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Results for “small molecule activation”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Materials for controlling the epitaxial growth of photoactive layers in photovoltaic devices

There is disclosed ultrathin film material templating layers that force the morphology of subsequently grown electrically active thin films have been found to increase the performance of small molecule organic photovoltaic (OPV) cells. There is disclosed electron-transporting material, such as hexaazatriphenylene-hexacarbonitrile (HAT-CN) can be used as a templating material that forces donor materials, such as copper phthalocyanine (CuPc) to assume a vertical-standing morphology when deposited onto its surface on an electrode, such as an indium tin oxide (ITO) electrode. It has been shown that for a device with HAT-CN as the templating buffer layer, the fill factor and short circuit current of CuPc:C60 OPVs were both improved compared with cells lacking the HAT-CN template. This is explained by the reduction of the series resistance due to the improved crystallinity of CuPc grown onto the ITO surface.

Forrest, Stephen R.↗
DOE OSTI2025

Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition

Selective inhibition of the more than 100 S1 family serine proteases is a long-standing challenge due to their active site similarity. Mesotrypsin, implicated in cancer progression, exemplifies these difficulties; no current inhibitors achieve selectivity over other human trypsins. We found an unexpected autoinhibited conformation of mesotrypsin via x-ray crystallography, revealing a cryptic pocket adjacent to the active site. Using high-throughput virtual screening targeting this cryptic pocket, we identified a conformationally selective small-molecule inhibitor that stabilizes the inactive state of mesotrypsin. This inhibitor demonstrates selectivity for mesotrypsin over other trypsins. Our findings challenge the accepted view of digestive trypsins as constitutively active enzymes lacking potential for allosteric regulation. Furthermore, analyses of other structures suggest that dynamic sampling of closed states with analogous allosteric cryptic pockets appears widespread among S1 serine proteases. These observations point to a potentially generalizable strategy to achieve selective inhibition, offering broad implications for drug development targeting serine proteases in cancer and other diseases.

Coban, Matt↗
DOE OSTI2022

Recent advances in cooperative activation of CO 2 and N 2 O by bimetallic coordination complexes or binuclear reaction pathways

The gaseous small molecules, CO 2 and N 2 O, play important roles in climate change and ozone layer depletion, and they hold promise as underutilized reagents and chemical feedstocks. Furthermore, productive transformations of these heteroallenes are difficult to achieve because of their inertness. In nature, these gases are cycled through ecological systems by metalloenzymes featuring multimetallic active sites that employ cooperative mechanisms. Thus, cooperative bimetallic chemistry is an important strategy for synthetic systems, as well. In this Perspective, recent advances (since 2010) in cooperative activation of CO 2 and N 2 O are reviewed, including examples involving s-block, p-block, d-block, and f-block metals and different combinations thereof.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

C 1 Chemistry on Metal Carbide Nanoparticles: Boosting the Conversion of CO 2 and CH 4

The studies described in this Perspective show that transition metal carbide (TMC) nanoparticles can be very useful for the activation of three molecules located at the heart of C 1 chemistry: H 2 , CH 4 , and CO 2 . They also can play a major role in the trapping and conversion of two major greenhouse gases. A combination of experiment and theory has shed light on the physical and chemical properties of these systems, which can be very different from those of bulk carbides. Molecular clusters of these compounds, which can be inserted inside the cages of zeolites or carbon nanotubes, have unsaturated metal and carbon atoms that frequently work in a cooperative way when dealing with hard-to-activate molecules, such as CH 4 and CO 2 . These molecular clusters can evolve into nanoparticles of small to medium size (<15 nm) that have unique carbon/metal ratios and structures not seen in the bulk metal carbides. Even when their structures are cuts from bulk lattices, the TMC nanoparticles have corner or edge atoms that are active for the cleavage and conversion of C–H and C–O bonds. In this paper, we cover experimental and theoretical studies with well-defined metal carbide nanoparticles prepared by different methods, free and supported on diverse substrates. The Perspective ends with a discussion of current challenges and potential applications.

