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At least 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Phase II Field Demonstration at Lansing Smith Generating Plant, Southport, Florida (Final Report)

The Final Technical Report: Field Test Design and Pressure Management Strategies for Phase II Field Demonstration of Optimal Pressure Control, Plume Management, and Produced Water Strategies presents the culmination of multi-year efforts under the U.S. Department of Energy’s Brine Extraction and Storage Test (BEST) program, led by EPRI in partnership with Gulf Power at the Plant Smith site near Panama City, Florida. The project was designed to evaluate and demonstrate the technical feasibility of managing subsurface pressures and fluid movement associated with large-scale CO₂ injection, using low-salinity water as a proxy fluid. Through a combination of field injection testing, reservoir modeling, and optimization studies, the research team developed and refined active and passive brine extraction strategies aimed at controlling injection-induced pressure buildup, mitigating risks of fault activation, and managing plume migration. The field demonstration incorporated a new injection well (TIW-2), a new monitoring/extraction well (TEMW-A), and an existing well (TIW-1) repurposed for passive pressure relief. Complementary geophysical monitoring was designed to track plume development and evaluate the effectiveness of pressure management strategies. The report details the integrated workflow encompassing wellfield development, regulatory permitting, model calibration, and survey design. It includes a comprehensive electromagnetic (EM) modeling and inversion study used to develop a cost-effective, time-lapse geophysical monitoring plan capable of imaging the evolving low-salinity plume within the highly saline Lower Tuscaloosa formation. Reservoir simulation results guided the design of the 17-month injection program and the timing of active extraction to maintain formation pressures below a hypothetical fault reactivation threshold. Supporting analyses evaluated potential injectivity risks related to clay fines migration and geochemical incompatibility, identifying practical mitigation measures such as salinity and pH control. The final design recommends a series of crosswell EM surveys—conducted before, during, and after injection—as the most effective and economical approach for plume imaging, supplemented by continuous downhole pressure and flow monitoring. Collectively, the study provides a field-ready framework for cost-effective pressure management and monitoring in support of future CO₂ storage projects.

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2026

Superconducting qubits for particle detection and fundamental tests of quantum mechanics

Many fundamental questions at the interface of quantum mechanics, gravity, and measurement remain relatively unexplored in the laboratory. These include whether spatial superpositions experience gravitational redshift, how the quantum Zeno effect propagates through entangled systems, and whether quantum information is globally conserved or fundamentally lost during measurement-induced wavefunction collapse. In this colloquium, I will discuss how superconducting qubits—developed primarily for quantum computing—can be repurposed as ultra sensitive detectors to probe these questions and to search for low-energy particle interactions. I will describe my work at Fermilab on stabilizing these devices to the level required for next-generation qubit-based sensors. This includes mitigating decoherence from infrared radiation and cosmic rays, using machine-learning techniques to accelerate superconducting qubit design, and leveraging the quantum Zeno effect to improve coherence times and suppress qubit frequency fluctuations. Together, these advances point toward a new class of quantum sensors capable of testing fundamental physics.

Seidel, Olivia [Fermilab]↗
DOE OSTI2024

Value of Nuclear Energy to the Reliability of the North American Power System: Results for Western and Eastern Interconnections

