UCLA

Special Bio-Inorganic Chemistry Seminar
2021-01-27 16:00 (America/Los_Angeles)
“ Exploring Metalloenzymes for Therapeutics and Sustainable Catalysis”
Abstract: Metalloenzymes are at the heart of numerous biological processes ranging from respiration and photosynthesis to natural product biosynthesis. Research in the Bhagi-Damodaran lab focuses on investigating structure, function and reaction mechanisms of metalloenzymes, and developing rational approaches to modulate their biological activities. Drawing from the core disciplines of biological, inorganic, and computational chemistry, our group utilizes protein engineering and small molecule discovery strategies to address pressing health and energy related challenges. In this seminar, I will describe our research efforts towards rewiring metalloenzyme-dependent redox signal transduction pathways for next-generation tuberculosis therapeutics. I will also discuss our research efforts towards re-programing non-heme iron enzymes for modular, versatile, and sustainable C-H bond halogenation catalysis.

Prioritizing the patient - The discovery of lorlatinib, a macrocyclic ALK inhibitor for the treatment of resistant and metastatic NSCLC
2021-01-28 16:00
Abstract: Primary and secondary mutations in anaplastic lymphoma kinase (ALK) are oncogenic. Insights into ALK acquired resistance were used to define a drug design strategy that led to the discovery of lorlatinib (Lorbrena; PF-06463922), a novel ATP-competitive macrocyclic inhibitor of ALK and ROS1 kinases. Structure based drug design, lipophilic efficiency and physicochemical property-based optimization provided inhibitors with overlapping broad-spectrum potency, low transporter efflux, and brain penetration. The small, cyclic design provided a unique structure with unique properties. NMR and other analytical methods were used to study the unique molecular properties, including atropisomerism for some analogues. Protein dynamics from x-ray crystallographic data and molecular dynamics simulations performed on ALK mutants shed light on the mechanisms of acquired resistance. Research culminated in the discovery of a first in patient candidate, Lorbrena, which was given Breakthrough Therapy status by the FDA in 2016 and approved in late 2018 for the treatment of patients with refractory ALK positive non-small cell lung cancer (NSCLC). Lorbrena is the first and only ALK tyrosine kinase inhibitor (TKI) approved for use after second-generation ALK TKIs. Recently, a Phase 3 study of Lorbrena in patients with previously untreated ALK-positive, advanced NSCLC met its primary endpoint by demonstrating significantly improved progression-free survival, as compared to Xalkori, which is currently primary standard of care. The FDA has accepted for Priority Review the supplemental New Drug Application (sNDA) for Lorbrena as a first-line treatment for patients with ALK-positive NSCLC based on the pivotal data from the CROWN study.

Chem 268: Prof. Tanja Kortemme
2021-01-29 15:30
“Switches, sensors, and new shapes: from design of new functions to cellular consequences of allostery”

Chem 228: Prof. Benjamin J Eggleton
2021-02-01 16:00
“Multidisciplinary (mission directed) research in nanotechnology at the University of Sydney”

Special Bio-Inorganic Chemistry Seminar
2021-02-03 16:00
“Structural Evidence for Dynamic Nitrogenase Metalloclusters”
Abstract: Nitrogenase catalyzes dinitrogen reduction to ammonia and is the only enzyme capable of supplying the world with a reduced form of ‘N’ that can be directly incorporated into biomolecules such as DNA and proteins. The most well-studied nitrogenase, molybdenum nitrogenase, consists of two component proteins, the Fe protein (a homodimer with a 4Fe4S cluster) and the MoFe protein (a heterotetramer with two complex metalloclusters per heterodimer). During catalysis, the two proteins associate, allowing ATP-dependent electron transfer from the Fe protein to the MoFe protein. In the as-isolated state, the MoFe protein active site (FeMo-cofactor) has an overall composition of [7Fe:9S:1C:1Mo]-R-homocitrate. This form of the FeMo-cofactor does not bind substrate and requires activation (by the Fe protein) prior to substrate binding. As a result, only recently have ligand bound states of the protein bound FeMo-cofactor been crystallographically determined. Selenium can function as a sulfur-surrogate, exchanging with labile sulfide groups under various conditions, resulting in Se-incorporated metalloclusters. In my talk, I will present crystallographic evidence for Se-incorporation into the nitrogenase metalloclusters and discuss the mechanistic implications of these findings.