03 NATURAL GAS↗
DOE OSTI2021

Suppression of hepatitis B virus through therapeutic activation of RIG-I and IRF3 signaling in hepatocytes

Hepatitis B virus (HBV) mediates persistent infection, chronic hepatitis, and liver disease. HBV covalently closed circular (ccc)DNA is central to viral persistence such that its elimination is considered the cornerstone for HBV cure. Inefficient detection by pathogen recognition receptors (PRRs) in the infected hepatocyte facilitates HBV persistence via avoidance of innate immune activation and interferon regulatory factor (IRF)3 induction of antiviral gene expression. We evaluated a small molecule compound, F7, and 5'-triphosphate-poly-U/UC pathogen-associated-molecular-pattern (PAMP) RNA agonists of RIG-I, a PRR that signals innate immunity, for ability to suppress cccDNA. F7 and poly-U/UC PAMP treatment of HBV-infected cells induced RIG-I signaling of IRF3 activation to induce antiviral genes for suppression of cccDNA formation and accelerated decay of established cccDNA, and were additive to the actions of entecavir. Our study shows that activation of the RIG-I pathway and IRF3 to induce innate immune actions offers therapeutic benefit toward elimination of cccDNA.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Probing the Behavior of Composition‐Tunable Ultrathin PtNi Nanowires for CO Oxidation and Small‐Molecule Electrocatalytic Reactions

We have successfully synthesized ultrathin nanowires of pure Pt, Pt 99 Ni 1 , Pt 9 Ni 1 , and Pt 7 Ni 3 using a modified room-temperature soft-template method. Analysis of both methanol oxidation reaction (MOR) and ethanol oxidation reaction (EOR) results found that the Pt 7 Ni 3 samples yielded the best performance with specific activities of 0.36 and 0.34 mA/cm 2 respectively. Additionally, formic acid oxidation reaction (FAOR) tests noted that both Pt and PtNi nanowires oxidize small organic molecules (SOMs) via an indirect pathway. CO oxidation data suggests little measurable performance without any pre-reduction treatment; however, after annealing in H 2 , we detected significantly improved CO 2 formation for both Pt 9 Ni 1 and Pt 7 Ni 3 motifs. These observations highlight the importance of pre-treating these nanowires under a reducing atmosphere to enhance their performance for CO oxidation. To explain these findings, we collected extended x-ray adsorption fine structure (EXAFS) spectroscopy data, consistent with the presence of partial alloying with a tendency for Pt and Ni to segregate, thereby implying the formation of a Pt-rich shell coupled with a Ni-rich core. Here, we also observed that the degree of alloying within the nanowires increased after annealing in a reducing atmosphere, a finding deduced through analysis of the coordination numbers and calculations of Cowley's short range order parameters.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Selective inhibition of human translation termination by a drug-like compound

Methods to directly inhibit gene expression using small molecules hold promise for the development of new therapeutics targeting proteins that have evaded previous attempts at drug discovery. Among these, small molecules including the drug-like compound PF-06446846 (PF846) selectively inhibit the synthesis of specific proteins, by stalling translation elongation. These molecules also inhibit translation termination by an unknown mechanism. Using cryo-electron microscopy (cryo-EM) and biochemical approaches, we show that PF846 inhibits translation termination by arresting the nascent chain (NC) in the ribosome exit tunnel. The arrested NC adopts a compact α-helical conformation that induces 28 S rRNA nucleotide rearrangements that suppress the peptidyl transferase center (PTC) catalytic activity stimulated by eukaryotic release factor 1 (eRF1). These data support a mechanism of action for a small molecule targeting translation that suppresses peptidyl-tRNA hydrolysis promoted by eRF1, revealing principles of eukaryotic translation termination and laying the foundation for new therapeutic strategies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Chromatin activity precipitation method and system

