Copper Reagents Research Articles

Step-by-step optimisation of the radiosynthesis of the brain HDAC6 radioligand [18F]FSW-100 for clinical applications

BackgroundHistone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [18F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [18F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [18F]FSW-100 radiosynthesis, including the 18F-fluorination reaction, semipurification of the 18F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand. Our findings will aid optimisation of radiosynthesis processes in general.ResultsIn the 18F-fluorination reaction, the amount of copper reagent was reduced without reducing the nonisolated RCY of the intermediate (50%), thus reducing the risk of copper contamination in the product injection solution. Optimising the solid-phase extraction (SPE) conditions for semipurification of the intermediate improved its recovery efficiency. The addition of anti-radiolysis reagents to the mobile phase for the HPLC purification of [18F]FSW-100 increased its activity yield in radiosynthesis using a high [18F]fluoride radioactivity of approximately 50 GBq. The SPE-based formulation method and additives for the injection solution were optimised, and the resulting [18F]FSW-100 injection solution was stable for over 2 h with a radiochemical purity of greater than 95%.ConclusionsOf all the reconsidered processes, we found that optimisation of the SPE-based semipurification of the intermediate and of the mobile phase for HPLC purification in particular improved the RCY of [18F]FSW-100, doubling it compared to that of the original protocol. The radioactivity of [18F]FSW-100 synthesized using the optimized protocol was sufficient for multiple doses for a clinical study.

A MOF@Metal Oxide Heterostructure Induced by Post‐Synthetic Gamma‐Ray Irradiation for Catalytic Reduction

AbstractMetal‐organic framework (MOF) based heterostructures, which exhibit enhanced or unexpected functionality and properties due to synergistic effects, are typically synthesized using post‐synthetic strategies. However, several reported post‐synthetic strategies remain unsatisfactory, considering issues such as damage to the crystallinity of MOFs, presence of impure phases, and high time and energy consumption. In this work, we demonstrate for the first time a novel route for constructing MOF based heterostructures using radiation‐induced post‐synthesis, highlighting the merits of convenience, ambient conditions, large‐scale production, and notable time and energy saving. Specifically, a new HKUST‐1@Cu2O heterostructure was successfully synthesized by simply irradiating a methanol solution dispersed of HKUST‐1 with gamma ray under ambient conditions. The copper source of Cu2O was directly derived from in situ radiation etching and reduction of the parent HKUST‐1, without the use of any additional copper reagents. Significantly, the resulting HKUST‐1@Cu2O heterostructure exhibits remarkable catalytic performance, with a catalytic rate constant nearly two orders of magnitude higher than that of the parent HKUST‐1.

A MOF@Metal Oxide Heterostructure Induced by Post-Synthetic Gamma-Ray Irradiation for Catalytic Reduction.

Metal-organic framework (MOF) based heterostructures, which exhibit enhanced or unexpected functionality and properties due to synergistic effects, are typically synthesized using post-synthetic strategies. However, several reported post-synthetic strategies remain unsatisfactory, considering issues such as damage to the crystallinity of MOFs, presence of impure phases, and high time and energy consumption. In this work, we demonstrate for the first time a novel route for constructing MOF based heterostructures using radiation-induced post-synthesis, highlighting the merits of convenience, ambient conditions, large-scale production, and notable time and energy saving. Specifically, a new HKUST-1@Cu2O heterostructure was successfully synthesized by simply irradiating a methanol solution dispersed of HKUST-1 with gamma ray under ambient conditions. The copper source of Cu2O was directly derived from in situ radiation etching and reduction of the parent HKUST-1, without the use of any additional copper reagents. Significantly, the resulting HKUST-1@Cu2O heterostructure exhibits remarkable catalytic performance, with a catalytic rate constant nearly two orders of magnitude higher than that of the parent HKUST-1.

A Comparative Study of Cationic Copper(I) Reagents Supported by Bipodal Tetramethylguanidinyl-Containing Ligands as Nitrene-Transfer Catalysts.

