Copper Complexes Research Articles

N-Heterocyclic Silylene-Cu(I) Complexes as Efficient Catalysts for Three-Component Coupling Reactions.

We have explored NHSi-supported copper(I) complexes as active and highly efficient catalysts for A3 (aldehyde-alkyne-amine) and KA2 (ketone-alkyne-amine) three-component coupling reactions to synthesize propargyl amines in excellent yields with high TOF under solvent-and additive-free conditions.

Photocatalysis Meets Copper Catalysis: A New Opportunity for Asymmetric Multicomponent Radical Cross-Coupling Reactions.

ConspectusIn recent years, radical-mediated cross-coupling reactions have emerged as a compelling strategy for achieving a rich diversity in molecular topologies under benign conditions. However, the inherent high reactivity of radicals presents considerable challenges in controlling reaction pathways and selectivity, which often results in a limited range of substrates and a constrained reaction profile. Given the capacity of visible-light photoredox catalysis to generate a wide variety of reactive radicals and radical ions in a controlled manner and the propensity of copper complexes toward radical species, we envisaged that the synergy between chiral copper catalysts and photoactive catalysts would pave the way for developing innovative strategies. This integration is poised to unlock a broad spectrum of enantioselective multicomponent radical cross-coupling reactions.In this Account, we describe our insights and recent efforts in the realm of enantioselective multicomponent radical cross-coupling reactions. These advancements have been achieved through the innovative application of dual photoredox/copper catalysis or bifunctional copper catalysis under visible light irradiation. Our work is systematically divided into two sections based on the activation modes. The first section focuses on photoinduced copper-catalyzed chiral C-C and C-O bond formation through a radical addition/nucleophilic trap sequence. Our discussion of chiral C-C bond formation is particularly concentrated on the asymmetric carbocyanation and carboarylation of vinylarenes, 1,3-enynes, and 1,3-dienes. Our findings underscore that irradiation with visible light can adeptly modulate the pace of radical generation, thus orchestrating consecutive reaction stages and ensuring the attainment of both chemo- and stereoselectivity. In the domain of chiral C-O bond formation, leveraging carboxylic acids as a nucleophilic oxygen source, we introduce a suite of esterification reactions of benzylic, allylic, and propargylic radicals. These radicals are derived from a variety of radical precursors, showcasing the versatility of our approach. The following section highlights our innovative discovery in the field of dual photoredox/copper catalysis, which enables enantioselective three-component radical transformations via the direct activation of aromatic alkenes. This methodology begins with the generation of formal distonic radical anions through the photocatalytic single-electron reduction of aromatic alkenes, thus, enabling orthogonal reactivity. Employing H2O, D2O, and CO2 as external electrophile agents, we have developed three types of radical cyanofunctionalization reactions: hydrocyanation, deuteriocyanation, and cyanocarboxylation. These reactions provide practical access to diversely functionalized chiral nitriles with high enantiomeric excess.Collectively, these synthetic methodologies highlight the immense potential inherent in the synergistic integration of photocatalysis and asymmetric copper catalysis. This Account aspires to deepen our comprehension of the advantages conferred by these catalytic systems, elucidating the crucial role of photocatalysis in facilitating enantioselective multicomponent radical cross-couplings. We anticipate that this Account will provide valuable insights and stimulate the evolution of innovative methodologies within this rapidly expanding field.

Natural Chiral Ligand Strategy: Metal-Catalyzed Reactions with Ligands Prepared from Amino Acids and Peptides

Amino acids and peptides are readily available biomolecules and can function as chiral ligands for transition metal catalysis. An example is the copper complex catalyzed 1,4-addition of dialkylzinc to acyclic enones, which employs peptide ligands. This review provides a dataset of amino acids and peptides reported in the literature proving to be effective ligands for metal-centered catalysts. Several parameters were highlighted, including amino acid combination, metal atoms, carboxyl and amino protecting groups, modification of natural amino acids, and the mechanism of catalysis. Along with analyzing physical-chemical properties, the SMILES representation for each amino acid and/or peptide was generated and made available online, providing an easy-to-use means of training machine learning models. This review offers an opportunity for the development of more efficient peptide ligands for enantioselective metal-centered catalysts. The available online dataset is a reliable manually curated table, it enables the benchmark for comparison of new terminal functional groups. Moreover, the review provides insight into the structures of the more successful peptide ligands and can be used as the foundation for the development of the next generation of peptide-based chiral ligands.

