Mononuclear Copper Research Articles

Hydrolysis of phosphate diester catalyzed by new mononuclear copper(II) complexes containing selenium ligands

AbstractThree new copper(II) mononuclear complexes containing different organoselenium groups (1–3) were synthesized and characterized by the following techniques: elemental analysis, IR and UV‐Vis spectroscopies, electrochemical and conductimetric analysis, and mass spectrometry. Three new complexes, with substituents made in the para position of the aromatic portion of the N,N‐bis(2‐(phenylselanyl)ethyl)amine ligand: p‐OCH3 (1), p‐CH3 (2), and p‐Cl (3), were synthetized to compare with the already published complex (4), with no substituents. The ligand coordinates to the copper(II) center in a tridentate way with Se, N, Se as donor atoms. The hydrolytic activity in phosphate diester cleavage of the complexes was investigated using 2,4‐BDNPP as substrate. The modifications in the ligand are reflected in the difference between the catalytic and activation parameters, where the kcat values follow the order: 4 > 2 > 3 > 1.

Oxygen reduction catalysis by [Cu(cyclen)Cl]Cl·H2O: The relationship of selectivity to proton in nonaqueous solution and aqueous solution

The reaction of 1,4,7,10‐tetraazacyclododecane (cyclen) with CuCl2·2H2O results in a novel five‐coordinated mononuclear copper complex, [Cu(cyclen)Cl]Cl·H2O, which has been characterized using physicochemical and spectroscopic methods. This copper complex can serve as a catalyst for oxygen reduction reactions (ORRs). The selectivity for 4e−/4H+ reduction to H2O νersus 2e−/2H+ reduction to H2O2 is determined by the relationship of the pKa value of the proton donor in nonaqueous solutions. The dissociation of Cl− from [Cu(cyclen)Cl]Cl·H2O creates an empty position on the copper centre, enabling to binding of dioxygen (O2) to form Cu(II)‐superoxo intermediate, which further reacts with a strong acid as a proton donor to form H2O and with a weak acid as a proton donor to form H2O2. Moreover, the faradaic efficiency for H2O2 production increases in an aqueous environment with the increase of pH.

Unraveling the delayed fluorescence mechanism of copper(I) halide-phosphine emitters from DFT calculations

Several copper complexes exhibiting luminescent properties have been studied. In this context, the possibility of incorporating them into the architecture of organic light-emitting diode (OLED) devices has been investigated to improve their efficiency and photophysical stability for predicting the suitability and character of the emissive material. Specifically, we unraveled the excitation mechanism of the Cu(I)X(dppt)(PPh3) complex [X = Br, I, dppt = 3,4-bis(diphenylphosphino)thiophene]. Since the intersystem crossing (ISC) depicts a necessary process, where the knowledge of the rate constant value enables the assessment of the suitability of the material, we calculated the reverse and intersystem crossing rates for the Cu(I) complexes contrasting with pure organic thermally activated delayed fluorescence (TADF) emitters, with the goal to emphasize that the structural design of the mononuclear copper(I) complexes results in similar singlet–triplet gaps, ΔEST, values (∼0.1 eV). Moreover, it shows a remarkable enhancement of spin–orbit coupling, which allows achieving ISC rates in the ns scale. The calculations were made in the Time-Dependent Density Functional Theory (TD-DFT) level framework with the accurate response of large molecules studied here.

LPMO‐like Activity of Bioinspired Copper Complexes: From Model Substrate to Extended Polysaccharides

AbstractPolysaccharide oxidative depolymerization is highly desirable to achieve recalcitrant biomass valorization. Inspired by recently discovered Lytic Polysaccharide Monooxygenases, mononuclear copper complexes have been prepared and studied in the literature. However, the activities were evaluated on different substrates and under various conditions. In this work we intended to establish a robust and reproducible activity assay, in aqueous solution at a pH close from neutrality and under mild conditions. We have evaluated several complexes on substrates of increasing complexity: the model substrate para‐nitrophenyl‐β‐D‐glucopyranoside (p‐NPG), cellobiose (glucose dimer), as well as on extended substrates (chitin, cellulose and bagasse from agave). The different assays were compared and proof‐of‐concept that bioinspired complexes can oxidatively promote polysaccharide depolymerization was obtained. Finally, we measured level of hydroxyl radicals released by the complexes under comparable experimental conditions and mechanistic pathways are discussed.

