Synthesis Tools Research Articles

MAxPy: A Framework for Bridging Approximate Computing Circuits to Its Applications

This paper presents MAxPy, a framework for bridging approximate computing (AxC) circuit design to its applications. MAxPy is an application-agnostic framework able to automatically build a cycle-accurate Python model of an approximate hardware design. This model can easily be emulated and integrated as a module in Python-based applications. We are herein proposing this framework aiming to build an AxC toolbox stimulating open research in academia to promote the integration of the existing and future open-source (i) AxC benchmarks, (ii) approximate logic synthesis tools, and (iii) P unit insights. In this paper, we demonstrate the use of MAxPy to explore the AxC design space of a Sobel filter hardware design as a case study exploiting a set of approximate adders combined with the data-driven approximate logic synthesis via probabilistic pruning. Then, we present a Pareto front for circuit area, energy, and delay reduction versus the application-level metrics: edge detection accuracy and structural similarity index (SSIM). The Pareto front results of the multiple AxC techniques herein explored show circuit area savings ranging from 40.4% to 59.1% for a 98.1% to 99.6% accuracy on edge detection application MAxPy code is open source in: github.com/MAxPy-Project

Programmable Plasma-Microdroplet Cascade Reactions for Multicomponent Systems.

The concept of programmable cascade reactions in charged microdroplets is introduced using carbon-carbon (C-C) bond formation via uncatalyzed Michael addition in a three-tier study culminating in programmable Hantzsch multicomponent, multistep reactions. In situ generated reactive oxygen species (ROS) from nonthermal plasma discharge are fused with charged water microdroplets (devoid of ROS) in real time for accelerated chemical reactions. This plasma-microdroplet fusion platform utilizing a coaxial spray configuration enabled product selection while avoiding unwanted side reactions. Hydrogen abstraction via ROS facilitated the formation of enolate anions without strong base use. Reaction enhancement factors >103 were calculated for plasma-microdroplet fusion versus microdroplet-only reactions. The platform programmability was showcased through (i) uncatalyzed 1,4-Michael addition of α,β-unsaturated carbonyls, (ii) novel C-C bond formation via the use of pro-electrophilic amine and alcohol substrates─activated through collisions in the microdroplet environment to serve as Michael acceptors, and (iii) selective Hantzsch cascade reaction with cross-coupling products, avoiding side reactions including N-alkylation and self-coupling product formation. Milligram quantity product collection is achieved, showcasing plasma-microdroplet fusion as an effective tool for preparative-scale synthesis. Thus, the controlled generation of ROS via plasma discharge during charged water microdroplet evolution establishes a green synthetic method for uncatalyzed C-C bond formation.

Hybrid Metal Catalysts as Valuable Tools in Organic Synthesis: An Overview of the Recent Advances in Asymmetric C─C Bond Formation Reactions

Carbon–carbon bond formation represents a key reaction in organic synthesis, resulting in paramount importance for constructing the carbon backbone of organic molecules. However, traditional metal-based catalysis, despite its advantages, often struggles with issues related to efficiency, selectivity, and sustainability. On the other hand, while biocatalysis offers superior selectivity due to an extraordinary recognition process of the substrate, the scope of its applicable reactions remains somewhat limited. In this context, Artificial Metalloenzymes (ArMs) and Metallo Peptides (MPs) offer a promising and not fully explored solution, merging the two fields of transition metal catalysis and biotransformations, by inserting a catalytically active metal cofactor into a customizable protein scaffold or coordinating the metal ion directly to a short and tunable amino acid (Aa) sequence, respectively. As a result, these hybrid catalysts have gained attention as valuable tools for challenging catalytic transformations, providing systems with new-to-nature properties in organic synthesis. This review offers an overview of recent advances in the development of ArMs and MPs, focusing on their application in the asymmetric carbon–carbon bond-forming reactions, such as carbene insertion, Michael additions, Friedel–Crafts and cross-coupling reactions, and cyclopropanation, underscoring the versatility of these systems in synthesizing biologically relevant compounds.

