Youn Jue (Eunice) Bae
Exciton-Coupled Coherent Magnons in a 2D Semiconductor
The information generated by qubits is localized and requires a medium that can shuttle information. Magnons that are coupled to qubits and optical photons can deliver information from qubits to optical photons, which can quickly deliver information at a long distance. Two-dimensional (2D) magnetic semiconductors are attractive candidates to serve as this magnon medium because they can hold both tightly-bound excitons with large oscillator strength and potentially long-lived coherent magnons due to the presence of bandgap and spatial confinement. In this talk, I will discuss magnon-exciton coupling in the 2D van der Waals (vdW) antiferromagnetic (AFM) semiconductor CrSBr. I will talk about how we optically launch coherent magnons and how these collective spin precessions (i.e. magnons) coherently modulate exciton energies. Then, I will discuss the in-plane propagating nature of coherent magnons in CrSBr from time- and space- resolved optical imaging experiments. The versatility of vdW heterostructures, strong coupling between magnons ( 0.1 meV) to excitons (1.3 eV), and relatively long coherent propagation length (7 µm) and time (10 ns) support that 2D magnetic semiconductors may be the ideal basis for optically accessible magnonics and quantum interconnects.
The University of North Carolina at Chapel Hill
Ni/Photoredox-Catalyzed Enantioselective Reductive Coupling of Epoxides Enabled by a Biimidazoline Ligand
Epoxides have served as privileged electrophiles for asymmetric catalysis for several decades, but approaches to stereoconvergent C–C bond formation with epoxides have remained limited. An asymmetric Ni/photoredox arylation of racemic styrene oxide derivatives was developed, enabled by a biimidazoline (BiIm) ligand to access valuable 2,2-diarylalcohol scaffolds. To elucidate the ligand features that engender high selectivity, multivariate linear regression analysis was performed with a library of bioxazoline (BiOx) and BiIm ligands revealing electron-donating ligands afforded higher ee’s. This surprising impact of ligand electronics was probed and corroborated with experimental and computational mechanistic studies. It was revealed that electron-donating ligands favor later a transition state in enantiodetermining reductive elimination, thus leading to improved selectivity. Overall, this study illustrates the effective interplay of computation, data science, and mechanistic experimentation to understand and design ligands for stereoconvergent Ni cross-coupling.
Mechanisorption: Storing Energy in Non-Equilibrium Materials through Active Adsorption
Numerous chemical processes, ranging from carbon capture and water remediation to catalysis and electrochemistry, involve the sorption of small molecules onto surfaces. However, over the past century, adsorption has been investigated extensively only in equilibrium systems, with a focus on the van der Waals interactions associated with physisorption and electronic interactions in the case of chemisorption. In this talk, I will present the first fundamentally new mode of adsorption—mechanisorption—since the observation of physisorption and chemisorption in the 1930s, which results from non-equilibrium pumping to form mechanical bonds between adsorbents and adsorbates. In this case, metal-organic framework (MOF) nanosheets and nanoparticles were grafted with polyethylene glycol (PEG) collecting chains to organize arrays of artificial molecular pumps, where active adsorption can be realized. Analogous to the mechanism in living organisms to control the active transport of ions across membranes, adsorbates are transported from one well-defined compartment—the bulk—to another well-defined compartment—the interface—thereby creating a very large chemical potential gradient commensurate with storing energy in a metastable state. This new non-equilibrium mechanisorption has wide implications for future applications in the contexts of molecular recognition, optoelectronics, drug delivery, carbon capture, and water desalination. In particular, the ability to use external energy to drive directional processes in mechanized extended frameworks augurs well for the future development of artificial molecular factories. Mechanisorption extends, in a fundamental manner, the scope and potential of adsorption phenomena and offers a transformative approach to control chemistry at surfaces and interfaces.
Proteins are smart: A single-molecule study of metal homeostasis signal transduction in E. Coli
Microbial antibiotic resistance is becoming a severe issue that urgently requires the development of new drug target. Metal homeostasis (Fe, Zn, Cu, Mn, etc.) is essential for bacteria’s survival in adverse environments and their pathogenesis in hosts and has recently drawn people’s attention as a novel target for antimicrobial treatment. Though previous in vitro studies have provided significant insights into the functions and mechanisms of numerous metal regulation systems, the key disadvantage is that they lack the native in vivo physiological environment, and information like the protein spatial distribution inside the cell, the cooperative interactions with other cellular components, and the intrinsic dynamics/kinetics is unknown, therefore limits the underlying mechanistic understanding.
