Single Step Research Articles

Development of one-step roll-to-roll system with incorporated vacuum sputtering for large-scale production of plasmonic sensing chips

The trade-off relationship between cost and performance is a major challenge in the development of surface-enhanced Raman spectroscopy (SERS) sensors for practical applications. We propose a roll-to-roll system with incorporated vacuum sputtering to manufacture Ag-coated nanodimples (Ag/NDs) on A4-scale films in a single step. The Ag/ND SERS platforms were prepared via O2 ion beam sputtering and Ag sputtering deposition. The concave three-dimensional spaces in the Ag/NDs functioned as hotspots, and their optimal fabrication conditions were investigated with two variables: moving speed and Ag thickness. The entire process was automated, which resulted in highly consistent optical responses (i.e., relative standard deviation of ∼10%). The activation of plasmonic hotspots was demonstrated by electric-field profiles calculated via the finite-difference time-domain method. The wavelength dependency of the Ag/ND platforms was also examined by dark-field microscopy. The results indicate that the developed engineering technique for the large-scale production of Ag/ND plasmonic chips would likely be competitive in the commercial market.

Degradation of pharmaceuticals and other emerging pollutants employing bi-metal catalysts/magnesium and/or (green) hydrogen in aqueous solution

Contaminations by pharmaceuticals, personal care products, and other emerging pollutants in water resources have become a seriously burgeoning issue of global concern in the first third of the twenty-first century. As societal reliance on pharmaceuticals continues to escalate, the inadvertent introduction of these substances into water reservoirs poses a consequential environmental threat. Therefore, the aim of this study was to investigate reductive degradation, particularly, catalytic hydrogenation regarding model pollutants such as diclofenac (DCF), ibuprofen (IBP), 17α-ethinylestradiol (EE2), or bisphenol-A (BPA), respectively, in aqueous solutions at lab scale. Iron bimetals (zero valent iron, ZVI, and copper, Cu, or nickel, Ni) as well as zero valent magnesium (Mg, ZVM) in combination with rhodium, Rh, or palladium, Pd, as hydrogenation catalysts (HK), were investigated. Studies were executed through various short-term batch experiments, with multiple sample collections, over a total range of 120 min. The results indicated that DCF was attenuated at over 90 % when exposed to Fe-Cu or a Fe-Ni bimetal (applied as a single model pollutant). However, when DCF was part of a mixture alongside with IBP, EE2, and BPA, the attenuation efficacy decreased to 79 % with Fe-Cu and 23 % with Fe-Ni. Conversely, both IBP and BPA exhibit notably low attenuation levels with both bimetals, less than 50 %, both deployed as single substances or in mixtures. No reaction (degradation) products could be identified employing LC-MS, but sometimes a release of the parent pollutant when applying an acetic acid buffer could be noted to a certain extent, suggesting adsorption processes on corrosion products such as iron hydroxide and/or oxides. Surprisingly, Mg in combination with Rh (Rh-HK) or Pd (Pd-HK) showed a significantly rapid decrease in the concentrations of DCF, EE2, and BPA, in part up to approximately 100 %, that is, within a few minutes only in part due to hydrogenation degradation reactions (related reaction products could actually be identified by LC-MS; adsorption processes were not observed here). Moreover, kinetic modeling of the DCF degradation with Mg-Rh-HK was conducted at different temperatures (15 °C, 20 °C, 25 °C, 35 °C) and varied initial concentrations (2.5 mg/L, 5.0 mg/L, 7.5 mg/L, 10.0 mg/L). The outcomes prove that the degradation of DCF at the Rh-HK’s surface followed a modified first-order kinetics, most probably by catalytic hydrodehalogenation and subsequent hydrogenation of the aromatic moieties (molecular hydrogen was provided by the corrosion of Mg). From the determined reaction rate constants at four different temperatures, the activation energy was estimated to be 59.6 kJ/mol by means of the Arrhenius equation what is in good agreement with similar results reported in the literature. This coupled hydrodehalogenation and hydrogenation approach may be upscaled into a new promising technical process for comprehensively removing such pharmaceuticals and similar pollutants in sewage plants in a single step, furthermore, even in combination with adsorption by activated carbon and/or ozonation which have already been established at some sewage plants in Switzerland and Germany recently.

