UCLA

Chem 278: Prof. Wenliang Huang
2021-03-31 16:00 (America/Los_Angeles)
“f-Block metal-arene interactions: from inverse sandwiches to redox chemistry”
Abstract: Recent years have witnessed the breakthrough of identifying unusual oxidation states of f-block elements in molecular compounds such as divalent rare earth metals and actinides, as well as tetravalent terbium and praseodymium. By taking advantage of the symmetry and energy match between the f/d orbitals of low-valent f-block ions and π* orbitals of arenes, we synthesized a series of metal arene complexes featuring an inverse-sandwich structure. We found that δ bonds are responsible for the unusual stability of the tetranionic arene anions in such compounds. Moreover, f-block ions show a significant covalent character, and the extent of covalent interaction increases according to the order: rare earth metals < thorium < uranium. Inspired by these metal-arene δ bonding interactions, as well as the traditional π-donor character of arene ligands, we designed a tripodal-type tris(amide) ligand system featuring an arene anchor. We anticipated that the amphiphilic nature of the arene backbone may support both low and high valent f-block metal centers. This strategy allowed us to stabilize multiple oxidation states of f-block metals with a single ligand and opened up new avenues in the redox chemistry of these ions.

Chem 268: Prof. Hernan Garcia
2021-04-02 15:30
“Dissecting Transcriptional Dynamics in Development One Burst at a Time”

OCDS Seminar: Prof. Karin Chumbimuni-Torres
2021-04-05 16:00
“Electrochemical biosensors for viruses and bacteria: new approaches and challenges”

Chem 278: Prof. Charles W. Machan
2021-04-07 16:00
“Earth-Abundant Molecular Catalyst System for the Reduction of Dioxygen and Carbon Dioxide”
Abstract: The steady increase in anthropogenic carbon dioxide (CO2) emissions and corresponding atmospheric concentrations continues to generate interest in using CO2 as a liquid fuel and commodity chemical precursor. The conversion of CO2 has the dual benefit of addressing its associated negative environmental effects and the diminishing supply of petrochemical feedstocks. At the heart of efficient reductive transformations are proton-coupled electron transfer (PCET) reactions, where electrons and protons move in a concerted way to mitigate kinetic and thermodynamic penalties. Mechanistic understanding of these reactions can inform the design of optimized catalyst structures with improved activity and selectivity for specific products. Another cathodic reaction, the electrocatalytic reduction of dioxygen (O2), has relevance to the development of more efficient fuel cells and can be similarly optimized through fundamental knowledge of the underlying PCET reactions. Molecular systems are well-positioned to provide a better understanding of these reactions because of the relative fidelity with which they can be characterized, as well as the possibility for systematic testing of structure-function relationships through iterative molecular design. In addition to developing new Fe-, Mn-, and Cr-based molecular electrocatalysts for these reactions, we are exploring the use of redox mediators and flow-based electrochemical reactors to understand how these reactions can be scaled relative to comparable heterogeneous systems.

Chem 228: Prof. Chanmin Su
2021-04-12 16:00
“Scanning probe microscopy for physical and chemical property characterizations at the nanoscale”

NSF Center for Integrated Catalysis Webinar Series
2021-04-13 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, April 13th, 2021 at 1:00 PM. We are pleased to invite all students, postdocs, faculty, and staff.

Perfluorocarbon nanomaterials as theranostic delivery vehicles
2021-04-13 16:00
Abstract: Perfluorocarbon nanoemulsions, droplets of fluorous solvent stabilized by a polymeric amphiphile dispersed in water, are an intriguing platform for drug delivery. The fluorous phase is biocompatible, has a high dissolved oxygen content, and is both lipophobic and hydrophobic, preventing the leaching of payloads. Here, we describe the use of perfluorocarbon nanoemulsions as a drug delivery platform in which the payload can be easily modified. First, we utilize the high oxygen solubility of perfluorocarbons to perform photodynamic therapy, a treatment modality that requires oxygen, photosensitizer, and light to produce cytotoxic reactive oxygen species. Next, we deliver pDNA solubilized by noncovalent fluorous tags, resulting in the transfection of cells. Lastly, a panel of polymeric amphiphiles were studied to determine design properties such as size, stability, payload release, cellular uptake and protein corona. With these design principles PFC nanoemulsions can be tailored to a desired application.

