UCLA

Theoretical Physical Chemistry Seminar - Dr. Henrik Larsson, Caltech
2021-01-26 14:00 (America/Los_Angeles) | CA
Molecules in quantum motion
In order to fully understand the nature of chemical reactions and molecular properties, we need to simulate both the electronic and vibrational motion quantum mechanically. However, simulations of quantum many body systems, such as molecules, scale exponentially with system size. I will explain how to tame this ‘curse of dimensionality’ by combining methods from the traditionally disjoint fields of electronic structure and nuclear dynamics. This combination has enabled the simulation of complex systems with unprecedented accuracy and speed. I will demonstrate how these methods make it possible to solve a diverse set of problems, ranging from characterizing hydrated protons on a molecular quantum level to the interaction of molecules with extreme short and intense light pulses on an attosecond time scale. I will demonstrate how these simulations provide new insight into complex experimental results.

Chem 228: Clarice D. Aiello
2021-01-25 16:00

Theoretical Physical Chemistry Seminar - Dr. Bingqing Cheng, Cambridge
2021-01-22 12:00
Predicting material properties with the help of machine learning
A central goal of computational physics and chemistry is to predict material properties using first-principles methods based on the fundamental laws of quantum mechanics. However, the high computational costs of these methods typically prevent rigorous predictions of macroscopic quantities at finite temperatures, such as chemical potential, heat capacity and thermal conductivity.
In this talk, I will first discuss how to enable such predictions by combining advanced statistical mechanics with data-driven machine learning interatomic potentials. As an example, for the omnipresent and technologically essential system of water, a first-principles thermodynamic description not only leads to excellent agreement with experiments, but also reveals the crucial role of nuclear quantum fluctuations in modulating the thermodynamic stabilities of different phases of water. As another example, we simulated the high-pressure hydrogen system with converged system size and simulation length, and found, contrary to established beliefs, supercritical behaviour of liquid hydrogen above the melting line. Besides thermodynamic properties, I will talk about how to compute the heat conductivities of liquids just from equilibrium molecular dynamics trajectories.
During the second part of the talk, I will rationalize why machine learning potentials work at all, and in particular, the locality argument. I’ll show that a machine learning potential trained on liquid water alone can predict the properties of diverse ice phases, because all the local environments characterising the ice phases are found in liquid water.

Novel GABA- and Ornithine Aminotransferase Inactivators and Potential New Treatments for Epilepsy, Addiction, Neuropathic Pain, and Hepatocellular Carcinoma
2021-01-21 16:00
Abstract: An imbalance in the levels of the inhibitory neurotransmitter g-aminobutyric acid (GABA) and the excitatory neurotransmitter L-glutamate can lead to convulsions. Inhibition of g-aminobutyric acid aminotransferase (GABA-AT), the enzyme responsible for the degradation of GABA, increases brain GABA levels, which has been shown to produce an anticonvulsant effect. Reduced brain GABA concentration also is a feature of neuropathic pain. A sharp rise in dopamine release is associated with a variety of addictive behaviors. This dopamine release can be attenuated by an increase in GABA; therefore, inactivation of GABA-AT also has an effect on addictive behavior. Inactivation of a related enzyme, ornithine aminotransferase (OAT) in hepatocellular carcinoma (HCC) has been shown to slow the growth of this cancer. In this lecture the design and mechanism of some of our GABA-AT inactivators will be discussed and how these compounds led to the design and discovery of CPP-115 and OV329, potent inactivators of GABA-AT, which have been found to have excellent pharmacokinetic and pharmacological properties for the potential treatment of epilepsy, neuropathic pain, and addiction. An analog related to CPP-115 was identified that does not inactivate GABA-AT but is a potent inactivator of OAT. Enzyme inactivator design and mechanism studies will be discussed, as well as in vitro and in vivo efficacy and pharmacokinetic results, toxicology studies, and a clinical trial with CPP-115.