The bipodal compounds [(TMG2biphenN-R)CuI-NCMe](PF6) (R = Me, Ar (4-CF3Ph-)) and [(TMG2biphenN-Me)CuI-I] have been synthesized with ligands that feature a diarylmethyl- and triaryl-amine framework and superbasic tetramethylguanidinyl residues (TMG). The cationic Cu(I) sites mediate catalytic nitrene-transfer reactions between the imidoiodinane PhI = NTs (Ts = tosyl) and a panel of styrenes in MeCN, to afford aziridines, demonstrating comparable reactivity profiles. The copper reagents have been further explored to execute C-H amination reactions with a variety of aliphatic and aromatic hydrocarbons and two distinct nitrene sources PhI = NTs and PhI = NTces (Tces = 2,2,2-trichloroethylsulfamate) in benzene/HFIP (10:2 v/v). Good yields have been obtained for sec-benzylic and tert-C-H bonds of various substrates, especially with the more electron-deficient catalyst [(TMG2biphenN-Ar)CuI-NCMe](PF6). In conjunction with earlier studies, the order of reactivity of these bipodal cationic reagents as a function of the metal employed is established as Cu > Fe > Co ≥ Mn. However, as opposed to the base-metal analogues, the bipodal Cu reagents are less reactive than a similar tripodal Cu catalyst. The observed fluorophilicity of the bipodal Cu compounds may provide a deactivation pathway.

Enhanced mixed flotation of copper–molybdenum ore using dodecyl dimethyl betaine-emulsified kerosene as environmentally friendly collector

One way to decrease carbon emissions during mineral processing is to reduce reagent dosage. This research focused on utilizing dodecyl dimethyl betaine to emulsify kerosene, which significantly reduced the dosage of mixed flotation reagents for porphyry copper–molybdenum ores. A comparative analysis indicated that the addition of this emulsifier decreased the kerosene dosage by over 50% while enhancing the performance indicators. The analysis also showed that the directional adsorption of dodecyl dimethyl betaine at the oil–water interface increased the negative charge on the oil droplet surface, improving the stability and dispersion of the oil droplets in the solution. Furthermore, the emulsifier strengthened the adsorption stability of kerosene on the hydrophobic mineral surfaces. The emulsified kerosene predominantly exerted a physical adsorption effect on the mineral surfaces, with the highest strengthening effect observed for molybdenite, followed by pyrite and chalcopyrite. The collector, with a lower reagent dosage, improved porphyry copper–molybdenum ore processing and reduced carbon emissions.

Enhanced detection of copper residues on citrus surfaces: An innovative copper fenton-catalysed colorimetric approach using creatinine and molybdenum trioxide

Accurate quantification of residual copper from inorganic copper reagents on the surface of citrus fruits is crucial for preventing diseases caused by excessive heavy metal intake. In this study, we developed a rapid colorimetric strategy for copper detection that is enhanced under near-neutral pH conditions, using molybdenum trioxide (MoO3) and creatinine for copper-Fenton catalysis. The introduction of MoO3 enriches the redox reactions of Cu2+/Cu+ within the complex formed by copper ions and creatinine, leading to enhanced copper-Fenton catalytic activity at near-neutral pH. In the presence of H2O2, this system oxidises colourless 3,3′,5,5′-tetramethylbenzidine (TMB) to blue oxTMB, thereby affording a sensitive colorimetric detection platform for Cu2+. The designed method offers high sensitivity for Cu2+ detection, with a linear range of 0.011.0 μg/mL and a detection limit as low as 0.007 μg/mL. This method was effectively used to analyse copper reagent residues on citrus surfaces, achieving recovery rates of 92.0%115.0%. With its high sensitivity, selectivity, simplicity, and low cost, this colorimetric method shows great potential as an effective approach for determining copper ion levels, particularly for monitoring copper residues in agricultural products.

