Complex CuL2 Research Articles

Synthesis, Spectroscopic, SC-XRD/DFT and Nonlinear Optical Response of New Halogenated Schiff Base Ligand and its Square Planar Complexes

This study details the synthesis and characterization analysis of a of new halogenated Schiff base ligand (E)-4-((5‑bromo-2-hydroxybenzyldene) amino) butanoic acid (HL) and its Square Planar trans-L2 Cu(II) complex. Characterization was performed using a suite of spectroscopic techniques, including 1H and 13C NMR, FT-IR, Raman, and UV–Vis spectroscopy, with thorough explanations and discussions of the spectral data. The structure of ligand and its complex CuL2 were elucidated through single-crystal X-ray crystallography. Additionally, the study extended to the computational domain, where the structural optimization, reactivity descriptors, and linear optical properties, as well as the static and dynamic first and second hyperpolarizabilities of HL, Cr(II)L2, Mn(II)L2, Co(II)L2 and Cu(II)L2 were investigated using DFT and TD-DFT calculation. Our results indicate that the second hyperpolarizability escalates as the atomic number of the transition metal increases. Moreover, it is inferred that the ligand examined holds the potential to be a superior material for second-order nonlinear optical applications.

Antimicrobial, photocatalytic action and molecular docking studies of imidazole-based Schiff base complexes

CoL2, NiL2, CuL2 and ZnL2 mononuclear Schiff base complexes were synthesized by using a condensation process between imidazole-2-carboxaldehyde and 2-aminobutyric acid. Infrared, electronic, elemental, and magnetic investigations were performed on the four coordinated mononuclear Schiff base complexes. The SEM images confirmed the particle size was micrometre range with different morphological appearances of the respective synthesized compounds. UV–vis. spectra were used to explore the photocatalytic activities of ML2 complexes, using methylene blue (MB) as a target dye impurity for degradation. All the complexes show good catalytic activity towards the degradation of MB. Among the catalysts, the CoL2 and CuL2 complexes exhibit maximum percentage degradation of 88 and 87.5 % respectively after 90 min. irradiation of sunlight. Conventional H-bond, hydrophobic, and π-alkyl-interactions are predominant, with excellent binding affinities, according to molecular docking studies of Schiff base with the observed biological receptors. The in vitro antimicrobial studies revealed that all synthesized ML2 complexes exhibit significant activities as compared to the ligand. The complex CuL2 shows maximum antimicrobial action against E. coli, S. aureus, and C. albicans.

BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma

Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.

The Bis(4-methoxy-2-hydroxybenzophenone) copper(II) Complex Used as a New Precursor for Preparation of CuO Nanoparticles

In this study, the reaction of 4-methoxy-2-hydroxybenzophenone (HL) with copper(II) nitrate three hydrate in a 1:2 molar ratio in methanol as solvent resulted in the formation of the complex CuL2. In order to prepare a suitable single crystal, slow evaporation technique was used, while for preparing complex nanoparticles, assisted ultrasound was used. Crystal structure of CuL2 was determined by single crystal X-ray diffraction. A square-planar geometry was found for CuL2. Finally, the complex was calcinated at 600 °C for 2.5 h. The final residue was CuO nanoparticles which were characterized by SEM and XRD. There is no peak for impurity in the XRD pattern. In this study, the reaction of 4-methoxy-2-hydroxybenzophenone (HL) with copper(II) nitrate three hydrate in a 1:2 molar ratio in methanol as solvent resulted in the formation of the complex CuL2. In order to prepare a suitable single crystal, slow evaporation technique was used, while for preparing complex nanoparticles, assisted ultrasound was used. Crystal structure of CuL2 was determined by single crystal X-ray diffraction. A square-planar geometry was found for CuL2. Finally, the complex was calcinated at 600 °C for 2.5 h. The final residue was CuO nanoparticles which were characterized by SEM and XRD. There is no peak for impurity in the XRD pattern.