2020-2021 Sigman Symposium
2021-04-15 10:00
The UCLA Molecular Biology Institute (MBI) will hold the 2020-2021 Sigman Symposium in honor of Professor David Sigman (1939-2001), who was an internationally renowned UCLA professor of chemistry and biological chemistry who illuminated the molecular mechanisms by which enzymes catalyze biological reactions and was one of the founding members of the MBI.
2020-2021 Sigman Award Honoree:
Professor Catherine DrennanDepartments of Chemistry and BiologyMassachusetts Institute of Technology andthe Howard Hughes Medical Institute
Kenote Address: “Shake, Rattle, & Roll:Capturing Snapshots of Ribonucleotide Reductase in Action”
Symposium Schedule – Thursday, April 15, 2021 – 10 am to 1:30 pm

Tribute to David Sigman: Prof. Steven Clarke
Guest Speaker: Prof. Douglas Rees (Caltech):“The Ns and Outs of Nitrogen Fixation”
Keynote introduction/award presentation: Prof. Keriann Backus
Keynote address: Prof. Catherine Drennan
Poster Session and Poster Prize Announcement

PosteSession: The poster session will feature immersion in an 8-bit world complete with “walking” around to interact with poster presenters and attendees, games, and more while providing an opportunity to share your science with our awardee, members of the UCLA community, and have a chance to win one of our poster prizes! Poster prizes will include Best Poster Prizes (up to four $250 prizes) and Honorable mention prizes (up to four $100 prizes) and will be selected with an audience voting component. All UCLA students and postdocs studying in any area of biology or chemistry are eligible to submit. To present a poster please fill out the google form with your poster title by Friday, April 2, 2021 and submit a png, jpeg, or gif image file of your poster to SigmanSymposium2021@gmail.com by Tuesday April 6, 2021. Poster prize winners will be announced after the poster session in a gather.town award ceremony.
For more information about the Sigman Symposium or poster session please visit the MBI website or email SigmanSymposium2021@gmail.com.

Electrophotocatalysis with a trisaminocyclopropenium ion
2021-04-15 12:00
Abstract: This lecture will describe some recent developments in the area of electrophotocatalysis, with a particular focus on a trisaminocyclopropenium (TAC) ion catalyst developed by our group.

Chem 268: Dylan Valencia
2021-04-16 15:30
Quinlan Group
“Biochemical Characterization of Mammalian Formin FHOD3 in Cardiomyocytes”

Chem 228: Prof. Hirofumi Tanaka
2021-04-19 16:00
“Reservoir computing device composed by chemical dynamics”

Trehalose glycopolymer as an excipient for insulin stabilization: safety, mechanism, optimization, and fluid properties
2021-04-20 16:00
Abstract: Biopharmaceutics are widely used to treat serious diseases, but the architectural and chemical complexity that makes proteins good therapeutics renders them susceptible to degradation and aggregation during manufacturing, transportation, and storage. Loss of intact biopharmaceutics causes patient under-dosing as well as adverse reactions. With the growth of biopharmaceuticals coming to market, the need increases for benign excipients to stabilize proteins against environmental stresses without posing a safety concern. A class of glycopolymers bearing a pendant trehalose, a natural sugar, were developed by our group and demonstrated the ability to stabilize a range of biopharmaceuticals. However, this research area had not yet explored the trehalose polymer for safety, mechanism of stabilization, physical properties, or potential optimization. This talk focuses on the ongoing efforts to expand our knowledge base in applying the methacrylate trehalose polymer as an excipient to formulate biopharmaceuticals. In particular, I will highlight the glycopolymer’s benign immunogenic, excretion, and biodistribution behaviors as well as how proteins are unaffected in vivo by the polymer. Next, because the mechanism by which proteins are stabilized as well as the conformation in which they are stabilized affects their onset of activity, I will show how the glycopolymer stabilizes insulin. Due to the importance of patient comfort and compliance, I will finally present my research into the fluid properties of the glycopolymer, optimization of insulin formulations, and optimized formulations properties. Altogether, this work shows specifically how insulin is stabilized by the methacrylate trehalose polymer and, more broadly, that the glycopolymer can be broadly applied as an excipient to stabilize therapeutic macromolecules safely and without significantly changing the in vivo response or physical properties.