Substitution of Secondary Propargylic Phosphates Using Aryl-Lithium-Based Copper Reagents

The substitution of secondary propargylic phosphates ROP(O)(OEt)2 where R = [Ph(CH2)2]C(H)(C≡CTMS)] Ph(CH2)2CH(OP(O)(OEt)2)(C≡CTMS) with copper reagents derived from PhLi and copper salts such as CuCl, CuCN, and Cu(acac)2 was studied to establish an ArLi-based reagent system. Among the reagents prepared, PhLi/CuCl (2:1) showed 98% α regioselectivity (rs), while PhLi/Cu(acac)2 was γ selective (>99% rs). PhLi prepared in situ from PhI and PhBr by Li-halogen exchange with t-BuLi was also used for the α selective substitution. A study using the (S)-phosphate disclosed 99% enantiospecificity (es) and the inversion of the stereochemistry. The substitution of five phosphates with substituted aryl reagents produced the corresponding propargylic products with high rs and es values. Similar reactivity and selectivity were observed with 2-furyl and 2-thienyl reagents, which were prepared via direct lithiation with n-BuLi.

Modular and Selective Access to Functionalized Alkynes and Allenes via the Intermediacy of Propargylic Acetates

We report an efficient one-pot, two-step procedure for the modular synthesis of α-difunctionalized alkynes and trisubstituted allenes by sequential cross-coupling of benzal gem-diacetates with organozinc or -copper reagents in the absence of external transition metals. The intermediacy of propargylic acetates enables the divergent and selective synthesis of these valuable products. This method features its readily accessible substrates, relatively mild conditions, wide scope, and scalability in practical synthesis.

Regioselective Alkynylation of Allylic Phosphates with Alkynyl Copper Reagents

AbstractWe developed an alkynylation of allylic phosphates with acetylenes in the presence of copper and magnesium salts. The reaction proceeded regioselectively to afford the corresponding 1,4‐enynes. Furthermore, the functional group tolerance of this reaction was established. As an application, the 1,4‐enyne intermediate involved in the synthesis of 13R,19S,20S‐trihydroxydocosapentaenoic acid could be efficiently synthesized.

Two-Step, One-Pot Pyrrole Synthesis by Iron-Catalyzed ­Carboamination/Copper-Mediated Cyclization

AbstractHerein we report a method for pyrrole synthesis via iron-catalyzed carboamination/copper-mediated cyclization that is completely regioselective for the formation of 1,2,4-trisubstituted products. This two-step, one-pot process offers significant improvements to previously reported conditions including the use of a readily available copper(I) source and a markedly less arduous experimental procedure. Exploration of the substrate scope reveals a variety of arylacetylenes undergo pyrrole formation to afford single isomer products. Isotopic labelling data points to a mechanism involving activation of the alkyne moiety by the copper(I) reagent during the cyclization step.

Copper-Mediated Three-Component Reaction for the Synthesis of N-Acylsulfonamide on DNA.

The DNA-encoded library (DEL) technology is a new method for discovering hit compounds for target proteins in the pharmaceutical industry. The N-acylsulfonamide functional group has been reported to exhibit various pharmacological activities, and based on this, the demand for a method that allows its introduction into the DEL platform has increased. In this report, a procedure for synthesizing N-acylsulfonamide functional groups applicable to DEL construction was developed in the presence of a copper reagent and water as a nucleophile from simple alkynes or sulfonyl azides, which are widely commercially available. Furthermore, we prove that a new alternative procedure can be used to construct a DNA-encoded library.

A Chiral Copper Catalyzed Site‐Selective O‐Alkylation of Carbohydrates

AbstractHighly regioselective alkylation of sugar hydroxyl groups has always been an important challenge in carbohydrate chemistry, especially for the selective alkylation of trans diols, there is no direct and efficient catalytic method so far. A chiral copper catalyzed universal highly site‐selective alkylation of trans‐diols method is realized. This reaction is performed under mild conditions and has broad substrate scope. The selectivity of the reactions can be controlled by adjusting the copper reagents and the chiral ligands. This method was also applied to the site‐selective modification of drugs and natural products.magnified image

Dynamic Kinetic Resolution Processes Based on the Switchable Configurational Instability of Allenyl Copper Reagents.

The configurational instability of allenyl copper reagents is unveiled. An experimental study highlights the crucial role of Li+ and of the reaction temperature in the control of the configurational stability of allenyl copper reagents. A judicious choice of the reaction conditions allows efficient dynamic kinetic resolution processes and gives a one-pot access to homopropargylic alcohols or amines bearing up to four contiguous defined stereogenic centers.

