Alternative Reagents Research Articles

Use of phytic acid for selective precipitation of undesirable metals (Al, Fe, Pb) contained in the leachates from hydrometallurgical processes

In hydrometallurgical processes, chemical precipitation is used either to recover dissolved valuable metals or to remove undesirable elements before electrolysis. Beside conventional reagents (Ca(OH)2, NaOH, Na2CO3…) many authors tried to replace them by bio-sourced compounds, but unfortunately, without necessarily leading to an industrial use. This paper describes a study on the possibility to use phytic acid to remove Al3+, Fe3+ and Pb2+ from acidic leachates. This reagent, present in cereals and considered as an antinutrient, can be recovered from soaking waters of corn. In this work, five metal phytates were synthesized and characterized by TGA and ICP-OES leading to the following formulae: Al3C6H9P6O24,7H2O, Cu6C6H6P6O24,8H2O, Fe3.5C6H7.5P6O24,15H2O, Pb6C6H6P6O24,10H2O and Zn6C6H6P6O24,6H2O. Solubility of each metal phytate was measured in pure water at 20 °C in order to determine their solubility product Ks not available in literature. The conditional solubility as a function of the pH was then established to predict the possibility to perform selective precipitation. The results showed that phytic acid could be an interesting alternative precipitation reagent, able, from a thermodynamical point of view, to remove Al3+, Fe3+ and Pb2+ from copper or zinc leachates.

Catalytic N-Alkylation of Anilines

The review summarizes data on modern approaches to N-alkylation of anilines using metal complex and heterogeneous catalysts based on palladium, platinum, rhodium, nickel, iron, copper, gold supported on various materials, as well as zeolites, metal oxides (titanium, iron, copper, and aluminum). The N-alkylation reactions of anilines with alkyl halides, alcohols, dimethyl carbonate, aldehydes, as well as with CO2/H2 and alkylation with alternative reagents are considered.

The effects of partially replacing amine collectors by a commercial frother in a reverse cationic hematite flotation

Iron ore froth flotation has recently been used to obtain pure minerals due to the depletion of high-grade deposits. Amine collectors have often been used in cationic reverse iron ore flotation to achieve the separation with quartz impurities. The main problem associated with these collectors is related to the control of frothing properties and the high cost of amine reagents. In this paper, we report the benefits of partial replacement of amine collectors with a frother in reverse cationic flotation of hematite. Surface tension and batch flotation experimental results indicated for the first time that replacing Flotigam EDA, an etheramine collector by more than 10% improved the flotation performance in both grade and recovery of hematite. It was also noted mild hematite entrainments for lower frother dosages whilst reagents cost estimation indicated profitability per ton of iron recovered. At higher frother dosage however, higher quartz recoveries were observed as a result of entrainment which led to satisfactory results in terms of iron grade in the sink, but results showed higher costs of reagents than when collector was used alone. From observed results, it was concluded that partially replacing amine collector by a frother does improve the performance of the flotation globally regardless of pronounced entrainment that was mainly due the mineralogy of the ore with notable amounts of locked particles in the lower sizes. Finally, it would be useful to investigate these findings with alternative reagents and on minerals with different mineralogical properties.

Amine–Boranes as Transfer Hydrogenation and Hydrogenation Reagents: A Mechanistic Perspective

AbstractTransfer hydrogenation (TH) has historically been dominated by Meerwein–Ponndorf–Verley (MPV) reactions. However, with growing interest in amine–boranes, not least ammonia–borane (H3N⋅BH3), as potential hydrogen storage materials, these compounds have also started to emerge as an alternative reagent in TH reactions. In this Review we discuss TH chemistry using H3N⋅BH3 and their analogues (amine–boranes and metal amidoboranes) as sacrificial hydrogen donors. Three distinct pathways were considered: 1) classical TH, 2) nonclassical TH, and 3) hydrogenation. Simple experimental mechanistic probes can be employed to distinguish which pathway is operating and computational analysis can corroborate or discount mechanisms. We find that the pathway in operation can be perturbed by changing the temperature, solvent, amine–borane, or even the substrate used in the system, and subsequently assignment of the mechanism can become nontrivial.

Amine-Boranes as Transfer Hydrogenation and Hydrogenation Reagents: A Mechanistic Perspective.

