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At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Strategies for fabricating aligned nano- and microfiber scaffolds: an overview for cell culture applications

The rapidly growing demand for cell manufacturing and in vitro tissue fabrication has led to the development of various technologies for biomimetic artificial extracellular matrix (ECM), including three major materials: hydrogels, fibrous scaffolds, and decellularized tissues. The latter two materials are closer to the biomimetic goal of replicating natural ECM. The scalability of the scaffolds made of decellularized tissues is limited. The development of 3D fibrous ECM is at the initial stage owing to the recent advantages of novel nanofiber spinning technologies. These novel technologies brought about simultaneous control over a range of critical characteristics, such as fiber diameter, length, material, draw ratio, spacing, and alignment into well-controlled 3D constructs. There is still a long way to go in designing 3D fibrous scaffolds based on cell response studies. The primary objective of this review is to provide an analysis of the recent progress in novel nano- and microfiber spinning methods and uncover their potential for precise fiber alignment into 3D structures.

Peranidze, Kristina [University of Georgia, Athens↗
DOE OSTI2022

Scalable Nano-Scaffold SOFC Anode Architecture Enabling Direct Hydrocarbon Utilization

This project is based on WVU’s pending patents, technology and aims to design and modify the internal surfaces of the Ni/YSZ anode from currently commercially viable Solid Oxide Fuel Cells (SOFCs) using the additive manufacturing process of Atomic Layer Deposition (ALD). The surface architecture/scaffold added onto the internal surface of the anode possesses an engineered nanostructure but it features only commonly-used oxide conductors and electro-catalyst materials. The surface layer possesses a minimum thickness of ~2-40 nm and is solely designed to control the surface reforming reactions and to increase catalytic activity. Three-dimensional (3D) nano scaffold architectures with the noble metal nano-catalyst, low-cost bimetallic catalytic alloys, and nano-scale ionic conducting oxide fully compatible with the state-of-the-art Ni/YSZ anode, were applied to the internal surface of the entire porous SOFC anode using ALD. In the present work, the surface scaffold architecture is essentially multi-functional at the nano-scale, facilitated by the multiple heterostructured interfaces. It will significantly enhance the power density and cell durability for direct hydrocarbon utilization by (1) increasing the number of electrochemical reaction sites to enhance the hydrogen/hydrocarbon oxidation reactions; (2) reducing carbon formation; (3) mitigating the coarsening of backbone Ni phase and the oxidation attack of Ni from oxidants (e.g., H2O, CO2); and (4) promoting the internal reforming capabilities, especially for natural gas applications. ALD is employed to generate stable anode surface architectures that are uniform, precisely controllable at the atomic scale, and accurately repeatable for processing. The engineered anode surface nano-scaffold architecture was cataloged and analyzed using High-resolution Transmission Electron Microscopy (TEM), and cell power/durability performance assessed via comprehensive electrochemical performance testing with commercial specimens and relevant environments using hydrocarbon fuels. To the best of our knowledge, this project is the First Report on ALD of Ni/YSZ. The actual achievement of this Project includes (1). Successful demonstration of 7 types of ALD layers on Ni/YSZ anode, including Co, Ni, Mn, Pt, Ru, ZrOx and multi-functional nano-composite. (1). Conformal coating and subsequently spontaneously pinning the discrete nano-catalyst, including the precious metal nano-catalyst and the Ni and Co catalysts, on the YSZ surface upon the electrochemical operation in the reduced atmosphere. Those nano-catalysts on the ionic-conducting YSZ provided excellent sites for promoting internal reforming; (2). Demonstrated ALD coating increased both catalytic activity and conductivity of Ni/YSZ. Conformal coating provided dopants and introduced additional electrical conducting pathways on the YSZ ionic conductor. The doped surface layer of YSZ with mixed conductivity thus further introduces the active triple phase boundaries adjacent to the ALD-coated nano-catalysts such as Pt, Co, and Ni that are pinned on the YSZ surface. The nano-composite ALD coating on Ni/YSZ anode has significantly increased cell durability; and (3). ALD coating of Ni/YSZ anode increased the power density of the entire cell by 300%. For a long time, the SOFC performance, such as the power density, was deemed hindered by the cathode. The sluggish oxygen reduction reaction (ORR) in the cathode was deemed as hindering the power density of the SOFCs. For the anode-supported commercial SOFCs, the cell performance is considered to be limited by the cathode's performance. For the first time in the field of SOFC, this project has demonstrated that (1). the performance of commercial SOFCs can be further increased by the ALD coating on Ni/YSZ anode backbone. (2). ALD coating on Ni/YSZ fuel electrodes results in the enhancement of power density, and increased reliability, robustness, and endurance of SOFCs, for their application using both hydrogen and hydrocarbon fuels over the entire operating temperature range of 650-800ºC for the inherently functional commercial cells. (3). ALD coating provides alternative approaches of exsolutions for introducing the stable catalyst onto the internal surface of the Ni/YSZ electrode. ALD coating could be much more versatile than exsolution in employing the catalysts with various chemistries onto the various backbones. (4). Due to the negligible amount of ALD materials coated onto the internal surface of the porous cathode of the as-fabricated cells, a peak power density increase up to 300 % induced by ALD coating was simultaneously achieved in terms of both power density and specific power. (5). The ALD coating developed through this project was applied to both the SOFC and Solid Oxide Electrolysis Cells (SOEC). SOEC’s face a similar but more demanding need to improve the fuel electrode's performance. It opens further research directions for electrocatalytic surface nanoionics with a wide range of chemistry. It will revolutionize our ability to render the formation of a nanostructured electrode that has been constantly pursued yet barely achieved for practical SOFC/SOEC applications. The research is also immediately transformative since both the preliminary data and the proposed work are on the direct implantation of nanoionics into the state-of-the-art inherently functional SOCs. It represents an immediate impact on the commercial sectors in SOC technology since the applied ALD processing is computer-controlled ALD coating using the commercial ALD systems, and it is scalable to both the single cells and SOC stacks.