Copper‐Mediated Phosphorylation of Arylsilanes with H‐Phosphonate Diesters

AbstractHerein we report a facile method for the synthesis of arylphosphonates via copper‐mediated the cross‐coupling reaction in the presence of 1, 10‐Phenanthroline and Ag2O. This method features a broad scope with respect to both the arylsilanes and H‐phosphonate diesters. Mechanistically, the reaction is proposed to involve oxidation by phosphinyl radical and reductive elimination process as the two key steps. With the optimized conditions established, various arylphosphonates were obtained up to 74% yield. This protocol is the first example of copper mediated the Ar−P bond formation of various arylsilanes with H‐phosphonates, and this novel methodology expands the applications of low cost and toxicity copper reagent in Ar−P bond construction.

Copper in Efficient Synthesis of Aromatic Heterocycles with Single Heteroatom

Aromatic heterocycles are important structural units in various naturally occurring compounds. Its abundance has drawn attention of synthetic chemists for decades. In the current scenario, new methodologies employing cheap transition metal reagents are highly desirable for efficient and practical synthesis of heterocyclic compounds. In this review article, strategies to synthesize aromatic heterocycles by inexpensive copper reagents have been discussed.

Ultrasound Accelerated Oxidation of Organic Dyes by a Micron‐Sized Copper/Peroxomonosulfate System

AbstractExperiments on the degradation of acid orange 7 (AO7) using micron‐sized zero‐valent copper (ZVC) are conducted in acidic aqueous solution under ultrasonic (US) irradiation. The US/ZVC/peroxymonosulfate (PMS) process for AO7 degradation is significantly better than that of an independent system. Based on the characterization of ZVC, it is observed that the corrosion speed of ZVC increases after ultrasound, owing to which a greater amount of Cu+ (0–3.03 mg L−1) and Cu2+ are produced. Exposure to US irradiation increases the available surface area of the catalysts to generate many new reactive sites for the degradation process. The AO7 degradation rate after the addition of a new copper reagent—neocuproine hemihydrate—from 6.33% to 100% proved that Cu+ is the main activator of PMS. Results indicated that free radicals (OH• and SO4−•) act as activators of PMS in the process. And higher ultrasound power, lower solution pH, and a larger ZVC dose are favorable for AO7 removal.

Photometric determination of copper (II) microquantities in pyrite

4-(2, 4-bis((2-aminoethyl)-imino)pentane-3-yl)diazenyl)benzoic acid was synthesized using 3-[4-carboxyphenylazo]pentanedione-2,4 (R) reagent obtained by the standard procedure. The composition and structure of the synthesized reagent is determined by the methods of elemental analysis and NMR spectroscopy. The complexation of copper (II) with 3-[4-carboxyphenylazo]pentanedione-2,4 (R) in the presence and in the absence of 8-hydroxyquinoline, diphenylguanidine and ethylenediamine was studied spectrophotometrically. Optimal conditions for complexation are specified and composition of homo- and mixed-ligand complexes are determined. When copper (II) interacts with R at pH 3 – 10, the maximum yield of the complex compound is observed at pH 5 λ max = 553 nm. The molar absorption coefficients and the stability constants of copper (II) complexes were determined. A range in which Beer’s law is valid is determined. Study of the complex with 8-hydroxyquinoline (Ox), diphenylguanidine (DPG) and ethylenediamine (ED) present showed that under the effect of these compounds, the optical density of the complex solutions significantly increases and the pH value of the medium providing optimal complexing shifts to the acidic region: pH 2 – 3. The maxima of the absorption of mixed-ligand complexes are observed at λ = 564 nm (CuR 2 -Ox), λ = 568 nm (CuR 2 -DFG), λ = 576 nm (CuR 2 -Ed). Comparison of the values of the stability constants of homo- and mixed-ligand Cu (II) complexes shows that CuR 2 -ED is more stable than the other ones under study. The effect of foreign ions and masking substances on complexation was studied. The selectivity of the obtained reagent for copper (II) determination, compared to the reagents of the same duty known from the literature appeared advantageous. The high selectivity of the studied reactions provided developing of a rapid method for copper determination in rocks. A procedure for the spectrophotometric determination of copper (II) in pyrite is developed.