Crystal structure and Hirshfeld surface analysis of a new mononuclear copper(II) complex: [bis-(pyridin-2-yl-κN)amine](formato-κO)(m-hy-droxy-benzoato-κ2O,O')copper(II).

A new mononuclear copper(II) complex, [Cu(C7H5O3)(HCO2)(C10H9N3)], containing mixed N- and O-donor ligands, 2,2'-di-pyridyl-amine (dpyam) and m-hy-droxy-benzoate (m-OHbenz), has been obtained from a solvent mixture. The coordination environment of the CuII ion is distorted square-pyramidal with a [N2O3] coordination set originating from the chelating dpyam and m-OHbenz ligands in the basal plane and the O atom of a formato ligand at the apical position. The crystal structure of the title complex is stabilized by N-H⋯O, O-H⋯O, C-H⋯O hydrogen-bonding, π-π and C-H⋯π inter-molecular inter-actions, which were qu-anti-fied by Hirshfeld surface analysis.

Nitrite and Nitric Oxide Interconversion at Mononuclear Copper(II): Insight into the Role of the Red Copper Site in Denitrification.

Nitrite (NO2 - ) and nitric oxide (NO) interconversion is crucial for maintaining optimum NO flux in mammalian physiology. Herein we demonstrate that [L2 CuII (nitrite)]+ moieties (in 2 a and 2 b; where, L = Me2 PzPy and Me2 PzQu) with distorted octahedral geometry undergo facile reduction to provide tetrahedral [L2 CuI ]+ (in 3 a and 3 b) and NO in the presence of biologically relevant reductants, such as 4-methoxy-2,6-di-tert-butylphenol (4-MeO-2,6-DTBP, a tyrosine model) and N-benzyl-1,4-dihydronicotinamide (BNAH, a NAD(P)H model). Interestingly, the reaction of excess NO gas with [L2 CuII (MeCN)2 ]2+ (in 1 a) provides a putative {CuNO}10 species, which is effective in mediating the nitrosation of various nucleophiles, such as thiol and amine. Generation of the transient {CuNO}10 species in wet acetonitrile leads to NO2 - as assessed by Griess assay and 14 N/15 N-FTIR analyses. A detailed study reveals that the bidirectional NOx -reactivity, namely, nitrite reductase (NIR) and NO oxidase (NOO), at a common CuII site, is governed by the geometric-preference-driven facile CuII /CuI redox process. Of broader interest, this study not only highlights potential strategies for the design of copper-based catalysts for nitrite reduction, but also strengthens the previous postulates regarding the involvement of red copper proteins in denitrification.

Nitrite and Nitric Oxide Interconversion at Mononuclear Copper(II): Insight into the Role of the Red Copper Site in Denitrification

AbstractNitrite (NO2−) and nitric oxide (NO) interconversion is crucial for maintaining optimum NO flux in mammalian physiology. Herein we demonstrate that [L2CuII(nitrite)]+ moieties (in 2 a and 2 b; where, L = Me2PzPy and Me2PzQu) with distorted octahedral geometry undergo facile reduction to provide tetrahedral [L2CuI]+ (in 3 a and 3 b) and NO in the presence of biologically relevant reductants, such as 4‐methoxy‐2,6‐di‐tert‐butylphenol (4‐MeO‐2,6‐DTBP, a tyrosine model) and N‐benzyl‐1,4‐dihydronicotinamide (BNAH, a NAD(P)H model). Interestingly, the reaction of excess NO gas with [L2CuII(MeCN)2]2+ (in 1 a) provides a putative {CuNO}10 species, which is effective in mediating the nitrosation of various nucleophiles, such as thiol and amine. Generation of the transient {CuNO}10 species in wet acetonitrile leads to NO2− as assessed by Griess assay and 14N/15N‐FTIR analyses. A detailed study reveals that the bidirectional NOx‐reactivity, namely, nitrite reductase (NIR) and NO oxidase (NOO), at a common CuII site, is governed by the geometric‐preference‐driven facile CuII/CuI redox process. Of broader interest, this study not only highlights potential strategies for the design of copper‐based catalysts for nitrite reduction, but also strengthens the previous postulates regarding the involvement of red copper proteins in denitrification.