This report documents the fulfillment of a milestone for the United States (U.S.) Department of Energy Office of Nuclear Energy Light Water Reactor Sustainability Program: completing a baseline study of regional impact of nuclear power plants and hydrogen production in maintaining grid services and power quality. Models have been comprehensively demonstrated for the Western Interconnection, or Western Electric Coordinating Council area, and in the Eastern Interconnection for scenarios representative of past extreme events (e.g., drought and heat waves). Understanding the impact on the reliability of the bulk electric system of any reduction in generation capacity from nuclear power, for any reason, is the motivation of this work. Factors that might lead to the premature or unplanned closure of nuclear plants, extended outages, or repurposing of nuclear power include: • Aging infrastructure: Many nuclear power plants in the U.S. are nearing the end of their designed operating lives. Upgrading aging infrastructure can be expensive, and some utilities may choose to retire plants rather than invest in costly upgrades. • Low wholesale electricity prices: The deregulation of the electricity market in many states has led to increased competition and driven down wholesale electricity prices, causing nuclear power operators to seek other revenue sources for their heat and power such as clean hydrogen production. • Renewables growth: The rapid growth of renewable energy sources like solar and wind power is posing a challenge to traditional generation sources like nuclear. While many see renewables as a key part of the clean energy transition, their intermittent nature requires additional grid solutions for reliable power supply. • The potential for regulatory decisions to be in conflict: In its 2021 rulemaking, EPA rule (86 FR 880), the Environmental Protection Agency (EPA) set a compliance date for the ban on processing and distribution in commerce of Decabromodiphenyl Ether (DecaBDE). Since DecaBDE is in many components, particularly wiring, of nuclear power plants which are deemed safety-related or important to safety, three plants would not have been able to restart after their 2023 spring outages, and numerous others would have faced issues in the near future. Fortunately, in this case, the EPA provided relief to the nuclear energy industry. The report provides a summary of the significant role nuclear energy plays in the United States’ power generation mix, supplying around 20% of the nation’s electricity generation, spread across 28 U.S. states. Nuclear power is reliable, mostly unaffected by weather and seasonal changes, and provides a consistent source of baseload power. In terms of capacity, nuclear power plants account for as much as 26% of balancing area power generation capacity. Nuclear power also provides a substantial contribution (e.g., 10% of the inertia in the Eastern Interconnection) of the synchronous spinning mass/inertia that buffers the rate at which frequency changes when a load and generation imbalance occurs (e.g., a large plant trips or a load is suddenly shed due to a transmission outage). This contribution is critical for maintaining grid stability during sudden changes in load or generation.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
DOE OSTI2026

Integrated Life Cycle and Techno-Economic Assessments of Central Appalachian Legacy Mine Sites for Biomass Development and Waste Coal Utilization

This project, funded by the U.S. Department of Energy – National Energy Technology Laboratory (DOE-NETL) under award DE-FE0032212, evaluated how legacy coal mine lands and coal refuse piles in Central Appalachia (West Virginia and Pennsylvania) can be reclaimed and repurposed to support biomass development and beneficial utilization of waste coal, with the long-term goal of supporting net-zero or net-negative greenhouse gas (GHG) pathways. The project had two primary objectives: 1. Characterize legacy mine sites (including site conditions, waste coal/refuse resources, and soil/ecosystem indicators) and develop reclamation and best management practices (BMPs) for biomass cultivation; and 2. Conduct integrated machine learning (ML)-assisted life cycle assessment (LCA) and techno-economic analysis (TEA) to quantify environmental and economic outcomes for multiple biomass and waste-coal utilization pathways. Across West Virginia, the team identified ~625 coal refuse sites covering ~19,705 acres, and developed methods to estimate refuse pile volume using digital elevation models (DEMs) and geospatial workflows. A large subset of sites received volume estimates totaling ~1.6 billion m³.

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2026

Biogas Utilization in Refuse Power Plants (BURP 2 )

The BURP 2 project investigated the technical and financial viability of co firing biogas with waste coal for power generation while using carbon capture and sequestration to achieve net negative emissions. A comparative assessment integrating geospatial mapping, technoeconomic analysis, and life cycle analysis was carried out to evaluate retrofitting an existing coal fired facility in West Virginia, versus developing a new greenfield power plant in Kentucky located near a low quality coal resource. The study found that CO 2 capture rates of 90% or higher, in combination with biogas feedstocks such as animal manure, could significantly reduce global warming potential compared to plants using neither biogas nor CO 2 capture systems. Economic feasibility depended heavily on federal tax credits and proximity to fuel sources. In both greenfield and retrofit scenarios, access to biogas played a key role. Because the retrofit site was located close to existing biogas resources, it represented a feasible option, whereas the greenfield site, being far from pipelines or biogas sources, would require prohibitively expensive biogas transport infrastructure. Overall, the research showed that repurposing waste or low-quality coal with renewable biogas and CO 2 capture systems could provide a viable approach for reducing carbon emissions in power production, if biogas resources are easily accessible and available in sufficient quantities.