Special Bio-Inorganic Chemistry Seminar
2021-01-20 16:00
“Chemical and Biological Design Approaches to Controlling Protons, Electrons, and Substrates for Sustainable Catalysis”
Abstract: The reductive transformation of small molecules into value-added products represents an attractive way to store sustainable energy in chemical bonds. Achieving this efficiently and selectively requires the careful management of not only the substrate and intermediates, but also the proton and electron equivalents. Both the synthesis of small molecule catalysts and the de novodesign of metalloproteins offer the means to control these multi-component reactions. A commonly observed strategy in biological systems to lower the barrier to reductive protonation of small molecules is concerted proton-electron transfer (CPET). However, the application of such a strategy to chemical catalysis has been lacking due to the paucity of approaches to generate CPET donors sufficiently reactive to functionalize molecules of interest ranging from N2 to ketones. Here, I will discuss our discovery that under the protic conditions relevant to nitrogen fixation catalysis that metallocenes can serve as CPET reagents and our subsequent design of functionalized cobaltocenes suitable to electrocatalytic CPET applications. I will then finish by touching on the computational, de novo design of non-heme iron proteins for O2-activation. These enzymes utilize a co-substrate to selectively generate a reactive metal-oxo intermediate that is useful for both C–H and olefin functionalization reactions. Nonetheless, such enzymes have been thus far little explored in the context of protein engineering.

NSF Center for Integrated Catalysis Webinar Series
2021-01-19 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, January 19th, 2021 at 1:00 PM. We are pleased to invite all students, postdocs, faculty, and staff.

Chem 268: Prof. Elizabeth Villa
2021-01-15 15:30
“Opening Windows into the Cell: Bringing Structure to Cell Biology Using Cryo-electron Tomography”

Expanding the genetic code - new chemistries in living system
2021-01-14 12:00
Abstract: Nature uses a limited set of twenty amino acids to synthesize proteins. In recent years it has become possible to site-specifically incorporate designer amino acids with tailored chemical properties into proteins in living cells by reprogramming the genetic code. Together with developments in designing chemical reactions that are applicable to and selective within living systems, these strategies have begun to have a direct impact on studying biological processes.
In this talk I will present our lab’s efforts to expand the genetic code and to endow proteins with novel chemical moieties within their physiological environment. By site-specifically incorporating artificial designer amino acids into proteins, we have developed tools to image and probe proteins, to study protein-protein interactions and to re-engineer and manipulate molecular networks and biological pathways in living cells.
We envision that these approaches and technologies will enable the study of biological processes that are difficult or impossible to address by more classical methods.

Special Bio-Inorganic Chemistry Seminar
2021-01-13 16:00
“Tuning the Reactivity Landscape of Metalloenzymes: From Active Site Modifications to Long-range Dynamic Effects”
Abstract: Metalloenzymes rely on transition metals within the protein scaffold to perform a wide variety of molecular transformations in biology. Synthetic models of metalloenzyme intermediates, inspired by the enzyme active site and its secondary coordination sphere, have provided systems for studying bond-forming/breaking events in well-controlled environments. However, recent evidence has suggested that the dynamic nature of proteins is intimately linked to enzyme function and activity, implying a reactivity landscape that is not only dependent on the ground state thermodynamics of the active site, but also on the long-range protein motions that orient the active site for optimum catalysis. The first part of this presentation will focus on the synthesis and reactivity of high-valent metal-oxo and metal-hydroxo corroles and corrolazines as models for reactive intermediates in Cytochrome P450. The role of electronic structure, peripheral ligand sterics, and Lewis acid effects on oxygen atom transfer and hydroxyl radical rebound reactivities were evaluated in the context of how the active site microenvironment tunes the reactivity of heme enzymes. The second part of the presentation will focus on our current efforts on characterizing activity-related protein motions in the non-heme enzyme soybean lipoxygenase (SLO-1). SLO-1 utilizes a well-defined hydrogen tunneling mechanism that is intrinsically dependent on the motions of the protein scaffold. Collectively, the findings from these research efforts have led to several fundamental insights regarding how reactivity is tuned from the active site and beyond, providing a possible blueprint for the design of efficient catalysts for biological and industrial applications.

Chem 228: Michelle Y. Simmons, Ph.D.
2021-01-11 16:00
“Engineering qubits in silicon with atomic precision”

NSF Center for Integrated Catalysis Webinar Series
2020-12-15 13:00
The NSF Center for Integrated Catalysis is delighted to announce that it will be hosting a monthly webinar series. The Fourth day of this series will be held on Tuesday, December 15th at 1:00 PM. We are pleased to invite all students, postdocs, faculty, and staff.