BEX2 Suppresses Mitochondrial Activity and Is Required for Dormant Cancer Stem Cell Maintenance in Intrahepatic Cholangiocarcinoma

Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma. Funding Statement: This research was supported in part by the Biomedical Research Core of Tohoku University Graduate School of Medicine. This research was supported in part by JSPS KAKENHI grant numbers JP: 19K08430, 17K10716, and 16K07132, and Practical Research for Innovative Cancer Control from AMED by grant number JP17ck0106197, The Cooperative Research Project Program of Joint Usage/Research Center at The Institute of Development, Aging and Cancer, Tohoku University, and Takeda Medical Foundation. Declaration of Interests: There are no financial conflicts of interest. Ethics Approval Statement: This study was conducted according to the principles expressed in the Declaration of Helsinki and was approved by the Ethics Committees at Miyagi Cancer Center (Natori, Japan) and Tohoku University Graduate School of Medicine (Sendai, Japan). The protocol of animal experiments was approved by the Miyagi Cancer Center Animal Care and Use Committee (permit number: MCC-AE-2019-8).

Novel class of mononuclear 2-methoxy-4-chromanones ligated Cu (II), Zn (II), Ni (II) complexes: synthesis, characterisation and biological studies

Abstract Two new 2-methoxy -4-chromanones were synthesized from 3-formylchromone and 2-aminopyridine/2-amino-5-nitropyridine in methanolic media and was characterised using various spectral and analytical techniques. Reactions of these ligands with copper (II), zinc (II) and nickel (II) acetates lead to the formation of a novel class of mononuclear co-ordination complexes. Synthesized complexes were structurally characterised using elemental analysis, IR, UV-Vis, EPR, thermo gravimetric analysis, conductivity studies, magnetic measurements and proton NMR. Spectroscopic analysis reveals that ligand behaves bidendately. The complexes were tested for their binding ability with HS-DNA and found to be intercalative. Complex NiL1 was found to possess the highest Kb value (5.1 × 105). The α-amylase and α-glucosidase inhibition ability of ligands and complexes were also explored. The tested compounds were found to be mild α-amylase inhibitors and strong α-glucosidase inhibitors, characteristically similar to most of the antidiabetic drugs. Among the synthesized compounds, complex CuL2 exhibited highest α-amylase inhibitory activity with IC50 = 0.251 ± 0.2 mM and complex CuL1 exhibited highest α-glucosidase activity with IC50 = 0.060 ± 0.3 mM. In addition, compounds were also screened for their antimicrobial efficacy. All complexes were found significantly potent, among which complex CuL1 the most active with MIC of 15.3 µg/mL against S. aureus (MTCC 96).

Photochemistry and Redox Chemistry of an Unsymmetrical Bimetallic Copper(I) Complex.

The bimetallic copper(I) complex Cu2L2 (cis-1) is formed with high diasteroselectivity from [Cu(NCCH3)4][BF4] and HL (4-tert-butyl phenyl(pyrrolato-2-yl-methylene)amine) in a kinetically controlled reaction. cis-1 features a rather short Cu···Cu distance of 2.4756(6) Å and is weakly emissive at room temperature in solution. Oxidatively triggered disproportionation of cis-1 yields elemental copper and the mononuclear copper(II) complex CuL2 (trans-2). One-electron reduction of trans-2 gives cuprate [2]- with a bent bis(pyrrolato) coordinated copper(I) entity. The imine donor atoms of [2]- can insert an additional copper(I) ion giving exclusively the bimetallic complex cis-1 closing the oxidation-elimination-reduction-insertion cycle.

Enantioselective hydrolysis of amino acid esters by non-chiral copper complexes equipped with bis (β-cyclodextrin)s