01 COAL, LIGNITE, AND PEAT↗
DOE OSTI2023

Software and Hardware Development for the Mu2e Trigger and Data Acquisition System

The Mu2e experiment at Fermilab will be 10,000 times more sensitive than previous experiments looking for muon-to-electron conversion. This precise and complex experimental apparatus will produce 200 million billion muons per year. The accelerator complex repurposes elements of the infrastructure that produced high energy proton and anti-protons beams for the Tevatron experiments to produce the high-intensity muon beams necessary for Mu2e and the Muon (g-2) experiments.

43 PARTICLE ACCELERATORS↗
DOE OSTI2026

Risks to the DOW Mission From Global Advanced Energy Adoption

Advanced energy technologies have the potential to enhance energy security and resilience; however, they can introduce new vulnerabilities even as they mitigate existing ones. This dichotomy highlights that both action and inaction carry strategic risks in a contested and logistically complex operating environment. Regardless of U.S. civilian or military adoption of such technologies, key allies and adversaries are on adoption paths that will impact the U.S. military at the tactical, operational, and strategic level. The global adoption of advanced energy technologies presents the potential for both positive and negative consequences for U.S. Department of Defense (DOD) missions in the next 10-20 years. Three categories of risk drivers are presented in this analysis: infrastructure-related, adoption-related, and response-related. Each risk type can generate consequences for DOD, including power disruptions, suboptimal DOD mission performance and operational effectiveness, higher costs and shortages for both legacy and advanced energy technologies, and loss of U.S. influence and strategic deterrent value. Specific impacts could include tactical impacts, operational impacts, and strategic impacts. Mitigation strategies could include energy resource and technology planning, cybersecurity, supply chain resilience, workforce development, exercises and simulations, investments in commercialized technology, operational testing and pilot programs, research into emerging technologies, partnerships and working groups, common standards, budget planning, and repurposing infrastructure.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2026

Filtration Performance of Simulated 200 West Area Waste Feeds

This report describes the scaled experimental system and approach used to examine dead-end filtration performance of representative 200W waste feeds. The scaled system, which was originally designed and assembled to test Tank Side Cesium Removal (TSCR) system performance with higher-than-expected solid loadings in 2021 (Schonewill et al. 2021), was repurposed to conduct the current experiments at ~1/145 of full scale (based on throughput). Six experimental runs were conducted with five different 200W waste feed simulants: three using a DEF module scaled for TSCR and three using a DEF module scaled for the 200W process modules (based on the current design for the Advanced Modular Pretreatment System). Each experiment was run continuously for multiple days with an operating approach prototypic of the full-scale system. Staff performing the experimental runs monitored performance, obtained data from calibrated process instruments, and collected samples for observation and analysis. The measured data are presented with a focus on assessing DEF performance – specifically, the filters’ differential pressure response to the five waste simulants, frequency and efficacy of backwashing, and baseline recovery between experimental runs; data related to ion exchange column performance are also discussed in cases where the opportunity arose. The experimental campaign demonstrated that the DEFs satisfied their primary function of protecting the ion exchange column from solid intrusion for all the representative simulants used. The filters readily handled solids loadings of =500 ppm (and even greater), especially the modules scaled to the 200W process modules. Adjustments to the processing flow rate and reductions in feed temperature were observed to affect the rate of differential pressure increase on the filters, but neither adversely affected the ability of the DEFs to perform their primary function. Backflushing reliably recovered filter performance in all runs, although it did not prevent irreversible fouling for one simulant. The run that exhibited irreversible fouling established that both the quantity and the nature of the solids being filtered need to be considered when projecting filter performance.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2026

Integrating Carbon Capture, Utilization, & Sequestration into Chemical Pulp Mills