Harnessing Conformational Dynamics to Engineer New Enzymes: Prof. Lynn Kamerlin, Uppsala University
2020-12-10 16:00
Harnessing Conformational Dynamics to Engineer New Enzymes
Understanding how new enzyme functions evolve, either on existing scaffolds, or completely de novo on previously non-catalytic scaffolds, is of great interest both from a fundamental biochemistry perspective, and from a biotechnological perspective. Several hypotheses have been put forward to rationalize enzyme evolution, one of which is that their conformational dynamics plays an important role in facilitating the emergence of new enzyme functions.[1-3] My team and I have invested substantial research effort into understanding enzyme multifunctionality in catalytically promiscuous enzymes,[4-7] as well as the structure-function-dynamics relationships shaping the evolution of new enzyme functions, in both natural and engineered active sites.[8-12] In this talk, I will discuss recent progress in this area, and illustrate how we have engineered conformational dynamics to generate a a de novo active site capable of catalyzing a non-natural reaction,[9] and then subsequently enhanced this activity using a simple computational approach, reaching catalytic efficiency comparable to that of naturally occurring enzymes.[13]
[1] James & Tawfik, Trends Biochem. Sci., 2003, 28, 361. [2] Tokuriki & Tawfik, Science, 2009, 324, 203. [3] Crean et al., J. Am. Chem. Soc., 2020, 142, 11324. [4] Barrozo et al., J. Am. Chem. Soc., 2015, 137, 9061. [5] Ben-David et al., J. Mol. Biol., 2015, 427, 1359. [6] Blaha-Nelson et al., J. Am. Chem. Soc., 2017, 139, 1155. [7] Purg et al., J. Am. Chem. Soc., 2017, 139, 17533. [8] Ma et al., Chem. Sci., 2016, 7, 1415. [9] Risso et al., Nat. Commun., 2017, 8, 16113. [10] Petrović et al., ACS Catal., 2017, 6, 6188. [11] Baier et al., eLife, 2019, 8, e40789. [12] Kaltenbach et al., Nat. Chem. Biol., 2018, 14, 548. [13] Risso et al., Chem. Sci. 2020, 11, 6134.

Chem 218 Student Exit Seminar: Victoria Basile
2020-12-10 12:00
“Nanostructured Nickel-Rich Cathode Materials for High-Capacity and Fast-Charging Lithium-Ion Batteries”
ABSTRACT: Fast-charging lithium-ion batteries are desired for use in personal electronics and electric vehicles, potentially allowing systems to charge devices in minutes rather than hours. Fast-charging can be achieved by nanostructuring battery materials, which decreases lithium-ion diffusion lengths and can suppress slow, rate-limiting phase transitions. This method of nanostructuring battery materials to enhance fast-charging performance has been shown in many anode materials. However, lithium-ion batteries are usually limited by the capacity of their cathodes (< 200 mAh/g). Unfortunately, fewer fast-charging cathode materials have been identified, and those that have been suffer from capacity loss upon nanostructuring. Here, we studied the nickel-rich cathode material LiNi0.80Co0.15Al0.05O2 (NCA), which has high-capacity and shows solid-solution behavior without a phase transitions in bulk materials. Because phase transitions do not limit intercalation kinetics in bulk NCA, materials only need to be nanostructured to decrease lithium-ion diffusion lengths to the point that solid-state diffusion is not rate limiting. Here we demonstrated the use of polymer templating, combined with sol-gel synthesis, to produce nanoporous NCA with medium and small particle sizes. We can then study the effect of size on the material’s electrochemical properties. Interestingly, we found that NCA materials with medium particle sizes perform best at fast rates. Their performance is better than that of bulk materials because of their decreased lithium-ion diffusion lengths, which allows for fast-charging. NCA materials with medium sized particles also out-perform materials with small particles, however, and this is because nickel-rich materials are highly air-sensitive, and the smaller particles have higher surface areas, leading to more undesirable reactions with air that produce insulating surface layers that can hinder lithium-ion diffusion at fast rates. These results indicate that the smallest particle sizes are not always optimal and that a balance exists between lithium-ion diffusion distances and surface reactivity for nickel-rich cathode materials.