Two non-chiral copper(II) complexes equipped with bis(β-cyclodextrin)s (bisCDs) were explored as hydrolase models for the enantioselective hydrolysis of two pairs of alkyl chain-possessing amino acid ester enantiomers. The two bisCD complexes are pyridine-linked with different CD cavity orientations, denoted as CuL1 (L1=2,6-bis(6-mono-amino-β-cyclodextrin-methyl)-pyridine) and CuL2 (L2=2,6-bis(3-mono-amino-β-cyclodextrin-methyl)-pyridine). Kinetic studies indicated that the “back-to-back” bisCD complex CuL1 showed higher catalytic efficiency and more pronounced enantioselectivity for all substrates than the “face-to-face” bisCD complex CuL2. Overall preference of l-isomers was observed for both complexes. In the presence of CuL1, the formation of catalyst-substrate Michaelis complexes during the hydrolysis was demonstrated by saturation kinetic study and Electrospray ionization mass spectrometry (ESI–MS) analysis. Enantiomer selectivity (vmaxL/vmaxD) value for N-Boc-N'-Boc-Lysine 4-nitrophenyl esters (Boc-Lys(Boc)-ONp), the longer alkyl-chain analogs, is twice of that for N-Boc-Alanine 4-nitrophenyl esters (Boc-Ala-ONp). The enantioselective hydrolysis of Boc-Lys(Boc)-ONp promoted by CuL1 was confirmed by chiral high-performance liquid chromatography (HPLC) analysis. The participation of CD cavities during enantioselective hydrolysis was investigated through inhibition assay. The enantioselectivity in hydrolyzing different amino acid esters promoted by CuL1 was compared. The mechanism involved in the cooperation of two adjacent CD cavities of bisCD was proposed.

Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1–S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.

Structural aspect of the phase transition between the polymorphous modifications of a liquid-crystalline copper complex CuL2 (L is 1-phenyl-3-methyl-4-dodecyliminomethylenepyrazol-5-onate)

The structure of copper(II) bis(1-phenyl-3-methyl-4-dodecyliminomethylenepyrazol-5-onate) CuL2 (I) at room temperature has been determined by X-ray crystallography. DSC study has shown that compound I undergoes a solid-phase low-temperature transition (T = −28°C) to modification II (its structure has been determined previously). The structures of both modifications are composed of complex molecules combined by π-π stacking into molecular dimers (MDs) which, being in close contact with adjacent MDs, form planar layers one MD thick. These layers remain unaltered during the phase transition. The essence of the transition is in that one of the two CH2)11(CH3)3 groups of the Cu complex at room temperature is in the “molten” state, which stimulates the rearrangement of the aliphatic zone of the crystal. As temperature changes, channels with potentially increased mobility of atoms are formed in the aliphatic zone. According to the concepts of supramolecular chemistry, the morphotropic transition occurs through a simple rotation by ±45° of the aliphatic moiety of the supramolecular assembly in the “nematic” CuL2 crystal.

Synthesis, characterization and bio-activity of nickel(II) and copper(II) complexes of a bidentate NS Schiff base of S-benzyl dithiocarbazate

The reaction of S-benzyldithiocarbazate (SBDTC) with 3-hydroxyacetophenone afforded a bidentate NS Schiff base HL (HL=benzyl-3-(3-hydroxyphenyl methyl ethylene)hydrazine carbodithioate) which on further reaction with nickel(II) and copper(II) salt yielded bis-chelated inner complexes, NiL2 and CuL2, respectively with deprotonated L ligand. The ligand and its complexes were characterized by physico-chemical techniques, viz., molar conductance, magnetic susceptibility measurement, IR, NMR, UV–Vis spectroscopy and mass spectroscopic techniques. The crystal structure of all the compounds was also characterized by single crystal X-ray crystallography. The ligand exists in its thione tautomeric form both in solution and in the solid state. In the complexes the two deprotonated ligands chelate the metal through the azomethine nitrogen and the thione sulfur atom with cis arrangement generating a tetrahedrally distorted square planar geometry around the metal center. Only complex CuL2 showed moderate analgesic activity at 60min compared to Diclofenac sodium, while all the test compounds exhibited good anti-inflammatory activity as compared to standard drug Indomethacin.

A curcumin-based TPA four-branched copper(II) complex probe for in vivo early tumor detection.

A multibranched Cu(II) complex CuL2 curcumin-based was synthesized and characterized by single-crystal X-ray diffraction analysis. The photophysical properties of the complex have been investigated both experimentally and theoretically. The results show that the target complex exhibits higher quantum yield and larger two-photon absorption (TPA) cross-section in the near infrared (NIR) region compared with its free ligand. The cell imaging studies in vitro and in vivo reveal that the complex shows good photostability and excellent tumor targeting capability to tested cancerous cells, which can be potentially used for early tumor detection.

Synthesis and crystal structure of a novel copper(ii) complex of curcumin-type and its application in in vitro and in vivo imaging.

