Heteroleptic Copper Research Articles

Centrosymmetric homo- and heteroleptic core paddle-wheel copper(II) carboxylates; Syntheses, crystal structures, antioxidant, anticancer and enzyme inhibition activity

Synthesis and characterization of homo- (C5H7N2)2[Cu2(3,5-F2C6H3CH2COO)6] (1) and heteroleptic [Cu2(3,5-F2C6H3CH2COO)4(2-CH3Py)2] (2) core paddle-wheel copper(II) carboxylates is reported in the present work. The characterization was made by spectroscopic techniques, elemental and single crystal XRD analyses. The single crystal XRD analysis revealed a rare homoleptic anionic copper(II) carboxylate complex (1) consisting 2-aminopyridinium counter cations and a neutral heteroleptic copper(II) carboxylate complex (2) consisting 2-methyl pyridine as a co-ligand. The copper ions adopted a distorted square pyramidal geometry in both the paddle-wheel dimeric complexes. To evaluate the biological potency of the synthesized complexes, in vitro antioxidant, enzymes inhibition and anticancer activities were performed. The synthesized complexes have shown overall better biological activity compared to the ligand acid. Complex 2 was the most potent DPPH (IC50 =180.96 ± 9.04 µg/mL) and •OH (IC50 = 189.51 ± 9.33 µg/mL) radicals scavenger, α-amylase (IC50 = 441.86 µg/mL) and acetylcholinesterase (IC50 = 88.62 µg/mL) inhibitor. Furthermore, complex 2 activity against malignant glioma U-87 cell line (IC50 = 21.95 µg/mL) was also highest among the tested compounds. However, complex 1 with an IC50 value of 51.83 µg/mL has shown somewhat better inhibition of the butyrylcholinesterase enzyme compared to the complex 2 (IC50 = 56.36 µg/mL).

Study of Electronic Structure and Simulation of Molecular Rearrangements of MOCVD Precursors to Predict Their Thermal Stability Upon Evaporation on the Example of Heteroleptic Copper(II) Complexes

Study of Electronic Structure and Simulation of Molecular Rearrangements of MOCVD Precursors to Predict Their Thermal Stability Upon Evaporation on the Example of Heteroleptic Copper(II) Complexes

Ligand conformation directed self-assembly of heteroleptic Cu(I) complexes and luminescent sensing properties for Zn2+

Heteroleptic Cu(N^N)(P^P) complexes have garnered significant attention owing to their various structures and remarkable photophysical properties. Four novel heteroleptic copper(I) complexes (C1•2BF4ˉ, C2•3BF4ˉ, C3•3PF6ˉ and C4•3PF6ˉ) of the type {(Cu(P^P))3(μ-HATN)} synthesized by ligand conformation-directed self-assembly methodology were reported herein. These copper(I) complexes with different coordination configuration could be obtained through a straightforward change in the rigidity and volume in different P^P ligand scaffolds. Furthermore, these copper(I) complexes exhibited exceptional visible light absorption, which were contributed to metal-to-ligand charge transfer and intra-ligand charge transfer. Moreover, these emissive heteroleptic Cu(I) complexes all displayed remarkable sensitivity and selectivity towards zinc ions in “turn-on” mode (intensity enhanced ca.60 times). The detection limitation of complex C1•2BF4ˉ reached to 5.10 × 10−9 M, which was lower than those reported fluorescent sensors. The possible sensing mechanism was investigated using ESI-Ms, NMR and DFT calculation. The reversible “on-off” fluorescent sensing behavior can be restored by treating the solution alternately with EDTA tetrasodium salt and Zn2+ salt.

A series of four-coordinate heteroleptic copper(I) complexes with diimine and β-diketiminate ligands

In this paper, a series of heteroleptic bis-chelate copper(I) complexes of the general formula Cu(N^N)(NacNacR), where N^N is the diimine ligand and NacNacR is the β-diketiminate ligand are introduced. The complexes are easily prepared by reacting NacNac ligands with CuOtBu in the presence of diimine ligands. The molecular structures of all complexes are characterized by NMR spectroscopy and X-ray crystallography. The studies of cyclic voltammetry and UV–vis absorption spectra show that the HOMO and the LUMO energy level can be tailored by changing the substitution pattern of each ligand. The oxidation potential is dependent on the NacNac ligand, and the reduction potential shows the dependence on the diimine ligand. Tunable redox potentials and a wide range of visible absorption can make these copper(I) complexes promising candidates for applications in solar light harvesting.