36 MATERIALS SCIENCE↗
DOE OSTI2025

Scaffolded and annotated nuclear and organelle genomes of the North American brown alga Saccharina latissima

Increasing the genomic resources of emerging aquaculture crop targets can expedite breeding processes as seen in molecular breeding advances in agriculture. High quality annotated reference genomes are essential to implement this relatively new molecular breeding scheme and benefit research areas such as population genetics, gene discovery, and gene mechanics by providing a tool for standard comparison. The brown macroalga Saccharina latissima (sugar kelp) is an ecologically and economically important kelp that is found in both the northern Pacific and Atlantic Oceans. Cultivation of Saccharina latissima for human consumption has increased significantly this century in both North America and Europe, and its single blade morphology allows for dense seeding practices used in the cultivation of its Asian sister species, Saccharina japonica. While Saccharina latissima has potential as a human food crop, insufficient information from genetic resources has limited molecular breeding in sugar kelp aquaculture. We present scaffolded and annotated Saccharina latissima nuclear and organelle genomes from a female gametophyte collected from Black Ledge, Groton, Connecticut. This Saccharina latissima genome compares well with other published kelp genomes and contains 218 scaffolds with a scaffold N50 of 1.35 Mb, a GC content of 49.84%, and 25,012 predicted genes. We also validated this genome by comparing the synteny and completeness of this Saccharina latissima genome to other kelp genomes. Our team has successfully performed initial genomic selection trials with sugar kelp using a draft version of this genome. This Saccharina latissima genome expands the genetic toolkit for the economically and ecologically important sugar kelp and will be a fundamental resource for future foundational science, breeding, and conservation efforts.

DeWeese, Kelly↗
DOE OSTI2020

Enzyme scaffolds and methods of use

Polypeptide scaffolds comprising enzymatic proteins are provided. The enzymatic polypeptide scaffolds comprise heterologous enzymes to form a heterologous metabolic pathway, and can be targeted to a substrate through a surface anchoring domain. The enzymatic polypeptide scaffolds leverage the high specificity and affinity protein/protein interaction between the cohesins and dockerins of microorganismal cellulosomes to form custom enzymatic arrays.

