Continuous Flow Conditions Research Articles

General, Modular Access toward Immobilized Chiral Phosphoric Acid Catalysts and Their Application in Flow Chemistry.

Chiral phosphoric acids (CPAs) are among the most frequently used organocatalysts, with an ever-increasing number of applications. However, these catalysts are only obtained in a multistep synthesis and are poorly recyclable, which significantly deteriorates their environmental and economic performance. We herein report a conceptually different, general strategy for the direct immobilization of CPAs on a broad scope of solid supports including silica, polystyrene, and aluminum oxide. Solid-state catalysts were obtained in high yields and thoroughly characterized with elemental analysis by inductively coupled plasma-optical emission spectrometry (ICP-OES), nitrogen sorption measurements, thermogravimetric analysis, scanning transmission electron microscopy/energy-dispersive X-ray spectroscopy (STEM/EDX) images, and solid-state NMR spectroscopy. Further, the immobilized catalysts were applied to a variety of synthetically valuable, highly stereoselective transformations under batch and flow conditions including transfer hydrogenations, a Friedländer condensation/transfer hydrogenation sequence, and Mannich reactions under cryogenic flow conditions. Generally, high yields and stereoselectivities were observed along with robust catalyst stability and reusability. After being used for 10 runs under batch conditions, no loss of selectivity or catalytic activity was observed. Under continuous-flow conditions, the heterogeneous system was in operation for 19 h and the high enantioselectivity remained unchanged throughout the entire process. We expect our approach to extend the applicability of CPAs to a higher level, with a focus on flow chemistry and a more environmentally friendly and resource-efficient use of these powerful catalysts.

Chloromethylation of Lignin as a Route to Functional Material with Catalytic Properties in Cross-Coupling and Click Reactions.

Invited for this issue's cover are researchers from Tallinn University of Technology (TalTech). The image depicts the lignin chemical evolution route from raw biomass through a greener chloromethylation procedure developed by the research team. It showcases the transformation into lignin-supported metal nanoparticles, serving as a catalyst for various chemical reactions in both batch and continuous flow conditions. The Research Article itself is available at 10.1002/cssc.202301588.

Electrochemical oxidation of glucose in alkaline environment—A comparative study of Ni and Au electrodes

The glucose oxidation reaction (GOR) was studied on Au and Ni electrodes by cyclic voltammetry (CV), rotating disk electrode (RDE) measurements coupled with Koutecky–Levich analysis, Differential Electrochemical Mass Spectrometry (DEMS), in situ Fourier Transform Infrared spectroscopy (FTIRS) and High Performance Liquid Chromatography (HPLC) analysis of the reaction products after electrolysis in potentiostatic mode under continuous flow conditions. This study allowed to identify the reaction products and propose tentative reaction mechanisms. On gold, glucose is adsorbed on metallic sites through its anomeric function (C1) resulting in the formation of gluconate as the main GOR product at potentials close to 0.6 V vs. RHE, with a selectivity towards gluconate close to 100% and a projected faradaic efficiency of ca. 70%. The conversion rate is rather low, close to 20%, due to poisoning of the surface, leading to a strong deactivation. At potentials above 0.7 V vs. RHE, the selectivity towards gluconate decreases and non-selective GOR oxidation proceeds through CC bond cleavage. On nickel, the GOR occurs at high potentials (close to 1.2 V vs. RHE) on Ni(OH)2 and NiOOH sites, and proceeds through C1C2 bond breaking, resulting in arabinose and formate. At higher potentials, the selectivity towards arabinose decreases, formate being the main reaction product.

Radical Mediated Decarboxylation of Amino Acids via Photochemical Carbonyl Sulfide (COS) Elimination.

Herein, we present the first examples of amino acid decarboxylation via photochemically activated carbonyl sulfide (COS) elimination of the corresponding thioacids. This method offers a mild approach for the decarboxylation of amino acids, furnishing N-alkyl amino derivatives. The methodology was compatible with amino acids displaying both polar and hydrophobic sidechains and was tolerant towards widely used amino acid-protecting groups. The compatibility of the reaction with continuous-flow conditions demonstrates the scalability of the process.

Development of Organ-on-a-Chip System with Continuous Flow in Simulated Microgravity.