Live cell single-molecule super-resolution imaging and tracking can probe the dynamic, kinetic and interactions of proteins in their natural environment while under controllable chemical cue, so is able to reveal the intrinsic working mechanisms. Here, we used this technique to investigate the CusS-CusR two-component system, one of the Cu homeostasis machineries in live E. coli, in combination with genetic manipulations. We found that the membrane sensor protein CusS interconverts between a clustered stationary state and a fast-moving mobilized state; we also precisely determined CusS’s affinity towards the response regulator (CusR) switches on immediately upon sensing Cu ion in the periplasm. The observed CusS mobilization upon Cu stress and its surprisingly early interaction with CusR likely ensures an efficient signal transduction by providing proper conformational change and avoiding futile protein cross-talks. To sum up, we obtained in vivo mechanisms about how E. coli maintains Cu homeostasis, which are unachievable through traditional bulk or in vitro measurement, and those results pave the way for designing novel efficient antibiotic treatment targeting metal regulations.
Fluctuations in Semiflexible Liquid Crystalline Polymers
Enhanced alignment of polymers in their nematic state are responsible for crucial mechanical and material properties of fibers found in both biology and chemical physics. Polymers with sufficient backbone bending rigidity or so called semiflexible polymers are particularly prone to forming nematic liquid crystalline phases with strong alignment at low temperatures and/or high concentrations. The strongly aligned phases are an excellent candidate for materializing conducting polymers for flexible electronics. Semiflexible polymers are also particularly useful in biophysics since DNA effectively acts like a rigid polymer on short length scales while as a flexible polymer on large lengths. DNA forms lyotropic crystalline phases in solutions in presence of crowding or presence of ions and induces supercoiling in plasmid DNA. The nematic phases also help in packing DNA into viral capsids. Hence understanding liquid crystalline polymer nematic behavior is of fundamental interest from both materials chemistry and biophysics perspective. Building on the exact single chain statistics of semiflexible polymers and mean-field solutions for both isotropic and nematic states, I will talk about extending the analytical theory for the free energy functional of semiflexible polymer blends with alignment interaction up to quadratic order in order to specifically understand the three Frank elastic (FE) constants of long wavelength splay, bend and twist modes of deformation. These deformations characterize the normal modes of the deviation of local nematic director field of liquid crystalline behavior. The theoretical picture suggests the three FE constants can be mapped to correlation functions involving real spherical harmonics. I will show results based on a wide range of polymer length, polymer rigidity traversing flexible to rigid rod limit as well as various strengths of local alignment field. In order to aid theoretical analysis, numerical simulations are also performed that shows excellent agreement with theory predictions. Taken together, this provides a concrete picture of first principles microscopic statistical mechanics theory and calculation of FE constants for polymers with arbitrary rigidity. Furthermore, the theory provides a roadmap to understanding membrane attached semiflexible polymer phase behavior and consequences of nematic-isotropic transition of the polymer on the mechanical properties of tethered membrane relevant to the cases protein brushes and membrane bound organelles.
Kinetic Frustration Controls LAT Protein Condensation
Progression of animal cell development relies on phase separation of a membrane bound protein called Linker for Activation of T-Cells (LAT) for signal transduction. We have developed a reaction-diffusion coarse-grained model for individual LAT proteins to study the thermodynamics of condensate formation and kinetics. We find that limited bond availability dictates condensation and creates unintuitive structural configurations which provide predictions on the microscopic structure. Our theoretical predictions are supported by experimental measurements of LAT phase separation and kinetics which display dynamic heterogeneity. Our results suggest how the kinetics may be used to control LAT condensation to allow the formation of unique stable condensates that may coexist in the cell.
Joomyung (Vicky) Jun
Massachusetts Institute of Technology
Gene Therapy Without the Genes: Cytosolic Protein Delivery via Traceless Bioreversible Strategy
While the biological roles of proteins are being discovered at a remarkable pace, the number of FDA-approved biological drugs is significantly lower than that of small molecules. The power and impact of protein therapeutics are substantially undermined because of the fundamental limitation: proteins cannot spontaneously cross the membrane. Conventional delivery techniques fail to address this fundamental problem in that protein cargo is predominantly delivered into cells via endocytosis, leading to degradation pathways. Thus, the ability to modulate protein surface to interrogate factors important for cell permeability is highly desired in both biological research and protein therapeutics. Addressing the fundamental limitation, we developed a bioreversible esterification strategy to endow proteins with the ability to enter the cytosol of human cells. Specifically, we show that the library of α-aryl-α-diazoacetamides can esterify carboxyl groups in proteins, enabling their delivery across cellular membranes. The ensuing esters are expected to be cleaved by intracellular esterases, reversing proteins back into their native form.