Bidentate NHC‐Containing Ligands for Copper Catalysed Synthesis of Functionalised Diaryl Ethers

Diaryl and heteroaryl ethers are important and common motifs in drug discovery and agrochemicals. Here we present a catalytic system for the copper catalysed arylation of phenols with aryl halides. Bidentate N‐heterocyclic carbene ligands provide a well‐defined catalytic system that enable low loading of copper in effective coupling reactions (0.5 mol% Cu or lower). The reaction scope of aryl iodides and aryl bromides is developed, that is tolerant of functional groups and a library of biaryl ethers with lead‐like properties is prepared. The presence of excess ligand (in a 1:3 ratio) is shown to be optimal to prevent catalyst degradation, presumably by avoiding decomplexation of the ligand. This is also supported by the catalytic results obtained with pre‐formed copper complexes. The kinetics of the reaction are examined and shown to be first order in copper, supportive of a well‐defined catalyst species, first order in phenol and aryl iodide, and zero order in base under the developed conditions. Computational studies performed using Minnesota MN15‐L parametrisation method support an oxidative addition–reductive elimination pathway. Reductive elimination would be turnover limiting and occurr through an intimate ion pair intermediate.

Flame Retardation of Polyamide 6 by Electro-Sprayed Phosphorus–Copper Complex Supported by Layered Silicate

Abstract The primary objective of this study was to demonstrate the effect of a phosphorus–copper complex on the flammability of polyamide 6 (PA6) materials, including organoclay-reinforced nanocomposites. The secondary objective was to compare the effectiveness of the deposition methods of the three-layer copper complex. Our previous work successfully revealed the effectiveness of reducing the flammability of polyamide composites by depositing phosphorus and copper compounds using a Layer-by-Layer technique. In the current work, we turned our attention to modifying the PA6 surface by electro-spray (ES) using the same flame retardants as before, and we investigated the effectiveness of the resulting surface protection against high temperatures during combustion. Surface roughness analysis revealed that the use of the ES method favors the formation of surface unevenness. The UL-94 test results showed that composite materials having 5-15 triple layers were among the best flammability classes compared to the others. Both types of materials tested also showed a tendency to reduce the heat release rate (HRR) by increasing the degree of surface coverage when using the electro-spray technique. Remarkably, deposition of 15 triple layers on the surface of the nanocomposite reduced the maximum HRR point by 20%. Graphical abstract

Deciphering Electrocatalytic Hydrogen Production in Water Through a Bioinspired Water-Stable Copper(II) Complex Adorned with (N2S2)-Donor Sites.

Electrocatalytic hydrogen production stands as a pivotal cornerstone in ushering the revolutionary era of the hydrogen economy. With a keen focus on emulating the significance of hydrogenase-like active sites in sustainable H2 generation, a meticulously designed and water-stable copper(II) complex, [Cl-Cu-LN2S2]ClO4, featuring the N,S-type ligand, LN2S2 (2,2'-((butane-2,3-diylbis(sulfanediyl))bis(methylene))dipyridine), has been crafted and assessed for its prowess in electrocatalytic H2 production in water, leveraging acetic acid as a proton source. The molecular catalyst, adopting a square pyramidal coordination geometry, undergoes -Cl substitution by H2O during electrochemical conditions yielding [H2O-Cu-LN2S2]2+ as the true catalyst, showcases outstanding activity in electrochemical proton reduction in acidic water, achieving an impressive rate of 241.75 s-1 for hydrogen generation. Controlled potential electrolysis at -1.2 V vs. Ag/AgCl for 1.6 h reveals a high turnover number of 73.06 with a commendable Faradic efficiency of 94.2 %. A comprehensive analysis encompassing electrochemical, spectroscopic, and analytical methods reveals an insignificant degradation of the molecular catalyst. However, the post-CPE electrocatalyst, present in the solution domain, signifies the coveted stability and effective activity under the specified electrochemical conditions. The synergy of electrochemical, spectroscopic, and computational studies endorses the proton-electron coupling mediated catalytic pathways, affirming the viability of sustainable hydrogen production.