Heteroleptic Copper(II) Complexes Containing an Anthraquinone and a Phenanthroline as Synthetic Nucleases and Potential Anticancer Agents

Two ternary copper(II) complexes with an anthraquinone and a N,N-heterocyclic donor, [Cu(dmp)(L)(H2O)](ClO4) (1), [Cu(bpy)(L)(dmso)](ClO4) (2), in which dmp = 2,9-dimethyl-1,10-phenanthroline, bpy = 2,2′-bipyridine, and HL = 1-hydroxyanthracene-9,10-dione were synthesized and fully characterized by conductivity, elemental, and spectral analyses (FTIR and UV-Vis; EPR and ESI-MS). The structure of 1 reveals that Cu(II) is bound to two oxygens of L, two nitrogens of dmp, and a molecule of water in the fifth position. In complex 2.1, Cu(II) is also pentacoordinated with an O-bonded dmso in the axial position. The presence of the heteroleptic complexes in solution was evidenced by ESI-MS, EPR in dmso solution and UV-Vis spectrophotometry. All complexes bind to CT-DNA with affinity constants of approximately 104. Complex 2 can nick plasmid DNA but no cleavage was performed by complex 1. The investigation of DNA interactions by spectrofluorimetry using ethidium bromide (EB) showed that it was displaced from DNA sites by the addition of the complexes. The complexes inhibited the growth of chronic myelogenous leukemia and human squamous carcinoma cells with low IC50 values, complex 1 being the most effective.

New binuclear copper(I) complexes with dual bioactivity: Synthesis, structural characterization and biological assays against bacteria and cancer

Novel binuclear heteroleptic copper(I) complexes based on mixed DPPE /thiocarbamoyl-pyrazoline ligands were synthesized and structurally characterized. Accordingly, the X-ray studies the three prepared complexes belong to the monoclinic crystalline system. All complexes 1, 2, and 3 possess similar structural behavior around the Copper(I) atoms which presented a distorted tetrahedral coordination geometry determined by using the τ4 (tau four) parameter analysis. The complete characterization of the prepared compounds also included HRMS-ESI(+), NMR and elemental analyses, MID infrared, and UV–Vis spectroscopies. TD-DFT studies were also performed to support the assignments and interpretation of the main absorption bands observed in the UV–Vis experiments. The binuclear CuI complexes were assayed against a panel of antibiotic-resistant (MDR) bacteria (S. aureus) and S. pseudointermedius (MDR isolated from dog skin) showing promising MIC (7.8 to 62.5 µg/mL) and MBC (15.6 to 62.5 µg/mL) values. Additionally, the binuclear complexes were also tested as anticancer agents against tumoral cells B16F10 and 4 T1 (metastatic murine melanoma and murine mammary carcinoma respectively) showing very low IC50 (0.16 to 0.6 µM) values.

Designing and Exploration of the Biological Potentials of Novel Centrosymmetric Heteroleptic Copper(II) Carboxylates.

Copper(II) complexes with a general formula [Cu2(3,4-F2C6H3CH2COO)4(L)2], where L = 2-methylpyridine (1) and 3-methylpyridine (2), are reported here. The FTIR spectra of the complexes confirmed the bridging bidentate coordination mode of the carboxylate ligand. The low (475 and 449 cm-1) and strong (727 & 725 cm-1) intensity bands in the FTIR spectra, due to Cu-N stretches and pyridyl ring vibrations, confirmed coordination of the 2-/3-methyl pyridine co-ligands in complexes 1 and 2, respectively. A binuclear paddlewheel structural arrangement with a square pyramidal geometry was confirmed for copper atoms in the complexes via single-crystal X-ray analysis. The DPPH, •OH radical, and α-amylase enzyme inhibition assays showed higher activities for the complexes than for the free ligand acid. The binding constant (Kb = 1.32 × 105 for 1 and 5.33 × 105 for 2) calculated via UV-VIS absorption measurements and docking scores (-6.59 for 1 and -7.43 for 2) calculated via molecular docking showed higher SS-DNA binding potential for 2 compared to 1. Viscosity measurement also reflected higher DNA binding ability for 2 than 1. Both complexes 1 and 2 (docking scores of -7.43 and -6.95, respectively) were found to be more active inhibitors than the free ligand acid (docking score of -5.5159) against the target α-amylase protein. This in silico study has shown that the herein reported compounds follow the rules of drug-likeness and exhibit good potential for bioavailability.