The U.S. pulp and paper industry presents a unique and largely untapped opportunity for large- scale carbon dioxide removal (CDR). Unlike most industrial sectors, pulp mills rely heavily on biomass, meaning that much of their carbon emissions originate from atmospheric CO₂ that was recently captured by plants. If this biogenic CO₂ can be captured and permanently stored, pulp mills can be transformed from carbon emitters into net carbon removal facilities. This project was motivated by that opportunity and aimed to develop and evaluate integrated, low-cost strategies for capturing, utilizing, and sequestering CO₂ within existing chemical pulping operations. The scope of this work focused on four complementary innovations designed to integrate seamlessly into kraft pulp mill infrastructure: (1) in situ CO₂ capture within the recovery cycle, (2) oxy-fuel retrofitting of the rotary lime kiln to produce a high-purity CO₂ stream, (3) ex situ CO₂ capture and mineralization using pulp mill residues (dregs, grits, and lime mud), and (4) beneficial reuse of these residues as mineral carbonate fertilizers. The project combined process modeling, laboratory experimentation, life cycle assessment (LCA), and field trials to evaluate the technical feasibility, economic viability, and environmental impact of these approaches. The results demonstrate that pulp mills can serve as effective platforms for carbon removal when equipped with integrated carbon capture systems. Process modeling showed that combining sodium spiking with oxy-fuel calcination significantly enhances CO₂ capture efficiency while reducing costs by up to 31% compared to conventional configurations. Experimental work further revealed that calcination behavior in high-CO₂ environments differs substantially from traditional systems, leading to the development of a new kinetic model that predicts reaction rates under these conditions. This model provides essential design guidance for next-generation decarbonized lime kilns. In parallel, the project demonstrated that alkaline mineral residues generated during pulping operations can be repurposed as a sustainable alternative to agricultural lime. Across a wide range of soils in the southeastern United States, these materials performed equivalently to commercial lime in adjusting soil pH while offering lower greenhouse gas emissions and reduced cost. Field and greenhouse studies confirmed that crop and tree growth responses were comparable, supporting their viability as a drop-in replacement. This co-product pathway provides a practical utilization strategy that offsets costs and improves overall system economics. A major contribution of this project is the first comprehensive life cycle assessment of carbon removal in pulp and paper systems across multiple system boundaries. Results show that retrofitted mills can achieve carbon removal efficiencies ranging from 12% to 92%, depending on how the system is defined. This finding highlights a critical issue in carbon accounting: reported performance is highly sensitive to methodological choices. By explicitly quantifying these differences, this work provides valuable guidance for policymakers, carbon registries, and project developers working to standardize carbon removal metrics. From a commercialization perspective, the technologies investigated in this project are well- aligned with existing industrial infrastructure, minimizing the need for entirely new facilities. 3 DE-EE0009413 Industry engagement throughout the project—including collaboration with pulp and paper companies, equipment manufacturers, and carbon removal developers—has accelerated the transition from research to deployment. Notably, a commercial developer is actively pursuing carbon capture projects at pulp mills in the southeastern United States and has cited this research as a contributing foundation. The emergence of voluntary carbon markets and long-term offtake agreements further strengthens the business case for implementation. The broader public benefits of this work are significant. By enabling large-scale carbon removal using existing industrial systems, this approach offers a near-term pathway to reduce atmospheric CO₂ concentrations while supporting domestic manufacturing and rural economies. The reuse of industrial residues as fertilizers reduces reliance on mined materials, lowers costs for farmers, and decreases environmental impacts associated with conventional lime production. In addition, the project has supported workforce development by training graduate students and researchers in carbon capture technologies, helping to build capacity in a critical area of national interest. In conclusion, this project demonstrates that integrated carbon capture, utilization, and sequestration in pulp mills is both technically feasible and economically promising. By combining process innovation, experimental validation, and systems-level analysis, the work advances the understanding of how biomass-based industries can contribute to climate mitigation. The findings provide a strong foundation for commercial deployment and offer a scalable solution for transforming a major U.S. industry into a source of durable carbon removal.

