Past Seminars & Events

Professor Yang Yang
Department of Chemistry and Biochemistry
University of California, Santa Barbara
Abstract

New Strategies for Stereoselective Radical Biocatalysis

Radical reactions have enjoyed widespread applications in both small molecule and macromolecule synthesis. However, it remains challenging to control the stereochemistry of radical transformations and to discover novel modes of radical catalysis which are not known in either organic chemistry or biochemistry. Combining synthetic chemistry, enzymology and protein engineering, our group advanced two new biocatalytic strategies for stereoselective free radical processes. First, by capitalizing on the innate redox properties of first-row transition-metal cofactors, we repurposed and evolved natural metalloproteins to catalyze unnatural radical reactions in a stereocontrolled fashion. Through a metalloenzyme-catalyzed halogen atom transfer mechanism (XAT, X = F, Cl, Br and I), a range of radical C–C, C–Br, and C–F bond forming reactions proceeded with excellent total turnover numbers (up to 20,000) and outstanding stereocontrol. Second, by merging visible light photoredox catalysis and biocatalysis, we advanced a novel mode of pyridoxal radical biocatalysis which is new to both chemistry and biology. Synergistic photobiocatalysis allowed us to repurpose structurally and functionally diverse pyridoxal phosphate (PLP)-dependent enzymes as radical enzymes, leading to novel radical PLP enzymology. Pyridoxal radical biocatalysis provides convergent, stereoselective, and protecting-group-free access to a range of useful non-canonical amino acids, including those bearing a stereochemical triad and/or tetrasubstituted stereocenters which remained difficult to prepare by other chemical and biocatalytic means. Furthermore, we demonstrate that the xploitation of biocatalyst-photocatalyst synergy affords a new paradigm to design and develop stereoselective intermolecular radical reactions with synthetic utility.

Yang Yang

Dr. Yang received his Ph.D. degree in Organic Chemistry in 2016 under the guidance of Prof. Steve Buchwald at MIT. In the Buchwald lab, he developed CuH-catalyzed methods for the asymmetric hydrofunctionalization of simple olefins. As an NIH Postdoctoral Fellow working with Prof. Frances Arnold at Caltech, Dr. Yang studied biocatalysis and protein engineering and developed biocatalytic asymmetric C–H amination. Dr. Yang started his independent career in the Department of Chemistry and Biochemistry at the University of California Santa Barbara in 2020. By integrating synthetic chemistry, biocatalysis, protein engineering and computational tools, the Yang group is reprograming nature’s biosynthetic machineries to address challenging problems in synthesis, catalysis and biomolecular engineering. The Yang group recently coined and implemented two new strategies to advance novel stereoselective biocatalytic reactions, including metalloredox radical biocatalysis and pyridoxal radical biocatalysis. Dr. Yang is a recipient of the Regent’s Junior Faculty Fellowship Award (2021), Faculty Career Development Award (2022), National Science Foundation (NSF) CAREER Award (2022), National Institutes of Health (NIH) Maximizing Investigators’ Research Award (2022), Thieme Chemistry Journals Award (2023), Army Research Office (ARO) Young Investigator Award (2023), Packard Fellowship (2023), Sloan Research Fellowship (2024), Department of Energy (DOE) Early Career Award (2024), Amgen Young Investigator Award (2024) and Novartis Early Career Award (2025).

Hosted by Professor Thomas Hoye

Dr. Suzanne Golisz
Research Chemist
Innospec Fuel Specialties
Abstract

Low temperature behavior of renewable diesel and blends with petroleum diesel

Use of renewable diesel (a.k.a. hydrogenated vegetable oil, HVO) is growing worldwide. While it’s tempting to think of renewable diesel as a drop-in replacement for petroleum diesel, we have determined that extra consideration is required for the use of renewable diesel in cold climates. Our primary modes of investigation have been to measure the cloud point, cold filter plugging point (CFPP), and pour point of blends of renewable diesel and petroleum diesel. Further, we have investigated the role of cold flow improvers and pour point depressants in lowering the CFPP and pour point. We found that additives continue to provide benefits. Lastly, we have evaluated the behavior of renewable diesel using a cold stage microscope. These experiments clearly show a difference in the wax crystallization behavior of renewable diesel versus petroleum diesel.