Organ-on-a-chip (OOC) is an innovative microfluidic device mimicking the structure and functionality of real tissue. OOCs typically involve cell culture with microfluidics to emulate the biological forces of different organ tissues and disease states, providing a next-generation experimental platform. When combined with simulated microgravity conditions, such as those produced by random positioning machines, they offer unique insights into disease processes. Microgravity has been shown to affect cellular behaviors, like proliferation and viability, though its influence on cell physiology is not fully explored. The primary objective of this study was to develop an OOC model with continuous flow under simulated microgravity. Cells cultured in static (non-continuous-flow) conditions exhibited clear growth reduction under microgravity conditions, showing more pronounced difference compared to continuous-flow conditions using an OOC setup. Although our results show that A549 cell viability under continuous flow decreased in microgravity compared to normogravity, this study demonstrates the successful development of a system capable of providing continuous flow in organ-on-a-chip (OOC) models within a random positioning machine.

A Label‐Free Multitechnique Approach to Characterize the Interaction of Bioactive Compounds with Biomimetic Interfaces

Extensive research has been conducted on biomimetic interfaces mimicking the complex and diverse microenvironment of cell membranes to gain insights into bioactive compound interactions and membrane biophysics modulation. The present study proposes an innovative approach that combines five prospective label‐free methodologies (derivative spectroscopy, synchrotron small‐ and wide‐angle X‐Ray scattering, attenuated total reflection–Fourier‐transform infrared spectroscopy, quartz‐crystal microbalance with dissipation, and surface plasmon resonance) to showcase their synergistic capabilities and complementarity in investigating drug–membrane interactions. This multitechnique approach combines the real‐time monitoring of the adsorption process under continuous flow conditions with the steady‐state perspective of this process. As a proof of concept, the interaction of three bioactive compounds (caffeine, testosterone, and diclofenac) with two biomimetic membrane interfaces (multistacked lipid bilayers and supported lipid bilayers) mimicking the more ordered lipid transient phases, with and without cholesterol (lo and so), that are responsible for a variety of membrane‐associated biological activities, is investigated. The biophysical effects of the bioactives are discussed using complementary data from real‐time and steady‐state experiments, including membrane adsorption and distribution, predicted location, and induced changes in order and fluidity, encompassing bilayer thickness, hydration, and area per lipid molecule.

Impairment of Listeria monocytogenes biofilm developed on industrial surfaces by Latilactobacillus curvatus CRL1579 bacteriocin

The effect of lactocin AL705, bacteriocin produced by Latilactobacillus (Lat.) curvatus CRL1579 against Listeria biofilms on stainless steel (SS) and polytetrafluoroethylene (PTFE) coupons at 10 °C was investigated. L. monocytogenes FBUNT showed the greatest adhesion on both surfaces associated to the hydrophobicity of cell surface. Partially purified bacteriocin (800 UA/mL) effectively inhibited L. monocytogenes preformed biofilm through displacement strategy, reducing the pathogen by 5.54 ± 0.26 and 4.74 ± 0.05 log cycles at 3 and 6 days, respectively. The bacteriocin-producer decreased the pathogen biofilm by ∼2.84 log cycles. Control and Bac− treated samples reached cell counts of 7.05 ± 0.18 and 6.79 ± 0.06 log CFU/cm2 after 6 days of incubation. Confocal scanning laser microscopy (CLSM) allowed visualizing the inhibitory effect of lactocin AL705 on L. monocytogenes preformed biofilms under static and hydrodynamic flow conditions. A greater effect of the bacteriocin was found at 3 days independently of the surface matrix and pathogen growth conditions at 10 °C. As a more realistic approach, biofilm displacement strategy under continuous flow conditions showed a significant loss of biomass, mean thickness and substratum coverage of pathogen biofilm. These findings highlight the anti-biofilm capacity of lactocin AL705 and their potential application in food industries.

In-situ Oxidation and Coupling of Anilines towards Unsymmetric Azobenzenes Using Flow Chemistry.