09 BIOMASS FUELS↗
DOE OSTI2021

The sPHENIX Experiment at RHIC

The sPHENIX experiment is the successor to the PHENIX experiment at RHIC and is optimized to study heavy flavor and jets arising from heavy ion collisions. The detector utilizes advanced technologies such as a monolithic active pixel vertex detector while also repurposing technologies originally from other high energy experiments such as BaBar, ATLAS and ALICE. The design and status of the sPHENIX detector is detailed along with the projected physics capabilities and planned measurements that the collaboration will work to achieve. sPHENIX is expected to begin data taking in 2023.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2025

Scale-up Unlearnable Examples Learning with High-performance Computing

Recent advancements in AI models, like ChatGPT, are structured to retain user interactions, which could inadvertently include sensitive healthcare data. In the healthcare field, particularly when radiologists use AI-driven diagnostic tools hosted on online platforms, there is a risk that medical imaging data may be repurposed for future AI training without explicit consent, spotlighting critical privacy and intellectual property concerns around healthcare data usage. Addressing these privacy challenges, a novel approach known as Unlearnable Examples (UEs) has been introduced, aiming to make data unlearnable to deep learning models. A prominent method within this area, called Unlearnable Clustering (UC), has shown improved UE performance with larger batch sizes but was previously limited by computational resources (e.g., a single workstation). To push the boundaries of UE performance with theoretically unlimited resources, we scaled up UC learning across various datasets using Distributed Data Parallel (DDP) training on the Summit supercomputer. Our goal was to examine UE efficacy at high-performance computing (HPC) levels to prevent unauthorized learning and enhance data security, particularly exploring the impact of batch size on UE’s unlearnability. Utilizing the robust computational capabilities of the Summit, extensive experiments were conducted on diverse datasets such as Pets, MedMNist, Flowers, and Flowers102. Our findings reveal that both overly large and overly small batch sizes can lead to performance instability and affect accuracy. However, the relationship between batch size and unlearnability varied across datasets, highlighting the necessity for tailored batch size strategies to achieve optimal data protection. The use of Summit’s high-performance GPUs, along with the efficiency of the DDP framework, facilitated rapid updates of model parameters and consistent training across nodes. Our results underscore the critical role of selecting appropriate batch sizes based on the specific characteristics of each dataset to prevent learning and ensure data security in deep learning applications. The source code is publicly available at https: // github. com/ hrlblab/ UE_ HPC .

Zhu, Yanfan [Vanderbilt University, Nashville, TN,↗
DOE OSTI2024

Environmental matrix and moisture are key determinants of microbial phenotypes expressed in a reduced complexity soil-analog

Soil moisture and porosity regulate microbial metabolism by influencing factors such as redox conditions, substrate availability, and soil connectivity. However, the inherent biological, chemical, and physical heterogeneity of soil complicates laboratory investigations into microbial phenotypes that mediate community metabolism. This difficulty arises from challenges in accurately representing the soil environment and in establishing a tractable microbial community that limits confounding variables. To address these challenges in our investigation of community metabolism, we use a reduced-complexity microbial consortium grown in a soil analog using a glass-bead matrix amended with chitin. Long-read and short-read metagenomes, metatranscriptomes, metaproteomes, and metabolomes were analyzed to test the effects of soil structure and moisture on chitin degradation. Our soil structure analog system greatly altered microbial expression profiles compared to the liquid-only incubations, emphasizing the importance of incorporating environmental parameters, like pores and surfaces, for understanding microbial phenotypes relevant to soil ecosystems. These changes were mainly driven by differences in overall expression of chitin-degrading Streptomyces species and stress-tolerant Ensifer. Our findings suggest that the success of Ensifer in a structured environment is likely related to its ability to repurpose carbon via the glyoxylate shunt while potentially using polyhydroxyalkanoate granules as a C source. We also identified traits like motility, stress resistance, and biofilm formation that underlie the degradation of chitin across our treatments and inform how they may ultimately alter carbon use efficiency. Together our results demonstrate that community functions like decomposition are sensitive to environmental conditions and more complex than the multi-enzyme pathways involved in depolymerization.

Rodriguez-Ramos, Josue A↗
DOE OSTI2021

Probing the SARS-CoV-2 main protease active site as a target to inhibit viral replication

SARS-CoV-2 replication involves the synthesis of two large proteins, which are inactive and harmless until the viral main protease enzyme (3CL M pro ) uses them as substrates, cleaving them into many smaller, functional products. Dr Andrey Kovalevsky and his team from Oak Ridge National Laboratory propose a design of novel inhibitors and the repurposing of clinical drugs developed to treat other diseases for the treatment of COVID-19. Finally, the team uses room temperature crystallography with X-rays and neutrons to guide structure-based and computer-assisted drug design and to assess the ability of drugs to inhibit the SARS-CoV-2 main protease, causing virus replication to stop.