Preparing for future public health crises by fostering a conducive environment

Abstract Vaccination is considered one of the most cost-effective public health interventions. Zoonotic diseases, which are transmitted from animals to humans, represent an escalating global health concern. Environmental degradation, wildlife trade, and intensified farming practices have disrupted natural ecosystems. This has not only heightened the risk of pathogens crossing species barriers but exacerbated the migrant crisis and deepened global inequalities, as vulnerable populations disproportionally bear the environmental and health burdens. Despite decades of awareness about these risks, the COVID-19 pandemic highlighted our lack of preparedness. At the same time, vaccination hesitancy has been revealed as an important factor in implementing universal vaccination coverage at the population level. Urgency drove innovation. Within months, new multidisciplinary and interdisciplinary approaches were implemented that enhanced our capacity to understand, treat, and protect against the virus. This led to deploying novel technologies, curbing the crisis, and even opening the door to emerging health technologies across a wide spectrum of innovation, from new medicinal products, including vaccines, to evidence synthesis tools, including for modelling and forecasting. Shifting from emergency measures to long-term management of COVID-19, there lies a critical opportunity to strengthen resilience and to increase preparedness against future health threats. The EUVABECO project seeks to harness this momentum by initiating pilot projects that test innovative vaccination tools in evidence-based selected reference practices. These pilots are planned to use suitable theoretical frameworks and consensus meetings to design and develop comprehensive implementation plans that will be shared with EU MS, thereby enhancing Europe’s preparedness and response capabilities against communicable diseases.

DeLoSo: Detecting Logic Synthesis Optimization Faults Based on Configuration Diversity

Logic synthesis tools are the core components of digital circuit design, which convert programs written in hardware description languages into gate-level netlists, and optimize the netlists. However, the netlist optimization is complex, with numerous optimization parameters to be configured. Any minor optimization faults in logic synthesis tools may cause circuit diagrams to significantly deviate from the original design, posing risks in target systems. We propose DeLoSo, the De tector of Lo gic S ynthesis o ptimization faults, the first method specifically designed to identify potential faults in the optimization processes of logic synthesis tools. DeLoSo relies on netlist differences and parameter variations to guide the generation of diverse Logic Synthesis Optimization Configuration (LSOC) combinations to thoroughly test the optimization process. DeLoSo consists of three components: LSOC generator, which generates diverse LSOC combinations through configuration recombination and mutation; LSOC diversity evaluator, which assesses the diversity of optimization configurations; and LSOC validator, which validates the generated LSOC combinations to discover optimization faults. DeLoSo identified 19 faults in two established logic synthesis tools (i.e., Vivado and Yosys); 15 of them have been fixed by vendors. Particularly, the community maintainers of Yosys have considered incorporating DeLoSo into Yosys’ existing test suite.

Bortezomib (BOR)‐Pegylated‐Gold Nanovector: Synthesis, Spectroscopic Evaluation and Diagnostic Tool as Galectin‐1 Biomarker

ABSTRACTIn this paper, we applied an original chemical methodology in which gold salt (HAuCl4) interacts with the chemotherapeutic drug (bortezomib; i.e., BOR) by chelation and then stacked with dicarboxylic acid‐terminated polyethylene‐glycol (PEG‐diacide) as a biocompatible surfactant. The suggested chemical protocol is rapid (“one‐pot”) and reproducible, providing the formation of a hybrid‐nanovector named BOR IN PEG‐AuNPs. In order to prove a therapeutic approach, our hybrid‐nanovector (BOR IN PEG‐AuNPs) interacts with Galectin‐1 (Gal‐1) protein biomarker under specific concentrations. The efficient concentration range of this nanovector is obviously profiled by tumor microenvironment (TME) heterogeneity, optimizing cells access to the interaction region. Considering several influential factors related to spatial mapping and physical profile in all extracellular matrix (ECM), drive a change in neighborhood electrical potential configuration, leading the nanovector response with biomarkers transcriptions, hence, patterning TME leads to promote antitumor immunity in favor of tumor suppression. Each step of chemical synthesis and detection was monitored by spectroscopic techniques (Raman; UV‐Vis spectroscopies) and transmission electron microscopy (TEM). Our study demonstrated that hybrid‐nanoparticle system represents a key to further synergic chemotherapeutic and diagnostic tools for the treatment of cancer.

