Cynthia J. Burrows
Distinguished Professor, Thatcher Presidential Endowed Chair of Biological Chemistry
Department of Chemistry, The University of Utah
- General Lecture
"Peering into the Dark Matter of DNA: Structures and Functions beyond Watson & Crick"
6:30 PM, PSH-151
Less than 2% of the human genome codes for the amino acid sequence of proteins. Why is all the rest of the DNA there? Some of it participates in orchestrating replication, some in the protection of the ends (telomeres), and some sections upstream of transcription start sites (promoters) control whether or not a gene is expressed as protein. All of these functions of DNA include guanine-rich sequences capable of folding into G-quadruplexes, four-stranded folds of DNA that differ dramatically from the classical base-pairing scheme of the Watson-Crick double helix. Furthermore, the G-rich sequences are sensitive to oxidative stress, converting to modified structures including 8-oxo-7,8-dihydroguanine (OG) and the hyperoxidized lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). Both the overall reactivity of a G residue in DNA or RNA and the final oxidized G product formed are highly dependent on sequence, solvent exposure and mechanism. For example, oxidation of G in G-quadruplex folds leads to very different outcomes compared to those in Watson-Crick B-helical duplexes. The location of G damage in turn has a profound effect on the stability of duplex vs. quadruplex structures. We propose that G-rich sequences respond to oxidative stress by selecting a secondary structure that can best accommodate the damaged base, and that ‘shape-shifting’ may be used as a signaling mechanism to affect transcription and repair. The implications are that nucleotide identity beyond the exome may be important in gene expression and disease, and that the definition of epigenetic modifications should be expanded to include guanine oxidation. Host: Dan Buttry
- Technical Presentation
“Single-Molecule Analysis of the Effects of Oxidative Stress on G:C-rich Sequences in DNA”
3:40 PM, PSH-151
Oxidative stress in the cell results in modifications to DNA and RNA bases and downstream events including effects on transcription and replication as well as signaling for repair. Ultimately, unrepaired damage in DNA leads to mutagenesis that is a contributing factor to cancer and other diseases. Our studies focus on base modifications arising from guanine (G) oxidation, including how and where they form in the genome. To investigate this, we have developed a single-molecule nanopore approach that is complementary to other biophysical techniques for interrogating nucleic acid structure. Specifically, the electrophoretic capture of DNA strands, either Watson-Crick duplexes or folded G-quadruplexes, inside a protein nanopore (alpha-hemolysin) embedded in a lipid bilayer provides information about the presence of oxidized bases as well as the dynamics of unfolding. In order to adapt this methodology to sequencing DNA for modified bases, we have developed a protocol for PCR amplification using a third base pair to mark the site of DNA modification. Host: Dan Buttry
Tobin J. Marks
Vladimir N. Ipatieff Professor of Chemistry and Professor of Materials Science and Engineering
Department of Chemistry, Materials Research Center, and the Argonne-Northwestern Solar Research Center, Northwestern University
- General Lecture
" Interface Science of Plastic Solar Cells"
6:30 PM, PSH-150
Interface Science of Organic Photovoltaics Tobin J. Marks Department of Chemistry, Materials Research Center, and the Argonne-Northwestern Solar Research Center Northwestern University, Evanston IL 60208, USA The ability to fabricate molecularly tailored interfaces with nanoscale precision offers means to selectively modulate charge transport, molecular assembly, and exciton dynamics at hard matter-soft matter and soft-soft matter interfaces. Such interfaces can facilitate transport of the “correct charges” while blocking transport of the “incorrect charges” at the electrode-active layer interfaces of organic photovoltaic cells. This interfacial tailoring can also suppress carrier-trapping defect densities at interfaces and stabilize them with respect to physical/thermal de-cohesion. For soft matter-soft matter interfaces, interfacial tailoring can also facilitate exciton scission and photocurrent generation in such cells. In this lecture, challenges and opportunities in organic photovoltaic interface science are illustrated for four specific and interrelated areas of research: 1) controlling charge transport across hard matter(electrode)-soft matter interfaces in organic photovoltaic cells, 2) controlling charge transport by specific active layer nano/microstructural organization in the bulk active material and at the electrodes, 3) controlling exciton dynamics and carrier generation at donor-acceptor interfaces in the active layer, 4) designing transparent conducting electrodes with improved properties. It will be seen that such rational interface engineering along with improved bulk-heterojunction polymer structures guided by theoretical/computational analysis affords exceptional fill factors, solar power conversion efficiencies greater than 9%, and enhanced cell durability. Host: Dan Buttry
- Technical Presentation
"Thermochemically Leveraged Strategies for Biofeedstock Catalysis"
3:40 PM, PSH-151
Thermodynamic Strategies for New Catalytic Process Design. Biofeedstock Processing via Tandem C-O Hydrogenolysis Tobin J. Marks Northwestern University, Evanston IL 60208 USA firstname.lastname@example.org Abstract This lecture focuses on thermodynamics/mechanism-based strategies for converting abundant biofeedstocks into useful chemicals. Thus, new approaches to the hydrogenolysis of C-O bonds are discussed with the ultimate goal being the processing of diverse biomass feedstocks. It is shown that selective hydrogenolysis of cyclic and linear etheric C-O bonds is effected by a tandem catalytic system consisting of recyclable metal triflate Lewis acids and supported palladium nanoparticles or related catalysts in either “green” ionic liquid solvents or in the neat substrates. In this tandem process, the metal homogeneous triflates catalyze the endothermic retro-hydroalkoxylation of the ether, with the supported palladium catalyst subsequently catalyzing the hydrogenation of the resulting intermediate alkenols, to afford saturated alkanols with high overall activity and selectivity. Kinetic and DFT computational studies show that the turnover-limiting step in these reactions is the retro-hydroalkoxylation, followed by rapid alkenol hydrogenation. Furthermore, the metal triflate catalytic activity scales approximately with the DFT-computed charge density on the triflate metal ion. With the most active of these catalysts, ethereal substrates are rapidly converted, via the alkenol, to the corresponding saturated hydrocarbons. In similar tandem processes, it is shown that esters and triglycerides are also rapidly and selectively converted to alcohols and, ultimately, to saturated hydrocarbons. The kinetics and mechanism of these ester hydrogenolysis processes, as deduced by experimental results and DFT computation, are compared and contrasted with those of the corresponding ethers Host: Dan Buttry