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

Gel electrolyte composite including ionic liquid and zwitterionic polymer scaffold

A gel electrolyte composite containing a nonvolatile electrolyte and a zwitterionic polymer scaffold in which the non-volatile electrolyte is a non-lithium-containing ionic liquid, a sodium-containing ionic liquid, or a lithium-containing ionic liquid and the zwitterionic polymer scaffold is formed from one or more zwitterionic monomers only or both one or more zwitterionic monomers and one or more non-zwitterionic monomers. The zwitterionic polymer scaffold contains 8 mol % or higher of zwitterions relative to the total content of the gel electrolyte composite when the nonvolatile electrolyte is a non-lithium-containing ionic liquid, and contains 1 mol % or higher of zwitterions relative to the total content of the gel electrolyte composite when the nonvolatile electrolyte is a sodium-containing ionic liquid or a lithium-containing ionic liquid. Also disclosed are a method of preparing the above-described gel electrolyte composite and an electrochemical energy storage device containing same.

D'Angelo, Anthony J.↗
DOE OSTI2025

Conformally coated scaffold design using water-tolerant Pr 1.8 Ba 0.2 NiO 4.1 for protonic ceramic electrochemical cells with 5,000-h electrolysis stability

Protonic ceramic electrochemical cells (PCECs) have potential as long-duration energy storage systems. However, their operational stability is limited under industrially relevant conditions due to the intrinsic chemical instability of doped barium cerate-based electrolytes and oxygen electrodes against H 2 O, as well as the poor electrode–electrolyte interfacial contact. Here, in this study, we present a conformally coated scaffold (CCS) design to comprehensively address these issues. A porous proton-conducting scaffold is constructed and conformally coated with Pr 1.8 Ba 0.2 NiO 4.1 electrocatalyst, which has high chemical stability against H 2 O, triple conductivity and hydration capability, and protects vulnerable electrolytes from H 2 O. The CCS structure consolidates the electrode–electrolyte interfacial bonding to enable fast proton transfer in the percolated network. This design enables PCECs to reach electrolysis stability for 5,000 h at −1.5 A cm−2 and 600 °C in 40% H 2 O. This work provides a general strategy to stabilize PCECs and offers guidance for designing resilient and stable solid-state energy storage systems.

Protonic ceramic electrochemical cell↗
DOE OSTI2024

A multifunctional technology platform for sorbent construction using polyacrylonitrile scaffolds

Polyacrylonitrile (PAN) is a synthetic polymer that shows high potential for use in a wide range of environmental remediation applications. PAN can be implemented in various ways within a batch or continuous process stream for use as a passive scaffold holding active gettering materials in place or where the PAN scaffold (e.g., beads, fiber mats, membranes) is functionalized with active chelating groups (e.g., amine, hydrazide, amidoximes, carboxyl). Application spaces covered in this review include remediation of heavy metals (e.g., Ag, As, Cd, Cr6+, Cu, Pb, Sb, and Se), high-dose fission products (e.g., 90Sr, 137Cs), radioiodine (i.e., 129I), noble gases (i.e., Xe, 85Kr), rare earths (e.g., Ce, Y), and actinides (e.g., Am, Pu, U). Methods for producing PAN composite sorbents are discussed. Options are also discussed for removing the PAN matrix following chemisorption of an active contaminant to minimize waste volumes requiring disposal.

polyacrylonitrile, composite sorbents, sulfides, a↗
DOE OSTI2021

Investigating Multiscale Spatial Distribution of Sulfur in a CNT Scaffold and Its Impact on Li–S Cell Performance

Ever increasing demand on high energy density batteries positions sulfur as a very promising cathode material for next-generation energy storage due to its high theoretical capacity of 1675 mAh/g. Electronically sulfur is highly insulating, and therefore integration of a conducting framework such as a carbon nanotube (CNT) scaffold with sulfur is a key aspect of the cathode design. Despite numerous efforts dedicated to S-CNT cathode development, increasing sulfur loading to above 1 mg/cm 2 while maintaining the cycling stability of the Li–S cell remains challenging. This could be partly due to the lack of understanding of the spatial distribution of sulfur in the CNT matrix and its location with respect to the morphology of the CNT scaffold. We demonstrate herein that the sulfur has a hierarchical distribution in the CNT cathode at high sulfur loading (>5 mg/cm 2 ) spanning multiple length scales (from nanometer to submillimeter). Sulfur infiltration into the CNT rather than the sulfur loading plays a key role in determining the redox reaction kinetics, Li + ion diffusion, and the galvanostatic cycling capacity and stability of Li–S cells. This study provides new insights for the design and fabrication of high loading, binder-free sulfur–carbon-based cathode architectures for next-generation high energy Li–S batteries.