Photo-catalyzedα-arylation of enol acetate using recyclable silica-supported heteroleptic and homoleptic copper(I) photosensitizers.

Earth-abundant photosensitizers are highly sought after for light-mediated applications, such as photoredox catalysis, depollution and energy conversion schemes. Homoleptic and heteroleptic copper(I) complexes are promising candidates in this field, as copper is abundant and the corresponding complexes are easily obtained in smooth conditions. However, some heteroleptic copper(I) complexes suffer from low (photo)stability that leads to the gradual formation of the corresponding homoleptic complex. Such degradation pathways are detrimental, especially when recyclability is desired. In here, we report a novel approach for the heterogenization of homoleptic and heteroleptic Cu complexes on silica nanoparticles. In both cases, the photophysical properties upon surface immobilization were only slightly affected. Excited-state quenching with aryl diazonium derivatives occurred efficiently (108-1010M-1s-1) with heterogeneous and homogeneous photosensitizers. Moderate but almost identical yields were obtained for thea-arylation of enol acetate using the homoleptic complex in homogeneous or heterogeneous conditions. Importantly, the silica-supported photocatalysts were recycled with moderate loss in photoactivity over multiple experiments. Transient absorption spectroscopy confirmed that excited-state electron transfer occurred from the homogeneous and heterogeneous homoleptic copper(I) complexes to aryl diazonium derivatives, generating the corresponding copper(II) center that persisted for several hundreds of microseconds, compatible with photoredox catalysis applications.

Sterically Encumbered Heteroleptic Copper(I) β-Diketiminate Complexes with Extended Excited-State Lifetimes.

One of the main challenges in developing effective copper(I) photosensitizers is their short excited-state lifetimes, usually attributed to structural distortion upon light excitation. We have previously introduced copper(I) charge-transfer chromophores of the general formula Cu(N^N)(ArNacNac), where N^N is a conjugated diimine ligand and ArNacNac is a substituted β-diketiminate ligand. These chromophores were promising regarding their tunable redox potentials and intense visible absorption but were ineffective as photosensitizers, presumably due to short excited-state lifetimes. Here, we introduce sterically crowded analogues of these heteroleptic chromophores with bulky alkyl substituents on the N^N and/or ArNacNac ligand. Structural analysis was combined with electrochemical and photophysical characterization, including ultrafast transient absorption (UFTA) spectroscopy to investigate the effects of the alkyl groups on the excited-state lifetimes of the complexes. The molecular structures determined by single-crystal X-ray diffraction display more distortion in the ground state as alkyl substituents are introduced into the phenanthroline or the NacNac ligand, showing smaller τ4 values due to the steric hindrance. UFTA measurements were carried out to determine the excited-state dynamics. Sterically encumbered Cu5 and Cu6 display excited-state lifetimes 15-20 times longer than unsubstituted complex Cu1, likely indicating that the incorporation of bulky alkyl substituents inhibits the pseudo-Jahn-Teller (PJT) flattening distortion in the excited state. This work suggests that the steric properties of these heteroleptic copper(I) charge-transfer chromophores can be readily modified and that the excited-state dynamics are strongly responsive to these modifications.

