Department of Chemistry and Biochemistry Seminars
Fall 2021
Friday, August 27 at 3:10 pm
Graduate Students Ian LaCroix, Conner Langeber, and Kilsia Mercedes will present "Structural Studies of Histones, RNA viruses, and Trauma: Graduate Student Research Perspectives"
Host: Prof. Brian Bothner
Friday, September 3 - OPEN
Friday, September 10 at 3:10 pm
Prof. Blaine Roberts (Emory University) will present "Ion Mobility Mass Spectrometry Reveal Hidden Post-translational Modifications of Amyloid Beta in Alzheimer’s Disease Brain"
Abstract: Part of the quest to understand neurodegenerative research requires a detailed accounting and measurement of the biological components in neurological cells, tissue and biofluids. Regulation of the abundance of proteins is one mechanism of regulating function and post-translational modification (PTM) is another. PTMs are often invisible to targeted assays like ELISA or westerns this includes modifications including phosphorylation and, more recently, the hidden isomeric modifications (e.g. iso-aspartate). Here we apply quantitative proteomics and ion mobility mass spectrometry to investigate the isomerization of amyloid beta peptide from human brain tissue. To our surprise we discovered that isomerization at aspartic acid makes up over 80% of the total peptide in Alzheimer’s disease brain. We show that the implementation of quantitative mass spectrometry and ion mobility reveal hidden biology and improve our understanding of the role of amyloid beta peptide in Alzheimer’s disease.
Host: Prof. Ed Dratz
Friday, September 17 at 3:10 pm
Dr. Paul Galatsis (Vibliome Therapeutics, Bozeman, MT) will present "Discovery and Preclinical Profiling of LRRK2 Kinase Inhibitors for the Treatment of Parkinson’s Disease."
Abstract
Parkinson’s disease (PD) is the most prevalent movement disorder and second most common neurodegenerative disease. Genome-wide association studies (GWAS) have confirmed that leucine-rich repeat kinase 2 (LRRK2) gain of function mutations represent the most common cause of familial PD. This presentation will illustrate how medicinal chemistry enabled a greater understanding of the LRRK2 biology associated with PD by discussing the identification, optimization, and preclinical profiling of potent, orally active, and brain penetrant LRRK2 inhibitors.
Host: Dr. Garrett Moraksi
Friday, September 24 at 3:10 pm
Mandatory Reporter Training for Graduate Students.
Policy 507, Board of Regents Policies and Procedures requires the university to provide training on sexual harassment and the campus policies and procedures for reporting sexual harassment. TAs, GTAs, GRAs are required to complete the training.
Ms. Jessica Feltner, Case Manager for the Office of Institutional Equity at MSU will lead the required training.
Friday, October 1 at 3:10 pm
Prof. Michael Learner (Oregon State University) will present "Graphite – A Review of Intercalation Chemistry and Some New Compounds Using Electride Solutions"
Abstract: Graphite is the first and perhaps the most well-studied intercalation host, and this chemistry is important for energy storage. But compared to other layered hosts, graphite chemistry and graphite intercalation compounds (GICs) show some unusual properties and have a more extensive range of guests. The application of these chemistries for anodes other than in Li ion cells, or for cathodes, appears promising but unsolved challenges remain. This talk will give an overview of the chemistry of graphite intercalation, describe our work preparing new acceptor-type graphite fluoroalkylanion GICs, and then go into more recent work on preparing GICs with group 1 and 2 metal cations from electride solutions.
Host: Prof. Nick Stadie
Friday, October 22 at 3:10 pm -OPEN
Friday, October 29 at 3:10 pm
Prof. Rock Mancini (Washington State University) will present “Smart Immunomodulators for Controlling Toll-Like Receptor and Macrophage-Inducible C-Type Lectin Receptor Signaling”
Abstract: Immunomodulators span a highly diverse chemical space with significant potential to enhance immunotherapeutic and vaccine efficacy alike. However, further implementation of synthetic immunomodulators in medicine requires meticulous control over biodistribution and pharmacokinetics to prevent side-effects, such as systemic inflammatory toxicity. To address this drug delivery problem, we synthetically impart stimuli-responsive characteristics to immunomodulators. To-date we have created stimuli-responsive “smart” immunomodulators that activate Toll-Like Receptors (TLRs) or Macrophage-Inducible C-Type Lectin (MINCLE) receptors on innate immune cells in response to unique stimuli present in target environments, such as solid tumors or vaccine adjuvant depots. This presentation will highlight two types of smart immunomodulators developed by our lab. First, we will discuss imidazoquinoline glycosides, a new class of TLR 7/8 agonist immunotherapeutic that exploits the aberrant carbohydrate metabolism of many chemo-resistant cancers. Second, thermoresponsive MINCLE agonists and their adaptogenic properties linking pyrexia to homeostasis will be discussed in the context of their potential use as vaccine adjuvants.
Host: Prof. Matt Cook
Friday, November 5 at 3:10 pm
Prof. Mary Watson (University of Delaware) will present "Cross-Couplings of Alkyl Amine and Alcohol Derivatives."