25 ENERGY STORAGE↗
DOE OSTI2020

Frenkel excitons in heat-stressed supramolecular nanocomposites enabled by tunable cage-like scaffolding

Delocalized Frenkel excitons—coherently shared excitations among chromophores—are responsible for the remarkable efficiency of supramolecular light-harvesting assemblies within photosynthetic organisms. The translation of nature’s design principles to applications in optoelectronic devices has been limited by the fragility of the supramolecular structures used and the delicate nature of Frenkel excitons, particularly under mildly changing solvent conditions and elevated temperatures and upon deposition onto solid substrates. Here, we overcome those functionalization barriers through composition of stable supramolecular light-harvesting nanotubes enabled by tunable (~4.3–4.9 nm), uniform (±0.3 nm) cage-like scaffolds. High-resolution cryogenic electron microscopy, combined with scanning electron microscopy, broadband femtosecond transient absorption spectroscopy and near-field scanning optical microscopy revealed that excitons within the cage-like scaffolds are robust, even under extreme heat stress, and control over nanocomposite dimensions is maintained on solid substrates. Our bio-inspired nanocomposites provide a general framework for the development of next-generation organic devices made from stable supramolecular materials.

14 SOLAR ENERGY↗
DOE OSTI2023

Cryo-EM structure determination of small therapeutic protein targets at 3 Å-resolution using a rigid imaging scaffold

Cryoelectron microscopy (Cryo-EM) has enabled structural determination of proteins larger than about 50 kDa, including many intractable by any other method, but it has largely failed for smaller proteins. Here, we obtain structures of small proteins by binding them to a rigid molecular scaffold based on a designed protein cage, revealing atomic details at resolutions reaching 2.9 Å. We apply this system to the key cancer signaling protein KRAS (19 kDa in size), obtaining four structures of oncogenic mutational variants by cryo-EM. Importantly, a structure for the key G12C mutant bound to an inhibitor drug (AMG510) reveals significant conformational differences compared to prior data in the crystalline state. The findings highlight the promise of cryo-EM scaffolds for advancing the design of drug molecules against small therapeutic protein targets in cancer and other human diseases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

A FeCrAl-Al2O3 Composite Produced via Laser Powder Bed Fusion of a Mixed Powder for Porous Catalyst Scaffolds

This study proposes a novel approach for synthesizing and etching bicontinuous FeCrAl-Al2O3 composites as a means for replacing FeCrAl foams as catalyst scaffolds in bio-driven alcohol reactors for jet-fuel production. Conventional FeCrAl foams suffer from poor availability and consequent high costs. New additive manufacturing techniques provide an opportunity to produce tailored foams in reasonable times and at acceptable costs. This research aimed to generate a porous FeCrAl structure by etching a bicontinuous FeCrAl-Al2O3 composite produced by laser powder bed fusion of amalgamated FeCrAl and Al2O3 powders. The composite powder for laser powder bed fusion is created by ball-milling FeCrAl and Al2O3 powders. This research focuses on achieving a bi-continuous FeCrAl-Al2O3 structure, essential for the selective removal of the ceramic phase. The influence of laser processing parameters on the microstructure was examined across a range of laser powers (60-120 W) and scan speeds (100-400 mm/s), showing that higher powers and speeds produce finer metal struts. A bi-continuous microstructure was consistently obtained, marking a key achievement. The Al2O3 removal process involved a two-step etching method using hydrochloric and phosphoric acids, tested across various etching times. The alumina phase was reduced from 36 vol% to 17 vol% (corresponding to an increase in porosity from 24 vol% to 43 vol%), showing the potential for use as a porous catalyst scaffold. This research demonstrates the potential for using additive manufacturing to produce porous FeCrAl structures capable of replacing hard-to-source FeCrAl foams.

