UCLA

Combining Synthetic Chemistry and Biology for Streamlining Access to Complex Molecules
2022-02-01 10:30 (America/Los_Angeles)
Abstract: By virtue of their unrivaled selectivity profiles, enzymes possess remarkable potential to address unsolved challenges in chemical synthesis. The realization of this potential, however, has only recently gained traction. Recent advances in enzyme engineering and genome mining have provided a powerful platform for identifying and optimizing enzymatic transformations for synthetic applications and allowed us to begin formulating novel synthetic strategies and disconnections. This talk will describe our recent efforts in developing a new design language in chemical synthesis that centers on the incorporation of biocatalytic approaches in contemporary synthetic logic. Case studies will focus on the use of this platform in the chemoenzymatic syntheses of complex natural products and also highlight how this platform could serve as a starting point to enable further biological and medicinal chemistry discoveries.

NSF Center for Integrated Catalysis Webinar Series
2022-02-01 10:30
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 1st, 2022 at 10:30 AM. We are pleased to invite all students, postdocs, faculty, and staff.

Chem 278: Special Inorganic Chemistry Seminar - Dr. Matthew Nava
2022-02-02 16:00
“Elucidation of Reactive Species and Biological Processes Enabled by Molecular Design”

Physical Chemistry Seminar: Dr. Daniel Straus, Princeton University
2022-02-03 12:00
Structural Surprises in Inorganic and Molecular Materials
Even in some of the most heavily studied materials, a careful structural analysis can solve stubborn mysteries. The first part of my talk focuses on cesium lead iodide (CsPbI3), an inorganic halide perovskite of interest for solar energy conversion that is unstable at room temperature. I use X-ray diffraction measurements to reveal that that the Cs atom rattles within its coordination polyhedron, causing the material’s thermodynamic instability. Next, I demonstrate the remarkable emergence of chirality in the self-assembled molecular material C60(SnI4)2, despite the very high icosahedral and tetrahedral symmetry of its constituent molecules. These results demonstrate that almost any molecular, nanocrystalline, or engineered precursor can be considered when designing chiral assemblies, allowing new classes of optical devices, asymmetric catalysts, and biological sensors to be imagined.

New Base-Promoted Reductive and Oxidative Coupling Reactions
2022-02-03 16:00
Abstract: Base-catalyzed reactions typically accomplish redox neutral transformations, such as the addition of pronucleophiles to electrophiles. Our group is developing mechanistic platforms for base-promoted reductive and oxidative coupling reactions to expand the capabilities of basic chemistry. This talk will discuss the development and synthetic potential of these processes in the context of two methodologies. This includes the reductive defluorinative coupling of trifluoromethylarenes with electrophiles and the oxidative coupling of arenes with nucleophiles. Mechanistic studies will also be included to highlight the generality and future applications of these new base-promoted processes.

Chem 268 - Nicholas Graham
2022-02-04 15:30
“Identifying and decoding the function of the post-translational modifications arginine methylation and phosphorylation with proteomics”

Dr. Vida Jamali - Postdoctoral Researcher, Alivisatos lab, University of California Berkeley
2022-02-07 12:00
Imaging, Learning, and Engineering of Soft Matter Systems at the Nanoscale
The motion and dynamics of nanoparticles and macromolecules in bulk and at interfaces is of fundamental importance in physics, chemistry, and biology. Liquid phase transmission electron microscopy (LPTEM) is an emerging technique which enables nanoscale visualization of the motion and dynamics of single nanoparticles in liquid environment with an unprecedented spatial and temporal resolution. However, in order to develop LPTEM as a tool for in situ single nanoparticle and macromolecule tracking, we first need to understand how the electron beam of a transmission electron microscope affects the particle motion in the liquid environment and near surfaces.
In this talk, I will present my recent work on studying the anomalous diffusive motion of a model system of gold nanorods dispersed in water and moving near the silicon nitride membrane of a commercial liquid cell in a broad range of electron beam dose rates. By leveraging the power of convolutional deep neural networks inspired by canonical statistical tests, I show that there is a crossover in diffusive behavior of nanoparticles in LPTEM from fractional Brownian motion at low dose rates, resembling diffusion in a viscoelastic medium, to continuous time random walk at high dose rates, resembling diffusion on an energy landscape with trapping sites. I will then discuss how this work forms the foundation to study equilibrium and nonequilibrium dynamic processes for a broad range of nanoparticles, interfaces, and fluids in chemical and biological systems.

