Examining the binding mechanism of 3,4-dihydro-3-(2-oxo-2-phenylethylidene)-quinoxalin-2(1H)-one and its fragments to Cu2+

The structure and stoichiometries of the complexes that could be formed between Cu²⁺ and 3,4-dihydro-3-(2-oxo-2-phenylethylidene)-quinoxalin-2(1H)-one (1) were investigated by various spectral techniques such as IR, fluorescence, UV–vis and electron paramagnetic resonance. The results suggest that initially 3?:?1 and 2?:?1 (1/Cu²⁺) complexes are formed at low Cu²⁺ concentration and upon adding more Cu²⁺, 1?:?1 (preferred) and 1?:?2 complexes are generated. Since 1 possesses two possible binding sites, further exploration was done by testing the binding ability of Cu²⁺ to fragments of 1, namely β-enaminoketone derivatives (2–3) and quinoxaline-2-one (4), and by executing calculations of thermodynamic parameters of the reaction between 1 and Cu²⁺ in ethanol, optimized geometries of the possible complexes, and estimation of stability constants at various stoichiometries. Consequently, a step-by-step binding mechanism is suggested for formation of various complexes between 1 and Cu²⁺.     

Design and synthesis of a new coumarin-based ‘turn-on’ fluorescent probe selective for Cu

The novel coumarin-based ‘turn-on’ fluorescent probe (E)-3-(2,5-dimethoxybenzylideneamino)-7-hydroxy-2H-chromen-2-one (MGM) was designed, synthesized, and characterized. This compound shows high selectivity for Cu⁺², combined with a large fluorescence enhancement upon binding to Cu²⁺. Benesi-Hildebrand and Job plots demonstrate that the stoichiometry of the Cu²⁺ complex formed is 2:1. Preliminary studies employing epifluorescence microscopy demonstrated that Cu⁺² could be imaged in human neuroblastoma SH-SY5Y cells treated with MGM.     

Study on the synthesis of novel fluorescent macrocyclic sensors and their sensitive properties for Cu2+ and Fe3+ in aqueous solution

In this work, we synthesised and characterised three novel fluorescence macrocyclic sensors containing optically active dansyl groups. The studies for the interaction of the synthesised compounds with various mental ions (Li⁺, Na⁺, K⁺, Ag⁺, Mg²⁺, Ca²⁺, Ba²⁺, Pb²⁺, Zn²⁺, Co²⁺, Cd²⁺, Hg²⁺, Ni²⁺, Cu²⁺, Mn²⁺, Cr³⁺, Al³⁺, Fe³⁺) were performed by fluorescence titration, Job’s plot, ESI-MS and DFT calculations. The results showed that the sensors 1a–1c displayed selective recognition for Cu²⁺ and Fe³⁺ ions and formed stoichiometry 1:1 complex through PET mechanism in DMSO/H₂O solution (1:1, v/v, pH 7.4 of HEPES). The binding constant (K) and detection limit were calculated.     

Development of gold nanoparticle based colorimetric method for quantitatively studying the inhibitors of Cu/Zn induced β-amyloid peptide assembly

In this paper, a kind of gold nanoparticle (GNP)-based colorimetric assay has been developed for studying the reversible interaction of β-amyloid peptide (Aβ) with Cu²⁺ and Zn²⁺, and quantitatively analyzing four inhibitors (i.e., EDTA, EGTA, histidine and clioquinol) of Cu²⁺/Zn²⁺ induced Aβ assembly. The inhibition efficiencies (e.g., half maximal inhibitory concentration, IC₅₀ value) of these inhibitors could be measured in this work. As far as we know, these IC₅₀ values were reported at the first time. In this assay, the streptavidin conjugated GNPs (SA-GNPs) were employed as indicators to monitor the Cu²⁺/Zn²⁺ induced aggregating/disaggregating behaviors of biotin modified β-amyloid 1–16 peptides (Aβ_1–16(biotin)). Because of high affinity of streptavidin (SA) with biotin, the aggregating/disaggregating of Aβ_1–16(biotin) results in the significant color change of SA-GNPs. Furthermore, we demonstrate that the assay can be used as an effective tool for designing anti-dementia drugs through quantitative analysis of the interactions of four representative inhibitors with Cu²⁺/Zn²⁺ induced Aβ assembly.     