Abstract: Alkyl amines are widely available, and easily prepared in high enantiomeric purity. In addition the amino group (NH2) can be carried through multi-step syntheses in protected form, and enables straightforward purification. These features are well appreciated in the use of alkyl amines for the preparation of nitrogen-containing products. We are expanding the toolkit of reactions of alkyl amines by developing cross-coupling reactions via cleavage of their carbon–nitrogen bonds. Capitalizing on the robust methods to prepare enantiopure benzylic amines, we have developed stereospecific cross-couplings of benzylic ammonium salts to deliver highly enantioenriched diaryl and triaryl alkanes, as well as benzylic boronates. This method was the first example of either an enantioselective or stereospecific cross-coupling of a benzylic electrophile with an arylboronic coupling partner.
Recognizing the abundance of primary alkyl amines with unactivated alkyl groups (not benzylic, allylic, or strained), we have also developed cross-couplings of alkyl pyridinium salts. These reactions efficiently convert alkyl amine derivatives into alkyl arenes, and provide new opportunities for the use of amines in synthesis. Our method is the first example of the cross-coupling of an alkyl amine derivative in which the C–N bond is not electronically or strain-activated. We have also extended this chemistry to cross-couplings of benzylic pyridinium salts to enable transformation of benzylic amino groups to aryl or vinyl substituents. Our more recent work with new coupling partners and new classes of alkyl pyridinium salts will also be presented.
Host: Prof. Sharon Neufeldt
This is a WEBEX only seminar. INVITE
Friday, November 12 at 3:10 pm
Prof. Will Broderick (Montana State University) will present "Radical Roles for Organometallic Chemistry, Photochemistry, and the Jahn-Teller Effect in Radical SAM Enzymes."
Abstract: Enzymes in the radical SAM (RS) superfamily use a [4Fe-4S] cluster and S-adenosyl-L-methionine (SAM) to initiate diverse radical-based reactions essential to life. Despite the limited sequence similarity and divergent reactions catalyzed, the RS enzymes employ a common mechanism for initiation of radical chemistry: a reduced [4Fe-4S]+ cluster in the active site is coordinated by the amino and carboxylate groups of SAM, and provides an electron needed for the reductive cleavage of SAM, generating a central 5’-deoxyadenosyl radical (dAdo•) intermediate that initiates reaction with substrate. Recently we showed that this reaction proceeds via an organometallic intermediate, denoted Ω, in which a SAM-derived 5’-deoxyadenosyl is directly bound via the 5’-C to the unique Fe of the [4Fe-4S] cluster. The involvement of Ω in catalysisthroughout the RS superfamily greatly expands the scope and significance of organometallic chemistry in biology. Our discovery of novel photochemistry between the [4Fe-4S]+ cluster and SAM has led to the ability to generate the long-elusive dAdo• radical via photoinduced electron transfer. Photoinduced ET studies on a wide range of RS enzymes provided the surprising observation that all produced either the dAdo• or •CH3 radicals, with the regioselectivity correlating with the SAM ribose ring pucker. Analysis of these results has led to a novel proposal for the origins of regioselectivity in the reductive cleavage of SAM, originating in the Jahn-Teller effect. These results will be discussed in the context of the overall mechanism of radical generation in RS enzymes.
Host: Prof. Joan Broderick
Byker Auditorium or WEBEX INVITE
Friday, November 19 at 3:10 pm
Graduate Student Jenna Mattice (Montana State University) will present her graduate research in a seminar titled "Non-photosynthetic Carbon Dioxide Fixation."
Abstract: 2-Ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC) is a member of the flavin and cysteine disulfide containing oxidoreductase family (DSOR) that catalyzes a unique reaction between atmospheric CO2 and a ketone/enolate nucleophile to generate acetoacetate. Here we present evidence that 2-KPCC, in contrast to the well-characterized DSOR enzyme glutathione reductase, undergoes conformational changes that facilitate catalysis. Using a suite of biophysical techniques including limited proteolysis, differential scanning fluorimetry, and native mass spectrometry in the presence of substrates and inhibitors we observed conformational differences between different ligand-bound species within the catalytic cycle. Analysis of site-specific amino acid variants indicated that 2-KPCC-defining residues within the active site are important for transducing these ligand induced conformational changes. We propose that these conformational changes promote substrate discrimination between H+ and CO2 to favor the metabolically preferred carboxylation product, acetoacetate.
Advisor: Prof. Brian Bothner
Friday, November 26 - HOLIDAY
Wednesday, December 1
Joshua Sinrud, a PhD graduate student in the Materials Science program will present his research in a seminar titled "Studying High Pressure Monopropellant Combustion Spectroscopy with Optical Spectroscopy."