Suzanne Golisz

Suzanne Golisz is an organometallic chemist who has been working in liquid fuels for the majority of her career. Prior to joining Innospec Fuel Specialties as the Technical Director of Cold Flow Improvers, Suzanne worked at both ExxonMobil and Chevron in fuel product quality. In her role at Innospec, Suzanne is responsible for the cold flow improver product line in the Americas. She is focused on ensuring that Innospec’s additive packages have the best performing technology to properly support their customer’s existing and future needs. Suzanne holds a Ph.D. in Chemistry from the California Institute of Technology and a B.S. in Chemistry from the University of Rochester. She is a volunteer career consultant with the American Chemical Society.

Hosted by Professor Ian Tonks

Professor Matt Golder
Department of Chemistry
University of Washington
Abstract

Masquerading Soft Materials: Anomalous Behavior in Macromolecular Design

The Golder Research Team utilizes fundamental prin- ciples of molecular structure to control synthetic poly- mer function. Many of society’s greatest advancements spanning health, sanitation, construction, electronics, and transportation have been enabled by the invention and application of plastics. Simultaneously, these ma- terials have created significant concerns about global sustainability, climate impact, and environmental pollu- tion. My laboratory aims to discover new materials and methods that unveil unexpected phenomena on the macroscopic scale; this overarching strategy will pro- duce next-generation designer plastics and reform how commodity plastics are utilized. In this talk, the team’s efforts towards these common goals will be outlined in the context of recent work centered on: (1) synthetic transformations fueled by initiator and methodology development, and (2) molecular design of new soft materials.

Matt Golder

Matt received his BS in Chemistry from the University of Rochester (NY) in 2010 where he conducted organometallic catalysis research with Prof. Patrick Holland. He was also DAAD RISE Scholar at HU Berlin with Prof. Stefan Hecht during his time as an undergraduate. Following graduation, he moved back to his home city of Boston, MA where he began graduate school in the lab of Prof. Ramesh Jasti at Boston University. He relocated with the lab to the University of Oregon in 2014, where he ultimately earned his PhD in Chemistry in 2015. His work on carbon nanohoop synthesis was recognized by a 2016 IUPAC-Solvay International Award for Young Chemists. Matt was then an NIH NRSA Postdoctoral Fellow in Prof. Jeremiah Johnson’s laboratory at the Massachusetts Institute of Technology where he worked on the synthesis of polymer drug delivery agents and unimolecular macromolecules. He began his independent career in the Department of Chemistry at the University of Washington in 2019. His group works at the interface of physical organic chemistry and polymer science to explore novel structural motifs to solve broad challenges centered on sustainability, engineering, and energy. He is the recipient of a Thieme Chemistry Journal Award, NSF CAREER Award, & Army Research Office Young Investigator Program Award, and is an ACS Division of Organic Chemistry Young Investigator and an ACS PMSE Early Investigator.

Hosted by Professor Alexander Grenning

Professor David Martin
University of Iowa
Abstract

New Strategies for Photocatalytic Bond Activation and Limonoid Synthesis

The activation of strong chemical bonds remains an important strategy for the conversion of abundant chemical feedstocks to value-added products. Photocatalysis continues to offer new methods for the activation of C–H, C–C and C–X bonds. We have developed photocatalytic C–H bond activation methods for the direct functionalization of hydrocarbons and other simple substrates, which led to the discovery of wavelength-selective catalytic behavior of some iron-based catalysts. We are also investigating the use of cobalt- and iron-catalyzed reactions for the functionalization of C–O bonds. Recent advances in the synthesis of neuroprotective limonoid natural products and biological probes will also be discussed.