苯乙烯三嗪衍生物的合成及在重金属离子识别中的应用

合成了2,4-二(2-噻吩乙烯基)-6-(4'-N,N-二甲氨基苯乙烯基)-1,3,5-均三嗪(2)并鉴定了其结构。在乙腈-水混合介质中,化合物2在355和416nm处呈现双吸收峰,加入Cu²⁺,Hg²⁺ 和Fe³⁺ 后,均在520nm附近形成新的吸收峰。化合物2与Cu²⁺、Hg²⁺ 和Fe³⁺ 均形成1:1型配合物,其结合常数分别为1.9×10⁵L·mol^-1,6.6×10³L·mol^-1,2.7×10³L·mol^-1。对照化合物4与金属离子的光谱响应与化合物2相似,仅吸收峰的位置不同。因此,可认为化合物2和4中三嗪环中的N和噻吩环中的S与Cu²⁺、Hg²⁺ 和Fe³⁺ 共同配位形成了稳定的金属配合物。     

Highly selective colorimetric naked-eye Cu2+ detection using new bispyrazolone silver nanoparticle-based chemosensor

In this work, we have successfully developed novel silver nanoconjugates of pyrazolone analogue and screened its chemosensing potential in aqueous medium. Bispyrazolone silver nanoparticles (Bispyra-AgNPs) were synthesised and characterised through FTIR, UV-visible spectroscopy and atomic force microscopy. The sensing ability was explored towards Ca²⁺, Cd²⁺, Co²⁺, Cu²⁺, Fe²⁺, Li⁺, Pb²⁺, La³⁺, Hg²⁺, Mg²⁺, Ni²⁺ and Ba²⁺ metal ions, respectively. Bispyra-AgNPs showed a highly quenching potential in selective recognition of Cu²⁺and colour of the solution immediately turned from yellow to purple, after the addition of Cu²⁺ in to the solution. The developed method also displayed a remarkable selectivity for Cu²⁺ over others interfering metal ions. The binding ratio and stoichiometry of host-guest complex was found to be 1:1 and determined by Job’s method. The propose method is facile and sensitive to detect Cu²⁺ with detection limit of 10 µM.     

A highly selective pyrene based fluorescent sensor toward Hg detection

A new pyrene-containing fluorescent sensor has been synthesized from 2,3,3-trimethylindolenine. Spectroscopic and photophysical properties of sensor are presented. The large change in fluorescence intensity (I/I₀ = 0.13) at 381 nm and affinity to Hg²⁺ over other cations such as K⁺, Na⁺, Ca²⁺, Mg²⁺, Pb²⁺, and Cu²⁺ make this compound a useful chemosensor for Hg²⁺ detection in hydrophilic media. The sensor (6.0 × 10⁻⁶ M) displays significant fluorescence quenching upon addition of Hg²⁺ in pH 7.4 HEPES buffer without excimer formation. Job’s plot analysis shows the binding stoichiometry to be 2:1 (host/guest).     

Spectrophotometric determination of the formation constants of some transition metal cations with a new synthetic Schiff base in dichloromethane and chloroform using rank annihilation factor analysis

The complex formation between a new synthesized Schiff base and the cations Ni²⁺, Co²⁺, Cu²⁺, Zn²⁺ in dichloromethane (DCM) and chloroform solutions was investigated spectrophotometrically using rank annihilation factor analysis (RAFA). The results of mole ratio plots and continuous variation data show the stoichiometry of complexation were found to be 1:1, and 2:1 metal ion to ligand. The stoichiometry was obtained as 1:1 metal ion to ligand ratio for Co²⁺, Ni²⁺ and Zn²⁺ in chloroform and 2:1 for Cu²⁺. In DCM the stoichiometry was obtained as 1:1 for Co²⁺ and 2:1 for Ni²⁺ and Zn²⁺ and a consecutive 2:1 metal ion to ligand ratio was obtained for Cu²⁺. Formation constants of these complexes were estimated by application of RAFA on spectrophotometric data. In this process the contribution of ligand was removed from the absorbance data matrix when the complex stability constant acts as an optimizing object and simply combined with the pure spectrum of the ligand, the rank of the original data matrix can be reduced by one by annihilating the information of the ligand from the original data matrix.     

Thermodynamic evaluation of the stability of the bone-seeking radiopharmaceutical [Lu]Lu(III)–DOTP under simulated blood plasma conditions

The stability and in vivo robustness of [¹⁷⁷Lu]Lu–DOTP as a potential bone-targeting radiopharmaceutical was determined with the aid of thermodynamic blood plasma modeling simulations. Glass electrode potentiometry was employed to measure the stability constants of the complexes of Lu³⁺ with DOTP. Similarly, the complexes of DOTP with a selection of the important physiological metal ions: Ca²⁺, Mg²⁺, and Cu²⁺ were determined, representing the typical interactions that the ligand would encounter upon administration. This made possible the construction of a blood plasma model of DOTP, aiding in establishing the potential susceptibility of the radiopharmaceutical. The ligand binds predominantly to calcium in vivo, accounting for 59.6% of that initially introduced as a component of the Lu–DOTP complex. Furthermore, due to a preference of the DOTP to bind to Cu²⁺ it causes mobilization of the ions in blood plasma, and would therefore indicate a deficiency if the ligand is administered at a concentration of 8.5 × 10⁻⁵ mol dm⁻³. The lutetium-ions are preferentially bound to DOTP, with as much as 98.1% of the Lu³⁺ occupying the ligand under physiological conditions.     