Methods and systems for identifying binding sites in macromolecules using small molecule mimics of naturally occurring molecules is disclosed. A reactive probe is provided that mimics small molecule cofactors. A target macromolecule is irreversibly bound to the probe in vivo to selectively pull down or precipitate probe-bound macromolecules. The macromolecules may be, but are not limited to, DNA, RNA, and proteins.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Molecular understanding of heteronuclear active sites in heme–copper oxidases, nitric oxide reductases, and sulfite reductases through biomimetic modelling

Heme-copper oxidases (HCO), nitric oxide reductases (NOR), and sulfite reductases (SiR) catalyze the multi-electron and multi-proton reductions of O 2 , NO, and SO 3 2- , respectively. Each of these reactions is important to drive cellular energy production through respiratory metabolism and HCO, NOR, and SiR evolved to contain heteronuclear active sites containing heme/copper, heme/nonheme iron, and heme-[4Fe-4S] centers, respectively. The complexity of the structures and reactions of these native enzymes, along with their large sizes and/or membrane associations, make it challenging to fully understand the crucial structural features responsible for the catalytic properties of these active sites. Here, we summarize progress that has been made to better understand these heteronuclear metalloenzymes at the molecular level though study of the native enzymes along with insights gained from biomimetic models comprising either small molecules or proteins. Further understanding the reaction selectivity of these enzymes is discussed through comparisons of their similar heteronuclear active sites, and we offer outlook for further investigations and areas of ongoing study.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

A Ranked-Orbital Approach to Select Active Spaces for High-Throughput Multireference Computation

The past decade has seen a great increase in the application of high-throughput computation to a variety of important problems in chemistry. However, one area which has been resistant to the high-throughput approach is multireference wave function methods, in large part due to the technicalities of setting up these calculations and in particular the not always intuitive challenge of active space selection. As we look toward a future of applying high-throughput computation to all areas of chemistry, it is important to prepare these methods for large-scale automation. Here, we propose a ranked-orbital approach to select active spaces with the goal of standardizing multireference methods for high-throughput computation. This method allows for the meaningful comparison of different active space selection schemes and orbital localizations, and we demonstrate the utility of this approach across 1120 multireference calculations for the excitation energies of small molecules. Our results reveal that it is helpful to distinguish the method used to generate orbitals from the method of ranking orbitals in terms of importance for the active space. Additionally, we propose our own orbital ranking scheme that estimates the importance of an orbital for the active space through a pair-interaction framework from orbital energies and features of the Hartree–Fock exchange matrix. Here, we call this new scheme the “approximate pair coefficient” (APC) method and we show that it performs quite well for the test systems presented.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Room Temperature Electrochemical Upgrading of Methane to Oxygenate Fuels

The overall objective of this project is to discover the nature of the electrochemically active sites and to uncover the mechanisms for the electrocatalytic transformation of small organic molecules to oxygenate products such as methanol, formaldehyde, carbon monoxide and ethylene. Among the feedstocks of interest in this study were: methane, carbon dioxide, and acetic acid. Methane is an incredibly attractive potential feedstock because of the recent discovery of large shale deposits; carbon dioxide is potentially a very available feedstock from carbon capture technologies; acetic acid (as well as CH4 and CO2 and ethanol) has potential as a bio-derived feedstock. This report summarizes the major results to date regarding the electrochemical transformation of CH4, CO2 and acetic acid to chemicals and fuels – with a primary focus on methane. It should be noted that this was a grant that was transferred to the University of South Carolina following the PI’s move from the University of Connecticut. Therefore, this report – as a summary document – contains the results over the entire duration of the project. In addition to the primary objective, the work in this project has led to synergistic discoveries that are advantageous to other fields including: catalyst layer deposition, anion exchange membrane fuel cells, CO2 capture and li-ion batteries. Those are very briefly discussed as well.