Son, Kwangtae↗
DOE OSTI2023

A scaffolded and annotated reference genome of giant kelp (Macrocystis pyrifera)

Abstract Macrocystis pyrifera (giant kelp), is a brown macroalga of great ecological importance as a primary producer and structure-forming foundational species that provides habitat for hundreds of species. It has many commercial uses (e.g. source of alginate, fertilizer, cosmetics, feedstock). One of the limitations to exploiting giant kelp’s economic potential and assisting in giant kelp conservation efforts is a lack of genomic tools like a high quality, contiguous reference genome with accurate gene annotations. Reference genomes attempt to capture the complete genomic sequence of an individual or species, and importantly provide a universal structure for comparison across a multitude of genetic experiments, both within and between species. We assembled the giant kelp genome of a haploid female gametophyte de novo using PacBio reads, then ordered contigs into chromosome level scaffolds using Hi-C. We found the giant kelp genome to be 537 MB, with a total of 35 scaffolds and 188 contigs. The assembly N50 is 13,669,674 with GC content of 50.37%. We assessed the genome completeness using BUSCO, and found giant kelp contained 94% of the BUSCO genes from the stramenopile clade. Annotation of the giant kelp genome revealed 25,919 genes. Additionally, we present genetic variation data based on 48 diploid giant kelp sporophytes from three different Southern California populations that confirms the population structure found in other studies of these populations. This work resulted in a high-quality giant kelp genome that greatly increases the genetic knowledge of this ecologically and economically vital species.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

DNA-functionalized scaffolds for drug capture applications

This disclosure is directed to structured compositions, including DNA-functionalized scaffolds, for drug capture, and methods and devices for sequestering chemotherapeutics from physiological fluids using the functionalized scaffolds.

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

Ene Reductase Enabled Intramolecular β–C–H Functionalization of Substituted Cyclohexanones for Efficient Synthesis of Bridged Bicyclic Nitrogen Scaffolds

Herein we report that ene reductases (EREDs) can facilitate an unprecedented intramolecular β-C–H functionalization reaction for the synthesis of bridged bicyclic nitrogen heterocycles containing the 6-azabicyclo[3.2.1]octane scaffold. To streamline the synthesis of these privileged motifs, we developed a gram-scale one-pot chemoenzymatic cascade by combining iridium photocatalysis with EREDs, using readily available N-phenylglycines and cyclohexenones that can be obtained from biomass. Further derivatization using enzymatic or chemical methods can convert 6-azabicyclo[3.2.1]octan-3-one into 6-azabicyclo[3.2.1]octan-3α-ols, which can be potentially utilized for the synthesis of azaprophen and its analogues for drug discovery. Here, mechanistic studies revealed the reaction requires oxygen, presumably to produce oxidized flavin, which can selectively dehydrogenate the 3-substituted cyclohexanone derivatives to form the α,β-unsaturated ketone, which subsequently undergoes spontaneous intramolecular aza-Michael addition under basic conditions.

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

Exciton Delocalization in Indolenine Squaraine Aggregates Templated by DNA Holliday Junction Scaffolds

Exciton delocalization plays a prominent role in the photophysics of molecular aggregates, ultimately governing their particular function or application. DNA is a compelling scaffold in which to template molecular aggregates and promote exciton delocalization. As individual dye molecules are the basis of exciton delocalization in molecular aggregates, their judicious selection is important. Motivated by their excellent photostability and spectral properties, here we examine the ability of squaraine dyes to undergo exciton delocalization when aggregated via a DNA Holliday junction (HJ) template. A commercially available indolenine squaraine dye was chosen for the study given its strong structural resemblance to Cy5, a commercially available cyanine dye previously shown to undergo exciton delocalization in DNA HJs. Three types of DNA-dye aggregate configurations—transverse dimer, adjacent dimer, and tetramer—were investigated. Signatures of exciton delocalization were observed in all squaraine-DNA aggregates. Specifically, strong blue shift and Davydov splitting were observed in steady-state absorption spectroscopy and exciton-induced features were evident in circular dichroism spectroscopy. Strongly suppressed fluorescence emission provided additional, indirect evidence for exciton delocalization in the DNA-templated squaraine dye aggregates. To quantitatively evaluate and directly compare the excitonic Coulombic coupling responsible for exciton delocalization, the strength of excitonic hopping interactions between the dyes were obtained by simultaneous fitting the experimental steady-state absorption and CD spectra via a Holstein-like Hamiltonian in which, following the theoretical approach of Kühn, Renger, and May, the dominant vibrational mode is explicitly considered. The excitonic hopping strength within indolenine squaraines was found to be comparable to that of the analogous Cy5 DNA-templated aggregate. The squaraine aggregates adopted primarily an H-type (dyes oriented parallel to each other) spatial arrangement. Extracted geometric details of dye mutual orientation in the aggregates enabled close comparison of aggregate configurations and the elucidation of the influence of dye angular relationship on excitonic hopping interactions in squaraine aggregates. Furthermore, these results encourage the application of squaraine-based aggregates in next generation systems driven by molecular excitons.