Chem 278: Prof. Jinyao Tang
2021-04-21 16:00
“Synthetic Nanorobot – from Individual Microswimmer to Active Swarm”
Abstract: Over 60 years ago, Prof. Richard Feynman envisioned that, in principle, machines could be made so tiny, we can use them to construct matters from atomic/molecular scale; nanorobots can perform surgeries and deliver drugs at cellar level. Sixty years later, the scientific community finds an inconvenient truth: many scientific challenges remain to be solved before nanodoctor can really enter clinics. In this talk, I will start with the realization of the synthetic microswimmers with optical navigation capability to discuss how light can be used to manipulate designed semiconductor microparticles at high precision. I will then showcase how simple theoretical consideration in surface kinetics can help make microswimmer particles more biocompatible and operational in the biological environment. At last, I will envision an intelligent, active swarm system based on complex chemical interaction networks which may be used as a true nanosurgeon in the future.

Chem 218 Student Exit Seminar: Fang-Chu Lin
2021-04-22 12:00
“Superparamagnetic Core/Shell Mesoporous Silica Nanoparticle for Magnetic Heating-Induced Anticancer Drug Delivery”
ABSTRACT: Superparamagnetic iron oxide nanoparticles (SPION) generate heat in the presence of an alternating magnetic field (AMF) and are used in clinics to treat cancers. Mesoporous silica nanoparticles (SPION@MSN) embedded with SPION possess the advantageous features of both the SPION core and the shell, i.e., localized magnetic heating and a high payload of various cargo molecules such as anticancer drugs, respectively. This talk focuses on the development of SPION@MSNs as a heat-activated drug delivery platform in which the precise drug release can be directly controlled by using AMF. To expand our knowledge base in this application, we first study the local heating mechanism of a SPION in suspension and in MSN. We carried out this investigation by using fluorescence depolarization based on detecting the mobility-dependent polarization anisotropy of two luminescence emission bands corresponded to the luminescent SPION core and the shell of the SPION@MSN. Utilizing the magnetic heating, we then designed a magnetically activated and enzyme-responsive SPION@MSN vehicle with extra-large pores to deliver and release anticancer peptides on-demand. We demonstrate that a SPION core can act as a nano-heater to stimulate a cascade drug release and high tumor-targeting/inhibiting efficiency can be achieved. Altogether, these works show the full potential of AMF-controlled core/shell nanoparticle vehicles for a more selected and precise dosage control.

Understanding the chemistry of volcanic RNA to treat cancer & COVID-19
2021-04-22 16:00
Abstract: N4-acetylcytidine is an ancient RNA modification catalyzed by an enzyme essential for human life. However, its distribution, dynamics, and function remain mysterious. In this seminar I will introduce my group’s work developing chemical tools to investigate RNA acetylation, why this led us to study an organism that thrives in solfatara (volcanic craters), and how we are using these fundamental studies to enable new therapeutic approaches.

Chem 268: Brendan Mahoney and Sudeepa Rajan
2021-04-23 15:30
Brendan Mahoney, Ph.D.
Clubb Group
“Leveraging a new fluorescent fusion sensor reveals that bacterial chaperones associate with one another to rapidly transfer heme”
~and~
Sudeepa Rajan, Ph.D.
Reisler Group
“Disassembly of fascin bundled actin filaments via their oxidation by Mical”

Chem 228: Prof. Andrew Pelling
2021-04-26 16:00
“Growing Cells on Apples, LEGOs and Bread. Why Developing Unconventional Biomaterials Matters.”