Development of a novel forming tool for the production of high-strength aluminum components with tailored properties

Because of growing environmental and technical requirements, the efficient manufacturing of components with tailored properties using recyclable materials is mandatory. The combination of high-strength aluminum alloys and thermal-assisted forming operations is an innovative method for the production of components with varying mechanical properties. By locally adjusting the cooling rates during a thermo-mechanical forming operation, it is possible to modify the microstructure and precipitation conditions. A subsequent aging operation causes different microstructural and mechanical characteristics. This allows both deep-drawing and adjustment of the component properties in one single step. For this reason, this contribution focuses on the production of components with tailored properties. With the aid of a non-contact measuring system, previous investigations have proved that mechanical material properties can be adapted during a forming process by adjusting the cooling rates. In this contribution, this knowledge is transferred to a novel temperature-controlled rectangular cup tool. A variation of the local tool temperature and holding duration in the tool will be carried out. Then, the mechanical and microstructural properties of the manufactured components will be characterized through hardness and DSC investigations. In addition, the influence of different tool temperatures on the component temperature, the sheet thickness distribution and process forces will be investigated. As a result, it has been demonstrated that mechanical, process-related and geometric advantages can be achieved by using locally temperature-controlled forming tools.

Numerical analysis of the energy efficiency of drying a flooded masonry wall by applying a variable drying air temperature profile

The masonry wall initially saturated with moisture and without internal or external water sources was considered to simulate the drying of a wall after a flood. Numerical calculations using the in-house non-equilibrium heat and moisture model were performed to investigate the impact of variable drying air temperature profiles on the drying efficiency of the thermo-injection method. A drying process lasting twelve days was simulated. Based on previous studies, four drying air temperature variation strategies, i.e., jump, stepwise, periodic, and constant temperature (reference), were computed and compared. The drying air temperature profile was changed from 20°C to 60°C with heating intervals of 24 h and different characterization strategies. The jump strategy changed rapidly in a single step. Stepwise one changed by 10°C after each heating interval, and the period strategy changed from 20°C to 60°C or from 60°C to 20°C after each heating interval. Furthermore, the relative humidity of the drying air corresponded to the three seasons in Poland (i.e., winter, summer, and spring) and ranged between 70% and 90% at ambient conditions. It was found that the proposed drying strategies with variable temperature profiles can reduce energy consumption compared to the reference strategy with a constant temperature.

Revolutionary Selection, Activation, and Expansion with Microbubbles for CAR-T Cell Manufacturing

Abstract Despite several chimeric antigen receptor-modified T cells (CAR-T) products being approved and commercialized, CAR-T cell therapy has manufacturing challenges. Conventional CAR-T therapies are manufactured by collecting apheresis material from a patient’s blood, then modifying the isolated T cells from the apheresis material to express a cancer cell-specific CAR, eventually infusing the CAR-T cells into a patient. Challenges include early exhaustion of the therapeutic cells, manual/laborious processes, and complex workflows. Akadeum’s innovative microbubble technology streamlines human T cell selection, activation, and expansion into a single step. Here, we demonstrate over 90% capture efficiency while reducing the selection process to under one hour. Because of the microbubbles’ natural buoyancy, T cell activation occurs at the top of the culture. As the T cells divide and the bound receptors are recycled, T cells fall to the bottom of the media, avoiding CD3/CD28 overstimulation. PD-1 expression is reduced throughout expansion compared to traditional activation workflows. T cell activation was not compromised, as evidenced by the upregulation of CD69, CD25, and HLA-DR+. Additionally, microbubble technology can increase the percentage of desired effector T cell populations. As CAR-T therapy expands, innovations like Akadeum's microbubble technology play a crucial role in overcoming manufacturing challenges and ensuring the development of high-quality, effective therapies.