36 MATERIALS SCIENCE↗
DOE OSTI2026

N -Terminal Octylated Peptoid Hydrogels as 3D-Printable Cell Scaffolds and Proteolytically Robust Cargo Depots

Supramolecular hydrogels that mimic the extracellular matrix (ECM) represent promising materials for tissue engineering and drug delivery. However, conventional hydrogels formed via the self-assembly of natural or synthetic building blocks often face a trade-off between biological functionality and biochemical stability, limiting their utility in long-term or protease-rich environments. Peptoids, a class of peptide-inspired, sequence-defined polymers, offer a compelling alternative due to their exceptional proteolytic resistance and bioactivity. Despite this potential, the development of supramolecular peptoid hydrogels has been hindered by the absence of backbone hydrogen bond donors, which limits long-range ordering necessary for efficient hydrogel formation. This work describes a short peptoid functionalized at the N-terminus with an octyl chain that readily self-assembles into hydrogels. Hydrophobic interactions among pendant octyl groups promote directional peptoid packing into highly ordered nanosheets, which interconnect to form a porous hydrogel network. These hydrogels exhibit tunable viscoelasticity, shear-thinning, and self-healing properties, enabling their use as inks for extrusion-based 3D printing. They support NIH-3T3 fibroblast adhesion, spreading, and proliferation, maintaining greater than 95% cell viability over 4 days. Moreover, the hydrogels retain their macroscopic integrity under protease-rich conditions, enabling sustained cargo release and uniform cellular uptake. Together, this study demonstrates a class of supramolecular peptoid hydrogelators that integrate biocompatibility, 3D printability, and proteolytic stability, providing a versatile platform for ECMmimetic scaffolds in regenerative medicine and long-term therapeutic delivery.

cargo delivery↗
DOE OSTI2021

Cryo-EM structure determination of small proteins by nanobody-binding scaffolds (Legobodies)

We describe a general method that allows structure determination of small proteins by single-particle cryo-electron microscopy (cryo-EM). The method is based on the availability of a target-binding nanobody, which is then rigidly attached to two scaffolds: 1) a Fab fragment of an antibody directed against the nanobody and 2) a nanobody-binding protein A fragment fused to maltose binding protein and Fab-binding domains. The overall ensemble of ~120 kDa, called Legobody, does not perturb the nanobody–target interaction, is easily recognizable in EM images due to its unique shape, and facilitates particle alignment in cryo-EM image processing. The utility of the method is demonstrated for the KDEL receptor, a 23-kDa membrane protein, resulting in a map at 3.2-Å overall resolution with density sufficient for de novo model building, and for the 22-kDa receptor-binding domain (RBD) of SARS-CoV-2 spike protein, resulting in a map at 3.6-Å resolution that allows analysis of the binding interface to the nanobody. The Legobody approach thus overcomes the current size limitations of cryo-EM analysis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Ene Reductase Enabled Intramolecular β–C–H Functionalization of Substituted Cyclohexanones for Efficient Synthesis of Bridged Bicyclic Nitrogen Scaffolds

Herein we report that ene reductases (EREDs) can facilitate an unprecedented intramolecular β-C–H functionalization reaction for the synthesis of bridged bicyclic nitrogen heterocycles containing the 6-azabicyclo[3.2.1]octane scaffold. To streamline the synthesis of these privileged motifs, we developed a gram-scale one-pot chemoenzymatic cascade by combining iridium photocatalysis with EREDs, using readily available N-phenylglycines and cyclohexenones that can be obtained from biomass. Further derivatization using enzymatic or chemical methods can convert 6-azabicyclo[3.2.1]octan-3-one into 6-azabicyclo[3.2.1]octan-3α-ols, which can be potentially utilized for the synthesis of azaprophen and its analogues for drug discovery. Furthermore, mechanistic studies revealed the reaction requires oxygen, presumably to produce oxidized flavin, which can selectively dehydrogenate the 3-substituted cyclohexanone derivatives to form the α,β-unsaturated ketone, which subsequently undergoes spontaneous intramolecular aza-Michael addition under basic conditions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