The Revolution Will Be Compartmentalized: Activity-Based and Cellular DNA-Encoded Library Technology
2021-04-27 16:00
Abstract: The NIH Molecular Libraries Program was founded to translate the discoveries of the Human Genome Project into therapeutics through a network of high-throughput screening (HTS) centers. A decade of discovery produced hundreds of probes—highly selective small molecules that modulate cellular function—but centralized HTS bears the same cost and infrastructure burdens of millennial DNA sequencing centers, restricting access to the technology and therefore the rate of probe discovery. We are building a distributable drug discovery platform analogous to next-generation DNA sequencing based on ultra-miniaturized solid-phase DNA-encoded libraries and microfluidic instrumentation for scalable, automated screening. I will overview chemical synthesis and microfluidic screening technology development efforts and describe their application to hit finding for two clinically relevant targets implicated in fibrosis and cancer. Looking toward the future, we are exploring approaches that directly translate genomic sequence into bioactive chemical probes, with the ultimate goal of fulfilling the originally promised pay dirt of the Human Genome Project.

Chem 278 Prof. Liu Research Group Seminar
2021-04-28 16:00
“Enhanced Gas Transport in Hybrid Bio-Inorganic CO2 and N2 Fixation Systems”
Abstract: With the surge of intermittent, renewable electricity, the storage of excessive electricity and reduction of CO2 or N2 into value-added chemicals is of great significance for a sustainable society. One viable route is to construct a hybrid inorganic-biological system that converts electricity into chemical energy and reduces CO2/N2 into commodity chemicals. In this general approach, water is electrochemically split into H2 and O2 and the yielded H2 is consumed by microbes as a reducing equivalent for CO2/N2 reduction. This system has demonstrated high efficiencies however, the output of the commodity chemicals is limited by the supply of the reducing equivalent, H2, within the system. While we can electrochemically control the rate of H2 production, the poor solubility of H2 in the aqueous environment results in a bottleneck. Here, we demonstrate the addition of perfluorocarbon (PFC) nanoemulsions to increase H2 solubility and improve the kinetic rate of gas transport to the microbes for enhanced chemical production. With PFC nanoemulsions applied to our hybrid CO2 fixation system, we maintained nearly 100% Faradaic efficiency over a range of applied current densities and increased the throughput 2.9 times at 2.0 mA/cm2. Similarly, by adding varying percentages of PFC nanoemulsion to our N2 fixation system we were able to control the H2 and O2 concentrations in solution and enhance N2 fixation. Overall, our research demonstrates the use of PFC nanoemulsions to enhance gas solubility and gas transport in aqueous solution for favorable reaction conditions and improved rates of chemical production.

Chem 218 Student Exit Seminar: Peiqi Wang
2021-04-29 12:00
“Van der Waals Integration beyond 2D Heterostructures”
Abstract: The integration of dissimilar materials to form heterostructures with designable electronic interfaces is central in modern electronic devices and has thus been a long pursuit in material science. The traditional integration methods such as metal evaporation, atomic layer deposition (ALD) and epitaxial growth typically rely on strong chemical bonds to combine the constituent materials. However, this approach has limited freedom in integrating materials with distinct structural or chemical compositions due to the lattice matching or process compatibility requirements. Inspired by the variety of 2D van der Waals (vdW) heterostructures, a physical transfer process exploiting the universal vdW force is proposed for damage-free integration of metal contact and 2D semiconductors to form pinning-free junctions approaching Schottky-Mott limit, opening up vast freedom for creating a new generation of vdW-integrated devices beyond the reach of traditional heterostructures. This talk summarizes our recent progress of vdW integration of high-quality contacts of nearly arbitrary metals, gate dielectrics and bulk semiconductors to create high-performance devices including 2D metal-oxide-semiconductor field-effect transistors (MOSFETs), metal-semiconductor FETs (MESFETs) and junction FETs (JFETs) based on bulk semiconductor β-Ga2O3, which all exhibit atomically clean and electronically sharp interfaces with nearly ideal electronic functions. These devices extend vdW integration to a broader library of materials for creating high-performance electronic devices and explore the potential of vdW integration as a general and efficient approach for circuit-level integration.