Dave Martin

Dave received his Bachelor’s degree from the University of British Columbia and spent 1 year as a medicinal chemist at Merck-Frosst in Montreal. In 2011, Dave obtained his Ph.D. from the University of California, Irvine where he worked with Prof. Chris Vanderwal on the application of Zincke aldehydes toward the synthesis of Strychnos alkaloids, including a short synthesis of strychnine. After pursuing post- doctoral research in the lab of Prof. Dave MacMillan in the area photoredox catalysis, Dave spent five years at the University of California, Riverside before moving to the University of Iowa in 2019. In 2022, he was promoted to associate professor with tenure. His main research interests are in developing new catalytic reactions, the synthesis of bioactive natural products and investigating their mechanism of action.

Hosted by Professors Christopher Douglas & Alexander Grenning

Professor Adam Duerfeldt

Associate Professor
Department of Medicinal Chemistry
University Of Minnesota

Short Stories v1: Compuchemical Biology and Blind Ambition

Professor Michael F. Freeman

Associate Professor
Department of Biochemistry, Molecular Biology, and Biophysics & The BioTechnology Institute 
University Of Minnesota

Biosynthetic and Structural Insights into Backbone-modified Peptide Natural Product

Pizza will be provided.

For more information, see the Fall Schedule

In many surveys, interpersonal conflict is the primary challenge that university faculty, staff and students find most stressful.  This isn't surprising. We move through high-intensity workplaces and social spaces feeling increased pressure from stakeholders (faculty members, students, staff, leaders) to have all the answers, all the time - and to express those answers in exactly the right way. Some of us face particular conflicts that seem impossible to resolve and particular colleagues who seem determined to be difficult.  And yet, the ability to experience tension and remain in relationship with those who cause it is a key strength regardless of field, discipline or context. This event explores practical tools to improve our resiliency and efficacy when conflict inevitably arises.

Julie Showers

Julie Showers retired in 2021 after serving as the University of Minnesota's Associate Vice President in the Office for Equity and Diversity.  Prior to that, she served as the Director of the Office of Conflict Resolution.  Before joining the University, Julie worked for over 25 years in private practice and as a senior officer at Northwest and Delta Air Lines.  Now a consultant, she specializes in helping people navigate conflict in healthy and effective ways and serves as an adjunct instructor at the University of Minnesota Law School. 

This workshop was funded by generous support from PPG.

Dr. Spencer P. Pitre
Assistant Professor
Oklahoma State University
Abstract

Nucleophilic Cobalt Photocatalysis and Organic Photoreductants: Two Enabling Approaches to Organic Synthesis

While carbon-centered radicals have become an increasingly important tool in organic synthesis, the breadth of radical precursors available to synthetic chemists remains underdeveloped. Many of the radical precursors employed in these methods require pre-functionalization of the initial feedstock chemical, adding undesired synthetic steps while generating additional byproducts after radical formation. Our lab’s research focuses on the development and advancement of nucleophilic cobalt photocatalysis and organic photoreductants, with the unifying theme of these programs being the expansion of the breadth of carbon radical precursors available to practitioners of the field. Our nucleophilic cobalt photocatalysis strategy leverages the unique reactivity of cobalt square planar complexes, like Vitamin B12, which can engage with electrophiles in SN2 reactions, generating Co(III)-alkyl intermediates that can be photolyzed under visible-light irradiation to generate carbon-centered radicals. Our contributions in this area leverage 1,2-dichloroalkyl electrophiles for the preparation of cyclopropanes. Our lab also focuses on utilizing organic photoreductants, such as halogen-bonding photocatalysts and organic anions, for the generation of carbon-radicals from alkyl and aryl halides and carbonyl compounds, circumventing the use of tin hydrides and ground state metal reductants generally required for activation of these substrates. Our contributions leveraging substituted hydroquinone photocatalysts and 1,4-dihydropyridine anions as organic photoreductants will be presented.