Kneller, Daniel↗
DOE OSTI2021

Models and Processes to Extract Drug-like Molecules From Natural Language Text

Researchers worldwide are seeking to repurpose existing drugs or discover new drugs to counter the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A promising source of candidates for such studies is molecules that have been reported in the scientific literature to be drug-like in the context of viral research. However, this literature is too large for human review and features unusual vocabularies for which existing named entity recognition (NER) models are ineffective. We report here on a project that leverages both human and artificial intelligence to detect references to such molecules in free text. We present 1) a iterative model-in-the-loop method that makes judicious use of scarce human expertise in generating training data for a NER model, and 2) the application and evaluation of this method to the problem of identifying drug-like molecules in the COVID-19 Open Research Dataset Challenge (CORD-19) corpus of 198,875 papers. We show that by repeatedly presenting human labelers only with samples for which an evolving NER model is uncertain, our human-machine hybrid pipeline requires only modest amounts of non-expert human labeling time (tens of hours to label 1778 samples) to generate an NER model with an F-1 score of 80.5%—on par with that of non-expert humans—and when applied to CORD’19, identifies 10,912 putative drug-like molecules. This enriched the computational screening team’s targets by 3,591 molecules, of which 18 ranked in the top 0.1% of all 6.6 million molecules screened for docking against the 3CLPro protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Sustainable Wood-Waste-Based Thermal Insulation Foam for Building Energy Efficiency

Wood is one of the most abundant biomaterials on Earth, which has been used for centuries in construction applications including furniture, roofing, flooring, and cabinetry. However, wood chips—which are a low-quality and plentiful waste byproduct of lumber milling, woodworking, and shipping operations—have low economic value and complicated disposal methods. In this paper, we propose a strategy for wood chip reuse through the fabrication of bio-based building insulation foam. Through a high-temperature chemical treatment delignification process, we introduced additional small pores within the wood chips, effectively lowering their thermal conductivity, and used them in combination with a binding agent to produce a porous insulation foam. The porous insulation foam achieved a low thermal conductivity of 0.038 W/(m·K) and a high compressive strength of 1.1 MPa (70% strain). These characteristics demonstrate that wood waste can be repurposed into an effective building material, addressing challenges in both waste management and sustainable construction.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2025

Total Recycling of Copper Cable Scrap and Production of Carbon Using Fast Microwave Technology

The recycling of cable scrap, particularly from discarded electrical wiring, is gaining significant attention due to the rising demand for copper and the need for sustainable management of electronic waste. Traditionally, mechanical and thermal processings have been used to recover copper and plastic from cables. However, these approaches are often energy-intensive, time-consuming, and costly in terms of equipment and labor. In this study, we present a simple and effective method for recovering materials from cable scrap using a domestic microwave oven. Cable pieces (2–2.5 cm long) were exposed to 700 W of microwave irradiation under rotation for 30 s, enabling the rapid and efficient separation of high-quality copper metal from the core wire, and activated carbon from the carbonized plastic sheath. Microwaves facilitate this process through Ohmic heating, which induces electrical resistance in the metal, generating heat that mechanically loosens the metal and carbonized plastic components. The process demonstrates high efficiency, achieving an 80% reduction in energy consumption compared to conventional processings. This fast and energy-efficient method shows strong potential for scaling up to industrial recycling, offering a cost-effective and environmentally friendly way to recover high-quality materials for further use or repurposing.

Bourlinos, Athanasios B. (ORCID:0000000256165993)↗
DOE OSTI2023

3-O-Methyltolcapone and Its Lipophilic Analogues Are Potent Inhibitors of Transthyretin Amyloidogenesis with High Permeability and Low Toxicity

Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson’s disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis.

59 BASIC BIOLOGICAL SCIENCES↗