“The Journey of Remdesivir from Respiratory Syncytial Virus to COVID-19”
2021-02-04 16:00
Abstract: SARS-CoV2, the causative agent of the COVID-19 pandemic, is an RNA virus that has efficient human to human transmission and carries significant morbidity and mortality for vulnerable patient populations. Remdesivir (Veklury®) is a broad-spectrum inhibitor of RNA viruses and the first agent to be approved for the treatment of COVID-19.
The seminar will introduce the concept of targeting RNA viruses through inhibition of the viral polymerase by nucleoside analogs, and then focus on the early discovery of the nucleotide prodrug, remdesivir for respiratory syncytial virus. Topics discussed will include structure-activity relationships, prodrug design, mechanism of action, and pharmacokinetics. The identification of the broad-spectrum activity of remdesivir toward RNA viruses including Ebola and SARS-CoV2 paved the next stage in the journey of remdesivir. Details on the synthesis and early route optimization to support the development of remdesivir for Ebola will be highlighted. Finally, a summary of the preclinical data evaluating remdesivir toward SARS-CoV2, and the clinical data that supported its regulatory approval for COVID-19, will conclude the talk.

Chem 268: Prof. John M. Denu
2021-02-05 15:30
“Metabolic control of post-translational modifications”

First-Principles Materials Prediction: From Sustainability to the Quantum Information Age - Prof. Yuan Ping, UCSC
2021-02-08 16:00
First-Principles Materials Prediction: From Sustainability to the Quantum Information Age
Theory-guided materials design is vital to the advancement of sustainability and quantum information science. First-principles theory entirely based on quantum mechanics without prior input parameters is the perfect tool. In order to reliably predict exotic quantum materials and out-of-equilibrium processes, many-body physics and quantum kinetic theory are important to bridge with first-principles methods.
In this talk, I will discuss our development on theory and numerical codes on many-body perturbation theory (MBPT), for accurate prediction of optical excitation and exciton recombination1,2,3. We will discuss how we use these methods to solve material problems in photoelectrochemical applications and predict spin qubit properties for quantum information science4,5. In particular, we will show an example on how substrate screening affects interfacial charge transfer and exciton energies, with our recently developed technique based on MBPT that applies for arbitrarily lattice-mismatched interfaces without strain6.
Next, I will show our recent method development on real-time open quantum dynamics with coupled spins, electrons, photons and phonons based on first-principles density-matrix approach7,8. We will discuss its important applications on understanding valley dynamics, spin transport as well as ultrafast coupled spin and carrier dynamics at finite temperature. This method will offer new and unbiased insights for spin and valley relaxation and decoherence in general systems, and determine design rules for new materials with ideal physical properties for spintronics, valleytronics, and quantum information science.
References:

[1] F. Wu, D. Rocca, and Y. Ping, Journal of Materials Chemistry C, 7, 12891, (2019).
[2] F. Wu, T. Smart, J. Xu, and Y. Ping, Physical Review B, 100, 081407(R) (2019).
[3] Y. Ping, D. Rocca, and G. Galli, Chem. Soc. Rev. 42, 2437 (2013).
[4] F. Wu, A. Galatas, R. Sundararaman, D. Rocca, and Y. Ping, Physical Review Materials, 1, 071001(R), (2017).
[5] T. Smart, K. Li, J. Xu, and Y. Ping, “Intersystem Crossing and Exciton-Defect Coupling of Spin Defects in Hexagonal Boron Nitride”, under review, arXiv:2009.02830 [cond-mat-mtrl-sci], (2021).
[6] C. Guo, J. Xu, D. Rocca and Y. Ping, Physical Review B, 102, 205113, (2020). Editors’ Suggestion.
[7] J. Xu, A. Habib, S. Kumar, F. Wu, R. Sundararaman, and Y. Ping, Nature Communications, 11, 2780, (2020).
[8] J. Xu, A. Habib, R. Sundararaman, and Y. Ping, “Ab initio Ultrafast Spin Dynamics in Solids”, under review, arXiv: 2012.08711 [cond-mat-mtrl-sci], (2021).