Chem 228: Michael B. Elowitz
2022-02-07 16:00
“Multicellular Circuit Design”

NSF Center for Integrated Catalysis Webinar Series
2022-02-08 12:30
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 8th, 2022 at 12:30 PM. We are pleased to invite all students, postdocs, faculty, and staff.

Chem 278: Special Inorganic Chemistry Seminar - Dr. Benjamin E. R. Snyder
2022-02-08 16:00
“Iron and Copper Active Sites in Porous Materials and Their Correlation to Metalloenzymes”

Strategic Bond Construction and Cleavage Enabled by Photocatalytic Radical Transformations
2022-02-09 10:30
Abstract: Radical chemistry is an important class of reactions in modern organic synthesis, due to the high reactivity and versatile bond formation and cleavage events that can happen with radical intermediates. One of the current challenges in radical chemistry is to generate these reactive open-shell intermediates from accessible starting materials under mild conditions. We have developed several powerful strategies to homolytically cleave strong X–H bonds and generate the corresponding X• radical via proton-coupled electron transfer (PCET). In this talk, I will present a photocatalytic intermolecular anti-Markovnikov hydroamination reaction of sulfonamides, and a remote C–H alkylation reaction of amides, enabled by the amidyl radicals generated via PCET. Moreover, we also developed a photocatalytic condition to conduct various carbocation reactions via mesolytic cleavage of alkoxyamine compounds. Lastly, to understand the remarkable chemoselectivity and improve the quantum efficiency of a set of photocatalytic hydroamination reactions, we performed detailed mechanistic studies, using advanced spectroscopic and electroanalytical tools to unveil the origin of the chemoselectivity of this reaction, and also improved the reaction quantum yields. Based on these studies, gram-scale synthesis of several dialkylamines were performed in a flow reactor.

Chem 278: Prof. Robert Macfarlane
2022-02-09 16:00
“Macroscopic Materials from Nanoparticle Assembly”

James Gaynor, Postdoc Fellow, University of California, Berkeley Seminar
2022-02-10 12:00
Stories of Coherence: From Vibronic to Electronic Phenomena
A robust understanding of chemical reactivity in excited states is essential for designing and discovering new ways of harnessing energy flow at the atomic and molecular level. Photo-induced coherent processes, which utilize atomic or molecular motions moving with a well-defined phase relationship, may enhance control over important photochemical events. This presentation explores a wide range of timescales over which coherence and decoherence occur in solution phase molecules, gas phase atoms, and in “atomic-like” excitations of a crystalline ionic solid. We will begin with a new perspective on the first two picoseconds of excited state charge transfer involving coupled electronic and vibrational (i.e., “vibronic”) motions in solution phase solar cell dye molecules. Next, pure electronic coherences in a noble gas are investigated in the absence of vibrational or environmental perturbations, lasting for hundreds of femtoseconds. Finally, we return to the condensed phase in the solid form, where many-body electron correlations appear to cause core-excited state dephasing on sub-10 femtosecond timescales.

Battery-Inspired Strategies for Electrocatalytic C–C and C–N Bond-Forming Reactions
2022-02-10 16:00
Abstract: The seminar will describe our efforts towards the development of scalable, mild, and general electrosynthetic methodologies for C–C and C–N/X coupling reactions. These electrosynthetic methodologies are largely possible because of a synergy between redox-active mediators developed by the energy storage community and transition metal catalysts. It will be shown that yields from electrocatalytic reactions are greatly improved by the incorporation of co-catalytic quantities of soluble battery compounds that mediate electron transfer with the coupling catalyst or protect the coupling catalyst from over-oxidation/reduction and degradation.
Employing mediators with properly tuned redox potentials and electron-transfer kinetics, we demonstrate electrocatalytic cross-electrophile coupling reactions of (hetero) aryl halides and alkyl halides that represent the state of the art in the area. Additionally, we demonstrate a broad scope for Chan-Lam coupling of amines and arylboronic acids in the absence of a chemical oxidants. Our studies reveal unique mechanisms that are only accessible under electrochemical conditions that enable cross coupling of tertiary electrophiles or arylchlorides: challenging substrates that are currently incompatible with any form of reductive activation.