To further expand the utility of α-aryl-α-diazoacetamides in protein delivery applications, we developed a more general and modular probe for reversible protein modification. Our probe consists of a diazo moiety for protein conjugation, a thiol-reactive group for late-stage functional diversification, and a self-immolative carbonate group to promote traceless release from the protein. We showed that our probe can generate a diverse set of protein conjugates modified with cell-penetrating peptides, targeting ligands, or PEG under mild conditions. Our strategy represents a significant advance over previous reversible strategies because protein mutagenesis is not required, modifications are done under mild conditions, the probe is synthetically accessible, and most importantly, it is potentially compatible with virtually any protein of interest. Therefore, this strategy implements a traceless means to deliver therapeutic proteins into the cytosol of live cells to combat “undruggable” disorders such as cancer.
Max-Planck-Institut für Kohlenforschung, Germany
Organocatalytic Asymmetric Protolactonization: The Missing Link
Despite the remarkable success of asymmetric electrophilic lactonization approaches that have proven useful for many years, stereoselective protolactonization has long remained an unsolved and well-recognized challenge. In this talk, I will present our recent mechanism guided discovery of a general catalytic asymmetric protolactonization protocol using a newly developed chiral imidodiphosphorimidate (IDPi) Brønsted acid catalyst. The method is operationally simple, scalable, and compatible with a wide variety of substrates. Its potential is showcased by concise syntheses of the sesquiterpenes (−)-boivinianin A and (+)-gossonorol. Through in-depth physical organic and DFT analyses, we also derive a nuanced picture of the mechanism and enantioselectivity of this reaction. Taken together, this talk will highlight how the complementary strengths of theory and experiment can be harnessed to address the challenges of catalysis research.
Chemoselective and Site-selective Reductions Catalyzed by a Supramolecular Host
Despite the impressive rate accelerations and divergent reactivity demonstrated by state-of-the-art supramolecular host-guest catalysts, examples of practical application beyond proof-of-concept type reactivity remain relatively scarce. Realization and subsequent optimization of supramolecular reactivity has largely hinged upon careful reagent control, where the substrate undergoing the transformation is modified to fit within the confines of the microenvironment. As such, general application of these methods to more complex, synthetically valuable intermediates and products is a fundamental challenge within the field. We addressed this longstanding challenge by exploring site-selective host-mediated reactivity on substrates that are only partially encapsulated. A host-catalyzed pyridine-borane reduction on a variety of small molecules such as enones, ketones, aldehydes, oximes, hydrazones, and imines that proceeds under basic, aqueous conditions was first developed. Unprotected lysine was employed as a partially encapsulated substrate, upon which excellent ε-selectivity for reductive amination was observed under host-catalyzed conditions. This supramolecular reaction was further applied to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin. These biomolecules represent the most complex substrates modified by microenvironment catalysis to date, and demonstrate the applicability of supramolecular methods in bioconjugation and late-stage functionalization of natural products.
University of Cincinnati
Electrocatalytic carbon dioxide reduction using metalloporphyrins bearing a single proton relay
Conversion of carbon dioxide (CO2) to useful products using solar energy is a potentially crucial technology for mitigating concerns about energy supply and climate change. One such useful product of CO2 reduction is carbon monoxide (CO), which is a precursor to many chemicals, including liquid fuels presently employed in transportation. The selective conversion of CO2 to CO requires the precise two protons and two electrons delivery to a catalyst’s active site. Metalloporphyrins bearing multiple pendant proton relay groups are recognized as robust catalysts in this research area. In my talk, electrocatalytic CO2 reduction will be discussed considering metalloporphyrin catalysts that feature a single proton relay group (2-hydroxyphenyl) at a meso-position and three phenyl groups at the remaining meso-positions in the porphyrin heterocycle (5-(2-hydroxyphenyl)-10,15,20-triphenylporphyrin, TPOH). The iron-substituted version of TPOH (FeTPOH) catalyzes CO2-to-CO conversion in acetonitrile solvent in the presence of weak Brønsted acids (water or phenol), and CO is the only detected product. In contrast, FeTPOH is a poor catalyst for CO2 reduction when the solvent is changed to dimethylformamide, or this molecular catalyst is immobilized onto the graphite electrodes. Interestingly, the drop cast films of cobalt analog (CoTPOH) on graphite electrodes activated CO2 more efficiently in the aqueous electrolyte at 0.2 V of overpotential. Cyclic voltammetry (CV) experiments show redox features that are consistent with the formation of a Co(III)−CO intermediate at near the CO2/CO thermodynamic potential that then releases CO upon further 1-electron reduction. Together, these results demonstrate a unique role for one proton relay as a local proton source, a hydrogen bond donor to CO2-bound intermediates, and a hydrogen-bonding partner to Brønsted acids, thus suggesting improvements in the design of new catalysts.