NSF Center for Integrated Catalysis Webinar Series
2021-02-09 13:00
The NSF Center for Integrated Catalysis is delighted to announce that it will be hosting a monthly webinar series. The next webinar of this series will be held on Tuesday, February 9th, 2021 at 1:00 PM. We are pleased to invite all students, postdocs, faculty, and staff.

Small molecule inhibitors of 15-prostaglandin dehydrogenase promote tissue repair and regeneration
2021-02-09 16:00
Abstract: Prostaglandin E2 promotes tissue repair and regeneration in multiple tissues. Small molecule inhibitors of the PGE2-degrading enzyme, 15-prostaglandin dehydrogenase, could elevate PGE2 levels in vivo with applications in multiple disease contexts. We have discovered two chemical series of enzyme inhibitors. Medicinal chemistry efforts have led to sub-nM inhibitors with excellent bioavailability and physicochemical properties. Lead compounds demonstrate activity in mouse models of inflammatory bowel disease, recovery from bone marrow transplantation, and neurodegeneration.

Chem 278: Prof. Cunjiang Yu
2021-02-10 16:00
“Rubbery Electronics”
Abstract: Seamlessly merging electronics with biology is of imminent importance in addressing grand societal challenges in health and joy of living. However, the main challenge lies in the huge mechanical mismatch between the current form of rigid electronics and the soft nature of biology. This talk will present a new type of electronics, namely “rubbery electronics”, with tissue-like softness and stretchability, which is constructed all based on elastic, rubbery electronic materials. The hope is that rubbery electronics could ultimately solve the challenge in seamless integration between biology and electronics. The innovations in rubbery electronic materials and devices set the foundation for rubbery electronics and integrated system. The presentation will feature our recent results in rubbery semiconductors, fully rubbery transistors, logic gates, integrated electronics, sensors, smart skins, neurologically integrated function systems, medical implants, etc.

Cancelled Chem 218 Student Exit Seminar: Arundhati Deshmukh
2021-02-11 12:00
Cancelled
“Tuning the Excitonic Properties of 2-Dimensional Molecular Aggregates across the Visible and Shortwave Infrared”
Molecular aggregates are non-covalent self-assemblies of chromophores wherein transition dipole moments of individual molecules couple coherently over long distances, forming delocalized excitons. This imparts exciting photophysical properties such as extreme blue or red shifts (seen in H- or J-aggregates respectively), narrow linewidths and high molar absorptivities. We modulate the transition dipole couplings within an aggregate via molecular packing, topology, and disorder in order to tune and explore new photophysical behaviors. In this talk, I will discuss the unusual situation that arises from 2D transition dipole coupling in sheet-like aggregates. In addition to traditional H- and J-aggregation, we find a new case of ‘I-aggregation’ which shows intermediate characteristics of H- and J-aggregates. I will also describe how we use thermodynamics of self-assembly to control the aggregate packing and thereby, tune excitonic properties. Using a three-component equilibrium model, I will lay down general principles for selectively stabilizing H- or J-aggregates, allowing us to construct a library of 2D J-aggregates with absorptions spanning the visible and shortwave infrared (SWIR) regions. Finally, I will show how subtle differences in chromophore structures within this library modulate the aggregate packing and eventually lead to distinct excitonic band pictures, that can be experimentally probed using temperature dependent spectroscopy. Overall, this work establishes molecular aggregation as a tunable avenue for accessing unusual photophysical properties and thus, opens up organic chromophores to new functionalities including SWIR imaging, plexitonics, and telecommunications.

Chem 268: Prof. William DeGrado
2021-02-12 15:30
“De novo design of function in water-soluble and membrane proteins”