Synthesis, Crystallization, Antimicrobial Activity, and Molecular Docking of Crystal bis(6-methoxy-7-methylpurine)-bis(μ-chloro) copper(II) Complex

Synthesis, Crystallization, Antimicrobial Activity, and Molecular Docking of Crystal bis(6-methoxy-7-methylpurine)-bis(μ-chloro) copper(II) Complex

Stabilizing Copper(I) Complexes by Terminal Olefinic Side Arms and Studying Their Reactivity Towards Oxidation

AbstractMany copper(I) complexes with aliphatic amine ligands have a strong tendency to disproportionate to copper(II) and elemental copper in solution at higher concentrations, making it difficult to isolate them and to study their reactivity. A series of copper(I) complexes with ligands based on tridentate N,N,N’,N’’,N’’‐pentamethldiethylenetriamine (Me5dien) were synthesized that included terminal olefinic and aromatic groups. It could be shown that the olefinic side arms stabilized some of the copper(I) complexes. Whether and how strongly the complexes were stabilized depended on the position and length of the olefinic sidearm. Additionally, the reactivity of the copper(I) complexes towards dioxygen was investigated.

Structural Effect of N-7 Alkylation in 6-Chloropurine on Cu (II) Binding: Effect of Anions and Magnetic Studies.

This study investigates the anion-directed assembly of discrete copper (II) complexes. The ligands of choice are two N7-alkyl-purine-based neutral ligands. These ligands facilitate the exclusive coordination through the N3 and N9 positions, preventing polymeric chain formation. Perchlorate ions promoted the formation of discrete paddlewheel-like complexes with the general formula [Cu2(μ-Pur)4(CH3CN)2]4+, while chloride ions yielded chloride-bridged dimers of the form [Cu2(Pur)2(μ-Cl)2Cl2]. Copper-copper bond distances within these complexes ranged from 2.92 to 2.98 Å. Magnetic susceptibility measurement of chloride-bridged complexes exhibited antiferromagnetic coupling, whereas paddlewheel complexes displayed more complex alternating ferromagnetic and antiferromagnetic interactions. Chloride-bridged compounds exhibited strong near-infrared absorption.

Copper‐Catalyzed Simultaneous Dehydrogenation and Enantioselective Allylic Oxidation of Alkanes Using Chiral Heterogeneous Ligands to Produce Allylic Esters and Theoretical Investigation of the Mechanism

ABSTRACTA new asymmetric method for preparing chiral allylic esters from various unactivated alkanes through simultaneous dehydrogenation and enantioselective allylic oxidation in the presence of chiral heterogeneous oxazoline–based ligands is reported for the first time. For this purpose, chiral amino oxazoline ligands, synthesized from chiral amino alcohols and cyanogen bromide, were immobilized on modified MCM‐41 mesoporous silica. These chiral heterogeneous ligands were then characterized using Fourier‐transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, and Brunauer–Emmett–Teller and Barrett–Joyner–Halenda techniques. Finally, copper complexes of these ligands were employed in the synthesis of chiral allylic esters, achieving the best result with a 90% yield and 77% enantiomeric excess. Evaluation of the recyclability of the chiral heterogeneous catalysts revealed that they can be reused three times without a noticeable reduction in the results. In addition, the mechanism of formation of the chiral allylic esters was investigated using a density functional theory method.

Synthesis, Spectroscopy and Biological Studies of Copper and Silver Complexes Derived from 2-Substituted Amino Propanoic Acid

Synthesis of copper and silver complexes were prepared from novel Schiff base ligand. These synthesized ligand and their metal complexes were characterized by elemental analysis, FT-IR, 1H NMR, UV-Vis and Mass spectrometry. The coordination of amino nitrogen, phenolic oxygen, and carboxylato oxygen atoms is shown by the infrared spectra.The Schiff bases and its complexes were screened for their in vitro antibacterial and antifungal studies against the bacteria Pseudomonas Aeruginosa (PA, Gram -ve), Bacillus Cirroflagellosus (BC, Gram +ve), Penicillium Notatium (PN) and Aspergillus Niger (AN) strains. The results of the antibacterial investigation show that the copper and silver complexes possess more potent bactericide and fungicide properties than the ligand.