03 NATURAL GAS↗
DOE OSTI2020

Halogenation-Dependent Effects of the Chlorosulfolipids of Ochromonas danica on Lipid Bilayers

The chlorosulfolipids are amphiphilic natural products with stereochemically complex patterns of chlorination and sulfation. Despite their role in toxic shellfish poisoning, potential pharmacological activities, and unknown biological roles, they remain understudied due to the difficulties in purifying them from natural sources. The structure of these molecules, with a charged sulfate group in the middle of the hydrophobic chain, appears incompatible with the conventional lipid bilayer structure. Questions about chlorosulfolipids remain unanswered partly due to the unavailability of structural analogues with which to conduct structure–function studies. Here, we approach this problem by combining enantioselective total synthesis and membrane biophysics. Using a combination of Langmuir pressure–area isotherms of lipid monolayers, fluorescence imaging of vesicles, mass spectrometry imaging, natural product isolation, small-angle X-ray scattering, and cryogenic electron microscopy, we show that danicalipin A (1) likely inserts into lipid bilayers in the headgroup region and alters their structure and phase behavior. Specifically, danicalipin A (1) thins the bilayer and fluidizes it, allowing even saturated lipid to form fluid bilayers. Lipid monolayers show similar fluidizing upon insertion of danicalipin A (1). Furthermore, we show that the halogenation of the molecule is critical for its membrane activity, likely due to sterically controlled conformational changes. Synthetic unchlorinated and monochlorinated analogues do not thin and fluidize lipid bilayers to the same extent as the natural product. Overall, this study sheds light on how amphiphilic small molecules interact with lipid bilayers and the importance of stereochemistry and halogenation for this interaction.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Active mechanisorption driven by pumping cassettes

Pumping macrocycles onto surfaces Numerous chemical processes, ranging from water purification to catalysis, involve sorption of small molecules onto surfaces. Typically, spontaneous attractive interactions favor the binding event. Feng et al . report a mechanisorption process that requires redox manipulations to pump macrocycles from bulk solution onto axles immobilized on a metal-organic framework. The resulting rotaxanes store energy through nonequilibrium charge concentration in their mechanical bonds. Ultimately, the technique could also prove useful for actively partitioning compounds with particular functionality between surface and bulk environments. —JSY

Science & Technology - Other Topics↗
DOE OSTI2022

Efficient and mechanically-robust organic solar cells based on vertical stratification modulation through sequential blade-coating

Mechanically durable organic solar cells (OSCs) with high efficiency are deemed as the ideal candidate for the power source of the next generation wearable electronic devices. However, the brittle nature of small molecules in most high-efficiency OSCs consisting of polymer and small molecule encourages easy formation of cracks in the photoactive film under deformation. Here, the vertical composition distribution of the active layer has been well optimized through sequential blade coating to realize highly deformable while efficient OSC. The optimized morphology exhibits distinct donor-rich and homogenous region distributed along the vertical direction in the bulk. The donor-rich region provides sufficient chain entanglements and strong interfaces beneficial for mechanical robustness of film, while homogeneously mixed region offers continuous interpenetrating network to maintain high device through-put, resulting in superior efficiency of 14.4% with high crack-onset strain (COS) of 30.5%. This efficiency versus COS combination is much higher than the best combination reported in all polymer systems (COS of 15.9% and efficiency of 11.1%). To the best of our knowledge, it is the highest COS value achieved in polymer-small molecule systems. As a result, the rational control over vertical stratification demonstrated here would guide researchers in the development of innovative wearable electronics.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Three-State Electrochiroptical Switches Derived from Chiral Stable Carbenes