Theoretical Chemistry Seminar - Predicting and Controlling Correlated Light-Matter Interactions - Prof. Prineha Narang, Harvard University
2021-02-16 12:00
Predicting and Controlling Correlated Light-Matter Interactions
Quantum systems host spectacular excited-state effects, but many of these phenomena remain challenging to control and, consequently, technologically under-explored. My research, therefore, focuses on how quantum systems behave, particularly away from equilibrium, and how we can harness these effects1. By creating predictive approaches to study dynamics, decoherence and photo-induced correlations in molecules and matter, our work could enable technologies that are inherently more powerful than their classical counterparts ranging from quantum information science, to ultra-high efficiency optoelectronic and energy conversion systems. In this talk, I will present work from my research group on describing, from first principles approaches, the microscopic dynamics, decoherence and optically-excited collective phenomena at finite temperature to quantitatively link predictions with 3D atomic-scale imaging, quantum spectroscopy, and macroscopic behavior. Capturing these dynamics poses unique theoretical and computational challenges. The simultaneous contribution of processes that occur on many time and length-scales have remained elusive for state-of-the-art calculations and model Hamiltonian approaches alike, necessitating the development of new methods in theoretical and computational quantum chemistry 2–4. I will introduce our work at the intersection of ab initio cavity quantum-electrodynamics and electronic structure methods to treat electrons, photons and phonons on the same quantized footing, accessing new observables in strong light-matter coupling. Building on this, I will show selected examples of our approach in ab initio design of active defects in quantum materials leveraging the chemical degree-of-freedom5–7 towards selectively linking these active defects 8–10. Finally, I will present an outlook on driving quantum chemical systems far out-of-equilibrium to control the coupled electronic and vibrational degrees-of-freedom 11–13.
References:

Head-Marsden, K., Flick, J., Ciccarino, C. J. & Narang, P. Quantum Information and Algorithms for Correlated Quantum Matter. Chem. Rev. (2020) doi:10.1021/acs.chemrev.0c00620.
Rivera, N., Flick, J. & Narang, P. Variational Theory of Nonrelativistic Quantum Electrodynamics. Phys. Rev. Lett. 122, 193603 (2019).
Flick, J., Rivera, N. & Narang, P. Strong light-matter coupling in quantum chemistry and quantum photonics. Nanophotonics 7, 1479–1501 (2018).
Flick, J. & Narang, P. Cavity-Correlated Electron-Nuclear Dynamics from First Principles. Physical Review Letters vol. 121 (2018).
Narang, P., Ciccarino, C. J., Flick, J. & Englund, D. Quantum Materials with Atomic Precision: Artificial Atoms in Solids: Ab Initio Design, Control, and Integration of Single Photon Emitters in Artificial Quantum Materials. Adv. Funct. Mater. 29, 1904557 (2019).
Hayee, F. et al. Revealing multiple classes of stable quantum emitters in hexagonal boron nitride with correlated optical and electron microscopy. Nat. Mater. 19, 534–539 (2020).
Ciccarino, C. J. et al. Strong spin–orbit quenching via the product Jahn–Teller effect in neutral group IV qubits in diamond. npj Quantum Materials 5, 75 (2020).
Neuman, T., Wang, D. S. & Narang, P. Nanomagnonic Cavities for Strong Spin-Magnon Coupling and Magnon-Mediated Spin-Spin Interactions. Phys. Rev. Lett. 125, 247702 (2020).
Wang, D. S., Neuman, T. & Narang, P. Dipole-coupled emitters as deterministic entangled photon-pair sources. Phys. Rev. Research 2, 043328 (2020).
Neuman, T. et al. A Phononic Bus for Coherent Interfaces Between a Superconducting Quantum Processor, Spin Memory, and Photonic Quantum Networks. arXiv [quant-ph] (2020).
Juraschek, D. M., Meier, Q. N. & Narang, P. Parametric Excitation of an Optically Silent Goldstone-Like Phonon Mode. Physical Review Letters vol. 124 (2020).
Juraschek, D. M., Narang, P. & Spaldin, N. A. Phono-magnetic analogs to opto-magnetic effects. Phys. Rev. Research 2, 043035 (2020).
Juraschek, D. M., Neuman, T., Flick, J. & Narang, P. Cavity control of nonlinear phononics. arXiv [cond-mat.mtrl-sci] (2019).

Special Biochemistry Seminar: Dr. James K. Nuñez
2021-02-16 13:00
“Programmable transcriptional memory by CRISPR epigenome editing”