Development of an Evaluation Instrument on Artificial Intelligence Search Tools for Evidence Synthesis

What Was the Question? There are conflicting calls for evidence synthesis producers to adopt or avoid recent Artificial Intelligence (AI) technologies. Our question was: How do we evaluate rapidly evolving AI tools to enhance the production of evidence syntheses and maintain quality standards? What Did We Do? To advance information retrieval science for producing evidence syntheses at Canada’s Drug Agency (CDA-AMC), the Research Information Services team developed a process to evaluate promising AI search tools. We inventoried 51 tools in the fall of 2023, established selection criteria, assessed specific attributes, and built a standalone instrument to support continuous monitoring and evaluation of new tools. What Did We Find? Rapid development of AI search tools requires a flexible evaluation instrument to inform adoption decisions and enable comparison between tools. We identified mandatory and desirable characteristics for suitable AI tools to assist with information retrieval tasks conducted by CDA-AMC. This work enabled the development of a flexible instrument to evaluate novel AI search tools for evidence synthesis. What Does This Mean? CDA-AMC operationalized a replicable process to monitor and evaluate AI search tools. Our approach to evaluating AI technologies will advance information retrieval methods by CDA-AMC, and our evaluation instrument will assist any evidence synthesis producer interested in adopting AI search tools.

Development of an Evaluation Instrument on Artificial Intelligence Search Tools for Evidence Synthesis

Canada’s Drug Agency has developed an instrument to monitor and evaluate artificial intelligence tools for information retrieval so that, as these tools evolve, we can leverage them appropriately. We are sharing our instrument to help other evidence synthesis producers evaluate and make use of artificial intelligence tools for information retrieval.

A hardware architecture for single and multiple ellipse detection using genetic algorithms and high-level synthesis tools

Ellipse detection techniques are often developed and validated in software environments, neglecting the critical consideration of computational efficiency and resource constraints prevalent in embedded systems. Furthermore, programmable logic devices, notably Field Programmable Gate Arrays (FPGAs), have emerged as indispensable assets for enhancing performance and expediting various processing applications. In the realm of computational efficiency, hardware implementations have the flexibility to tailor the required arithmetic for various applications using fixed-point representation. This approach enables faster computations while upholding adequate accuracy, resulting in reduced resource and energy consumption compared to software applications that rely on higher clock speeds, which often lead to increased resource and energy consumption. Additionally, hardware solutions provide portability and are suitable for resource-constrained and battery-powered applications. This study introduces a novel hardware architecture in the form of an intellectual property core that harnesses the capabilities of a genetic algorithm to detect single and multi ellipses in digital images. In general, genetic algorithms have been demonstrated to be an alternative that shows better results than those based on traditional methods such as the Hough Transform and Random Sample Consensus, particularly in terms of accuracy, flexibility, and robustness. Our genetic algorithm randomly takes five edge points as parameters from the image tested, creating an individual treated as a potential candidate ellipse. The fitness evaluation function determines whether the candidate ellipse truly exists in the image space. The core is designed using Vitis High-Level Synthesis (HLS), a powerful tool that converts C or C＋＋functions into Register-Transfer Level (RTL) code, including VHDL and Verilog. The implementation and testing of the ellipse detection system were carried out on the PYNQ-Z1, a cost-effective development board housing the Xilinx Zynq-7000 System-on-Chip (SoC). PYNQ, an open-source framework, seamlessly integrates programmable logic with a dual-core ARM Cortex-A9 processor, offering the flexibility of Python programming for the onboard SoC processor. The experimental results, based on synthetic and real images, some of them with the presence of noise processed by the developed ellipse detection system, highlight the intellectual property core’s exceptional suitability for resource-constrained embedded systems. Notably, it achieves remarkable performance and accuracy rates, consistently exceeding 99% in most cases. This research aims to contribute to the advancement of hardware-accelerated ellipse detection, catering to the demanding requirements of real-time applications while minimizing resource consumption.