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide.

The chemosensor properties of a bimetallic terbium(III)/copper(II) complex functionalized with a 4-(2-pyridyl)-1,2,3-triazole ligand for the detection of Cu2+ ions and, aqueous and gaseous hydrogen sulfide was investigated. The 4-(2-pyridyl)-1,2,3-triazole ligand functions both as an antenna chromophore and a receptor for Cu2+ ions; the Cu2+ complex was shown to be a chemosensor for the detection of aqueous hydrogen sulfide. The chemosensor exhibited significant reversibility over multiple cycles, observed with the sequential addition of Na2S followed by Cu2+ ions. The limit of detection for aqueous hydrogen sulfide was 0.63 μM (20 ppb). No luminescent changes of the bimetallic terbium(III)/copper(II) complex were observed in the presence of gaseous hydrogen sulfide, and thus this sensor can only be used for the detection of aqueous hydrogen sulfide.

Enhanced Electrochemical Performance of Copper(II) Metal Organic Framework‐Ternary Quantum Dots Composite towards the Detection of Bisphenol A

AbstractTernary quantum dot metal organic framework (MOFs) composite sensor formulated as (ZnInSe2@[Cu(2‐HNA)2(H2O)]) with an enhanced electrochemical performance was synthesized from a copper(II) metal‐organic framework complex ([Cu(2‐HNA)2(H2O)]) and ZnInSe2 ternary quantum dot (TQDs). The compounds were characterized by Fourier transform infrared spectroscopy, Ultraviolet‐Visible spectroscopy, transmission electron microscopy, scanning electron microscopy, single crystal X‐ray crystallography, and photoluminescence. Molecular structure of the copper(II) complex revealed a distorted square pyramidal geometry with two molecules of 2‐hydroxy‐1‐naphthaldedyde at the basal planes as bidentate chelating ligands with a coordinated water molecule at the apical position. TEM micrographs revealed monodispersed composite with an average particle size of 3.2 nm. The composite and its precursors were used as ectrochemical sensor for the detection of bisphenol A, using cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy. The composite modified on a gold electrode exhibited enhanced electrochemical performance in comparison to those of the MOFs and TQDs. The reaction process at the surface of the modified electrode with the composite is diffusion controlled with a limit of detection, and limit of quantitation of 4.70 nM and 14.26 nM over a concentration range of 10–50 nM (S/N=3). The gold modified composite electrode is stable and could serve as a model for the development of electrochemical sensor to determine BPA.

Selectivity Control in Nitroaldol (Henry) Reaction by Changing the Basic Anion in a Chiral Copper(II) Complex Based on (S)-2-Aminomethylpyrrolidine and 3,5-Di-tert-butylsalicylaldehyde.

This article is a continuation of our previous research on the catalytic capability of a chiral copper complex based on commercially available (S)-2-aminomethylpyrrolidine and 3,5-di-tert-butylsalicylaldehyde with various counter-anions in the asymmetric Henry reaction. Our findings indicate that depending on the type of base used, chiral nitroalcohols with yields up to 98% and ee values up to 77%, as well as β-nitrostyrenes with yields up to 88%, can be produced. Additionally, it has been found that the outcome of the reaction and the catalytic properties of copper (II) complexes (S)-Cu1 and (S)-Cu2 are influenced by the structure of the aldehyde used.

Optical and surface properties of Schiff base ligands and Cu(II) and Co(II) complexes