Three heteroleptic copper(I) complexes with [Cu(P˄P)N2]+ structure and their fluorescence sensing for VOCs

The design and research of luminescent and volatile organic compound (VOC) fluorescent sensing materials are of great significance and challenge. We report herein the ligand substitution reaction and VOC sensing of new heteroleptic [Cu(P˄P)N2]+ type copper(I) complexes. Firstly, three new complexes 1–3 were designed by utilizing a chelate diphosphine ligand 4,5‐bis(diphenylphosphino)‐9,9‐dimethylxanthene (Xantphos) and synthesized by the substitution reaction of different N‐containing ligands of 4‐PBO (1), 3‐PBO (2), and 4,4′‐Bipy (3) (4‐PBO = 2‐(4′‐pyridyl)‐benzoxazole, 3‐PBO = 2‐(3′‐pyridyl)‐benzoxazole, 4,4′‐Bipy = 4,4′‐bipyridine), respectively. Three complexes were characterized by elemental analysis, spectroscopic analysis (IR, UV–Vis), single‐crystal X‐ray diffraction (SCXRD), and photoluminescence study. The SCXRD study revealed that complexes 1 and 2 both exhibit a molecular structure with tetrahedral copper(I) complex cation and hexafluorophosphate anion, while complex 3 differs in that its cation is a binuclear copper(I) structure bridged by 4,4′‐bipyridine. Three complexes 1–3 present supramolecular ribbon, supramolecular dimer, and supramolecular framework structure, respectively. Some differences of their UV–Vis absorption spectra were explained by TD‐DFT calculation and wavefunction analysis. It is found that 1 has an abnormal luminescence blue shift, and a luminescence mechanism through the high‐energy T2 excited state is proposed by TD‐DFT calculation. Based on 3, a fluorescent test strip was developed, and its fast and selective fluorescent sensing of pyridine vapor through quenching mechanism was successfully realized. The fluorescent quenching mechanism of the material was also studied, and it was proposed that the quenching should be attributed to the photoinduced electron transfer (PET) mechanism.

Changing Directions: Influence of Ligand Electronics on the Directionality and Kinetics of Photoinduced Charge Transfer in Cu(I)Diimine Complexes.

A key challenge to the effective utilization of solar energy is to promote efficient photoinduced charge transfer, specifically avoiding unproductive, circuitous electron-transfer pathways and optimizing the kinetics of charge separation and recombination. We hypothesize that one way to address this challenge is to develop a fundamental understanding of how to initiate and control directional photoinduced charge transfer, particularly for earth-abundant first-row transition-metal coordination complexes, which typically suffer from relatively short excited-state lifetimes. Here, we report a series of functionalized heteroleptic copper(I)bis(phenanthroline) complexes, which have allowed us to investigate the directionality of intramolecular photoinduced metal-to-ligand charge transfer (MLCT) as a function of the substituent Hammett parameter. Ultrafast transient absorption suggests a complicated interplay of MLCT localization and solvent interaction with the Cu(II) center of the MLCT state. This work provides a set of design principles for directional charge transfer in earth-abundant complexes and can be used to efficiently design pathways for connecting the molecular modules to catalysts or electrodes and integration into systems for light-driven catalysis.

Sulfonamido-Pincer Complexes of Cu(II) and the Electrocatalysis of O2 Reduction.

Heteroleptic copper complexes of an asymmetrical pincer ligand containing a central anionic sulfonamide donor (pyridine-2-yl-sulfonyl)(quinolin-8-yl)-amide (psq), which contains a central anionic sulfonamido donor have been prepared. Meridional κ3-N,N″,N‴ binding with the co-ligands acetate, chloride, or acetonitrile (MeCN), trans to the central sulfonamido N-donor, is revealed by the X-ray crystal structures of [Cu(OAc)(psq)(H2O)], [CuCl(psq)]2, and [Cu(psq)(MeCN)](PF6). Either overall distorted square pyramidal or octahedral geometries of the copper atom are satisfied by coordinated water in the case of the acetate complex or interactions with periphery sulfonamido oxygen atoms on adjacent molecules in the dimeric chloride and 1D polymeric acetonitrile complexes. The cyclic voltammogram (CV) of [Cu(OAc)(psq)(H2O)] shows a quasi-reversible CuII/CuI reduction at -0.930 V (vs Fc+/Fc0, MeCN), and an irreversible CuII/CuI reduction for [Cu(psq)(MeCN)](PF6) is seen at -0.838 V. This signal is split into two quasi-reversible redox processes on the addition of 2,2,2-trifluoroethanol (TFE). This suggests that TFE pushes a solution equilibrium toward a dimeric acetate complex analogous to [CuCl(psq)]2, which shows two quasi-reversible waves at -0.666 V and -0.904 V vs Fc+/Fc0 consistent with its dimeric solid-state structure. A comparison of the CVs of [Cu(OAc)(psq)(H2O)] under either a N2 or an O2 atmosphere revealed that this complex catalyzes turnover electro-reduction of O2 to H2O2 and H2O. The rate of reaction increases on addition of a weak organic acid, and a coulombic efficiency of 48% for H2O2 was determined by iodometric titration. We propose that a CuI complex formed on electroreduction binds O2 to yield an intermediate superoxide complex. On electron and proton transfer to this species, a bifurcated route back to the O2-activating CuI complex is feasible with either release of H2O2 or O-O cleavage resulting in the liberation of H2O. The CuI complex is regenerated by subsequent reduction and protonation to close the cycle.