New Synthetic Opportunities through Organic Photocatalysis”
2021-04-29 16:00
Abstract: Development of new synthetic strategies via organic photocatalysis in our group was described. Both photoacidic activity and photoredox activity of organic photocatalysts were discussed. A series of phenol-conjugated acridinium-based organic photoacids were rationally designed, synthesized and studied alongside commercially available phenolic catalyst, eosin Y. In the presence these photoacid catalysts and light, synthetic glycals underwent activation and coupled with a range of alcohols to afford 2-deoxy-glycosides in good yields with excellent a-selectivity. Moreover, a recent development of photo Lewis acid catalyst was described. In addition, a photocatalytic N-radical cascade reactions were discussed, including synthesis of pyrroloindolines, rapid synthesis of flustramide B, and remote allylation of uncativated sp3 C-H bonds.

Chem 268: Sean D. Gallaher and Einav Tayeb-Fligelman
2021-04-30 15:30
Sean D. Gallaher, Ph.D.
Merchant Group
“Prokaryotic-style polycistronic gene expression in eukaryotic green algae”
~and~
Einav Tayeb-Fligelman, Ph.D.
Eisenberg Group
“Modulation of Amyloid Formation of the Nucleoprotein of SARS-CoV-2”

OCDS Seminar: Prof. Markita Landry
2021-05-03 16:00
“Nanomaterials Enable Delivery of Genetic Material Without TransgeneIntegration in Mature Plants”

Molecular recognition tools for chemistry in living systems
2021-05-04 16:00
Abstract: The introduction of unnatural functionality in biological systems coupled with detection using bioorthogonal chemical reactions revolutionized the field of chemical biology by enabling the investigation biological processes in live cells and simple organisms. However the translation to complex organisms has led to less than optimal results with high background noise due to cross reactivity with activated reagents. This work investigates the utilization of non-covalent chemistry and bioorthogonal host-guest pairs to obtain more efficient labeling of living systems. Complexation between a host and guest is diffusion-limited, hence can be efficient in dilute environments. The cucurbit[n]uril scaffold has been utilized to determine the minimum binding affinity required for efficient bioorthogonal complexation and investigate how guest size and charge affects the introduction of guests as unnatural metabolites. Carboranes, a cucurbit[7]uril guest class that can be removed “on demand” from the host cavity, were found compatible with metabolic glycoengineering and were successfully incorporated on the cell surface. The cucurbit[7]uril-carborane system serves as the first example of bioorthogonal complexation and answers fundamental questions required for the further development of bioorthogonal host-guest pairs.

Chem 278: Prof. Henry S. La Pierre
2021-05-05 16:00
“Electron (De) Localization in f-Element Systems: From Fundamental Questions to QIS Design Principles”
Abstract: The La Pierre group studies how collective magnetic, physical, and chemical properties arise from electron (de)localization phenomena in f-element systems. Our studies include the development of solid-state and solution methodologies for the synthesis of novel lanthanide and actinide (Th – Pu) materials and complexes. These synthetic efforts are paired with synchrotron and neutron spectroscopies and physical property studies to break down the challenge of understanding the electronic structure of f-element systems. Particularly in solid-state systems, the f-elements present unique valence electronic structures due the near degeneracies engendered in these systems and strong electron correlation. Our efforts to-date have focused on the synthesis and analysis of systems governed by one of three phenomena: magnetic super-exchange (i.e. exchange coupled systems), multi-configurational electronic structures (ground state degeneracy including hybridization with ligand/band states), and mixed-valence metal ions (i.e. mixed f/d occupancy and mixed-oxidation states). Understanding and controlling the manifestation of these phenomena in molecular systems is crucial for understanding the interplay of these phenomena underpinning topological insulators such as SmB6 and PuB6 and superconductors such as CeCoIn5 and PuCoGa5. In turn, the group has employed this expanded fundamental understanding of f-element electronic structure to construct components of quantum information technologies (e.g. qubits, single-molecule magnets).