Innovative dispersion techniques of graphene nanoplatelets (GNPs) through mechanical stirring and ultrasonication: Impact on morphological, mechanical, and thermal properties of epoxy nanocomposites

Graphene nanoplatelets (GNPs) have attracted tremendous interest due to their unique properties and bonding capabilities. This study focuses on the effect of GNP dispersion on the mechanical, thermal, and morphological behavior of GNP/epoxy nanocomposites. This study aims to understand how the dispersion of GNPs affects the properties of epoxy nanocomposite and to identify the best dispersion approach for improving mechanical performance. A solvent mixing technique that includes mechanical stirring and ultrasonication was used for producing the nanocomposites. Fourier transform infrared spectroscopy was used to investigate the interaction between GNPs and the epoxy matrix. The measurements of density and moisture content were used to confirm that GNPs were successfully incorporated into the nanocomposite. The findings showed that GNPs are successfully dispersed in the epoxy matrix by combining mechanical stirring and ultrasonication in a single step, producing well-dispersed nanocomposites with improved mechanical properties. Particularly, the nanocomposites at a low GNP loading of 0.1 wt%, demonstrate superior mechanical strength, as shown by increased tensile properties, including improved Young's modulus (1.86 GPa), strength (57.31 MPa), and elongation at break (4.98). The nanocomposite with 0.25 wt% GNP loading performs better, according to the viscoelastic analysis and flexural properties (113.18 MPa). Except for the nanocomposite with a 0.5 wt% GNP loading, which has a higher thermal breakdown temperature, the thermal characteristics do not significantly alter. The effective dispersion of GNPs in the epoxy matrix and low agglomeration is confirmed by the morphological characterization. The findings help with filler selection and identifying the best dispersion approach, which improves mechanical performance. The effective integration of GNPs and their interaction with the epoxy matrix provides the doorway for additional investigation and the development of sophisticated nanocomposites. In fields like aerospace, automotive, and electronics where higher mechanical performance and functionality are required, GNPs' improved mechanical properties and successful dispersion present exciting potential.

Seamless integration of GEM, a density based-force field, for QM/MM simulations via LICHEM, Psi4, and Tinker-HP.

Hybrid quantum mechanics/molecular mechanics (QM/MM) simulations have become an essential tool in computational chemistry, particularly for analyzing complex biological and condensed phase systems. Building on this foundation, our work presents a novel implementation of the Gaussian Electrostatic Model (GEM), a polarizable density-based force field, within the QM/MM framework. This advancement provides seamless integration, enabling efficient and optimized QM/GEM calculations in a single step using the LICHEM Code. We have successfully applied our implementation to water dimers and hexamers, demonstrating the ability to handle water systems with varying numbers of water molecules. Moreover, we have extended the application to describe the double proton transfer of the aspartic acid dimer in a box of water, which highlights the method's proficiency in investigating heterogeneous systems. Our implementation offers the flexibility to perform on-the-fly density fitting or to utilize pre-fitted coefficients to estimate exchange and Coulomb contributions. This flexibility enhances efficiency and accuracy in modeling molecular interactions, especially in systems where polarization effects are significant.

Enhancing biomarker detection in human serum for lung cancer diagnosis: Aqueous biphasic systems for simultaneous depletion of high-abundance proteins and efficient extraction of CYFRA 21–1

Analysing biomarkers in human serum could be used as an effective and less invasive approach for the diagnosis of lung cancer; however, biomarker detection reliability is highly limited due to matrix effects. Herein, aqueous biphasic systems (ABS) are studied as platforms for human serum pretreatment, allowing the simultaneous depletion of high abundant proteins and biomarker extraction. By using ABS varying the polyethylene glycol (PEG) molecular weight between 400 and 6000 g·mol−1 and adopting phosphate buffer as the other phase-forming component, the depletion of the high abundance serum proteins immunoglobulin G (IgG) and human serum albumin (HSA) is induced at the ABS interphase, through precipitation, forming a three-phase partitioning system (ABS-TPP). Maximum depletion efficiencies of 99 % for IgG and 70 % for HSA were achieved in one step using PEG 1500-based ABS-TPP. On the other hand, lung cancer biomarkers, such as CYFRA 21–1, are extracted to the PEG-rich phase of the same ABS-TPP with recovery yields of 91 %. This work shows that a proper selection of the PEG molecular weight in the ABS composition leads to the efficient depletion of high-abundance proteins and extraction of cancer biomarkers from human serum, in a single step, confirming the potential of ABS for sample pretreatment to improve biomarker analysis.

Studies on Comprehensive Total Synthesis of Natural and Pseudo-Natural Products for Drug Discovery.