Chem 268 - David Moffet
2022-02-11 15:30
“Untangling Amyloid: Slowing the Progression of Type 2 Diabetes”

Chem 228: David Pine
2022-02-14 16:00
“Self-assembly of colloidal diamond for photonics”

Chemical Strategies for Regulating DNA-Interactive Proteins: Targeting APOBEC Cytosine Deaminases and the N-Myc Transcription Factor
2022-02-15 16:00
Abstract: Our laboratory focuses on the development of small molecule ligands and enzymatic inhibitors of proteins that interact with nucleic acids. We utilize biophysical and biochemical assays to screen chemical libraries to discover protein-binding ligands, which are then optimized using iterative rounds of molecular design, synthesis, and biological evaluation. Our overarching goals are to develop chemical probes to enable the discovery of new biology by the biomedical research community, as well as develop novel and patentable therapeutic compounds for clinical development by a pharmaceutical partner. In this vein, two programs from our laboratory, the discovery of APOBEC inhibitors and N-Myc degraders, will be presented.
APOBEC enzymes are a family of 7 human DNA cytosine-to-uracil deaminases that degrade foreign DNA as part of the innate immune response to pathogen infection. However, APOBEC enzymes have been shown to contribute C-to-U/T mutations that enable virus and cancer cell genomic mutations that confer resistance to drug therapies. Consequently, small molecule APOBEC inhibitors may have utility as “anti-mutation” therapies that slow or prevent the evolution of resistance mutations that defeat targeted drug therapies. Our work to develop first-in-class APOBEC inhibitors will be presented.
The Myc family of transcription factors are master regulators of proliferation in the majority of human cancers. In the case of childhood neuroblastomas, which are the most prevalent cancer in children under 1-year of age, N-Myc is a validated therapeutic target and molecular diagnostic. A vulnerability of N-Myc in many neuroblastomas is that N-Myc is stabilized from proteolytic degradation by Aurora kinase A (Aurora-A). We have developed novel chemical degraders of Aurora-A, such as HLB-0532259, that elicit the degradation of Aurora-A and the concomitant degradation of N-Myc. HLB-0532259 also exhibits potent antiproliferative activity in neuroblastoma cells and xenograft mouse models. Our work to develop novel N-Myc degraders will be presented.

Investigating Selectivity in Complex Systems: from Total Synthesis to Glycan Labeling
2022-02-16 10:30
Abstract: The indole diterpenoids constitute a family of natural products that exhibit potent and selective Big Potassium (BK) ion channel inhibition. We have developed a unified synthetic strategy towards the indole diterpenoid class, culminating in the total synthesis of several representative congeners, including paspaline A and emindole PB. Density functional theory calculations are utilized to interrogate a simplifying key bond formation in a predictive capacity to aid in the selection of the most favorable precursor substrate. This work highlights how retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time- consuming and expensive empirical evaluation. Furthermore, these studies provide modular entry to privileged indole diterpenoid class of natural products, enabling their application as tool compounds for interrogating BK channel dynamics, as well as therapeutic leads for channelopathies linked to BK channel dysregulation.
Glycans are ubiquitous and play important biological roles, yet chemical methods for probing their structure and function within cells remain limited. Strategies for studying other biomacromolecules, such as proteins, often exploit chemoselective reactions for covalent modification, capture, or imaging. Unlike amino acids that constitute proteins, glycan building blocks lack distinguishing reactivity because they are composed primarily of polyol isomers. Moreover, encoding glycan variants through genetic manipulation is complex. To address these limitations, we have developed a new, generalizable strategy for monomer-selective glycan modification that exploits the reactivity of cellular glycosyltransferases by designing reagents with bioorthogonal handles that function as substrate surrogates. Further, we demonstrate the utility of these labeling reagents by using them to study the biosynthesis, localization, and dynamics of cell wall glycans in mycobacteria.