Experimenting innovative active sound design to reduce driver weariness in electric vehicles

With the current electrification trend in the automotive industry, electric vehicle sonification, both interior and exterior alike, has become common practice. To provide drivers with an alternative to the familiar thermal engine rumble, car manufacturers have been exploring many sound design strategies. Quite often however, these designs suffer from a form of weariness that the driver may feel over time, many of them eventually choosing to simply turn off these sounds meant to help them. The goal of the present work is to address this issue by proposing some experimental active sound design strategies whose goal is to break the relative monotony of classical electric vehicle sound design. This is achieved thanks to the combination of advanced seamless audio synthesis tools and generic preprocessing of vehicle data to create new audio control parameters allowing us to explore uncharted grounds for electric vehicle active sound design.

Efficient Synthesis of Hydrobenzoin through NHC Catalysis: A Sustainable Approach for C−C Bond Formation

AbstractA facile and practical one‐pot synthesis of hydrobenzoin has been developed from the readily available aromatic aldehydes, under NHC catalysis. Basically, the present research elucidates a novel, sustainable approach for the synthesis of hydrobenzoin, capitalizing on the catalytic prowess of N‐heterocyclic carbene (NHC) and utilizing sodium borohydride (NaBH4) as an effective reducing partner in this one‐pot conversion. By harnessing the unique reactivity of NHCs, this methodology enables the efficient formation of C−C bonds, leading to the streamlined synthesis of hydrobenzoin with high yields while tolerating various functional groups. Furthermore, this catalytic system offers notable advantages in terms of atom economy, mild reaction conditions, and operational simplicity, making it a promising strategy for sustainable chemical synthesis. The detailed mechanistic insights provided herein shed light on the underlying catalytic pathways, facilitating a deeper understanding of the reaction mechanism. Overall, this study underscores the significant potential of NHC catalysis as a versatile tool for the sustainable synthesis of valuable organic compounds, thereby contributing to the advancement of green chemistry principles and the pursuit of environmentally benign chemical processes.

Generation of alkene radical cation for thioxanthone-TfOH complex-catalyzed intramolecular cyclization using a photoredox catalysis strategy

Photo catalysis has comprehensively become a powerful tool in organic synthesis, and organic molecules are thriving as catalyst. The thioxanthone-TfOH complex (9-HTXTF) as photoredox catalyst with high oxidative capacity can be applied in single electron reduction of alkene affording alkene radical anion as a key intermediate. To transform this intermediate from radical anion to radical cation, a well-designed strategy is proposed with N-arylacrylamides as substrate. Based on its single electron transfer (SET) with 9-HTXTF*, N-radical cation is generated and then transformed to alkene radical cation by intramolecular conjugated system. By using this photoredox catalysis strategy, we developed a 9-HTXTF-catalyzed photochemical cyclization of alkenes, which further expands the applications of this catalyst. The entire cyclization is metal-free and without sacrificing agents, which conforms to atom economy and environmental friendliness.

PEPR DIADEM: Priority Equipment and Research Program on the development of innovative materials using artificial intelligence

IntroductionThe quest to develop efficient, sustainable materials from non-critical, non-toxic resources is one of today's most formidable challenges in the current context of energy, transport, digital or healthcare transitions. In response, France launched the pioneering Priority Equipment and Research Program (PEPR) DIADEM in 2022. This innovative initiative, focused on DIscovery Acceleration for the Deployment of Emerging Materials (DIADEM), leverages Artificial Intelligence (AI) to accelerate the innovation chain from conception to realization, revolutionizing Materials Science sustainably.With a strategic emphasis on scientific synergy, PEPR DIADEM aims to expedite the discovery and development of novel materials essential for contemporary and future societal challenges. To achieve this, the program seeks to catalyze breakthroughs in areas ranging from energy efficiency to transportation, digitalization, and healthcare, covering a broad spectrum of materials from metallic alloys to functional nanostructures.Aligned with the Green Deal framework's ambitious targets, PEPR DIADEM addresses the urgent need for accelerated sustainable materials research. By utilizing cutting-edge technologies like rapid synthesis and characterization tools, automation, digital simulations, data management, AI, additive manufacturing, and thin film engineering, the program is set to significantly reshape the materials science landscape.As PEPR DIADEM embarks on its journey of innovation, it not only advances scientific knowledge but also holds the promise of addressing current global challenges and paving the way for a more sustainable and prosperous future.