Agnes E. Thorarinsdottir
Electrocatalytic Oxygen Evolution Reaction in Acid Using EarthAbundant Elements: The Case of Bismuth Oxide
The realization of highly active and acid-stable oxygen evolution reaction (OER) catalysts that
comprise earth-abundant elements will greatly expand the horizon of energy science as it
enables the widespread implementation of large-scale electrochemical energy conversion and
storage technologies. For instance, electrochemical reduction of carbon dioxide (CO2) offers a
sustainable and scalable route to the storage of intermittent renewable energy, such as solar,
in the form of carbon-neutral fuels and chemicals when the necessary reducing equivalents
are harvested from water; however, the energy efficiency and carbon efficiency remain far too
low for large-scale deployment. These low efficiencies primarily originate from (1) the high
overpotential for OER at the anode under acidic conditions and (2) the rapid and
thermodynamically favorable reaction of CO2 with hydroxide to form bicarbonate and
carbonate under basic conditions, resulting in high operating cell voltages and drastic losses
of CO2, respectively. The operation of electrochemical CO2 reduction under acidic conditions
is further hampered by the lack of acid-stable catalysts devoid of precious metals.
One strategy toward achieving catalysts comprising inexpensive elements suitable for OER
operation in acid centers on embedding active transition metal oxide OER catalysts in acid stable p-block metal oxide host matrices. Historically, the OER activity and stability in these
mixed metal oxide systems have been assumed to be decoupled; however, the catalytic
activity of the p-block structural oxides has been largely overlooked. Indeed, the active metals
leach from the oxide matrices during long-term OER operations and the observed OER activity
may predominantly be derived from the host matrix itself. In this talk, I will present our work
that demonstrates that bismuth oxide is active and exceptionally stable OER catalyst in acid,
underscoring the non innocent role that p-block metal oxides may play in mixed metal OER
catalysis in acidic environments.
Sibel Ebru Yalcin
Multimodal Nanoscope Discovers Bacteria Produced, Electronically Conductive, Micrometer-Long Cytochrome Nanowires by Correlating Structure with the Function
Cells compute with chemistry and semiconductors compute with transistors – but both operate by controlling the flow of electrons. Biochemistry typically allows electron flow in proteins only over a few nanometers whereas semiconductors use wires that can conduct quickly over long distances. What if cells have designed biomolecules that behave like wires? To breathe, living cells typically use oxygen-like soluble, membrane-ingestible molecules to dump electrons generated in metabolism. But I have found that to “breathe” in hot, anoxic environments that mimic early earth, soil bacteria, Geobacter have evolved nanowires, made up of polymerized cytochrome proteins, to export electrons to extracellular acceptors that could be hundreds of cell lengths away (Cell 2019, Nature Chem.Bio. 2020, Nature 2021). Rather than waiting for oxygen-like molecules to form and be taken up by cells, life can instead employ cytochrome nanowires to grow in harsh environments. These nanowire-forming cytochromes are widespread in diverse microbes and are essential for extracellular respiration. I will present recent discoveries that resolve two decades of confounding observations in thousands of publications that thought of these nanowires as pili filaments (Current Opinion in Chemical Biology 2020). By correlating cryo-electron microscopy with Multimodal Chemical and Functional Imaging (Physical Biology, 2020) combined with a suite of electrical, biochemical and physiological studies, we find that, rather than pili, nanowires are composed of cytochromes OmcS and OmcZ that transport electrons via seamless stacking of hemes over micrometers. I will discuss the physiological need for two different nanowires and their potential applications for sensing, synthesis, and energy production.