Transfer hydrogenation (TH) has historically been dominated by Meerwein–Ponndorf–Verley (MPV) reactions. However, with growing interest in amine–boranes, not least ammonia–borane (H3N⋅BH3), as potential hydrogen storage materials, these compounds have also started to emerge as an alternative reagent in TH reactions. In this Review we discuss TH chemistry using H3N⋅BH3 and their analogues (amine–boranes and metal amidoboranes) as sacrificial hydrogen donors. Three distinct pathways were considered: 1) classical TH, 2) nonclassical TH, and 3) hydrogenation. Simple experimental mechanistic probes can be employed to distinguish which pathway is operating and computational analysis can corroborate or discount mechanisms. We find that the pathway in operation can be perturbed by changing the temperature, solvent, amine–borane, or even the substrate used in the system, and subsequently assignment of the mechanism can become nontrivial.

Propylphosphonic Anhydride (T3P®) as Coupling Reagent for Solid‐Phase Peptide Synthesis

AbstractAmidation is the predominant reaction within the pharmaceutical setting, and it is attracting greater attention due to the increased demand for therapeutic peptides. The high therapeutic efficacy and safety profile of peptides have placed these molecules in prime position within the pharmaceutical arena, which is reflected by these molecules receiving several approvals from various regulatory agencies each year. In this context, the demand for developing efficient strategies for peptide synthesis has also risen. Although propylphosphonic anhydride (T3P®), which has been recently proposed as a green coupling reagent, has shown good performance in solution, it has never been applied to solid‐phase peptide synthesis (SPPS). Here we test the use of T3P® for SPPS. Satisfactory yields were achieved with a mild activation protocol. Various green solvents were tested and proved to be compatible with this coupling reagent. Several commonly used reagents cause allergic reactions or are susceptible to explosion under certain conditions. To overcome these issues, we propose T3P® as a potential alternative coupling reagent in SPPS.

Tuning Tetrazole Photochemistry for Protein Ligation and Molecular Imaging.

Photochemistry provides a wide range of alternative reagents that hold potential for use in bimolecular functionalisation of proteins. Here, we report the synthesis and characterisation of metal ion binding chelates derivatised with disubstituted tetrazoles for the photoradiochemical labelling of monoclonal antibodies (mAbs). The photophysical properties of tetrazoles featuring extended aromatic systems and auxochromic substituents to tune excitation toward longer wavelengths (365 and 395 nm) were studied. Two photoactivatable chelates based on desferrioxamine B (DFO) and the aza-macrocycle NODAGA were functionalised with a tetrazole and developed for protein labelling with 89 Zr, 64 Cu and 68 Ga radionuclides. DFO-tetrazole (1) was assessed by direct conjugation to formulated trastuzumab and subsequent radiolabelling with 89 Zr. Radiochemical studies and cellular-based binding assays demonstrated that the radiotracer remained stable in vitro retained high immunoreactivity. Positron emission tomography (PET) imaging and biodistribution studies were used to measure the tumour specific uptake and pharmacokinetic profile in mice bearing SK-OV-3 xenografts. Experiments demonstrate that tetrazole-based photochemistry is a viable approach for the light-induced synthesis of PET radiotracers.

An AIE‐based enzyme‐activatable fluorescence indicator for Western blot assay: Quantitative expression of proteins with reproducible stable signal and wide linear range

AbstractWestern blot is a commonly used experimental method to analyze the protein expression. However, the most commonly used chromogenic indicator based on chemiluminescence is limited by narrow linear range and unstable quantitative reproducibility, whereas the recently developed fluorescent indicator suffers from poor detection limit. Herein, we report an enzyme‐activatable fluorescence indicator to quantify proteins with reproducible stable signal and wide linear range, through introducing the hydrophilic alkaline phosphatase (ALP)‐triggered phosphoric acid moiety into our established aggregation‐induced emission (AIE) building block of quinoline‐malononitrile (QM). In this strategy, the indicator DQM‐ALP disperses well in both aqueous and lipid environments to exhibit initial “off” fluorescence, but when exposing to the ALP‐coupled secondary antibody on the PVDF membrane, the specific enzymatic turnover would liberate hydrophobic AIE luminogen (AIEgen) QM‐OH to emit strong luminescence, thereby achieving an ideal “off‐on” state for sensitively imaging proteins with high signal‐to‐noise (S/N) ratio. Moreover, benefiting from the excellent signal stability of AIE fluorophore, DQM‐ALP indicator exhibits superior quantitative analysis of protein expression with high reproducibility. Upon taking advantage of the AIEgens to reduce high concentration‐induced luminance quenching, the linear quantification range is extremely expanded. In contrast with the traditional chemiluminescent indicator, the AIE‐based enzyme‐activatable indicator DQM‐ALP not only greatly improves the signal stability for quantitative reproducibility, but also expands the linear quantification range, and further provides a practical alternative reagent for fluorescence Western blot assay.