Spencer P. Pitre

Spencer was born and raised in the small Canadian province of Prince Edward Island. In 2012, he completed his B.Sc. with Honours in Chemistry at the University of Prince Edward Island with a minor in Physics. During his time at UPEI, he worked in the lab of Dr. Brian Wagner, focusing on structure-activity relationships of modified β-cyclodextrins for host- guest chemistry. As an undergraduate, Spencer also spent time at the National Research Council of Canada in Ottawa working under the supervision of Dr. Linda Johnston, where he studied the photo-uncaging of ceramides in supported lipid bilayers. In 2012, Spencer joined the group of Juan (Tito) Scaiano at the University of Ottawa as a Ph.D. student. His research in the Scaiano group focused on developing metal- free alternatives for visible-light photoredox catalysis, developing new mechanistic tools for characterization of photochemically-initiated chain reactions, and using heterogeneous semiconductors to catalyze photoredox transformations. After graduating from uOttawa in 2017, Spencer escaped the cold Canadian winters by joining the lab of Larry Overman at the University of California, Irvine as a NSERC Postdoctoral Fellow. Spencer’s research in the Overman lab focused on utilizing tertiary alcohols as radical precursors for the alkylation of medicinally relevant heterocycles and developing a Lewis acid catalyzed 1,4-radical addition reaction. In 2019, Spencer joined Oklahoma State University as an assistant professor, where he is interested in exploring new reactivity regimes in photoredox and cobalt catalysis.

Hosted by Professor Alexander Grenning

Alison Narayan, Ph.D.
Mary Sue Coleman Collegiate Professor in the Life Sciences; Research Professor, U-M Life Sciences Institute; Professor, Department of Chemistry, U-M College of Literature, Science, and the Arts; Director, U-M Program in Chemical Biology
Abstract

Biocatalysis and complex molecule synthesis

Natural sources, such as plants, fungi and microbes, have historically provided compounds with potent pharmaceutical properties. While it can be challenging to build complex natural products in a lab using existing chemistry methods, Nature has perfected these biosynthetic pathways. The work described leverages the power of Nature’s tools for building complex molecules to synthesize novel molecules with therapeutic potential. The reactivity and selectivity of enzymes from natural product pathways are often unparalleled in existing chemical methods. Enzymes with potential synthetic utility are used as a starting point for engineering biocatalysts with (1) broad substrate scope, (2) high catalytic efficiency, and (3) exquisite site- and stereoselectivity. These biocatalytic methods are employed to efficiently synthesize biologically active complex molecules.

Alison Narayan

Alison Narayan’s main research interest lies in using enzymes to synthesize small molecules with important biological activity or with value as synthetic building blocks. Her research program engages trainees from diverse backgrounds who have growing expertise in organic synthesis, molecular biology, chemical biology, as well as analytic and computational chemistry. 

Narayan completed her undergraduate studies in chemistry at the University of Michigan before earning a Ph.D. in organic chemistry from the University of California, Berkeley, where she worked with Prof. Richmond Sarpong. She returned to the University of Michigan as a postdoctoral research fellow in the lab of David Sherman. 

Narayan started her research program as an Assistant Professor in the Department of Chemistry and the Life Sciences Institute at Michigan in 2015. Since this time Alison and her research group have been recognized as a part of C&ENs Talented 12, an Alfred P. Sloan Fellow, a Cottrell Scholar, Cope Scholar and as the inaugural recipient of the Life Sciences Institute Outreach award. Alison is currently the Mary Sue Coleman Collegiate Professor at the Life Sciences Institute and a Professor of Chemistry. In addition, she is the director of the Program in Chemical Biology, an interdepartmental PhD and MS program and the Associate Director of the NSF Center for Chemoenzymatic Synthesis.

Hosted by Professor Courtney Roberts

Professor Theodore Betley
Erving Professor of Chemistry
Department of Chemistry & Chemical Biology
Harvard University
Abstract

Stabilizing radical chemistry

Our group kinetically traps reactive intermediates from group transfer catalysis or small molecule activation processes. Using molecular design, we can use steric confinement or Lewis acid coordination to stabilize reactive radicaloid ligands. We examine the electronic structure of the transition metal-element multiple bonds using a variety of spectroscopic and theoretical means. The electronic structure of the ensuing complexes will be examined for efficacy in group transfer catalysis. As the nuclearity of the reaction site expands, we examine how oxidation state and ligand field effects influence small molecule activation and redox distribution throughout the cluster cores.