A novel multibranch Cu(ii) complex CuL2·C4H8O2 (L = 1,7-bis(4-ethyloxy-3-methyloxy-phenyl)-1,6-heptadiene-3,5-dione) was obtained and its crystal structure was determined. The linear photophysical properties, two-photon absorption (2PA), and photostability behavior of the obtained complex were investigated. The experimental results show that the complex exhibits a larger 2PA cross-section in the NIR region, higher quantum yield and photostability and lower cytotoxicity. The in vitro study utilized the human breast cancer MCF-7 cell line that was imaged by two-photon fluorescence microscopy. The tumor targeting capability of the complex on tumor-bearing nude mice in vivo demonstrated its high targeting capability to test cancerous cells. These results suggest that the Cu(ii) complex is a promising probe for in vivo imaging.

Crystal structure of bis[2-((E)-(p-tolylimino) methyl)-6-bromo-4-chlorophenol]copper(II)

A new complex CuL2 1 [HL = 2-((E)-(p-tolylimino) methyl)-6-bromo-4-chlorophenol] is obtained and characterized using the single crystal X-ray diffraction analysis. The crystal belongs to the monoclinic system, P21/c space group, with a = 13.3203(13) A, b = 12.3052(11) A, c = 17.8664(17) A, β = 105.3420(10)°, V = 2824.1(5) A3, Z = 4, Dc = 1.672 g/cm3, R1 = 0.0686. The geometry around copper(II) is intermediate between square planar and tetrahedral. The units of the complex are linked via weak intermolecular Br…Br contracts, leading to the formation of one-dimension (1D) chains along the b axis; the multipoint Cu…Cl intermolecular interactions extend the 1D chain into a 2D layer.

Metallomicellar Catalysis: Hydrolysis of PNPP Catalyzed by Copper(II), Zinc(II), Cerium(IV) Complexes with Long Alkyl Pyridine Ligands in CTAB Micellar Solution

A kind of new functional surfactant with substituted long alkyl pyridine was synthesized and its Ce(IV), Zn(II), and Cu(II) complexes were used as hydrolytic metalloenzyme models. The hydrolysis of p-nitrophenyl picolinate (PNPP) catalyzed by the metallomicelles in CTAB micellar solution was investigated at different pH and 30°C. Kinetic parameters of catalytic hydrolysis were obtained by employing the ternary complex kinetic model for metallomicellar catalysis. Effects of the structure of ligands and microenvironment of reaction on the hydrolytic reaction of PNPP have been discussed in detail. From the apparent rate constants (k obsd ) of the catalytic hydrolysis of PNPP, it can be seen that the catalytic effect of complexes of ligand L2 with long hydrocarbon chain was stronger than that of ligand L1, and complex CuL2 showed higher catalytic efficacy on the hydrolytic reaction than those of ZnL2 and CeL2. However, experiment results in this article showed that ZnL2 and CeL2 are more susceptible to environment than CuL2. The catalytic mechanism was proposed, and the possibly active species for the catalytic hydrolysis of PNPP was determined to be the hydroxylated metal complex.

Copper(II) complexes of the antihypertensive drug nadolol

AbstractThe complexation of the non-selective β-blocker nadolol, HL, 1 with copper(II) leads to formation of mono-and dinuclear complexes depending mainly on the metal-to-ligand molar ratio. The mononuclear violet complex CuL2·2Solv, 2, was obtained in a soluble form at metal-to-ligand molar ratio Cu(II): HL ≤ 1: 10 in methanolic or slightly alkaline aqueous solutions. The dinuclear green complex Cu2L2Cl2·H2O, 3 was synthesized at Cu(II): HL ≥ 1: 2 molar ratio in methanolic solutions. The complexes were studied using spectral (UV-Vis, FT-IR, EPR), magnetochemical, thermogravimetric methods and elemental analysis. In the complexes nadolol acts as a monoanionic bidentate ligand coordinated to copper(II) through the NH-and the deprotonated OH-groups of its aminoalcohol fragment.