Functional mimic for catechol oxidase and phenoxazinone synthase: Structural, spectral, electrochemical and catalytic properties of mononuclear copper(II) complex

A promising bioinspired metallocatalyst [Cu(L1)2(L2)] (L1 = P-hydroxybenzoic acid, L2 = N1,N1-dimethylpropane-1,3-diamine) has been produced and characterized in accordance with reports. In the octahedron arrangement around the copper ion, the elongation along one axial direction and one equatorial direction results in a distorted geometry Molecular assembly shows both inter and intra molecular H-bonding along with CH---π interactions evident from the Hirhsfeld surface analysis. The fingerprint plot discloses the relative contribution of percentage of intermolecular contacts (H⋯H, C⋯H and O⋯H) in the complex. The EPR, CV, and UV analyses collectively support that the complex exhibits such activity via oxygen dependant enzymatic radical pathway. Furthermore, these activities are observed under fully aerobic conditions in which 3,5-di-tert-butylcatechol (3,5-DTBC) and 2-amino phenol (2-AP) are used as model substrates. Michaelis-Menten analysis derived from the pseudo first-order reaction kinetics established that this complex shows extremely high catalytic activity towards 3,5- DTBC and 2-AP (Kcat 1.729 × 105 h−1 and 0.260 × 105 h−1). The suggested mechanism has been supported by UV spectra data in which formation of hydrogen peroxide by observing the appearance of spectral band at λmax 353 nm indicates the active participation of molecular oxygen in the catalytic process.

Synthesis, characterization and biological evaluation of three novel copper(II) clonixinate complexes with methylpyridines: Insights into structure, DNA and BSA binding properties and anticancer activity

Three novel mononuclear copper(II) complexes 1–3 with clonixinate anion (clon) derived from clonixin (Hclon) and α-, β-, or γ-methylpyridine (α-, β-, or γ-pic) were synthesised. The compounds were characterised by IR, UV–Vis and EPR spectroscopy and elemental analysis. The redox properties of the prepared complexes were studied by square wave voltammetry. The structure of the complexes [Cu(clon)2(α-pic)2] (1), [Cu(clon)2(β-pic)2] (2), [Cu(clon)2(γ-pic)2] (3) was determined by single-crystal X-ray analysis and the intermolecular interactions were studied by Hirshfeld surface analysis. The interaction of the studied complexes with calf thymus DNA was investigated by UV–Vis absorption titration and further investigation of the possible intercalative mechanism of action was carried out by fluorescence quenching studies with ethidium bromide-DNA adduct monitored via fluorescence emission spectroscopy. Interactions with bovine serum albumin were also evaluated by fluorescence emission spectroscopy. The cytotoxicity and selectivity of 1–3 were studied in vitro on a human breast cancer cell line (MCF-7), a lung cancer cell line (A549), a human glioblastoma cell line (U-118MG) and healthy human fetal lung fibroblast cells (MRC-5). All three complexes showed low to moderate ability to interact with calf thymus DNA, probably through partial intercalation, high and reversible binding to serum albumin and promising cytotoxic effects on the MCF-7 cancer cell line with reasonable selectivity for complexes 1 and 2. Finally, the mitochondrial respiratory capacity of MCF-7 tumour cells was also studied and showed a reduced activity after the addition of the studied complexes.

The Schiff base hydrazine copper(II) complexes induce apoptosis by P53 overexpression and prevent cell migration through protease-independent pathways.