A review on the green and sustainable synthesis of silver nanoparticles and one-dimensional silver nanostructures.

The significance of silver nanostructures has been growing considerably, thanks to their ubiquitous presence in numerous applications, including but not limited to renewable energy, electronics, biosensors, wastewater treatment, medicine, and clinical equipment. The properties of silver nanostructures, such as size, size distribution, and morphology, are strongly dependent on synthesis process conditions such as the process type, equipment type, reagent type, precursor concentration, temperature, process duration, and pH. Physical and chemical methods have been among the most common methods to synthesize silver nanostructures; however, they possess substantial disadvantages and short-comings, especially compared to green synthesis methods. On the contrary, the number of green synthesis techniques has been increasing during the last decade and they have emerged as alternative routes towards facile and effective synthesis of silver nanostructures with different morphologies. In this review, we have initially outlined the most common and popular chemical and physical methodologies and reviewed their advantages and disadvantages. Green synthesis methodologies are then discussed in detail and their advantages over chemical and physical methods have been noted. Recent studies are then reviewed in detail and the effects of essential reaction parameters, such as temperature, pH, precursor, and reagent concentration, on silver nanostructure size and morphology are discussed. Also, green synthesis techniques used for the synthesis of one-dimensional (1D) silver nanostructures have been reviewed, and the potential of alternative green reagents for their synthesis has been discussed. Furthermore, current challenges regarding the green synthesis of 1D silver nanostructures and future direction are outlined. To sum up, we aim to show the real potential of green nanotechnology towards the synthesis of silver nanostructures with various morphologies (especially 1D ones) and the possibility of altering current techniques towards more environmentally friendly, more energy-efficient, less hazardous, simpler, and cheaper procedures.

Использование очищенных сточных вод для орошения

The possibility of using purified wastewater from iron ions with an alkaline reagent based on the fruit shells of cereal crops for irrigation of agricultural crops is shown. The germination rate of oat, wheat and barley seeds when using industrial effluents purified with a traditional and alternative reagent reaches 97 % compared to the control.

Selection and characterisation of Affimers specific for CEA recognition

Carcinoembryonic antigen (CEA) is the only blood based protein biomarker at present, used for preoperative screening of advanced colorectal cancer (CRC) patients to determine the appropriate curative treatments and post-surveillance screening for tumour recurrence. Current diagnostics for CRC detection have several limitations and development of a highly sensitive, specific and rapid diagnostic device is required. The majority of such devices developed to date are antibody-based and suffer from shortcomings including multimeric binding, cost and difficulties in mass production. To circumvent antibody-derived limitations, the present study focused on the development of Affimer proteins as a novel alternative binding reagent for CEA detection. Here, we describe the selection, from a phage display library, of Affimers specific to CEA protein. Characterization of three anti-CEA Affimers reveal that these bind specifically and selectively to protein epitopes of CEA from cell culture lysate and on fixed cells. Kinetic binding analysis by SPR show that the Affimers bind to CEA with high affinity and within the nM range. Therefore, they have substantial potential for used as novel affinity reagents in diagnostic imaging, targeted CRC therapy, affinity purification and biosensor applications.

PD-L1 Expression in Chinese Patients with Advanced Non-Small Cell Lung Cancer (NSCLC): A Multi-Center Retrospective Observational Study.