Objectives. To study the transition of electrons in 1,2-phenyl(4’-carboxy)benzylidene Schiff base ligand and transition metal ions, optical properties, as well as the surface chemistry of supported transition metals using diffuse reflectance spectroscopy (DRS); to study the roughness and morphology of the Schiff base ligand and its complexes using atomic force microscopy (AFM).Methods. DRS, AFM, and Fourier-transform infrared spectroscopy instruments were used to identify electron transitions, optical properties, and surface morphology in Schiff base ligands and their complexes.Results. The DRS revealed the d–d transitions and charge transfer shifts of all compounds, and helped identify the structure of the ligand. One of the optical properties studied was the energy gap calculation of the ligand and its complexes. The copper complex exhibited more semiconducting behavior with surface morphology properties such as surface roughness parameters lower than those of the ligand and the cobalt complex. This can be attributed to the smaller size of the copper atom, as well as lower electron transitions compared to the cobalt complex and the square planar bonding shape.Conclusions. In Schiff base ligands, the reflectance spectrum bands reveal three electron transitions: n→π*, π→π*, and σ→σ* transitions. In cobalt complexes, four transitions are indicated: 4A2(F)→4T1(F), 4A2(F)→4T1(P), charge transfer bands, and tetrahedral geometry. Copper complexes exhibit three transitions: 2B1g→2A1g, 2B1g→2Eg, and charge transfer bands, with a square planar geometry for their structure. The energy gap calculations were 2.42, 2.29, and 2.30 eV, respectively. In the case of the SH ligands, copper complexes, and cobalt complexes, all compounds exhibited semiconductor properties. However, the complexes displayed increased conductivity due to the influence of the metal and coordination structure.

Optimization of Antiproliferative Properties of Triimine Copper(II) Complexes.

Cu(II) complexes with 2,2':6',2″-terpyridines (terpy) and 2,6-bis(thiazol-2-yl)pyridines (dtpy) with 1- or 2-naphtyl and methoxy-naphtyl were synthesized to elucidate the impact of the triimine core, naphtyl linking mode, and presence of methoxy groups on the antiproliferative activity of [CuCl2(Ln)]. Their antiproliferative effect was analyzed in ovarian (A2780) and colorectal (HCT116) carcinomas and colorectal carcinoma resistant to doxorubicin (HCT116-DoxR) cell lines and in normal human fibroblasts. Among all complexes, the 1- and 2-naphtyl substituted terpy Cu(II) complexes (Cu1a and Cu1b) showed the strongest cytotoxicity, namely, in HCT116-DoxR 2Dcells and were also capable of inducing the loss of cell viability in 3D HCT116-DoxR spheroids. Their intracellular localization, capability to increase reactive oxygen species (ROS), and interaction with DNA (nonintercalative mode) trigger oxidative DNA cleavage leading to cell death by apoptosis and autophagy. Cu1a and Cu1b do not show in vivo toxicity in a chicken embryo and can interact with bovine serum albumin (BSA).

Ligand-Based Radical Reactivity of Metal Thiosemicarbazones Prompts the Identification of Platinum(II)-Based Cytoprotectants.

CuATSM, a copper(II) complex of a bis(thiosemicarbazone) of diacetyl, prevents oxidative cell death and acts as a neuroprotectant in vivo, prompting its evaluation to treat amyotrophic lateral sclerosis and other neurodegenerative conditions in the clinic. We recently demonstrated that CuATSM functions as a potent radical-trapping antioxidant (RTA), inhibiting lipid peroxidation and associated ferroptotic cell death by a noncanonical mechanism based on radical addition to the ligand backbone. Herein we report our investigations of the generality of this reactivity, which include studies of corresponding complexes of various other metals, including Co, Ru, Ni, Pd, Pt, and Au. Inhibited autoxidations of styrene and dioxane reveal that most of these complexes exhibit RTA activity, consistent with ligand-based reactivity, but the identity of the metal atom nevertheless plays a role. In particular, analyses of the electronic structures of the complexes of metals within the same group (i.e., the group 10 metals Ni, Pd and Pt) highlight how the metal atom can modulate the ligand-based reactivity by enabling spin delocalization to the other thiosemicarbazone moiety. The RTA activity determined in organic solution largely translates to phospholipid bilayers and mammalian cells, where most complexes inhibited lipid peroxidation and associated ferroptotic cell death. A preliminary structure-activity study revealed Pt complexes with potencies eclipsing those of archetype ferroptosis inhibitors ferrostatin-1 and liproxstatin-1, suggesting that Pt (and to a lesser extent Ni) bis(thiosemicarbazone)s may be better suited to optimization for therapeutic development than those based on Cu.