Natural products are important for the development of pharmaceuticals and agrochemicals; thus, their synthesis and medicinal chemistry research is critical. Developing a total synthesis pathway for natural products confirms their structure and provides the opportunity to modify the structure in a targeted manner. A simple modification of a single oxidation step can increase the biological activity, or the complexity of the molecule can alter the property. Herein, we discuss the asymmetric total synthesis of dihydroisocoumarin-type natural products, the creation of novel antibacterial compounds through partial structural modification, and the development of antioxidants with high activity and low toxicity through dimerization strategies.

Reinforcement of thin hot-stamped components by fiber reinforced plastic structures with optimized fatigue strength properties

Multi-material structures in the automotive industry hold great potential for lightweight design, body construction, and functionalization due to their favorable mechanical properties and reduced structural weight. The combination of metal and plastic, in particular, is commonly used to enhance the overall properties of the end product when compared to single-material structures.This paper describes a process development with a hot-stamping and an extrusion tool. By means of this tool, a thermally assisted extrusion process can be used to join GMT (Glass Mat reinforced Thermoplastics) and 22MnB5 steel in a single process step. Through adhesion, the GMT adheres to the rough surface of the AlSi(aluminum-silicon)-coated 22MnB5. Test components were manufactured and through static tests the influence of process parameters was evaluated. Assuming that the parameters determined for the reference component are already sufficient for a design in the vehicle, the reduction of the steel thickness of the structure from 1.5 mm to 1.2 mm can be recommended on the basis of the results obtained. This is accompanied by a reduction in the mass of the test structure used while maintaining or improving its dynamic and static properties. Further weight savings appear possible through further component and process optimization.

High energy supercapacitance of magnetic PANI/Ni2O3 nanocomposite and its magnetic structural repair

A magnetically auto healable and robust supercapacitor from a nanocomposite of PANI68.1 %: Ni2O331.9 % (PNi) synthesized in an in situ single step method, is achieved. PNi provided an exceptional character of healing the structural damage of PANI by the magneticity of Ni2O3 nanoparticles and showed a feature of increase in energy storage with increase in No. of charge/discharge cycles. The PNi exhibited a cyclic stability up to 16,800 cycles without significant reduction in initial Cs. The energy storage parameters achieved after 10,000 cycles are specific capacitance (Cs) of 347.6 F g−1, specific energy (E) of 69.52 W h kg−1, which is in the regime of E of Ni-metal hydride batteries of 0.9–1.3 V potential range, and specific power (P) of 8.571 kW kg−1 at 3 A g−1. Therefore, the PNi would be of a potential electrode material for the fabrication of long withstanding, robust and self - magnetically healable supercapacitor that delivers high energy.

Utility of Triethyloxonium Tetrafluoroborate for Chloride Removal during Sarcosine N-Carboxyanhydride Synthesis: Improving NCA Purity.

The clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality making high-purity sarcosine N-carboxyanhydride (Sar-NCA) as monomer for its production inevitable. Within this report, we present the use of triethyloxonium tetrafluoroborate in Sar-NCA synthesis with focus on amino acid and chloride impurities to avoid the sublimation of Sar-NCAs. With a view towards upscaling into kilogram or ton scale, a new methodology of monomer purification is introduced by utilizing the Meerwein's Salt triethyloxonium tetrafluoroborate to remove chloride impurities by covalent binding and converting chloride ions into volatile products within a single step. The novel straightforward technique enables access to monomers with significantly reduced chloride content (<100 ppm) compared to Sar-NCA derived by synthesis or sublimation. The derived monomers enable the controlled-living polymerization in DMF and provide access to pSar polymers with Poisson-like molecular weight distribution within a high range of chain lengths (Xn 25-200). In conclusion, the reported method can be easily applied to Sar-NCA synthesis or purification of commercially available pSar-NCAs and eases access to well-defined hetero-telechelic pSar polymers.

The Role of Intramolecular Reactions and Chemical Degradation in the Apparent Biotransformation Pathways of a Series of SYK Inhibitors.

