UCLA

Chem 218 Student Exit Seminar: Mary Grumbles
2021-02-18 12:00 (America/Los_Angeles)
“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.

Break-it-to-Make-it Strategies for Chemical Synthesis Inspired by Complex Natural Products”
2021-03-04 16:00
Abstract: Natural products continue to inspire and serve as the basis of new medicines. They also provide intricate problems that expose limitations in the strategies and methods employed in chemical synthesis. Several strategies and methods that have been developed in our laboratory and applied to the syntheses of architecturally complex diterpenoid alkaloids, indole alkaloids, and several Lycopodium alkaloids, will be discussed. In addition, new ways to employ C–C bond cleavage in synthesis will be presented (i.e., break-it-to-make-it strategies).

Chem 268: Prof. Benjamin Falcon
2021-03-05 13:30
“Amyloid conformers in neurodegenerative disease”

Chem 228: Peter Dahlberg, Ph.D.
2021-03-08 16:00
“Combining cryogenic single-molecule fluorescence measurements and CryoEM: New methods with applications from biology to physical chemistry”

Chem 218 Student Exit Seminar: Wenfei Li
2021-03-10 12:00
Developing Highly Efficient Electronic Structure Theory Methods for Large Scale Simulations
Electronic structure simulations are now becoming an indispensable tool in chemistry research. The overall goal is to develop methods that give accurate results without sacrificing efficiency. In our group, we incorporate various computational techniques to drastically reduce the cost of simulations. This allows us to run large scale simulations that were not previously possible. Our major innovation is stochastic quantum chemistry, where we replaced the summation over thousands of deterministic orbitals to an average over much smaller number of stochastic orbitals, and sometimes only a few suffices. This leads to significant increase in efficiency. In this seminar, I will talk about my two projects under the stochastic quantum chemistry framework. The first project involved developing an embedding stochastic framework, where a sub-system of interest is treated using deterministic orbitals, while the rest of the system is treated using stochastic orbitals. This way, we can selectively reduce the stochastic errors associated with that sub-system. The second project involved finding an optimal DFT starting point for our stochasticGW code. Apart from that, I will also introduce our orthogonal projector augmented wave package. Compared with the norm-conserving pseudopotential approach, the PAW method will allow a lower kinetic energy cutoff, hence greatly enhances the efficiency of electronic structure theory simulations.

Chem 278: Prof. Long Luo
2021-03-10 16:00
Electrifying Inorganic and Organic Synthesis
Abstract: Electrochemical synthesis is a powerful tool for formulating functional materials and moleculesbecause it offers an additional level of control over the synthesis relative to its chemical counterpart by fine-tuning mass transfer, potential, or current. Electrochemical synthesis also allows the convenient analysis of chemical reaction thermodynamics and kinetics using the current signal generated during the electrochemical synthesis. In this talk, two recent advancements in electrochemical synthesis will be presented: (1) Electrochemical gelation of nanoparticles and (2) Alternating current electrolysis for organic synthesis.

Chem 218 Student Exit Seminar: David Reilley
2021-03-11 12:00
Chemical Change in Protein Molecular Dynamics: Developing Computational Tools for Metal Binding and pH Sensitivity
Molecular dynamics (MD) is a powerful tool to study atomic scale changes in proteins underpinning biological pathways. However, simulations traditionally sample a fixed chemical state and struggle to achieve quantitatively accurate energies, making comparisons of different chemical ensembles challenging. Hybrid quantum mechanical-classical approaches (QM/MM) can provide accurate energies for small regions of interest, such as the active site, but cannot readily capture all chemical transformations relevant to protein function. This talk will focus on developments and applications of hybrid methods to study the metal binding preferences and pH sensitivity of proteins. We will first discuss how we used QM/DMD combined with a competitive metal affinity method, a semi-empirical thermodynamic cycle, to obtain relative binding affinities for a wide range of metals to human serum transferrin (hTF), an iron transport protein. Our results clarified a mechanism for promiscuous metal binding in hTF and the role the protein may play in transport of non-physiological and potentially cytotoxic metals. We will then discuss the development of a titration feature for constant pH simulations with DMD (titr-DMD). Our method features stochastic protonation and deprotonation of amino acids while treating solvent implicitly, which makes it computationally efficient compared to other techniques. We successfully benchmarked titr-DMD on experimentally verified pH-dependent conformational changes. Our work demonstrates the utility of molecular dynamics, and QM/DMD in particular, to study chemical changes in proteins with good accuracy and speed.

CIC Careers in Green Chemistry Seminar Series
2021-03-11 13:00
The Center for Integrated Catalysis is hosting a new seminar series called the “Careers in Green Chemistry.” With these webinars, we aim to bring speakers from a wide variety of careers, linked through green chemistry, to come talk about their current job as well as the career path that led them to that position. We are pleased to invite all students, postdocs, and faculty.

CANCELLED - Chem 268: Prof. Hernan Garcia
2021-03-12 15:30
“Dissecting Transcriptional Dynamics in Development One Burst at a Time”

Chem 218 Student Exit Seminar: Arundhati Deshmukh
2021-03-18 12:00
“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.

NSF Center for Integrated Catalysis Webinar Series
2021-03-19 13:00
“Invention of Catalysts for Synthesis of New Plastics”
Abstract: This presentation will begin with a brief discussion of the properties of polyethylene and the synthesis of various forms of polyethylene via early metal catalysts and via free radical processes. Following this short discussion, I will discuss our thought processes in developing late metal olefin polymerization catalysts and focus particularly on the chemistry of Ni(II) and Pd(II) diimine-derived catalysts. The talk will finish with a discussion of issues surrounding copolymerization of ethylene and polar vinyl monomers and a mechanistic dissection of the copolymerization of ethylene with vinyl trialkoxysilanes using both Pd(II) and Ni(II) diimine catalysts.

Chem 278: Prof. Wenliang Huang
2021-03-31 16:00
“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

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.