Structural, spectroscopic, and biological properties of an asymmetric Cu (II) Schiff-base complex: Synthesis, DNA/BSA interactions, and antimicrobial potential with experimental and computational insights

A copper (II) complex with the asymmetric bidentate Schiff-base ligand (E)-2-(((4-chlorophenyl) imino) methyl) phenol was synthesized and characterized using FTIR and UV–VIS spectroscopy. Photoluminescence studies were conducted on both the copper (II) complex and the free ligand. XRD analysis revealed the copper (II) complex crystallizes in the monoclinic system, space group P21/c. The complex structure was optimized using DFT calculations with B3LYP/6-31G+(d,p) and Lanl2dz basis sets, with QTAIM and NBO analyses confirming complex formation. The energy gap of the copper (II) complex was determined to be 3.701 eV (alpha state) and 2.764 eV (beta state). MEP analysis of the optimized structure indicated a hydrophobic environment around the nitrogen atom, with the molecule exhibiting overall hydrophobicity. The chlorine atoms were identified as potential nucleophilic sites. The antimicrobial efficacy of a Schiff base copper (II) complex was evaluated against selected pathogenic bacteria (B. subtilis, B. megaterum, K. pneumoniae, E. coli) and the fungus Candida albicans. Among these C. albicans for complex showed larger zones (11–15.5 mm) at higher concentrations such as 2 and 2.5 mg/mL. Molecular docking studies suggested strong binding affinity between the complex and the target protein, this was further supported by obtained root means square deviations, root means square fluctuations, radius of gyration and hydrogen bond values during simulations. The binding free energy between BSA and the copper (II) complex was calculated as −8.7 kcal/mol, indicating significant interaction. However, only weak van der Waals interactions were observed between the complex and DNA. Toxicity studies revealed the copper (II) complex had minimal irritant effects on ocular and cutaneous tissues, with a low lethal dose. In comparison, Tricresyl phosphate showed moderate to severe ocular irritancy and modest cutaneous irritancy.

The Effect of Intramolecular Proton Transfer on the Mechanism of NO Reduction to N2O by a Copper Complex: A DFT Study.

DFT calculations were performed to explore the mechanism underlying the reduction of NO to N2O by a CuI complex. A nitrosyl complex reacts with another NO molecule and the CuI complex, leading to the formation of a dicopper-hyponitrite complex (Cu2N2O2). The first steps follow a common pathway until the formation of the intermediate [CuII-N2O2]+, after which the reaction pathway diverges into three Cu2N2O2 species: κ2-N,N', κ2-O,O', and κ3-N,O,O'. These species yield different products along their respective reaction pathways. In the case of the κ2-N,N' and κ3-N,O,O' species, the subsequent steps involve a methanol-mediated proton transfer and N-O bond cleavage, resulting in the generation of N2O and [CuII-OH]+. Conversely, for the κ2-O,O' species, two proton transfers occur without N-O bond cleavage, leading to the formation of H2N2O2 and [CuII]2+. H2N2O2 spontaneously converts into N2O and H2O. These computational results elucidate how the coordination mode of hyponitrite influences reactivity and provide insights into NO reduction via proton transfer. Notably, switching of the N2O2 coordination mode to metal ions from N to O was not required, offering insights for more efficient NO reduction strategies in the future.

Evaluation of size-based distribution of components in VYXEOS® liposomal formulation using asymmetric flow field-flow fractionation

VYXEOS® is the first FDA-approved dual-API liposomal formulation containing two different chemotherapeutics, daunorubicin and cytarabine at a 1:5 molar ratio. Analysis of bulk formulation does not provide insight to size-based distribution of APIs and excipients, therefore asymmetrical flow field-flow fractionation (AF4) was utilized for the size-based separation of VYXEOS® liposomes and collected size fractions were further analyzed for the concentrations of APIs, lipid excipients, and copper. Analysis results revealed a significant variation in API distribution across the size fractions, with the larger liposomes encapsulating a higher ratio of cytarabine to daunorubicin compared to the smaller liposomes, while lipid excipient composition was held constant across the size range. We attribute the size-based variation of API ratios to structural change during API loading and sequence of API loading. Cytarabine is first passively loaded into liposomes containing copper gluconate, and then daunorubicin is actively loaded using copper gradient where the daunorubicin is retained in the liposomes as a copper complex. This method can be extended to characterize various single and dual-API liposomal nanocarriers during drug product development and/or post market quality control.