Abstract: Monopropellants are liquid propellants that don’t require a separate oxidizer to combust. They are commonly used for applications where atmospheric oxygen is not available such as underwater and space propulsion. Despite their widespread usage, monopropellant combustion mechanisms remain poorly characterized due to their complexity and difficulties associated with making real-time, operando measurements. Monopropellant combustion often requires high pressures (≥ 20bar), creating challenging demands for any attempt to identify molecular species present as the fuel burns. This talk will describe a novel high-pressure, liquid propellant strand burner capable of burning monopropellant continuously at pressures as high as 80 bar while allowing optical access to the flame. The continuous flow of liquid monopropellant to the flame reaction zone allows for a stable monopropellant flame that can be observed and characterized using a host of optical methods including imaging, emission spectroscopy and Raman spectroscopy. Our studies of nitromethane combustion show that at low pressures (≤ 30 bar), nitromethane ignites at the same temperature in both air and in N2. Increasing the pressure in the combustion assembly to 40 bar and higher causes the monopropellant ignition temperature (in N2) to increase by ~100˚C compared to bipropellant (in air) combustion. While the origin of this effect remains unconfirmed, it likely reflects differences in ignition reaction mechanism. Flame emission spectroscopy (FES) shows complex, rotationally resolved spectral features between 675 and 800 nm. This spectrum has been assigned to emission from vibrationally excited water as it relaxes from its (3,0,1) state back to its ground state. Interestingly, spectral lines and relative intensities are independent of ambient atmospheric composition. Efforts are underway to assign specific ro-vibrational transitions so that flame temperatures can be calculated using Boltzmann statistics. Further FES studies have shown additional species in the nitromethane flame and these species are currently awaiting assignment. This talk will conclude with FES data from a more complex fuel - isopropyl nitrate or IPN - and a description of an ambitious effort to improve detection limits by developing cavity enhanced Raman spectroscopy (CERS). When fully developed, CERS will be integrated with our high-pressure burner and will be capable of detecting species with concentrations as low as parts per billion.
Josh works in the laboratory of Prof. Rob Walker.
3 pm in the Byker Auditorium or WEBEX
Friday, December 3 at 3:10 pm
Prof. Dan Weix (University of Wisconsin, Madison) will present "New Chemical Space from Cross-Electrophile Coupling."
Abstract: Cross-electrophile coupling is the broadly-defined union of two different electrophiles through transition-metal catalysis under reducing conditions. By avoiding pre-formed carbon nucleophiles, cross-electrophile coupling avoids the challenges of substrate availability and functional group compatibility associated with these organometallic reagents. Substitution of a second electrophile for the organometallic partner in cross-couplings offers the potential to dramatically increase the number and types of molecules that can be easily made because of the large number of commercially available carbon electrophiles (>1 million R-X vs. ~5 thousand R-B(OH)2) and the low cost of all components. We have demonstrated reactions that couple organic halides with enones, aryl halides with alkyl halides, acid chlorides and thioesters with alkyl halides, and aryl halides with aryl triflates. Along the way, we have demonstrated their high functional-group compatibility and shed light on why certain reactions are cross-selective and others are not. This talk will briefly introduce the mechanistic underpinnings of selectivity in cross-electrophile coupling reactions and then discuss recent developments and new reactions. In particular, this talk will explore the use of new types of electrophiles, such as N-hydroxyphthalimide esters and N-alkylpyridinium salts, and less reactive electrophiles, such as organic chlorides, ketones, and organic sulfonate esters. Finally, applications to industrial challenges both large and small will be presented
Host: Prof. Sharon Neufeldt
Friday, December 10 at 3:10 pm -
Prof. Rob Paton (Colorado State University) will present "Predicting Organic Reactivity and Stability – Combining Quantum Chemistry and Machine Learning."
Abstract: This presentation highlights the application and suitability of different representations, from expert-guided “engineered” descriptors to automatically “learned” features, in different prediction tasks relevant to organic and organometallic chemistry, where differing amounts of training data are available. These tasks include statistical models of stereo- and enantioselectivity, thermochemistry, and kinetics developed using experimental and quantum chemical data.
Host: Prof. Matt Cook
Byker Auditorium or by WEBEX
Spring 2022
Wednesday, January 5 2 pm
PhD Defense in Chemistry. Steven Rehbein will defend his PhD beginning with a seminar (TBD).
Advisor: Prof. Sharon Neufeldt
Friday, January 21 SPECIAL TIME @ 8 am
Prof. Cornelia Welte (Radboud University, Nijmegen)
Host: Prof. Roland Hatzenpichler
WEBEX only
Friday, January 28
Friday, February 4
Prof. Uttam Tambar (UT- Southwestern)
Host: Prof. Matt Cook
Friday, February 11
Friday, February 18
Friday, February 25
Friday, March 4
Prof. Kim See (Caltech)
Host: Prof. Nick Stadie
Friday, March 11
Friday, March 18 SPRING BREAK
Friday, March 25
Graduate Student Seminar in Biochemistry. Stephanann Costello
Co-advisors: Valerie Copie and Frances Lefcort
Friday, April 1
Prof. Kristopher Waynet (Univ. of Idaho)
Host: Prof. Matt Cook
Friday, April 8
Friday, April 15 NO CLASSES
Friday, April 22
Prof. Gojko Lalic (Univ. of Washington)
Host: Prof. Matt Cook
Friday, April 29
Prof. Jeff Bandar (Colorado State)
Host: Prof. Matt Cook
Friday, May 6