Although chemotherapy has increased the life expectancy of cancer patients, its toxic side effects remain a major challenge. Recently, organometallic compounds, such as Schiff base copper complexes, have become promising candidates for next-generation anticancer drugs owing to their unique anticancer activities. In this study, binuclear copper(II) complex-1 and mononuclear copper(II) complex-2 were examined to analyze their anticancer mechanisms further. For this purpose, a viability test, flow cytometry analysis of apoptosis and the cell cycle, migration assay, and gene expression analysis were performed. According to our results, complex-1 was more cytotoxic than complex-2 at 24/48-h intervals. Our findings also demonstrated that both complexes induced apoptosis at IC50 concentrations and arrested the cell cycle at the G1-S checkpoint. However, complex-1 accelerates cell cycle arrest at the sub-G0/G1 phase more than complex-2 does. Furthermore, gene expression analysis showed that only complex-1 induces the expression of p53. Interestingly, both complexes induced Bcl-2 overexpression. However, they did not affect MMP-13 expression. More interestingly, both complexes inhibited cell migration in different ways, including amoeboid and collective, by recruiting protease-independent pathways. This study confirmed that adding several metal cores and co-ligands increased the activity of the complex. It also appeared that Cu-containing complexes could prevent the migration of cancer cells through protease-independent pathways, which can be used for novel therapeutic purposes.

Elucidation of the Electrocatalytic Nitrite Reduction Mechanism by Bio-Inspired Copper Complexes.

Mononuclear copper complexes relevant to the active site of copper nitrite reductases (CuNiRs) are known to be catalytically active for the reduction of nitrite. Yet, their catalytic mechanism has thus far not been resolved. Here, we provide a complete description of the electrocatalytic nitrite reduction mechanism of a bio-inspired CuNiR catalyst Cu(tmpa) (tmpa = tris(2-pyridylmethyl)amine) in aqueous solution. Through a combination of electrochemical studies, reaction kinetics, and density functional theory (DFT) computations, we show that the protonation steps take place in a stepwise manner and are decoupled from electron transfer. The rate-determining step is a general acid-catalyzed protonation of a copper-ligated nitrous acid (HNO2) species. In view of the growing urge to convert nitrogen-containing compounds, this work provides principal reaction parameters for efficient electrochemical nitrite reduction. This contributes to the investigation and development of nitrite reduction catalysts, which is crucial to restore the biogeochemical nitrogen cycle.

The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)-Phenanthroline Complexes.

Mononuclear copper(II)-phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)-phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)-phenanthroline complexes 1 and 2 is reported, comprising of 2,9-dimethyl-1,10-phenanthroline or 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9-dimethyl-1,10-phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50-fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold-standard anti-CSC agent). Spectacularly, 1 exhibits >100-fold greater potency toward three-dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti-breast CSC properties of binuclear copper(II)-phenanthroline complexes.

A mononuclear N,N,N,O donor schiff base Cu(II) complex inhibits bacterial biofilm formation and promotes apoptosis and cell cycle arrest in prostate cancer cells

In this work, we report a distorted square pyramidal mononuclear copper(II) complex [Cu(L)(NCS)] (1) which was obtained by the reaction of the aqueous solution of ammonium thiocyanate to a methanolic solution of copper nitrate trihydrate and corresponding Schiff-base ligands. Schiff bases, HL (C12H19N3O) act as a tetradentate Schiff base, derived from 1:1 condensation of o-hydroxyacetophenone and diethylenetriamine. The synthesized complex has been successfully characterized based on elemental analysis and Infrared (IR) spectroscopy. The structure of complex 1 was confirmed by single-crystal X-ray diffraction study. In our study, we investigated synthesis, structural characterization, antimicrobial, anti-biofilm, and anti-cancer activity, and plausible mechanism of action of a novel mononuclear copper(II) schiff base complex. Increasing microbial resistance to several commercially available or traditional antimicrobial compounds has become a major global health concern at present time. The mononuclear copper(II) complex exhibited potential antibacterial activity against two strains of the gram-negative pathogen Pseudomonas aeruginosa. The copper compound dependent damage of bacterial cell membrane and inhibition of bacterial biofilm formation were also identified. Moreover, complex 1 inhibited prostate cancer cell growth, and migration by inducing apoptosis and arresting the cell cycle at the G2/M phase. Based on the results, we are suggesting our novel mononuclear copper(II) compound as a potential candidate for the development of new antibacterial and anti-cancer drugs.