Radical-mediated click-clip reactions

Click reactions, which are characterized by rapid, high-yielding, and highly selective coupling of two reaction partners, are powerful tools in synthesis but are rarely reversible. Innovative strategies that reverse such couplings in a precise and on-demand manner, enabling a click-clip sequence, would greatly expand the technique’s versatility. Herein, a click and clip reaction pair is demonstrated by manipulation of a sulfilimine linkage. Phenothiazines and amines are rapidly and quantitatively coupled through oxidative sulfilimine bond formation with N-bromosuccinimide, and the resulting sulfilimine bromides then undergo quantitative reversion to the phenothiazines and amines through photoreduction at 380 nanometers. This protocol enables fabrication of depolymerizable macromolecules and reversible modification of aminosaccharides, demonstrating high selectivity and efficiency for manipulating sulfilimine linkages in complex systems.

Return on investment of tobacco control measures: a systematic review protocol.

The objective of this systematic review will be to estimate the return on investment (ROI) and social return on investment (SROI) on tobacco control measures. Tobacco consumption has been proven to be associated with a huge epidemiological, humanistic, and economic burden. National and international organizations are making concerted efforts to control tobacco use. However, currently, there are no conclusive estimates of the ROI and SROI of such programs and policies. This review will include all studies that evaluate the ROI or SROI on tobacco control programs and policies on tobacco users and probable tobacco users globally. This review will follow the JBI methodology for systematic reviews of economic evidence. Databases to be searched will include Embase (Ovid), MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Health Economic Evaluation Database (HEED), National Health Service Economic Evaluation Database (NHS EED), CEA Registry, LILACS, Science Direct, Web of Science, EconLit, and Google Advanced Search. Gray literature will also be searched for in non-academic databases, including the websites of various civil societies and non-governmental organizations involved in tobacco control. Two independent reviewers will screen titles/abstracts, and later full-text studies. Critical appraisal will be conducted using the JBI checklist for economic evaluations and the SROI Quality Framework. Data will be extracted and synthesized using JBI data extraction forms and synthesis tools. The MPOWER framework will be considered for data synthesis across all selected studies using narrative synthesis, tables, and figures. PROSPERO CRD42023391591.

Multi-objective, multi-constraint high-throughput design, synthesis, and characterization of tungsten-containing refractory multi-principal element alloys

Refractory multi-principal element alloys (RMPEAs) have gained interest recently due to their superior properties at elevated temperatures, including outstanding yield and ultimate strengths, high thermal conductivity, and resistance to creep. RMPEAs can be designed to exhibit a wide range of properties by tailoring their composition. However, the vast chemical design space makes brute-force experimental screening inefficient and costly. In this work, we follow a closed-loop, iterative computational/experimental screening approach that combines computational alloy design methodologies with high-throughput synthesis and characterization tools to explore the vast RMPEAs space and design new RMPEAs that satisfy multiple objectives and constraints. In particular, we targeted compositions with yield strengths higher than 50 MPa at 2000 °C, W content of more than 30 at.% for high-temperature strength and operability up to 2000 °C, narrow solidification range for additive manufacturability, competitive ductility metrics, among other property constraints. We evaluated the mechanical properties and microstructure of 58 alloys designed in 5 batches, in both as-cast and homogenized conditions, synthesized using vacuum arc melting, utilizing scanning electron microscopy, X-ray diffraction, Vickers microhardness, nanoindentation, and high-temperature compression testing. Based on the microhardness screening experiments in each batch, the best-performing alloys were selected for scale-up. High-temperature compression at 1800 °C was performed in these alloys, demonstrating that the designed alloys exhibit up to five times higher yield strength than a pure tungsten benchmark. We conclude that W-containing RMPEAs designed in this study merit further consideration for next-generation structural materials for ultra-high temperature applications.

Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N-Arylquinazolinones.