Theodore Betley

Betley graduated from the University of Michigan with a B.S.E. in Chemical Engineering in 1999, but decided engineers make too much money. Chemists do not, so he completed his doctoral work with Jonas Peters at Caltech in 2005, and his postdoctoral work at MIT in the labs of Dan Nocera. He started his independent career at Harvard in 2007 studying small molecule activation processes using base metals. He was promoted to Full Professor in 2014 and is now the Erving Professor of Chemistry, Director of Graduate Studies, and, gratefully, no longer the Department Chair.

Hosted by Michael Harris

Facundo M. Fernández
Regents’ Professor and Vasser-Woolley Chair in Bioanalytical Chemistry, School of Chemistry and Biochemistry, Georgia Institute of Technology
Abstract

Mass Spectrometry and the Origins of Life 

Jay G. Forsythe ¹, Anton S. Petrov ¹, Sheng-Sheng Yu ², Ramanarayanan Krishnamurthy ³, Martha A. Grover ², Nicholas V. Hud ^1,4, Facundo M. Fernandez ^1,4,*

¹ School of Chemistry and Biochemistry, Georgia Institute of Technology.
² School of Chemical & Biomolecular Engineering, Georgia Institute of Technology.
³ Department of Chemistry, The Scripps Research Institute.
⁴ Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology.
* [email protected]

A pressing question in origins-of-life research is how polypeptides arose from amino acids before the ribosome. In 1953, Miller demonstrated the abiotic synthesis of amino acids in the now-famous spark-discharge experiment¹. Soon after, Fox and Harada began to explore the formation of peptides from amino acids via condensation at high temperatures². These reactions were facilitated by proportionally higher concentrations of amino acids with acidic side chains (e.g., aspartic acid, D) and resulted in the production of “proteinoids,” condensation products containing covalent cross-links not found in coded proteins. In their 1960 manuscript, Fox and Harada speculated about the diversity of proteinoid sequences, yet conceded that “a complete answer to the question of whether the amino acid residues are distributed in a random or other arrangement may require a complete assignment of residues in one molecular species,” a task beyond the analytical capabilities of the time³. 

In subsequent years, the proteinoid concept was displaced by the hypothesis that either RNA or proto-RNA gave rise to life⁴. Nevertheless, to this day, condensation reactions of amino acids are thought to have played a key role in a potentially symbiotic proto-nucleic acid and proto-peptide world⁵. Peptide condensation studies at temperatures lower than those of Fox and Harada, or with the aid of chemical agents, confirmed that abiotic production of peptides was indeed possible, but chain lengths were generally limited to dimers and trimers with low yields⁶. In recent studies, this length barrier has been surpassed, and certain proto-peptides have been shown to form aggregate structures⁷. 

Together with collaborators from the NSF/NASA Center for Chemical Evolution, we introduced a model prebiotic pathway for peptide formation based on ester–amide exchange reactions between α-amino acids and α-hydroxy acids⁸, amino acid structural analogs found in meteorites and model prebiotic reactions⁹. Subjecting these mixtures to sequential hot-dry/cool-wet water evaporation and rehydration cycles led to depsipeptides—peptide-like oligomers containing both amide and ester backbone linkages that were detected by high resolution mass spectrometry. Ester linkages are kinetically and thermodynamically favored but susceptible to hydrolysis, whereas amide linkages are more stable; therefore, depsipeptide sequences became progressively enriched with amide bonds over the course of various dry–wet cycling programs. In the absence of hydroxy acids, peptide bond formation did not spontaneously occur, confirming the plausible role of hydroxy acids as cobuilding blocks of proto-peptides. Successful depsipeptide formation with various amino acid and hydroxy acid monomers and their mixtures was achieved¹⁰, including glycine, glycolic acid, L-alanine, D-alanine, L-lactic acid, L-leucine, and L-serine. These mixtures were investigated using new mass spectrometry approaches inspired by modern proteomic techniques. Additional experients showed that these condensation reactions can be carried out in charged electrosprayed droplets with even higher yields than in batch mode, opening the possibility for proto-peptide formation at a number of prebiotically-relevant interfaces.