In vitro metabolism studies of the spleen tyrosine kinase inhibitors AZ-A and AZ-B identified four unusual metabolites. M1 (mass-to-charge ratio 411) was formed by both molecules and was common to several analogs (AZ-C to AZ-H) sharing the same core structure, appearing to derive from the complete loss of a pendent 3,4-diaminotetrahydropyran ring and pyrazole ring cleavage resulting in a nonobvious metabolite. M2-M4 were formed by AZ-A and a subset of the other compounds only and apparently resulted from a sequential loss of H2 from parent. Initial attempts to isolate M3 for identification were unsuccessful due to sample degradation, and it was subsequently found that M2 and M3 underwent sequential chemical degradation steps to M4. M4 was successfully isolated and shown by mass spectrometry and NMR spectroscopy to be a tricyclic species incorporating the pyrazole and the 3,4-diaminotetrahydropyran groups. We propose that this arises from an intramolecular reaction between the primary amine on the tetrahydropyran and a putative epoxide intermediate on the adjacent pyrazole ring, evidence for which was generated in a β-mercaptoethanol-trapping experiment. The loss of the tetrahydropyran moiety observed in M1 was found to be enhanced in an analog that was unable to undergo the intramolecular reaction step, leading us to propose two possible reaction pathways originating from the reactive intermediate. Ultimately, we conclude that the apparently complex and unusual metabolism of this series of compounds likely resulted from a single metabolic activation step forming an epoxide intermediate, which subsequently underwent intramolecular rearrangement and/or chemical degradation to form the final observed products. SIGNIFICANCE STATEMENT: The current work provides an unusual biotransformation example showing the potential for intramolecular reactions and chemical degradation to give the appearance of complex metabolism arising from a single primary route of metabolism.

Spectroscopic analysis of the bacterially expressed head domain of rotavirus VP6.

The rotavirus capsid protein VP6 forms the middle of three protein layers and is responsible for many critical steps in the viral life cycle. VP6 as a structural protein can be used in various applications including as a subunit vaccine component. The head domain of VP6 (VP6H) contains key sequences that allow the protein to trimerize and that represent epitopes that are recognized by human antibodies in the viral particle. The domain is rich in β-sheet secondary structures. Here, VP6H was solubilised from bacterial inclusion bodies and purified using a single affinity chromatography step. Spectral (far-UV circular dichroism and intrinsic tryptophan fluorescence) analysis revealed that the purified domain had native-like secondary and tertiary structures. The domain could maintain structure up to 44°C during thermal denaturation following which structural changes result in an intermediate forming and finally irreversible aggregation and denaturation. The chemical denaturation with urea and guanidinium hydrochloride produces intermediates that represent a loss in the cooperativity. The VP6H domain is stable and can fold to produce its native structure in the absence of the VP6 base domain but cannot be defined as an independent folding unit.

Diagnosing Gestational Diabetes by a Single Step Procedure and Care is a Propitious Step Towards Containing the Epidemic of Diabetes

Diagnosing Gestational Diabetes by a Single Step Procedure and Care is a Propitious Step Towards Containing the Epidemic of Diabetes

Development of novel 9H-carbazole-4H-chromene hybrids as dual cholinesterase inhibitors for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease affecting mental ability and neurocognitive functions. Cholinesterase enzymes affect concentration of acetylcholine in the brain, leading to dementia. Thus, there is an urgent need to develop novel dual cholinesterase inhibitors as possible anti-AD drugs. Herein, we have designed and synthesized a novel series of 9H-carbazole-4H-chromenes 4(a-l) through a one-pot three-component reaction of salicylaldehydes (1), hydroxycarbazole (2) and N-methyl-1-(methylthio)-2-nitroethenamine (3) using triethylamine as a catalyst in ethanol. Synthetic transformation involves the formation of two C-C bonds and one C-O bond in a single step to obtain desired analogs. The rapid one-pot reaction does not require chromatographic purification, proceeds under mild conditions, and exhibits good tolerance toward various functional groups with high synthetic yields. Synthesized compounds were screened for cytotoxicity using MTT assay in BV-2 microglial cells. These compounds were then in-vitro screened against acetylcholinesterase (AChE) and butyrylcholinestrase (BuChE) enzymes. Most of these ligands have shown dual cholinesterase inhibitory activity compared to the standard drug. In-vitro results showed that the compounds 4a and 4d have promising anticholinesterase response against both cholinesterase enzymes (4a, AChE IC50: 5.76µM, BuChE IC50: 48.98µM; 4d, AChE IC50: 3.58µM, BuChE IC50: 42.73µM). In-vitro results were validated by molecular docking and dynamic simulation at 100ns. Molecular docking and molecular dynamics simulation study strongly supported structural features present in these analogs. Together, these analogs could be exploited to develop dual anti-cholinesterase candidates to treat AD in combination with other drugs.