Visible light-driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of deracemization of allenes have been established, where the activated energy of photosensitizer should surpass that of the substrates, representing an intrinsic requirement. Accordingly, this method is not applicable for axially chiral molecules with significantly high triplet energies. In this study, we present a photoredox catalytic deracemization approach that enables the efficient synthesis of valuable yet challenging-to-access axially chiral 2-azaarene-functionalized quinazolinones. The substrate scope is extensive, allowing for both 3-axis and unmet 1-axis assembly through facile oxidation of diverse central chiral 2,3-dihydroquinazolin-4(1H)-ones that can be easily prepared and achieve enantiomer enrichment via deracemization. Mechanistic studies reveal the importance of photosensitizer selection in attaining excellent chemoselectivity and highlight the indispensability of a chiral Brønsted acid in enabling highly enantioselective protonation to accomplish efficient deracemization.

Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N‐Arylquinazolinones

AbstractVisible light‐driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of deracemization of allenes have been established, where the activated energy of photosensitizer should surpass that of the substrates, representing an intrinsic requirement. Accordingly, this method is not applicable for axially chiral molecules with significantly high triplet energies. In this study, we present a photoredox catalytic deracemization approach that enables the efficient synthesis of valuable yet challenging‐to‐access axially chiral 2‐azaarene‐functionalized quinazolinones. The substrate scope is extensive, allowing for both 3‐axis and unmet 1‐axis assembly through facile oxidation of diverse central chiral 2,3‐dihydroquinazolin‐4(1H)‐ones that can be easily prepared and achieve enantiomer enrichment via deracemization. Mechanistic studies reveal the importance of photosensitizer selection in attaining excellent chemoselectivity and highlight the indispensability of a chiral Brønsted acid in enabling highly enantioselective protonation to accomplish efficient deracemization.

Cell-free protein synthesis with technical additives - expanding the parameter space of in vitro gene expression.

Biocatalysis has established itself as a successful tool in organic synthesis. A particularly fast technique for screening enzymes is the in vitro expression or cell-free protein synthesis (CFPS). The system is based on the transcription and translation machinery of an extract-donating organism to which substrates such as nucleotides and amino acids, as well as energy molecules, salts, buffer, etc., are added. After successful protein synthesis, further substrates can be added for an enzyme activity assay. Although mimicking of cell-like conditions is an approach for optimization, the physical and chemical properties of CFPS are not well described yet. To date, standard conditions have mainly been used for CFPS, with little systematic testing of whether conditions closer to intracellular conditions in terms of viscosity, macromolecules, inorganic ions, osmolarity, or water content are advantageous. Also, very few non-physiological conditions have been tested to date that would expand the parameter space in which CFPS can be performed. In this study, the properties of an Escherichia coli extract-based CFPS system are evaluated, and the parameter space is extended to high viscosities, concentrations of inorganic ion and osmolarity using ten different technical additives including organic solvents, polymers, and salts. It is shown that the synthesis of two model proteins, namely superfolder GFP (sfGFP) and the enzyme truncated human cyclic GMP-AMP synthase fused to sfGFP (thscGAS-sfGFP), is very robust against most of the tested additives.

Advancing the design of heterogeneous catalyst: Copper-montmorillonite for regioselective alkyne hydroamination

Transition metal catalysts supported on natural materials offer promising avenues for sustainable organic synthesis. In this study, we present the synthesis, characterisation, and catalytic performance of copper nanoparticles supported on montmorillonite K10 (CuMK10) as a heterogeneous catalyst for hydroamination reactions. CuMK10, synthesised through a robust and established nanoparticle synthesis methodology, demonstrates remarkable catalytic efficiency and selectivity in the synthesis of imines via hydroamination of terminal alkynes. The catalyst exhibits exceptional regioselectivity, predominantly yielding Markovnikov products, demonstrating its potential as a versatile tool in organic synthesis. Moreover, CuMK10 shows favourable reusability, offering economic benefits and practical utility due to its ease of recovery and reuse. Comprehensive structural and mechanistic studies provide insights into the catalyst's performance, paving the way for the development of efficient and environmentally benign catalytic systems.