Objective: This study aimed to investigate the prevalence of tumor programmed death-ligand 1 (PD-L1) expression in Chinese patients with advanced Non-Small Cell Lung Cancer (NSCLC).Methods: Tumor tissues with histologically confirmed stage IIIB/IV NSCLC were retrospectively obtained from 10 centers in China. PD-L1 expression was determined using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA) and the samples were repetitively assayed with the PD-L1 IHC 22C3 Ab concentrate (Agilent, Santa Clara, CA, USA).Results: Out of 901 patients who met the inclusion criteria, 879 (97.6%) had evaluable PD-L1 data. The number of patients with a PD-L1 tumor proportion score (TPS) < 1%, 1-49%, and ≥ 50% (corresponding to PD-L1 non-expression, low expression, and high expression) was 424 (48.2%), 266 (30.3%), and 189 (21.5%), respectively. PD-L1 expression was more likely to be found in patients younger than 75 years, men, current or former smokers, those with good performance status (PS) scores, and those with a wild-type epidermal growth factor receptor (EGFR). PD-L1 TPS ≥ 50% and ≥ 1% were respectively 28.0% and 50.2% among patients negative for both EGFR mutation and anaplastic lymphoma kinase (ALK) rearrangement. PD-L1 expression determined using the 22C3 antibody concentrate and pharmDx kit had comparable results.Conclusions: The prevalence of PD‑L1 expression in advanced NSCLC was consistent with that reported in the global EXPRESS study. Age, gender, smoking history, PS scores, and EGFR/ALK mutation status affected PD-L1 expression. The 22C3 antibody concentrate appears to be an alternative reagent for the PD-L1 assay.

A one-enzyme RT-qPCR Assay for SARS-CoV-2, and Procedures for Reagent Production

Given the scale of the ongoing COVID-19 pandemic, the need for reliable, scalable testing, and the likelihood of reagent shortages, especially in resource-poor settings, we have developed an RT-qPCR assay that relies on an alternative to conventional viral reverse transcriptases, a thermostable reverse transcriptase/DNA polymerase (RTX) (Ellefson et al., 2016). Here we show that RTX performs comparably to the other assays sanctioned by the CDC and validated in kit format. We demonstrate two modes of RTX use &amp;ndash; (i) dye-based RT-qPCR assays that require only RTX polymerase, and (ii) TaqMan RT-qPCR assays that use a combination of RTX and Taq DNA polymerases (as the RTX exonuclease does not degrade a TaqMan probe). We also provide straightforward recipes for the purification of this alternative reagent RTX. We anticipate that in low resource or point-of-need settings researchers could obtain the available constructs and begin to develop their own assays, within whatever regulatory framework exists for them.

Triethylamine-methanol mediated selective removal of oxophenylacetyl ester in saccharides.

A highly selective, mild, and efficient method for the cleavage of oxophenylacetyl ester protected saccharides was developed using triethylamine in methanol at room temperature. The reagent proved successful against different labile groups like acetal, ketal, and PMB and also generated good yields of the desired saccharides bearing lipid esters. Further, we also observed DBU in methanol as an alternative reagent for the deprotection of acetyl, benzoyl, and oxophenylacetyl ester groups.

A simplified SARS-CoV-2 detection protocol for research laboratories.

Widespread testing is required to limit the current public health crisis caused by the COVID-19 pandemic. Multiple tests protocols have been authorized by the food and drugs administration (FDA) under an emergency use authorization (EUA). The majority of these protocols are based on the gold-standard RT-qPCR test pioneered by the U.S. Centers for Disease Control and Prevention (CDC). However, there is still a widespread lack of testing in the US and many of the clinical diagnostics protocols require extensive human labor and materials that could face supply shortages and present biosafety concerns. Given the need to develop alternative reagents and approaches to provide nucleic-acid testing in the face of heightened demand and potential shortages, we have developed a simplified SARS-CoV-2 testing protocol adapted for its use in research laboratories with minimal molecular biology equipment and expertise. The protocol utilizes TRIzol to purify the viral RNA from different types of clinical specimens, requires minimal BSL-1 precautions and, given its high sensitivity, can be easily adapted to pooling samples strategies.