Special Biochem/PChem Seminar - Eitan Lerner
2022-02-16 14:00
“Structure-function relationship of an unstructured protein – the alpha-Synuclein case”

Chem 278: Prof. Thomas Kempa
2022-02-16 16:00
“Precision Synthesis of Quantum Material Building Blocks”

Dr. Joonho Lee. Postdoctoral Fellow, Columbia University/Google Quantum AI Seminar
2022-02-17 12:00
Challenging Problems in Quantum Chemistry: How to Diagnose Them and How to Tackle Them
Quantum chemistry has become an indispensable tool in revealing the microscopic details of molecules and materials such as barrier heights, interaction energies, and correlation functions. The nature of electronic correlation is sometimes controversial, obscuring the optimal choice of quantum chemistry methods with minimal computational effort and the desired accuracy. First, I will discuss a computational framework that addresses this question using regularized perturbation theory. Second, I will also discuss several challenging problems beyond the scope of such perturbation theory. I will argue that these problems can be tackled by methods based on auxiliary-field quantum Monte Carlo. Lastly, I will present my latest development of a new quantum-classical hybrid algorithm in this context, which represents the largest quantum computation of chemical systems on a quantum computer to date.

Searching for Selective Catalytic Reactions in Complex Molecular Environments
2022-02-17 16:00
Abstract: This lecture will describe recent developments in our efforts to develop catalysts for asymmetric reactions, in particular for the preparation of densely functionalized, stereochemically complex structures. Over time, our foci have been on enantioselectivity, site-selectivity and chemoselectivity. In much of our current work, we are studying issues of enantioselectivity as a prelude to the extrapolation of catalysis concepts to more complex molecular settings where multiple issues are presented in a singular substrate. Mechanistic paradigms, and their associated ambiguities – especially in light of catalyst or substrate conformational dynamics – will figure strongly in the lecture, raising analogies to enzymes. Finally, several interesting – and often unexpected – collaborations with colleagues in industry will be discussed.

Chem 268 - Jennifer Niven Shepherd
2022-02-18 15:30
“Characterization of RquA – a novel enzyme used in microbial rhodoquinone biosynthesis”

Chemistry at the Biomedicine Interface: Synthesis and Catalysis
2022-02-22 10:30
Abstract: Chemical reactivity can be utilized in many ways, including to improve synthetic access to new molecules and to devise tools to advance biomedicine. ‘Synthesis and catalysis’ are two themes interwoven throughout this presentation, which describes 1) the development of short synthetic routes to (–)-picrotoxinin, (–)-picrotin, and 5-methyl-picrotoxinin enabled by a late-stage strong-bond activation strategy for the long term goal of interrogating GABAa receptor combinatorial diversity, 2) the development of three methods for alkene hydrofunctionalization using Mn- and Co- hydrogen atom transfer chemistry, and 3) two studies in catalysis centered on one-carbon metabolism which improve understanding of how one-carbon metabolites contribute to health and disease.

Chem 278: Prof. Sara Skrabalak - MilliporeSigma Inorganic Nano-Materials Lecture
2022-02-23 16:00
“Multimetallic Nanomaterials by Design”

Insight-Driven Strategies in Catalysis for Selective Functionalizations
2022-02-24 16:00
Abstract: Detailed understanding of catalytic transformations is key to designing better catalysts and overcome pertinent challenges in synthesis. This talk will give insights on case studies and reactivity designs recently undertaken in our laboratory. The focus will be on multinuclear metal catalysis for the chemoselective and modular construction of molecules, the exploration of organogermanes in catalysis, and the development of synthetic strategies towards novel fluorinated motifs. Experimental and computational tools were applied in these studies.

Chem 268 - Hung Ton-That
2022-02-25 15:30
“Sortase-catalyzed surface assembly in monoderm bacteria”

Chem 248 - Organic Chemistry Student Seminar
2022-02-28 15:00
Harnessing Bifunctional Ligands for Regioselective C–H Bond Functionalization

Chem 228: Robijn Bruinsma
2022-02-28 16:00
“Physics and the HIV-1 virus”

Chem 228: Prof. Denis Usvyat
2022-03-01 11:00
“High-accuracy Theoretical Treatment of Defects in Periodic Systems”