Determining Efficacy and Persistence of the Wood Preservative Copper Chrome Arsenate Type C against The Wood Destroying Insects and Treated Wood Durability

The wood preservative Copper chrome arsenate (CCA type C) is one of the most common wood preservatives in the world, its effectiveness depends on performance, leach resistance, depth of penetration and persistence within treated wood tissue. The persistence of the preservative copper chrome arsenate typeC within four species of treated wood using full-cell pressure technique (double vacuum and pressure) and fixation of the preservative at 45˚C and 75% R.H was investigated. Bioassay tests were carried out to evaluate the performance of CCA-C treated wood against biological destruction and wood borers infestation using the powder post beetles Lyctus africanus (Lyctidae: Coleoptera).The treated wood samples at a concentration of 3% showed high resistance and durability against L. africanus attack through a period of four years, also the treated wood exposed to leaching process for two weeks showed resistance to L. africanus, which confirms the successful fixation of the CCA within the wood tissue and was not affected by leaching process. For all the tested treated wood species, the samples were free of L. africanus attack and no exit holes were recorded. It was found that, despite the cutting off treated wood blocks and exposing the internal parts (cross-section) of the wood to the beetles to lay eggs, wood is still resistant to beetles’ infestation, which confirms the deepening of the preservative into treated wood, also the penetration depth of the preservative (CCA) inside the wood tissue was measured using Ferro-Cyanide Potassium as a copper reagent. It was observed that, the internal tissue color (cross-section) of the treated wood has been changed to brown as a result of the penetration of copper into the treated wood. According to elemental analysis of the concentration of CCA components within treated wood after 48 months, very large differences among all wood species in retaining of elements were observed. Arsenic is clearly the least stable element in wood tissue. copper was the most affected element by leaching for all wood species. However, the residual CCA level was sufficient enough to prevent attacks and decay by L. africanus. ), Consequently, the full-cell pressure technique with (vacuum 30 in Hg) and the positive pressure of (10 bar) can be considered successful to preserve hardwood species against wood borers attack and maximize the penetration depth of the preservative within wood tissue.

Spectroscopic Studies of Naproxen and Indomethacin Reactions with Copper (II) Reagent and their Micro Determination through Ion - Pair Formation and their Biological Activities

Spectroscopic Studies of Naproxen and Indomethacin Reactions with Copper (II) Reagent and their Micro Determination through Ion - Pair Formation and their Biological Activities

The Carbonylation of Phenylcopper Tri-n -Butylphosphine Complex [PhCu.P(n-Butyl)3] Produces the Symmetrical Ketone Benzophenone

The Carbonylation of Phenylcopper Tri-n -Butylphosphine Complex [PhCu.P(n-Butyl)3] Produces the Symmetrical Ketone Benzophenone Jennifer A. Ebert, Greg W. Ebert Abstract In 1972 Jeffrey Schwartz of Massachusetts Institute of Technology published a seminal paper on the reaction of carbon monoxide with alkylcopper complexes to form symmetrical ketones (Schwartz, 1972). This was one of the earliest examples of the carbonylation of an organocopper reagent and gave a tantalizing glimpse into the possibility of forming copper acyl anion complexes. While that work examines alkylcopper reagents in some detail, no mention is made concerning the study of aromatic copper reagents. We were interested in exploring whether or not a similar approach could be used to carbonylate and convert arylcopper reagents into symmetrical aryl ketones thereby opening up this reaction to aromatic organocopper compounds. We now wish to report the successful carbonylation of phenylcopper tri-n-butylphosphine complex [PhCu.P(n-butyl)3] to produce the symmetrical ketone benzophenone: PhCu.P(n-butyl)3 + CO → Ph-C(O)-Ph Full Text: PDF DOI: 10.15640/jcb.v7n2a2