Lattice-water tweaked Cis-Trans isomerism of a copper(II)-dipyridylamine-azide complex and their aggregation features

This work highlights an interesting study on lattice-water mediated cis-trans isomerism of hydrated mononuclear copper(II) complexes, [Cu(dpa)2(N3)2].xH2O (x = 1,2) containing bidentate chelatant 2,2′-dipyridyl amine (dpa) and co-ligand, azide ion (N3−) and their aggregation characteristics. A variation in the water–methanol (v/v) solvent mixture leads to a successful synthesis of the geometric isomers of the mononuclear hydrated copper(II) complexes. X-ray crystallography evaluates the crucial role of lattice water along with various non-classical forces for the isomeric existence of the copper complexes. Thermal gravimetric analysis, Hirshfeld surface and energy framework analysis attribute the significant contribution of dispersive forces in the formation and preferential isolation of the geometric isomers. Further, the aggregation properties of the geometric isomers have been assessed with spectroscopic characterization attributing an interesting change in the photophysical, structural and morphological features of the molecular aggregates. The facets of the structural and physicochemical properties of the geometrical conformers and their molecular aggregates have also been unveiled.

On the Redox Equilibrium of TPP/TPPO Containing Cu(I) and Cu(II) Complexes

Copper(II) clusters of the type [CuII4OCl6L4] (L = ligand or solvent) are a well-studied example of inverse coordination compounds. In the past, they have been studied because of their structural, magnetic, and spectroscopic features. They have long been believed to be redox-inactive compounds, but recent findings indicate a complex chemical equilibrium with diverse mononuclear as well as multinuclear copper(I) and copper(II) compounds. Furthermore, depending on the ligand system, such cluster compounds have proven to be versatile catalysts, e.g., in the oxidation of cyclohexane to adipic acid. This report covers a systematic study of the formation of [CuII4OCl6(TPP)4] and [CuII4OCl6(TPPO)4] (TPP = triphenylphosphine, PPh3; TPPO = triphenylphosphine oxide, O=PPh3) as well as the redox equilibrium of these compounds with mononuclear copper(I) and copper(II) complexes such as [CuIICl2(TPPO)2], [{CuIICl2}2(TPPO)2], [{CuIICl2}3(TPPO)2], [{CuII4Cl4}(TPP)4], and [CuICl(TPP)n] (n = 1–3).

Study of the Degradation of Dyes by a Mononuclear Copper Complex Forming a Zigzag Chain

The titled mononuclear complex [Cu (L)] with the formally tetradentate schiff base ligand, [N,N’-bis (2-hydroxy-3-methoxybenzylidene)-1,3-diaminopropan-2-ol] has been synthesized and characterized using IR spectroscopy and elemental analysis. Crystal structure has been determined by XRD which reveals the pseudo octahedral complex geometry and the use of hydroxo bridges between two neighbor units to form a 1D coordination polymer. The use of this complex as a catalyst for the degradation of two textile dyes, in the presence of the appropriate amount of H2O2 and a UV light source has given very good results with yields exceeding 98% after 50 minutes.