Molecular switches, especially azobenzenes, are used in numerous applications, such as molecular solar thermal storage (MOST) systems and photopharmacology. The Baeyer-Mills reaction of anilines and nitrosobenzenes has been established as an efficient synthetic method for non-symmetric azobenzenes. However, nitrosobenzenes are not stable, depending on their substitution pattern and pose a health risk. An in-situ oxidation of anilines with Oxone® was optimized under continuous flow conditions avoiding isolation and contact. The in-situ generated nitrosobenzene derivatives were subjected to a telescoped Baeyer-Mills reaction in flow. That way azobenzenes with a broad substituent spectrum were made accessible.

Investigating heat exchanger tube performance: second law efficiency analysis of a novel combination of two heat transfer enhancement techniques

AbstractIn the study, the focus was on evaluating the second law efficiency of a heat exchanger tube operating under continuous heat flux and turbulent flow conditions. The evaluation involved the use of a hybrid GnP and Fe3O4 and modified coiled wire as passive heat transfer enhancement techniques. The primary objective was to investigate the impact of these combined techniques on thermal and hydraulic performance, entropy generation number, Bejan number and second law efficiency. To achieve this, different mass fractions of GnP and Fe3O4 nanoparticles were used in the hybrid nanofluid, along with two forms of modified coiled wire: barrel type and hourglass type. The experimental results indicated that the utilization of hybrid nanofluids and modified helical inserts led to a noticeable improvement in the second law efficiency of the heat exchanger tube. However, it was observed that the differences in entropy generation number and Bejan number between the barrel and hourglass types were not significant, mainly due to higher frictional losses associated with the latter. The highest recorded second law efficiency was 0.416, while the lowest entropy generation number was 0.118. These values were achieved through the combined use of GnP and Fe3O4 with a mass fraction of 0.4% and a barrel-type coiled wire insert with a pitch ratio of 0.5.

Generation of long-chain fatty acids by hydrogen-driven bicarbonate reduction in ancient alkaline hydrothermal vents

The origin of life required membrane-bound compartments to allow the separation and concentration of internal biochemistry from the external environment and establish energy-harnessing ion gradients. Long-chain amphiphilic molecules, such as fatty acids, appear strong candidates to have formed the first cell membranes although how they were first generated remains unclear. Here we show that the reaction of dissolved hydrogen and bicarbonate with the iron-rich mineral magnetite under conditions of continuous flow, alkaline pH and relatively low temperatures (90 °C) generate a range of functionalised long-chain aliphatic compounds, including mixed fatty acids up to 18 carbon atoms in length. Readily generated membrane-forming amphiphilic organic molecules in the first cellular life may have been driven by similar chemistry generated from the mixing of bicarbonate-rich water (equilibrated with a carbon dioxide-enriched atmosphere) with alkaline hydrogen-rich fluids fed by the serpentinisation of the Earth’s iron-rich early crust.

Comparative Analysis of Deterministic Fundamental Diagrams Representative of Continuous and Interrupted Traffic Flow on Selected Regional Road in Croatia

Since the inception of the traffic flow theory, numerous traffic flow models have been formulated by scholars in an effort to more accurately delineate the relationships between various traffic flow parameters. However, only a limited number of studies have explored the distinctions between fundamental traffic diagrams, which characterize continuous and interrupted traffic flow conditions. Addressing this research lacuna, we compared twelve “speed–density” and “flow–density” models fitted to empirical data collected under continuous and interrupted traffic flow conditions on a selected regional road in Croatia. The empirical data used to develop these models were extracted from video footage captured by an unmanned aerial vehicle on two representative road segments during characteristic peak and off-peak hours on workdays. Our analysis reveals that, depending on the selected traffic flow model and prevailing traffic flow conditions, the practical capacity of the observed regional road is estimated to be in the range from 799 to 2333 veh/h/lane. It was also discovered that the considered models reach practical capacity at a significantly different density under continuous and interrupted traffic stream conditions, i.e., between 37 and 129 veh/km/lane. The conducted t-tests underscore the need to employ distinct “speed–density” and “flow–density” regression functions for modeling continuous and interrupted traffic stream conditions.