The 2‐Pyridyl Problem: Challenging Nucleophiles in Cross‐Coupling Arylations

AbstractAzine‐containing biaryls are ubiquitous scaffolds in many areas of chemistry, and efficient methods for their synthesis are continually desired. Pyridine rings are prominent amongst these motifs. Transition‐metal‐catalysed cross‐coupling reactions have been widely used for their synthesis and functionalisation as they often provide a swift and tuneable route to related biaryl scaffolds. However, 2‐pyridine organometallics are capricious coupling partners and 2‐pyridyl boron reagents in particular are notorious for their instability and poor reactivity in Suzuki–Miyaura cross‐coupling reactions. The synthesis of pyridine‐containing biaryls is therefore limited, and methods for the formation of unsymmetrical 2,2′‐bis‐pyridines are scarce. This Review focuses on the methods developed for the challenging coupling of 2‐pyridine nucleophiles with (hetero)aryl electrophiles, and ranges from traditional cross‐coupling processes to alternative nucleophilic reagents and novel main group approaches.

The 2-Pyridyl Problem: Challenging Nucleophiles in Cross-Coupling Arylations.

Azine‐containing biaryls are ubiquitous scaffolds in many areas of chemistry, and efficient methods for their synthesis are continually desired. Pyridine rings are prominent amongst these motifs. Transition‐metal‐catalysed cross‐coupling reactions have been widely used for their synthesis and functionalisation as they often provide a swift and tuneable route to related biaryl scaffolds. However, 2‐pyridine organometallics are capricious coupling partners and 2‐pyridyl boron reagents in particular are notorious for their instability and poor reactivity in Suzuki–Miyaura cross‐coupling reactions. The synthesis of pyridine‐containing biaryls is therefore limited, and methods for the formation of unsymmetrical 2,2′‐bis‐pyridines are scarce. This Review focuses on the methods developed for the challenging coupling of 2‐pyridine nucleophiles with (hetero)aryl electrophiles, and ranges from traditional cross‐coupling processes to alternative nucleophilic reagents and novel main group approaches.

Selective Preference of Antibody Mimetics over Antibody, as Binding Molecules, for Diagnostic and Therapeutic Applications in Cancer Therapy

Despite wider use of monoclonal and polyclonal antibodies as therapeutic and diagnostic detection agents for different types of cancers, their limitations for biomedical applications have forced scientists to design alternate next-generation molecular binding reagents, the so-called antibody mimetics. The ultimate aim to produce antibody mimetics is to out-perform the intrinsic limitations of antibodies related to their binding affinities, tumor penetration, temperature, and pH stability. The current review highlights the advanced characteristics and constructional modification of alternate antibody mimetics, compared to animal source generated antibodies and their improved bioanalytical chemistry; especially in cancer treatment as a diagnostic and therapeutic tool.

Selective Preference of Antibody Mimetics over Antibody, as Binding Molecules, for Diagnostic and Therapeutic Applications in Cancer Therapy

Despite wider use of monoclonal and polyclonal antibodies as therapeutic and diagnostic detection agents for different types of cancers, their limitations for biomedical applications have forced scientists to design alternate next-generation molecular binding reagents, the so-called antibody mimetics. The ultimate aim to produce antibody mimetics is to out-perform the intrinsic limitations of antibodies related to their binding affinities, tumor penetration, temperature, and pH stability. The current review highlights the advanced characteristics and constructional modification of alternate antibody mimetics, compared to animal source generated antibodies and their improved applications in bioanalytical chemistry; especially in cancer treatment as a diagnostic and therapeutic tool.

Potassium Oxalate as an Alternative Activating Reagent of Corn Starch-Derived Porous Carbons for Methane Storage.

Fossil fuels are a main source of energy but also the major contributor to global warming. Therefore, the needs for alternative renewable and sustainable energy sources such as natural gas is increasing; nevertheless, for practical use, efficient gas storage materials of alternative fuels are essential. Activated carbons (ACs) are a promising candidate as gas storage materials due to their narrow micropore size distribution and high porosity. Appropriate selection of the activating reagents is key factor for the preparation of high-performance ACs. Recently, potassium hydroxide is the most widely used activating reagent, but its application for plant-scale production is reluctant by its toxicity and high corrosiveness. Hence, in this study, the less corrosive and easy manageable potassium oxalate salt was used as an alternative reagent to prepare ACs from corn starch, for methane storage. The products were characterized based on their N₂ adsorption-desorption isotherms at 77 K and on their specific surface area and pore size distributions, respectively calculated via the Brunauer-Emmett-Teller (BET) equation and the non-local density functional (NLDFT) theory. The methane storage capacities and adsorption cycles were investigated with a high-pressure adsorption instrument operating at 298 K and 35 bar.