Chem 278: Prof. Michael T. Yeung
2020-12-09 16:30
“Metallic and Covalent Bonding in Materials: Role in Properties, Structure, and Stability”
Abstract: The search for new ultraincompressible, superhard materials has been performed largely through trial and error. Despite the difficulties in synthesizing such materials, interest in this field has blossomed with recent experimental and theoretical results. Such progress has led to the development of superhard metal borides, ultraincompressible nitrides, and strong carbides. By studying the origin of strength from previously discovered ultraincompressible, hard materials, we hope to gain new insight into this rapidly growing field. In particular, we propose a focus on bonding and microstructure to understand why some materials are ultraincompressible and superhard.

Midstream Presentation: Keaton Barr
2020-12-08 16:00
Keaton Barr
Chanfreau Group
“Transcriptional Roadblocks Protect Against Pervasive Transcription, and the Regulation of a Manganese Transporter via the Endoribonuclease Rnt1p”

Chem 228: Prof. Theodore Goodson
2020-12-07 16:00

Chem 268: Joe Loo
2020-12-04 15:30

Lessons from molecular evolution: from origin of life to phage-based nanomaterials
2020-12-03 16:00
Abstract:
Molecular evolution is a walk over a fitness landscape, in which populations explore sequence space through mutation and ‘climb’ up fitness peaks. The topography of the fitness landscape governs potential pathways for evolution and determines whether fitness can be optimized by natural selection. We are making exhaustive maps of fitness landscapes for catalytic RNA (ribozymes) by combining in vitro selection with a massively parallel kinetic assay using high-throughput sequencing. In addition, we take advantage of the ongoing natural selection of phages in order to engineer phage-based nanomaterials for detection and killing of pathogenic bacteria. These nanomaterials combine evolutionarily optimized attachment strategies of phages with the controllable nature of nanomaterials to circumvent some obstacles to phage therapy.

Chem 218: First Principles Many-Body Theory and Quantum Dynamics for Materials Prediction - Prof. Yuan Ping, UCSC
2020-12-03 12:00
First Principles Many-Body Theory and Quantum Dynamics for Materials Prediction
Materials prediction is the ultimate solution for ending blind experimental search within an expansive material parameter space. First-principles theory entirely based on quantum mechanics without prior input parameters is the perfect tool for new material design. In order to predict exotic quantum materials and out-of-equilibrium processes, many-body physics and quantum kinetic theory are needed to bridge with first-principles methods.
In this talk, I will discuss the past development on theory and numerical codes of solving the Bethe-Salpeter equation without explicit empty states, for accurate prediction of optical excitation and exciton recombination. I will show the recent developments on radiative and phonon-assisted nonradiative exciton recombination in two-dimensional materials and spin defects. Next, I will show our recent method development on real-time quantum dynamics with coupled spins, electrons, photons and phonons based on first-principles density-matrix approach. This method will offer new and unbiased insights for spin relaxation and decoherence in general systems, and determine design rules for new quantum materials with ideal physical properties for spintronics and quantum information science.

Chem 278: Dr. Evan Doud
2020-12-02 16:30
“Beyond Traditional Superatom Ligands and Cores”
Abstract: As technological development continues to advance at a rapid pace, there is an increasing need for next-generation materials. There are several fundamental challenges associated with developing these novel materials, including understanding the nature of the electronic contacts and tuning the specific properties of a material. In the context of novel ligands and core compositions of superatoms, this talk will first describe how Near Edge X-ray Absorption Fine Structure (NEXAFS) and X-ray Photoelectron Spectroscopy (XPS) coupled with Density Functional Theory (DFT) calculations were used to determine the geometry and structure of N-heterocyclic carbenes (NHCs) on a Au(111) surface. Followed by a demonstration of how a novel in situ reduction technique was used to probe the conductance of NHCs on the single molecule level using the Scanning Tunneling Microscopy – Break Junction (STM-BJ) technique. Finally, the synthesis of nickel phosphinidene superatoms from the uncommon organocyclophosphine precursor will be discussed

Midstream Presentation: Troy Lucas Lowe
2020-12-01 16:00
Troy Lucas Lowe
S. Clarke Group
“Responses of a Protein Arginine Methyltransferase (PRMT7) to Intracellular Stress”

Chem 228: Prof. Amber Krummel
2020-11-30 16:00
“Exploiting Molecular Vibrations to Visualize Chemical Structures & Dynamics in Advanced Materials”