Aminobenzoate-defected UiO-66(Zr)–NH2 frameworks: Scalable synthesis and characterizations for adsorptive denitrogenation from model fuel

In this work, imperfection UiO-66-NH2 frameworks (AUiO-66-NH2) were engineered and scalably produced by a continuous flow method with the assistance of 4-aminobenzoate (ABA) modulators. ABA modulators competed with MOF ligands to bond to Zr4+ clusters under continuous flow conditions, producing AUiO-66-NH2 frameworks containing aminobenzoate linkers and ligand-missing defects. The average ligand deficiency per Zr6 unit of defective AUiO-66(Zr)–NH2 framework ranged from 0.75 ∼ 2.36 upon changing ABA/H2N-BDC molar ratio and reaction temperature, thereby adjusting their porosity and exposing more metal open sites of Zr4+. The batch removal of N-containing compounds (NCCs), including quinoline (QUN) and 2-methyl pyrrole (MPR) in n-octane indicated that the ABA-modulated UiO-66-NH2 samples had improved adsorption capability compared to the perfect MOF. Noticeably, the adsorption performances were further enhanced by protonating 2.5AUiO-66-NH2 to 2.5AUiO-66-NH3+ owing to the synergetic effects of acid-base interaction, H-bonds, cation-π interactions, and π-π stacking interactions between adsorbent and adsorbate. Density functional theory (DFT) calculations further revealed that the NCCs preferably accumulated onto the protonated AUiO-66-NH3+ rather than AUiO-66-NH2. The AUiO-66-NH3+ exhibited adsorbing capacities of ∼204 mg/g and ∼275 mg/g for MPR and QUN, respectively, and obeyed the pseudo-second-order kinetic model. Finally, the continuous fixed-bed adsorptions of these NCCs in model fuel over the AUiO-66-NH3+ pellets (3 mm × 6 mm) showed that 1.0 g of adsorbent can purify with ∼28 L and ∼49 L liquid fuel containing MPR and QUN with a concentration of 1 mg L−1. These state that combining continuous-flow synthesis and defect engineering of the UiO-66-NH2 could be a promising strategy to produce efficient adsorbent materials for upgrading liquid fuel.

A copper(ii) bromide/NMO system for α-amination of esters under continuous-flow conditions with reduced catalyst loading

A new copper(ii) bromide/N-methylmorpholine N-oxide (NMO)-promoted method for α-amination of esters under continuous-flow conditions, with reduced catalyst loading is reported.

Photo-induced microfluidic production of ultrasmall platinum nanoparticles.

We describe here the synthesis of ultrasmall Pt nanoparticles (NPs) obtained by a robust and reliable protocol using UV-Vis photoreduction of a platinum salt precursor, under continuous flow conditions. These ligand-free Pt NPs were rapidly dispersed onto a solid support or stabilized towards aggregation as a colloidal solution by the addition of an appropriate ligand in the reaction mixture. The proposed protocol exploits a microfluidic platform where the Pt4+ precursor is photo-reduced to small Pt0 NPs (1.3 nm) at room temperature in the presence of ethanol, without any additional reducing agent. We apply the protocol to prepare Pt NPs highly dispersed on carbon support (Pt/C) proven to be a very efficient heterogeneous catalyst for both the hydrosilylation of terminal alkynes and hydrogenation of nitroaromatic compounds, selected as model reactions. Furthermore, we exploit the versatility of this microfluidic approach to produce stabilized aqueous/ethanol colloidal solutions of Pt NPs, employing a ligand of choice (e.g., PVP or a thiol-ligand). These colloids offer long-term storage and further ligand modification. We showcase the synthesis of biocompatible glycol-stabilized Pt nanoparticles as an exemplary application.

Highly enantioselective synthesis of both enantiomers of tetrahydroquinoxaline derivatives via Ir-catalyzed asymmetric hydrogenation.

A novel Ir-catalyzed asymmetric hydrogenation protocol for the synthesis of chiral tetrahydroquinoxaline (THQ) derivatives has been developed. By simply adjusting the reaction solvent, both enantiomers of mono-substituted chiral THQs could be selectively obtained in high yields with excellent enantioselectivities (toluene/dioxane: up to 93% yield and 98% ee (R); EtOH: up to 83% yield and 93% ee (S)). For 2,3-disubstituted chiral THQs, the cis-hydrogenation products were obtained with up to 95% yield, 20 : 1 dr, and 94% ee. Remarkably, this methodology was also applicable under continuous flow conditions, yielding gram-scale products with comparable yields and enantioselectivities (dioxane: 91% yield and 93% ee (R); EtOH: 90% yield and 87% ee (S)). Unlike previously reported Ir-catalyzed asymmetric hydrogenation protocols, this system exhibited a significant improvement as it required no additional additives. Furthermore, comprehensive mechanistic studies including deuterium-labeling experiments, control experiments, kinetic studies, and density functional theory (DFT) calculations were conducted to reveal the underlying mechanism of enantioselectivities for both enantiomers.