Fungicidal and Stimulating Effects of Heteroleptic Copper Complex on the Germination and Phytosafety of Plants

At present, when the whole world is intensively switching to organic farming, the refusal or minimization of the usage of chemical plant protection products and synthesized fertilizers is a very urgent issue for the agro-industrial complex (AIC). Accordingly, the solution to the problems of increasing yields and ensuring the fight against pathogenic components should be carried out in accordance with the principles of “green” chemistry. In this regard, the usage of heteroleptic complexes based on carboxylic and amino acids with biogenic metals is dictated not only by their availability, low cost, and ability to increase crop yields but also by fungicidal activity, lower toxicity, and easy biodegradability, which lists them among the “green” and cost-effective plant biostimulants. In the present work, for the first time, a heteroleptic complex based on succinic acid and glycine, with the formula [Cu(succ)(gly)], was developed for usage as a fungicidal biostimulant, which has the ability to significantly reduce the number of pathogens. We found that this compound has a layered structure and was able to increase soybean germination up to 100%.

A novel heteroleptic Cu(II)-phenanthroline-UDCA complex as lipoxygenase inhibitor and ER-stress inducer in cancer cell lines

A new heteroleptic copper(II) compound named C0-UDCA was prepared by reaction of [Cu(phen)2(OH2)](ClO4)2 (C0) with the bile ursodeoxycholic acid (UDCA). The resulting compound is able to inhibit the lipoxygenase enzyme showing more efficacy than the precursors C0 and UDCA. Molecular docking simulations clarified the interactions with the enzyme as due to allosteric modulation. The new complex shows antitumoral effect on ovarian (SKOV-3) and pancreatic (PANC-1) cancer cells at the Endoplasmic Reticulum (ER) level by activating the Unfolded Protein Response. In particular, the chaperone BiP, the pro-apoptotic protein CHOP and the transcription factor ATF6 are upregulated in the presence of C0-UDCA. The combination of Intact Cell MALDI-MS and statistical analysis have allowed us to discriminate between untreated and treated cells based on their mass spectrometry fingerprints.

Chemoenzymatic Dynamic Kinetic Resolution of Secondary Alcohols and Amines Employing Copper-Based Photocatalysis

A tandem photo- and biocatalytic dynamic kinetic resolution of secondary alcohols and amines was achieved employing a commercially available lipase, Candida antarctica lipase B (CALB), and a heteroleptic copper complex. The process is an example of using copper-based photocatalysis to promote hydrogen atom transfer (HAT) processes employing thiyl radicals. Screening of 48 complexes and 5 disulfides identified Cu(dtbbpy)(DPEPhos)BF4 and (Ph3SiS)2 as an optimal catalyst system to promote the HAT process. The catalytic system represents a general system for radical-mediated racemization applicable to both aliphatic and aromatic alcohols and amines (18 examples, 60 → 97% yield, 76 → 99% ee).

Structure-Property Relationships in a New Family of Photoactive Diimine-Diphosphine Copper(I) Complexes.

A new family of heteroleptic diimine-diphosphine copper(I) complexes is reported, with six new complexes compared to benchmark [Cu(bcp)(DPEPhos)]PF6 . These new complexes are based on 1,4,5,8-tetraazaphenanthrene (TAP) ligands with representative electronic properties as well as substitution patterns and DPEPhos and XantPhos as diphosphine ligands. Their photophysical and electrochemical properties were investigated and correlated with the number and position of substituents on the TAP ligands. Stern-Volmer studies using Hünig's base as reductive quencher demonstrated the influence of the complex photoreduction potential and of the excited state lifetime on the photoreactivity. This study refines the structure-property relationship profile for heteroleptic copper(I) complexes and confirms that such profiles are of high interest to design new copper complexes as optimized photoredox catalysts.

