomedical imaging, catalysis, photonic devices, and light harvesting. The incorporation of atomically precise clusters in photovoltaic devices will be discussed in detail, as well as the use of photovoltaics to help elucidate some of the properties of clusters that are fundamental to their use in light harvesting and other applications as well.