OCDS Prof. Tanja Ćuk
2021-02-17 16:00
Resolving a catalytic mechanism at an electrode surface with high time-resolution:
Experimental identification of theoretical descriptors
Abstract: Catalytic mechanisms at electrode surfaces guide the development of electrochemically-controlled energy storing reactions and chemical synthesis. The intermediate steps of these mechanisms are challenging to identify experimentally, but are critical to understanding the speed, stability, and selectivity of product evolution. In my group, we employ photo-triggered vibrational and electronic spectroscopy to time-resolve the catalytic cycle at a surface, identifying meta-stable intermediates and critical transition states which connect one to another. The focus is on the highly selective water oxidation reaction at the semiconductor (SrTiO3)-aqueous interface, triggered by an ultrafast light pulse in an electrochemical cell. Here, I will summarize the work done to date by the group: the structure and dynamics of the initial intermediates that trap charge (Ti-O*- and Ti-O*+-Ti) from their picosecond birth at the surface through the next event at microseconds, suggested to be the formation of the first O-O bond of O2 evolution. There will be a focus on how time-resolving the intermediates leads to experimental identification of largely theoretical descriptors of oxygen evolution, such as the binding energy of the first meta-stable, electron-deficient oxygen intermediates (generally, M-OH*). In so doing, reaction conditions that shift equilibria become an important, independent axis to the time & energy axes of the spectroscopy. While many open questions remain, these experiments provide and benchmark the opportunity to quantify intermediates at an electrode surface and follow a heterogeneous catalytic cycle in time.

Chem 218 Student Exit Seminar: Mary Grumbles
2021-02-18 12:00
“Strategies for Modulating Stabilities of Soft and Hard Hybrid Materials with Boron Clusters”
Carbon chemistry is ubiquitous across the development of modern materials. In comparison, use of boron building blocks is underdeveloped, owing to the historic instability of simple boranes. Polyhedral boranes, however, fundamentally differ from their borane precursors and exhibit exceptional chemical stability as a result of three-dimensional, delocalized aromaticity. My talk will highlight the utility of polyhedral boranes to generate hybrid materials with unique stability profiles. Specifically, I will discuss the use of polyhedral boranes as matrices for ion shuttling, highlighting the tolerance of these species to repeated electrochemical cycling in the presence of both moisture and water. After, I will discuss efforts to amend unprotected peptides with polyhedral boranes. My talk will highlight the distinct physical and chemical properties of the resulting bioconjugates, emphasizing the ability of these species to slow proteolytic degradation. Finally, I will describe ongoing efforts within the Spokoyny lab to develop and investigate these hybrid borane materials.

Recent progress in the discovery of non-hormonal male contraceptive agents
2021-02-18 16:00
Abstract: There is a global need for novel contraceptive methods because worldwide about 40% of pregnancies are still unintended, about 42 million pregnancies are terminated by abortion, and 658 women per day die of pregnancy-related problems in the US (CDC 2020). While many contraceptive options exist for women, fewer are available for men. Testosterone-based contraceptives for men have been investigated for 60 years but challenges remain for commercialization. For these reasons and to provide couples with additional safe and reversible options for contraception, the development of non-hormonal contraceptives for both men and women is highly desirable to assist with family planning and reduce unintended pregnancies. Advances in the understanding of reproductive biology have provided many testis-specific targets that are under investigation for the discovery and development of a male contraceptive agent that involve reduction of sperm counts, effect spermiation, prevent sperm maturation, or block sperm motility. However, developing agents that are highly effective, very safe and completely reversible is a very significant challenge. Recent progress on the discovery of inhibitors for the testis-specific bromodomain (BRDT) will be discussed. Based on the discovery that some kinase inhibitors are dual kinase/bromodomain inhibitors (ACS Chem. Biol. 2013, 8, 2360 and ACS Chem. Biol. 2014, 16, 1160) efforts towards the discovery of selective BRDT monovalent and bivalent BRDT inhibitors will be presented.

Chem 228: Prof. Deji Akinwande
2021-02-22 16:00
“Adventures with Atomic Materials: from Flexible/Wearable Electronics to Memory Devices”

