Research Highlights
Agapie Group
Synthesis and electronic properties of nitrogen-rich nanographene
A polycyclic aromatic hydrocarbon displaying twelve edge nitrogen centers for a 42 π-electron system is reported. This compound was synthesized via Sonogashira coupling of pyrimidine precursors, [2+2+2] cycloaddition of bis(aryl) alkynes, and anionic cyclodehydrogenation. Spectroscopy, electrochemistry, and computational results suggest a narrowing of the HOMO–LUMO gap compared to the N-free analogue. Metal coordination affects the optical properties of the extended π system.
Arnold Lab
Reaction Discovery Using Spectroscopic Insights from an Enzymatic C–H Amination Intermediate
Engineered hemoproteins can selectively incorporate nitrogen from nitrene precursors like hydroxylamine, O-substituted hydroxylamines, and organic azides into organic molecules. Although iron-nitrenoids are often invoked as the reactive intermediates in these reactions, their innate reactivity and transient nature have made their characterization challenging. Here we characterize an iron-nitrosyl intermediate generated from NH2OH within a protoglobin active site that can undergo nitrogen-group transfer catalysis, using UV–vis, electron paramagnetic resonance (EPR) spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques. The mechanistic insights gained led to the discovery of aminating reagents─nitrite (NO2–), nitric oxide (NO), and nitroxyl (HNO)─that are new to both nature and synthetic chemistry. Based on the findings, we propose a catalytic cycle for C–H amination inspired by the nitrite reductase pathway. This study highlights the potential of engineered hemoproteins to access natural nitrogen sources for sustainable chemical synthesis and offers a new perspective on the use of biological nitrogen cycle intermediates in biocatalysis.
Goddard Group
The G Protein-First Mechanism for Activation of the Class B Glucagon-like Peptide 1 Receptor Coupled to N-Terminal Domain-Mediated Conformational Progression
Recently, there has been a great deal of excitement about new glucagon-like peptide 1 receptor (GLP-1R) agonists (e.g., semaglutide and tirzepatide) that have received FDA approval for type 2 diabetes and obesity. Although effective, these drugs come with side effects that limit their use. While research efforts continue to focus intensively on long-lasting, orally administered GLP-1R medications with fewer side effects, a major impediment to developing improved GLP-1R medications is that the mechanism by which an agonist activates GLP-1R to imitate signaling is not known. Here we present and validate the G protein (GP)-first mechanism for the GLP-1R supported by extensive atomistic simulations.
Hsieh-Wilson Lab
Chemoenzymatic Labeling, Detection and Profiling of Core Fucosylation in Live Cells
Core fucosylation, the attachment of an α-1,6-linked-fucose to the N-glycan core pentasaccharide, is an abundant protein modification that plays critical roles in various biological processes such as cell signaling, B cell development, antibody-dependent cellular cytotoxicity, and oncogenesis. However, the tools currently used to detect core fucosylation suffer from poor specificity, exhibiting cross-reactivity against all types of fucosylation. Herein we report the development of a new chemoenzymatic strategy for the rapid and selective detection of core fucosylated glycans.
Manthiram Lab
INonidealities in CO2 Electroreduction Mechanisms Revealed by Automation-Assisted Kinetic Analysis
In electrocatalysis, mechanistic analysis of reaction rate data often relies on the linearization of relatively simple rate equations; this is the basis for typical Tafel and reactant order dependence analyses. However, for more complex reaction phenomena, such as surface coverage effects or mixed control, these common linearization strategies will yield incomplete or uninterpretable results. Cohesive kinetic analysis, which is often used in thermocatalysis and involves quantitative model fitting for data collected over a wide range of reaction conditions, requires more data but also provides a more robust strategy for interrogating reaction mechanisms. In this work, we report a robotic system that improves the experimental workflow for collecting electrochemical rate data by automating sequential testing of up to 10 electrochemical cells, where each cell can have a different electrode, electrolyte, gas-phase reactant composition, and applied voltage.
Nelson Lab
A Geometrically Flexible Three-Dimensional Nanocarbon
The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations.
Peters Group and Reisman Group
Teaching an Old Metal New Tricks
Scaling up the versatile reagent samarium diiodide to quantities large enough to be used in industrial settings has proved challenging. It's air sensitive and often needs to be prepared fresh and in large quantities – therefore not efficient enough to use for reactions on an industrial scale.
As reported in the August 23 issue of the journal Science, Caltech chemists in the Peters group and the Reisman group have succeeded in solving this scaling-up riddle. Their solution allows the samarium diiodide reagent to, essentially, recycle itself for repeated use in a single reaction, which means large amounts of solvents and fresh preparations are no longer needed.
Robb Group
Mechanically Triggered Bright Chemiluminescence from Polymers by Exploiting a Synergy between Masked 2-Furylcarbinol Mechanophores and 1,2-Dioxetane Chemiluminophores
Mechanoluminescence, or the generation of light from materials under external force, is a powerful tool for biology and materials science. However, direct mechanoluminescence from polymers remains limited. The Robb group has now developed a modular design strategy for mechanoluminescent polymers that achieves bright green light emission from both organic and aqueous polymer solutions upon mechanical stimulation with ultrasound. This research could open the door to a host of exciting applications in optoelectronics, sensing, bioimaging, optogenetics, and other areas.
See Group
Alkali-independent Anion Redox in LiNaFeS2
Although Na-ion batteries (SIBs) present a promising and more sustainable solution compared to Li-ion batteries, SIBs have comparatively lower energy density and suffer from irreversible charge storage due to the size and mass of Na+. In recent years, the investigation of Li-rich materials has revealed employing multielectron redox that couples cation and anion redox is a method to improve capacity. Coupling anion and cation redox could be a way to improve the low energy density of Na-ion cathodes, but the influence of the large Na+ on these electrochemical processes is not well understood. Here, we leverage the mixed-alkali nature of LiNaFeS2 to compare its behavior in Li vs Na half cells.
Shan Lab
A Master Regulator of Protein Production
Approximately 40% of the mammalian proteome undergoes N-terminal methionine excision and acetylation, mediated sequentially by methionine aminopeptidase (MetAP) and N-acetyltransferase A (NatA), respectively. Both modifications are strictly cotranslational and essential in higher eukaryotic organisms. The interaction, activity and regulation of these enzymes on translating ribosomes are poorly understood. Here we perform biochemical, structural and in vivo studies to demonstrate that the nascent polypeptide-associated complex (NAC) orchestrates the action of these enzymes.
Stoltz Group
Systematic Route to Construct the 5–5–6 Tricyclic Core of Furanobutenolide-Derived Cembranoids and Norcembranoids
Herein, we present a highly efficient method for constructing the intricate 5–5–6 fused ring system commonly found in the polycyclic furanobutenolide-derived cembranoid and norcembranoid natural product family with remarkable diastereoselectivity, utilizing an intramolecular Diels–Alder reaction as the cornerstone. Notably, employing a propargyl ether tether as the dienophile yields significant enhancements in the transformation process compared to its propargyl ester counterpart, as demonstrated in our previous total synthesis of havellockate. This advancement holds promising implications for future investigations, offering a streamlined pathway for rapidly assembling the tricyclic core characteristic of this diverse family of natural products.