Copper(II) complexes with 4-amino-α-(t-butylaminomethyl)-3,5-dichlorobenzyl alcohol hydrochloride (Clenbuterol). Crystal structures of the binuclear and mononuclear Cu(II) complexes with Clenbuterol

Abstract Two new copper(II) complexes with the bronchodilator Clenbuterol (HL) have been synthesized: the binuclear complex Cu2L2Cl2 · 4DMSO (1) and the mononuclear CuL2 · 2CH3OH (2) and have been studied using electronic, IR and EPR spectra, magnetochemical, thermogravimetric and single-crystal X-ray diffraction methods. Each of the Cu(II) centres in the binuclear complex 1 is four coordinated by one terminal chlorine and one nitrogen atom, and by two bridging oxygen atoms from two different ligand molecules. Each molecule of the binuclear complex also links four DMSO molecules by hydrogen bonds of the types S O⋯H2N and S O⋯HN. The overall structure is built by sheets of Cu2L2Cl2, parallel to the ab plane, separated by layers of DMSO. In the mononuclear moiety 2, Cu(II) is coordinated bidentately with the N and O atoms of two Clenbuterol ligands, forming a nearly square-planar complex CuL2. Two CH3OH molecules are also incorporated in the unit cell, forming hydrogen bonds between the hydroxyl hydrogen atom of CH3OH and the oxygen atoms of the ligands, CH3OH⋯O(1). Both structures correlate well with the spectral, magnetochemical and thermal behaviour of complexes 1 and 2.

Copper(II) Chelate Complex with N -(2,4-Dichlorophenoxy)acetyl-N,N-Dimethylhydrazine: Crystal and Molecular Structure

X-ray diffraction analysis of the copper(II) chelate complex CuL2 (where L is the deprotonated imid-ol form of N,N-dimethyl-2,4-dichlorophenoxyacetohydrazide (HL)) was performed (3826 reflections, R = 0.039, wR = 0.043). Crystals are monoclinic, a = 8.365(7) A, b = 23.090(7)A, c = 12.713(3) A, β = 95.12(6)°, space group P21/c, Z = 4. The slightly distorted square environment of the copper cation is composed of two N atoms of the dimethylamino groups and two O atoms of the deprotonated imidol groups. Both N and O atoms are located in trans-positions relative to each other. Additional coordination of electron-donor atoms is prevented by methyl groups, in which the C atoms are at a distance of 2.837 to 2.918 A from the central ion.

Synthesis, Physicochemical Properties, and Structure of Heterocyclic β-Aminovinyl Ketones and Related Copper(II) Complex

Heterocyclic β-aminovinyl ketones (HL) and the copper complex CuL2 are synthesized and studied by IR and 1H NMR spectroscopies. The crystal structure of one of the tautomeric HL molecules is determined by X-ray diffraction analysis. The crystals are triclinic: a = 9.261(6) A, b = 9.448(6) A, c = 11.310(5) A, α = 96.74(5)°, β = 99.46(5)°, γ = 93.60(5)°, space group P\( \overline 1 \). The compound has the form of a ketoamine tautomer. The structure contains intramolecular and intermolecular hydrogen bonds. The latter link the molecules into the center-symmetric dimers.

Incorporation of 2-(5-amino-3,4-dicyano-2H-pyrrol-2-ylidene)-1,1, 2-tricyanoethanide in crosslinked polyvinylformal: Formation and properties of the Copper(II) complex in the matrix

The metal(II) coordinating anion 2-(5-amino-3,4-dicyano-2H-pyrrol-2-ylidene)-1,1,2-tricyanoethanide (C11N7H 2 − , L′, λmax = 570 nm) has been incorporated by impregnation as the sodium salt in a membrane (0.1 mm thick) of crosslinked polyvinylformal (PVF) at a concentration 1.5 × 10−3 M. The L′-doped PVF membrane, soaked in a concentrated aqueous solution of Cu2+ (0.1 M), changes colour from violet to blue on formation of the corresponding pure bis-pyrrolizinato complex CuL2 (λmax = 660 nm). The CuL2-doped PVF membrane reacts in the gas phase on exposure to species (X) that are copper-coordinating ligands stronger than L, generating the reverse colour change to violet. The remarkable stability towards water of CuL2/PVF is a promising indication for prospective use of ML2 complexes, incorporated in polymeric membranes, for the detection of (X) species in the atmosphere even in the presence of moisture, or directly in aqueous solutions.