Medicinal Chemistry and Pharmacology of Antivirals Targeting Influenza Virus, Enterovirus D68, and SARS-CoV-2
2021-02-23 12:00
Abstract: Respiratory viruses pose a persistent threat to public health and global economy. However, there is a lack of effective antiviral countermeasures against many of these highly transmissible pathogens. In this presentation, I will present a few projects on the development of small molecule antivirals against the influenza virus, enterovirus D68 (EV-D68), and SARS-CoV-2. Throughout the talk, I will discuss the experience and lessons learned from academic drug discovery including target identification, hit prioritization, and translational research. For influenza virus project, we have developed antivirals targeting the viral M2-S31N proton channel and the viral polymerase PA-PB1 interactions. The lead compounds have shown potent in vitro and in vivo antiviral activity against both Tamiflu-sensitive and resistant influenza viruses. EV-D68 is a respiratory virus that mainly infect children and cause flu-like symptoms. In severe cases, the infection can lead to neurological symptoms called acute flaccid myelitis. There is currently no antiviral or vaccine available for EV-D68. We have made promising progress in developing antivirals targeting the viral VP1 capsid, the 2A protease and the 2C protein. The lead compounds have shown broad-spectrum antiviral activity against multiple enteroviruses including poliovirus. For the SARS-CoV-2 project, we are among the first to discover structurally diverse compounds as the viral main protease (Mpro) inhibitors and have solved multiple X-ray crystal structures. Subsequent structure-based drug design led to the discovery of the both covalent and non-covalent Mpro inhibitors with potent enzymatic inhibition and cellular antiviral activity. Overall, the lead compounds we have developed against influenza virus, EV-D68, and SARS-CoV-2 have promising translational potential and continuous development might lead to the first-in-class broad-spectrum antivirals.

Special Biochemistry Seminar: Dr. Anum Glasgow
2021-02-24 13:00
“Building dynamic, functional proteins to understand and treat disease”

Chem 278: Prof. Anne McNeil
2021-02-24 16:00
Synthetic Approaches to Sustainable Polymers
Abstract: Plastics have completely transformed our lives, while at the same time having a significant negative impact on our environment. Our research is aimed at developing synthetic approaches to more sustainable polymers. This talk will highlight two projects ongoing within our group. In one, we aim to make a processable, thermoplastic that fully degrades back to monomer after use in a fully closed loop. In the other, we aim to use synthetic chemistry to give a current high-production-volume plastic a second life, attenuating its impact on the environment.

Chem 218 Student Exit Seminar: Dane Stanfield
2021-02-25 12:00
A Tale of Two Doping Mechanisms: Controlling the Formation of Charge Transfer Complexes in Chemically Doped Semiconducting Polymers
Doping of organic semiconductors has emerged as a viable route for the inexpensive fabrication of numerous electronic devices such as light emitting diodes, thin film transistors, and thermoelectric generators. The p-type doping of polymer based semiconductors like P3HT is achieved through the introduction of chemically strong oxidizing agents like F4TCNQ that usually undergo integer charge transfer, removing an electron from the extended conjugation network, leaving behind a charged hole in its place that is free to conduct at the bulk level. In contrast, p-type doping of small molecule based semiconductors typically results in formation of charge transfer complexes, where close spatial contact and orbital overlap between the host and guest species cause fractional charge transfer to occur. It has to date remained unclear why polymeric based semiconductors show a preference for doping via integer charge transfer while their small molecule counterparts usually undergo formation of fractional charge transfer complexes. In this talk, we will discuss recent advances in our understanding of the mechanisms that drive these two different types of charge transfer interactions in conjugated polymers. We show that it is possible to exert control over the type and abundance of each type of charge transfer interaction through the simple selection of processing solvent solubility parameters. We are also able to assign two structurally unique packing arrangements that correspond to integer or fractional charge transfer and compare the relative thermal stabilities of these two polymorphs. Finally, we show that the CN groups found on the dopant molecule, F4TCNQ, can serve as a probe of the local electric field strength and thus the environment of the charge carriers as detected via the vibrational stark effect. Overall, this improved understanding of polymer-dopant interactions allows us to provide new guidelines for enhancing the doping efficiency and limiting the occurrence of fractional charge transfer states in doped semiconducting polymers.