Chiral redox switches have been used to develop stimuli-responsive materials and organic electronics wherein small molecule chirality produces new functionality. Despite the widespread use of stable carbenes in redox-active materials and asymmetric synthesis, their integration into chiral redox switches remains largely unexplored. Herein, we show that chiral stable carbenes can be used to construct helically chiral overcrowded alkenes which function as three-state electrochiroptical switches. Redox-driven (de)aromatization triggers the reversible exchange of helical and axial chirality via a helically chiral π-radical cation. Due to dramatic changes in both electronic and geometric structure, including the inversion of helical chirality, each state exhibits distinct chiroptical properties. As a proof of concept, we demonstrate multiple cycles of electrochemical ON–OFF switching and sign inversion of the electronic circular dichroism response. Overall, this work establishes chiral stable carbenes as promising building blocks for chiral and redox-switchable materials.

Chirality↗
DOE OSTI2022

Structural and dynamic mechanisms of GABA A receptor modulators with opposing activities

γ-Aminobutyric acid type A (GABA A ) receptors are pentameric ligand-gated ion channels abundant in the central nervous system and are prolific drug targets for treating anxiety, sleep disorders and epilepsy. Diverse small molecules exert a spectrum of effects on γ-aminobutyric acid type A (GABA A ) receptors by acting at the classical benzodiazepine site. They can potentiate the response to GABA, attenuate channel activity, or counteract modulation by other ligands. Structural mechanisms underlying the actions of these drugs are not fully understood. Here we present two high-resolution structures of GABA A receptors in complex with zolpidem, a positive allosteric modulator and heavily prescribed hypnotic, and DMCM, a negative allosteric modulator with convulsant and anxiogenic properties. These two drugs share the extracellular benzodiazepine site at the α/γ subunit interface and two transmembrane sites at β/α interfaces. Structural analyses reveal a basis for the subtype selectivity of zolpidem that underlies its clinical success. Molecular dynamics simulations provide insight into how DMCM switches from a negative to a positive modulator as a function of binding site occupancy. Together, these findings expand our understanding of how GABA A receptor allosteric modulators acting through a common site can have diverging activities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition

Cbl-b is a RING-type E3 ubiquitin ligase that is expressed in several immune cell lineages, where it negatively regulates the activity of immune cells. Cbl-b has specifically been identified as an attractive target for cancer immunotherapy due to its role in promoting an immunosuppressive tumor environment. A Cbl-b inhibitor, Nx-1607, is currently in phase I clinical trials for advanced solid tumor malignancies. Using a suite of biophysical and cellular assays, we confirm potent binding of C7683 (an analogue of Nx-1607) to the full-length Cbl-b and its N-terminal fragment containing the TKBD-LHR-RING domains. To further elucidate its mechanism of inhibition, we determined the co-crystal structure of Cbl-b with C7683, revealing the compound’s interaction with both the TKBD and LHR, but not the RING domain. Here, we provide structural insights into a novel mechanism of Cbl-b inhibition by a small-molecule inhibitor that locks the protein in an inactive conformation by acting as an intramolecular glue.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Dimer Acceptor Adopting a Flexible Linker for Efficient and Durable Organic Solar Cells

Abstract Organic solar cells (OSCs) have advanced rapidly due to the development of new photovoltaic materials. However, the long‐term stability of OSCs still poses a severe challenge for their commercial deployment. To address this issue, a dimer acceptor ( d T9TBO) with flexible linker is developed for incorporation into small‐molecule acceptors to form molecular alloy with enhanced intermolecular packing and suppressed molecular diffusion to stabilize active layer morphology. Consequently, the PM6 : Y6 : d T9TBO‐based device displays an improved power conversion efficiency (PCE) of 18.41 % with excellent thermal stability and negligible decay after being aged at 65 °C for 1800 h. Moreover, the PM6 : Y6 : d T9TBO‐based flexible OSC also exhibits excellent mechanical durability, maintaining 95 % of its initial PCE after being bended repetitively for 1500 cycles. This work provides a simple and effective way to fine‐tune the molecular packing with stabilized morphology to overcome the trade‐off between OSC efficiency and stability.

Chemistry↗