References

1. Miller, S. L., A production of amino acids under possible primitive earth conditions. Science 1953, 117 (3046), 528-9.
2. Fox, S. W.; Harada, K., Thermal copolymerization of amino acids to a product resembling protein. Science 1958, 128 (3333), 1214.
3. Fox, S. W.; Harada, K., The Thermal Copolymerization of Amino Acids Common to Protein. J Am Chem Soc 1960, 82 (14), 3745-3751.
4. Hud, N. V.; Cafferty, B. J.; Krishnamurthy, R.; Williams, L. D., The Origin of RNA and "My Grandfather's Axe";. Chem. Biol. 2013, 20 (4), 466-474.
5. Bowman, J.; Hud, N.; Williams, L., The Ribosome Challenge to the RNA World. Journal of Molecular Evolution 2015, 80 (3-4), 143-161.
6. Rode, B. M., Peptide and the origin of life. Peptides 1999, 20 (6), 773-786.
7. Greenwald, J.; Friedmann, M. P.; Riek, R., Amyloid Aggregates Arise from Amino Acid Condensations under Prebiotic Conditions. Angew Chem Int Edit 2016, 55 (38), 11609-11613.
8. Forsythe, J. G.; Yu, S. S.; Mamajanov, I.; Grover, M. A.; Krishnamurthy, R.; Fernandez, F. M.; Hud, N. V., Ester- Mediated Amide Bond Formation Driven by Wet-Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth. Angew Chem Int Edit 2015, 54 (34), 9871-9875.
9. Peltzer, E. T.; Bada, J. L., Alpha-Hydroxycarboxylic Acids in Murchison Meteorite. Nature 1978, 272 (5652), 443-444.
10. Forsythe, J. G.; Petrov, A. S.; Millar, W. C.; Yu, S. S.; Krishnamurthy, R.; Grover, M. A.; Hud, N. V.; Fernandez, F. M., Surveying the sequence diversity of model prebiotic peptides by mass spectrometry. Proc. Natl. Acad. Sci. U. S. A. 2017, 114 (37), E7652-E7659.

Facundo M. Fernández

Prof. Facundo M. Fernández is the Regents’ Professor and Vasser-Woolley Chair in Bioanalytical Chemistry in the School of Chemistry and Biochemistry at the Georgia Institute of Technology. He received his BSc and MSc in Chemistry from the Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires in 1995, and his PhD in Analytical Chemistry from the same University, in 1999. Between 2000 and 2001, he was a postdoc in the research group of Richard N. Zare in the Department of Chemistry at Stanford University. Between 2002- 2003, he joined the group of Vicki Wysocki in the Department of Chemistry at the University of Arizona as a senior postdoc and then research scientist. Prof. Fernandez is internationally renowned for his work in bioanalytical chemistry, with his research focusing on the development of new tools for assaying small volume samples, tissues, and single cells, and applying such methods to better understanding diseases such as cancer, CF and IBD. He is the author of 220+ peer- reviewed publications, has presented 225+ invited lectures, and graduated 31 Ph.D. and M.Sc. students. He is also the academic director for the Systems Mass Spectrometry Core (SyMS-C) at the Parker H. Petit Institute for Bioengineering and Bioscience at Georgia Tech, where he oversees a portfolio numerous mass spectrometers from most major vendors. He has received several awards, including the NSF CAREER award, the CETL/BP Teaching award, the Ron A. Hites best paper award from the American Society for Mass Spectrometry, and the Beynon award from Rapid Communications in Mass Spectrometry, among others. He serves on the editorial board of The Analyst and as an Associate editor for the Journal of the American Society for Mass Spectrometry and Frontiers in Chemistry. His current research team of 15-20 people is interested in metabolomics, development of new ionization sources, MS imaging, machine learning and ion mobility spectrometry. The research is supported by agencies such as NIH, NSF, NASA, IARPA and DoD. In his free time, he enjoys camping and off-roading with his family, kayaking, and climbing summits to connect with other nerdy people using a tiny ham radio.

Hosted by Professor Varun Gadkari