Gaze-based intention estimation: principles, methodologies, and applications in HRI

Intention prediction has become a relevant field of research in Human-Machine and Human-Robot Interaction. Indeed, any artificial system (co)-operating with and along humans, designed to assist and coordinate its actions with a human partner, would benefit from first inferring the human’s current intention. To spare the user the cognitive burden of explicitly uttering their goals, this inference relies mostly on behavioral cues deemed indicative of the current action. It has been long known that eye movements are highly anticipatory of the single steps unfolding during a task, hence they can serve as a very early and reliable behavioural cue for intention recognition. This conceptual review aims to draw a line between insights in the psychological literature on visuomotor control and relevant applications of gaze-based intention recognition in technical domains, with a focus on teleoperated and assistive robotic systems. Starting from the cognitive principles underlying the relationship between intentions, eye movements, and action, the use of eye tracking and gaze-based models for intent recognition in Human-Robot Interaction is considered, with prevalent methodologies and their diverse applications. Finally, special consideration is given to relevant human factors issues and current limitations to be factored in when designing such systems.

Expanding the capabilities of MuGENT for large-scale genetic engineering of the fastest-replicating species, Vibrio natriegens.

Vibrio natriegens is an emerging model organism for molecular and biotechnological applications. Its fast growth, metabolic versatility, and ease of genetic manipulation provide an ideal platform for synthetic biology. Here, we develop and apply novel methods that expand the genetic capabilities of the V. natriegens model system. Prior studies developed a method to manipulate multiple regions of the chromosome in a single step. Here, we provide new resources that diversify the utility of this method. We also provide a technique to remove the required genetic tools from the cell once the manipulation is performed, thus establishing "clean" derivative cells. Finally, we show the full extent of this technique's capability by generating one of the largest chromosomal deletions reported in the literature. Collectively, these new tools will be beneficial broadly to the Vibrio community and specifically to the advancement of V. natriegens as a model system.

Efficient single-step mechanosynthesis route of nanostructured Hf0.2Nb0.2Ta0.2V0.2Zr0.2C0.5N0.5 High Entropy Carbonitride Powder

Nowadays high entropy carbides (HECs) are an important group of advanced ceramics. They are composed by at least by five transition metals (TMs) in nearly equiatomic proportion and disordered distributed in the cationic sublattice of face centered cubic structures, with carbon atoms in the octahedral interstitial voids, with general formula (TM1,TM2,TM3,TM4,TM5)C. These HECs belong to the recent novel group of ultra-high temperature ceramics (UHTCs), with superior properties in comparison with the constituent binary carbides. However, the synthesis of those HECs can be modified to develop high entropy carbonitrides, HECNs, where the C are partially substituted by N, to form a solid solution in the anionic sublattice, with expected improved properties as UHTCs, but they are in an incipient state of development. Here, we report the synthesis and deep characterization of a non-previously obtained Hf0.2Nb0.2Ta0.2V0.2Zr0.2C0.5N0.5 HECN, via a facile, single step and reproducible solid-gas reaction mechanosynthesis route. The synthesis was successfully completed in a planetary ball mill device, after 2h of milling time, at 400 rpm and using a ball-to- powder ratio of 60:1 in a pure N2 atmosphere at room temperature. The as-synthesized HECNs powdered showed nanostructured morphology and outstanding high-temperature oxidation resistance up to 1500 °C.

Nitrate reduction enables safer aryldiazonium chemistry.

Aryldiazonium salts remain a staple in organic synthesis and are still prepared largely in accord with the protocol developed in the 19th century. Because of the favorable reactivity that often cannot be achieved with other aryl(pseudo)halides, diazonium chemistry continues to grow. Facile extrusion of dinitrogen contributes to the desired reactivity but is also reason for safety concerns. Explosions have occurred since the discovery of these reagents and still result in accidents. In this study, we report a diazonium chemistry paradigm shift based on nitrate reduction using thiosulfate or dihalocuprates as electron donors that avoids diazonium accumulation. Because nitrate reduction is rate-limiting, aryldiazoniums are produced as fleeting intermediates, which results in a safer and often more efficient deaminative halogenation in a single step from anilines.