New Strategies for the Efficient Preparation of Bioactive Compounds
2021-02-25 16:00
Abstract: Novel technologies, preparative methods and synthetic strategies often represent a critical part of the investigation of new design ideas for bioactive compounds. Traditionally, natural products were considered to be the most challenging targets, but frequently medicinal chemistry structure-activity relationship (SAR) studies are also limited in practice by synthetic tractability. This presentation will select two to three topics from currently ongoing projects in our group that have benefited from key contributions from technological, methodological, and strategic innovations.
For example, we have recently reported the synthesis of iminothienopyridinediones through photooxygenation reactions. Our lead structure in this series was found to be a potent inhibitor of the oncogenic, dual-specific phosphatase PTP4A3 (in vitro IC50 ~35 nM), as well as its family members PTP4A1 and PTP4A2. The SAR analysis as well as the scale-up of the iminothienopyridinedione chemotype were greatly facilitated by in-flow techniques, first using fluoroelastomer tubing and a compact fluorescent lamp (CFL), and then a 3-D printed polypropylene cartridge system under LED light irradiation.
Another case study to be presented focuses on strategic innovations in the total synthesis and the investigation of the CNS/GPCR effects of Ergot Alkaloids. In particular, the influence of scaffold rearrangement and stereochemistry on the serotonin (5-HT) receptor modulation of Ergot Alkaloid analogs will be highlighted, a biological property that is significant for their potential for future development as anti-depression and anti-anxiety pharmaceuticals.

Chem 268: Prof. Martin Kampmann
2021-02-26 15:30
“Elucidating cellular pathways controlling protein aggregation, spread and toxicity in neurodegenerative disease”

Chem 228: Ben Zhong Tang
2021-03-01 16:00
“Aggregology: Science beyond Molecules”

Proximity-enabled Reactivity for Biological Studies
2021-03-02 12:00
Abstract: To genetically introduce new chemical reactivity into live systems, we engineered the genetic code to encode a new class of unnatural amino acids (Uaas), the latent bioreactive Uaas. These Uaas, after being incorporated into proteins, specifically react with target natural amino acid residues via proximity-enabled reactivity, enabling the selective formation of new covalent linkages within and between proteins both in vitro and in live systems. These diverse reactivities, inaccessible to natural proteins, open doors to novel protein engineering, biological research, and therapeutic applications. I will present specific examples of using the proximity-enabled reactivity to probe ligand-receptor binding, to identify elusive protein-protein interactions, and to develop covalent protein drugs for cancer immunotherapy.

Dissertation Seminar: Cliff Boldridge
2021-03-03 12:30
“Specificity in Protein-Protein Interactions: High-Throughput Characterization of Rationally Designed and Naturally Evolved Coiled-Coil Networks”

Chem 278: Prof. Sheng Xu
2021-03-03 16:00
Controlled epitaxial growth and fabrication of hybrid halide perovskites
Abstract: Organic–inorganic hybrid halide perovskites have demonstrated tremendous potential for next-generation electronic and optoelectronic devices due to their remarkable carrier dynamics. Current studies are mostly focused on polycrystals, since controlled growth of high-quality single crystals is challenging. In this presentation, I will discuss strategies that enabled the first chemical epitaxial growth of single-crystal hybrid halide perovskites. Using advanced microfabrication, homo-/hetero-epitaxy, and a low-temperature solution method, single crystals can be grown with controlled locations, morphologies, orientations, and strain levels. By a lifting off approach, single-crystal thin films can be transferred from the epitaxial substrate to a general flexible substrate. This approach opens up broad opportunities for hybrid halide perovskite materials based high-performance electronic and optoelectronic devices.

Chem 218 Student Exit Seminar: Sophia King
2021-03-04 12:00
Controlling the Architecture of Nanoporous Materials to Regulate their Thermal Conductivity and Optical Transparency for Energy Efficient Windows
Transparent, low thermal conductivity coatings can be applied to windows to increase the energy efficiency of buildings. Amorphous material such as silica make good thermal insulators due to their local atomic disorder that impedes heat conduction. Moreover, pores can be added to the material to further reduce heat conduction by decreasing the material density while adding interfaces can additionally scatter heat carriers. This concept is often used in highly porous silica aerogels, which are valued for their ultra-low thermal conductivities. However, these aerogels significantly scatter light, and therefore cannot be used for applications that require high optical transparency. This talk focuses on our ongoing efforts to design silica-based coating that are insulating as well as optically transparent. First, I will describe our efforts using mesoporous thin films to expand on our fundamental understanding of heat transport in nanoporous, silica-based materials. Next, I will discuss how the knowledge gained from these thin film studies influenced our design of novel precursors and a scalable synthetic method to produce monoliths that can be used in thermal insulation applications. Finally, I will describe our efforts to use small angle X-ray scattering (SAXS) to follow structural changes in porous materials with the goal of understanding how surface chemistry and drying dynamics influence pore structure to produce materials with desired thermal conductivity and optical quality.