Synthesis and characterization of a copper (II) compound with a new N3Py2 core ligand: Influence of methyl substitution on structural parameters and catalytic mimicking activity

A mononuclear copper (II) compound [Cu(L1)](ClO4)21 containing nonheme N3Py2 pentadentate ligand N1,N3-dimethyl-N1-(3-(methyl(pyridin-2-ylmethyl)amino)propyl)-N3-(pyridin-2-ylmethyl)propane-1,3-diamine) have been synthesized and characterized by several methods. A new ligand L1 has been prepared by methylation of secondary -NH of L2 (N1-(pyridin-2-ylmethyl)-N3-(3-((pyridin-2-ylmethyl)amino)propyl)propane-1,3-diamine) at and characterized by NMR spectroscopy. Compound 1 has been characterized by single-crystal X-ray crystallography and spectroscopic techniques. It crystallizes in a centrosymmetric space group P21/n and adopts a distorted square-pyramidal geometry with τ5= 0.13. We also prepared compound [Cu(L2)](ClO4)22, and its structural properties were compared with 1. The geometry of 1 is nearly SP, while compound 2 is intermediate between SP and TBP. We then investigated the applications of 1 and 2 in phenoxazinone synthase and catecholase activity. The results suggest compound 1 was more effective in both activities than 2.

Transesterification of RNA model induced by novel dinuclear copper (II) complexes with bis-tridentate imidazole derivatives.

Two novel bis-tridentate imidazole derivatives were conveniently synthesized using a 'one-pot' method. Their dinuclear (Cu2L1Cl4, Cu2L2Cl4) and mononuclear (CuL1Cl2, CuL2Cl2∙H2O) copper (II) complexes were synthesized to comparably evaluate their reactivities in the hydrolytic cleavage of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) as a classic RNA model. Single crystals of Cu2L1Cl4 and Cu2L2Cl4 indicate that both of them are centrosymmetric, and each central copper ion is penta-coordinated. Regarding the transesterification of HPNP, both of dinuclear ones exhibited excess one order of magnitude rate enhancement in contrast with auto-hydrolysis reaction. Under comparable conditions, dinuclear complexes displayed no more than twofold increase in activity over their mononuclear analogues, which verifies the lack of binuclear cooperation effect due to long Cu-to-Cu space.

Quantitative Electromerism of a Well-defined Mononuclear Copper Complex Through Reversible Intramolecular Metal-Ligand Electron Transfer.

Copper amine oxidases are enzymes that exhibit in their active site a mononuclear copper complex and a 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor; in the oxidative half of the catalytic cycle, the enzymes regulate their activity by a temperature-dependent electron transfer equilibrium between the CuII complex with the reduced, aminoquinol form of the cofactor and the reactive CuI complex with the corresponding oxidized, semiquinone form of the cofactor. Here, we report the first mononuclear copper complex with redox-active ligands showing quantitative, reversible electromerism between a CuII eletromer with reduced, neutral ligand and a CuI electromer with an oxidized, radical monocationic ligand. The CuII form, being exclusively present at low temperature, exhibits a lower enthalpy (like the enzymes), but the CuI complex exhibits a higher entropy and is exclusively present at room temperature in CH2Cl2 solution. Further analysis, based on six different copper complexes, discloses a large solvent effect on electromerism.

Nuclearity Control in Molecular Copper Phosphates Derived from a Bulky Arylphosphate: Synthesis, Structural and Magnetic Studies

AbstractStarting from sterically encumbered 2,6‐di‐tert‐butylphenyl phosphate (dtbppH2) and co‐ligand 3,5‐dimethyl pyrazole (dmpz), it is possible to isolate either mono‐, di‐ or tetranuclear copper phosphates by varying the copper source and making attendant changes in the reaction conditions. For example, reaction of copper nitrate with dtbppH2 and dmpz at 60 °C leads to the isolation of the mononuclear copper phosphate [Cu(dtbppH)2(dmpz)(MeOH)2] (1) as the only product. However, the use of copper acetate in place of copper nitrate and conducting the reaction at the room temperature leads to the formation of both dinuclear [Cu(dtbpp)(dmpz)2]2 (2) and tetranuclear [Cu2(dtbpp)(dmpz)2(OAc)(MeO)]2 (3) from the same reaction mixture. Compounds 2 and 3 could be isolated in pure form through fractional crystallization. Copper phosphates 1–3 have been characterized by both analytical and spectroscopic methods including EPR and magnetic measurements. The molecular structures of all three compounds were established through single crystal diffraction studies. Dc magnetic measurements indicate antiferromagnetic interactions between the metal centres in all the compounds.