Efficient construction of a β-naphthol library under continuous flow conditions.

A β-naphthol library has been efficiently constructed utilizing a mild continuous flow procedure, relying on a tandem Friedel-Crafts reaction and starting from readily available arylacetyl chloride and alkynes. Multiple functionalized β-naphthols can be acquired within 160 s in generally high yields (up to 83%). Using an electron-rich phenylacetyl chloride derivative (4-OH- or 4-MeO-) provides spirofused triene dione as the primary product. A scale-up preparation affords a throughput of 4.70 g h-1, indicating potential large-scale application. Herein, we present a rapid, reliable, and scalable method to obtain various β-naphthols in the compound library.

Direct observation of carbon slurry flow behavior and its effect on electrochemical performance in a microfluidic electrochemical flow capacitor.

Carbon slurries have been used as "flowable electrodes" in various electrochemical systems, and the slurry flow characteristics play an important role in the system electrochemical performance. For example, in an electrochemical flow capacitor (EFC), activated carbon particles must pass electrical charge from a stationary electrode to surrounding particles via particle-electrode and particle-particle interactions to store energy in the electric double layer. So far, particle behaviors under a continuous flow condition have not been observed due to the slurry's opacity, and studies of the device's performance thus have been mainly on a bulk level. To understand the relation between the hydrodynamic behavior and the electrochemical performance of carbon slurries, we have constructed a microfluidic EFC (μ-EFC) using transparent materials. The μ-EFC allows for direct observation of particle interactions in flowing carbon slurries using high-speed camera recording, and concurrent measurements of the electrochemical performance via chronoamperometry. The results indicate an interesting dependence of the particle cluster interaction on the flowrate, and its effect on the slurry charging/discharging behavior. It is found that an optimal flowrate could exist for better electrochemical performance.

Bromine radical release from a nickel-complex facilitates the activation of alkyl boronic acids: a boron selective Suzuki-Miyaura cross coupling.

In this study, without utilizing any exogenous activator or strong oxidants, we successfully employed inactivated and easily accessible alkyl boronic acids (BAs) as coupling partners in a photocatalyzed Suzuki-Miyaura reaction under batch and continuous-flow conditions. Detailed mechanistic studies suggest a unique BA activation pathway, via a plausible radical transfer event between a bromine radical (formed in situ via a photo-induced homolysis of the Ni-Br bond) and the empty p-orbital on the boron atom. Subsequently, the necessity to tune the BA oxidation potential by means of hydrogen-bonding interaction with solvents or Lewis acid-base type interactions is replaced by a novel halogen radical transfer (XRT) mechanism. The mechanistic hypothesis has been supported by both control experiments and DFT calculations.

Sustainable upgrading of glycerol into glycidol and its derivatives under continuous-flow conditions

This study develops a safe and efficient flow process to convert glycerol, a biodiesel byproduct, into glycidol and its derivatives. The method has significant environmental and economic benefits compared to conventional glycidol synthesis routes.

Development of an in vitro setup for flow studies in a stented carotid artery bifurcation.

To investigate flow conditions in a double-layered carotid artery stent, a bench-top in vitro flow setup including a bifurcation phantom was designed and fabricated. The geometry of the tissue-mimicking phantom was based on healthy individuals. Two identical phantoms were created using 3D-printing techniques and molding with PVA-gel. In one of them, a clinically available CGuard double-layer stent was inserted. Measurements were performed using both continuous and pulsatile flow conditions. Blood flow studies were performed using echoPIV: a novel ultrasound-based technique combined with particle image velocimetry. A maximum deviation of 3% was visible between desired and measured flow patterns. The echoPIV measurements showed promising results on visualization and quantification of blood flow in and downstream the stent. Further research could demonstrate the effects of a double-layered stent on blood flow patterns in a carotid bifurcation in detail.