Synthesis and characterization of a luminescent diphosphine and aromatic N-heterocyclic copper(I) coordination polymer

Luminescent Cu(I) complexes have drawn considerable attention as alternative materials to precious transition metal complexes due to their low cost and electron configuration. Discrete heteroleptic diamine-diphosphine copper(I) complexes have been investigated owing to their outstanding photophysical features. However, heteroleptic copper(I) coordination polymers remain mostly unexplored. Herein, we report the synthesis and photophysical characterization of a heteroleptic copper(I) coordination polymer by employing bidentate oxybis(2,1-phenylene)bis(diphenylphosphine) (POP) diphosphine and nitrogen heterocyclic 5-[4-(1-imidazolyl)phenyl]-2H-tetrazole (ipt) as ligands. By utilizing the mixed-solvent strategy, a one-dimensional (1D) linear chain was constructed under solvothermal reaction conditions. Temperature-dependent emission spectra combined with decay time measurements demonstrate that emission originated from triplet phosphorescence at ambient temperature.

6-(Thiophen-2-yl)-2,2′-bipyridine]bis(triphenylphosphine) Copper(I) Tetrafluoroborate

The novel heteroleptic copper (I) complex [6-(thiophen-2-yl)-2,2′-bipyridine]bis(triphenylphosphine) copper(I) tetrafluoroborate (1), formulated as [CuL(PPh3)2]BF4, was synthesized in two steps, utilizing the diimine type ligand L = 6-(thiophen-2-yl)-2,2′-bipyridine and triphenylphosphine (PPh3). The compound was characterized both in the solid state and in solution by employing single crystal X-ray diffraction, IR, UV, and NMR spectroscopies. The complex is an orange emitter that demonstrates a photoluminescence quantum yield of 2.6% in the solid state.

Heteroleptic Copper Complexes as Catalysts for the CuAAC Reaction: Counter-Ion Influence in Catalyst Efficiency

A series of nine cationic heteroleptic aryl-BIAN-copper(I) (BIAN = bis-iminoacenaphthene) complexes with the general formula [Cu((E-C6H4)2BIAN)(PPh3)2][X] (E = p-Me, p-iPr, o-iPr; X = BF4, OTf, NO3) 1X–3X were synthesized and fully characterized using several analytical techniques, including NMR spectroscopy and single-crystal X-ray diffraction. Except for complexes 2BF4 and 3BF4, which were already reported in our previous works, all remaining complexes are herein described for the first time. Two different strategies were used for the preparation of the complexes: complexes bearing BF4− or OTf− counter-ions (1BF4, 1OTf, 2OTf, and 3OTf) were obtained using the appropriate copper(I) precursors [Cu(NCMe)4][BF4] or [Cu(NCMe)4][OTf], whereas for derivatives 1NO3–3NO3, [Cu(PPh3)2NO3] was used. Their activity as catalysts for the copper azide-alkyne cycloaddition (CuAAC) was assessed alongside other high activity, previously reported Cu(I) complexes. Comparative studies to determine the influence of the counter-ion and of the aryl substituents were performed. All complexes behaved as active catalysts under neat reaction conditions, at 25 °C and in short reaction times without requiring the use of any additive, with complex 2NO3 being the most efficient derivative, along with other NO3−-bearing complexes.

Controlling the Photofunctionality of a Polyanionic Heteroleptic Copper(I) Photosensitizer for CO2 Reduction Using Its Ion-pair Formation with Polycationic Ammonium in Aqueous Media.

A water-soluble trianionic heteroleptic copper(I) photosensitizer having four sulfonate groups (CuPS3- ) was found to afford the 1 : 2 ion-pair adduct with dicationic alkylammonium (hexamethonium) cations (HM2+ ) in aqueous media, leading to exhibit excellent photophysical and photocatalytic performances owing to the substantial suppression of water-derived non-radiative decay of the photoexcited state.