Midstream Presentation: Maria Flores and Logan Scott Richards
2020-11-24 16:00
Maria Flores
Rodriguez Group
“Investigating the atomic structures of prion-like assemblies formed by CPEB3”
and
Logan Scott Richards
Rodriguez Group
“Structural Characterization of LECT2 Systemic Amyloidosis”

Interfacial Chemistry of Colloidal Nanocrystals to Direct Energy Conversion: Prof. Brandi Cossairt, University of Washington
2020-11-23 16:00
Interfacial Chemistry of Colloidal Nanocrystals to Direct Energy Conversion
We are interested in developing colloidal nanocrystals for wide-ranging applications in energy interconversion. Our approach leverages the extraordinary properties of nanoscale systems and applies design principles of molecular inorganic chemistry. This talk will focus on two key research themes. First, we will explore how interfacial chemistry can be used to control the photophysics and emissive properties of colloidal semiconductor nanocrystals. Second, we will explore interfacial chemistry concepts to control the inner-sphere reactivity of colloidal electrocatalysts for multi-proton, multi-electron transformations. Ligand etching, ligand exchange, and covalent functionalization will be presented as complementary methods to alter electrocatalytic interfaces by tuning the activity, selectivity, and bulk interfacial properties. Ultimately, we are viewing nanocrystal interfaces as platforms for coordination chemistry that will direct function.

Chem 228: Prof. Brandi Cossairt
2020-11-23 16:00
“Interfacial Chemistry of Colloidal Nanocrystals to Direct Energy Conversion”

Chem 268: Steve Clarke
2020-11-20 15:30

Writing the rules for targeting dynamic proteins
2020-11-19 16:00
Abstract: Transcriptional coactivators and their partner transcription factors have been labeled as intrinsically disordered, fuzzy, and undruggable. We propose that the identification of conserved mechanisms of engagement between coactivators and their cognate activators should provide general principles for small-molecule modulator discovery. Towards that end, biophysical characterization of the structurally divergent coactivator Med25 reveals that it forms short-lived and dynamic complexes with three different transcriptional activators and that conformational shifts are mediated by a flexible substructure of two dynamical helices and flanking loops. Analogous substructures are found across eukaryotic coactivators. Further, targeting one of the flexible structures with a small molecule modulates Med25-activator complexes. Thus, the two conclusions of the work are actionable for the discovery of small-molecule modulators of this functionally important protein class.

Chem 278: Prof. Caroline Saouma
2020-11-18 16:30
“Thermodynamic and Mechanistic Studies of C02Reduction Catalysts”
Abstract: The increase in global energy demands, coupled with growing environmental concerns, necessitates the development of viable technologies to store solar energy. Towards this end, my group is focused on developing efficient catalysts that convert CO2 to CO, methanol or formic acid. My talk will first describe our mechanistic studies on known CO2 hydrogenation catalysts, whereby mechanistic insight is gleaned through thermochemical studies, and allows for tuning the product selectivity. We also have uncovered a unique mechanism for CO2 hydrogenation, whereby CO2 must first bind to the ligand before subsequent reduction occurs. I will then discuss how we have used the same thermochemical approach to study the mechanism of electrocatalytic CO2 reduction in a combined carbon capture & reduction system. Finally, I will present a novel ligand scaffold that, when put on Co, allows for both the hydrogenation of CO2 to formate and the electrochemical reduction of CO2 to formate; this is unique in that no H2 is produced electrocatalytically. The collective work underscores the importance of the effective hydricity as a parameter of interest and in using thermochemical parameters to rationalize and uncover alternative mechanisms. The studies presented are contextualized in developing an understanding of how to rationally design energy-efficient CO2 reduction catalysts.

Midstream Presentation: Carter Lantz
2020-11-17 16:00
Carter Lantz
Loo Group
“Mass Spectrometry Analysis of Amyloid Proteins and their Interaction with the Aggregation Inhibiting Compound CLR01”

NSF Center for Integrated Catalysis Webinar Series
2020-11-17 13:00
The NSF Center for Integrated Catalysis is delighted to announce that it will be hosting a monthly webinar series. The second day of this series will be held on Tuesday, November 17th at 1:00 PM. We are pleased to invite all students, postdocs, faculty, and staff.