Chem 218 Student Exit Seminar: Jack Fuller
2021-05-06 12:00
Secondary Coordination Effects in Artificial Biotin-Streptavidin Metalloenzymes
Designing artificial metalloenzymes is of interest because they combine the catalytic activity of possibly non-physiological but highly catalytically potent metals and the selectivity and mild operational conditions enabled by the protein. This talk will focus on joint theory-experiment efforts to design Rh and Ir artificial metalloenzymes, catalyzing the formation of 5-membered and 6-membered N-heterocycles. The biotin-streptavidin system has been used as a relatively simple and robust platform to create metalloenzymes by embedding organometallic catalysts in the protein. The monomeric streptavidin is known to retain the fold upon many different mutations, thus enabling the control over the second coordination sphere of the metal and fine-tuning of the metal electronic properties in a variety of ways without losing the entire structure. Biotin-Sav artificial metalloenzymes prepared in this way and containing Rh/Ir(Cp*) have shown improved reactivity and selectivity over simpler organometallic catalysts. We aimed to both explain the improved activity and to enhance it further by strategic mutagenesis. We have analyzed the secondary coordination effects using quantum mechanistic calculations, bonding analysis, and hybrid quantum mechanical/molecular mechanical simulations. In collaboration with experiment, we probed a library of mutants. In particular, we show that the pi-pi interaction between the catalyst and a tyrosine sidechain decreases rate-determining barriers. Additional residues in the vicinity of Tyr contribute to the quality of the pi-pi contact and the reactivity tuning. More remote mutations within the protein scaffold affect the protein structure and dynamics slightly, and thus affect the pi-pi contact indirectly, also impacting the activity. Successful and failed strategic and accidental mutations were made with the goal of improving the pi-pi contact, and will be discussed. Finally, we demonstrated that the activity correlates the most with the properties of the ensemble of states within the protein dynamics, showcasing the need for rapid QM/MM sampling in this work.

Strain molecules assist peptide and protein synthesis, a new venue for thiolactones
2021-05-06 16:00
Abstract: The broad application of macrocycles has illustrated significant potential as therapeutic agents. 12-membered ring cyclotetrapeptides are particularly attractive entities among all the cyclic peptides. Compared with macrocycles of larger ring size, the characteristic head-to-tail or end-to-end peptidyl backbone provides intrusive structural motif of circular peptides grants distinct biological properties such as resistance to degradation, enhanced conformational stability, and increased epitope interactions with other biomolecules. Ability to acquire a sufficient quantity of high purity of cyclo-tetrapeptide could significantly promote their chemical and biological studies.
It is worth noting that the traditional coupling methods to achieve chemical synthesis of macrocycles have been a formidable challenge, requiring fully protected linear precursors and harsh conditions to achieve activation of the C-terminal residue for the cyclization. The harsh activation conditions are required to overcome the entropy barrier during the coupling often lead to epimerization of the C-terminal amino acid residue and peptide oligomerization. The practical strategy to attain macrocycles with a consensus sequence of L-cyclo(Pro-Xxx-Pro-Xxx), where Xxx = Val, Tyr, Leu, Phe, are elusive. There is the urgent need to develop a strategy to prepare circular tetrapeptides. Based on our previously reported β-thiolactone mediated chemistry, iii we were able to construct tetra-cyclic peptides in high yields. The strategy could be applied to produce a broad number of all-L-cyclo-tetrapeptides and the reactions were performed at room temperature in the aqueous buffer. The β-thiolactone furnished cyclization protocol prevented the amino acid epimerization during the cyclization and proved as a powerful general strategy for cyclic peptide synthesis.

Chem 268: Hannah Bailey
2021-05-07 15:30
Quinlan Group
“Utilizing Drosophila melanogaster to understand the role of actin dynamics in oogenesis”

Chem 228: Prof. Andreas Heinrich
2021-05-10 16:00
“Taking Electron Spin Resonance to the Single Atom and Molecule”

NSF Center for Integrated Catalysis Webinar Series
2021-05-11 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, May 11th, 2021 at 1:00 PM. We are pleased to invite all students, postdocs, faculty, and staff.