Synthesis and evaluation of benzothiazolyl and benzimidazolyl asparagines as amino acid based selective fluorimetric chemosensors for Cu

A series of emissive N-tert-butyloxycarbonyl benzyl ester asparagines bearing benzothiazole and benzimidazole units at the side chain, functionalised with electron donor or acceptor groups, were evaluated as novel amino acid based fluorimetric chemosensors for transition metal cations, such as Cu²⁺, Zn²⁺, Co²⁺ and Ni²⁺. Selective removal of the protecting groups at the N- and C-terminals was carried out in order to assess the influence of the presence of blocking groups on the overall coordination ability. The results indicate that there is a strong interaction through the donor N, O and S atoms at the side chain of the various asparagines, with high selectivity towards Cu²⁺ in a 1:1 complex stoichiometry. Association constants and detection limits for Cu²⁺ were calculated. The photophysical and metal ion sensing properties of these asparagines suggest that they can be suitable for incorporation into peptidic chemosensor frameworks.     

Study of Bulk Membrane Transport of Some Heavy Metal Cations Using Three Macrocyclic Ligands Containing Oxygen and Nitrogen Heteroatoms

The transport experiments of Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Ag⁺ and Pb²⁺ metal cations were carried out by dibenzo-18-crown-6 (DB18C6), dibenzyl-diaza-18-crown-6 (Dibenzyl-diaza-18C6) and di-tert-butyl-dibenzo-18-crown-6 (Di-tert-butyl-DB18C6) using chloroform (CHCl₃), 1,2-dichloroethane (1,2-DCE) and nitrobenzene (NB) organic solvents as liquid membranes. The source phase contained equimolar concentration of these metal cations and the source and receiving phases being buffered at pH=5 and pH=3, respectively. The obtained results show that the selectivity and the efficiency of transport for these heavy metal cations change with the nature of the ligand and also the organic solvents, which were used as liquid membranes in these experiments. A good selectivity was observed for silver (I) ion by dibenzyl-diaza-18C6 in all membrane systems. Dibenzo-18C6 and di-tert-butyl-DB18C6 showed the highest transport efficiency for cobalt (II) ion. The effect of stearic acid on transport efficiency was also investigated and the results show that the efficiency of transport of the heavy metal cations increases in the presence of this organic acid.     

"Off-On" based fluorescent chemosensor for Cu2+ in aqueous media and living cells

A novel Cu²⁺-specific “off-on” fluorescent chemosensor of naphthalimide modified rhodamine B (naphthalimide modified rhodamine B chemosensor, NRC) was designed and synthesized, based on the equilibrium between the spirolactam (non-fluorescence) and the ring-opened amide (fluorescence). The chemosensor NRC showed high Cu²⁺-selective fluorescence enhancement over commonly coexistent metal ions or anions in neutral aqueous media. The limit of detection (LOD) based on 3 × δ_blank/k was obtained as low as 0.18 μM of Cu²⁺, as well as an excellent linearity of 0.05-4.5 μM (R = 0.999), indicating the chemosensor of high sensitivity and wide quantitation range. And also the coordination mode with 1:1 stoichiometry was proposed between NRC and Cu²⁺. In addition, the effects of pH, co-existing metal ions and anions, and the reversibility were investigated in detail. It was also demonstrated that the NRC could be used as an excellent “off-on” fluorescent chemosensor for the measurement of Cu²⁺ in living cells with satisfying results, which further displayed its valuable applications in biological systems.     

Fluorescence switch-on sensor for Cu by an amide linked lower rim 1,3-bis(2-picolyl)amine derivative of calix[4]arene in aqueous methanol

A highly selective fluorescence switch on sensor, L for detecting Cu²⁺ has been synthesized by introducing a bis-(2-picolyl)amine moiety at the lower rim of a calix[4]arene platform via amide linkage. Binding properties of L toward ten different biologically relevant Mⁿ⁺ ions have been studied by fluorescence and absorption spectroscopy in methanol and aqueous methanol. L was found to detect Cu²⁺ selectively down to a concentration of 196 and 341 ppb, respectively, in methanol and 1:1 aqueous methanol even in the presence of other metal ions. The composition of the complex has been found to be 1:1 based on the Job plot and is further confirmed by ESI MS. The role of calix[4]arene platform as well as the pre-organized binding core in the selective recognition of Cu²⁺ has been demonstrated by studying appropriate reference molecules. The possible modes of binding of L with Cu²⁺ have been modeled by computational calculations. L and its Cu²⁺ complex could very well be differentiated based on the nano-structural features observed in SEM and AFM.     

New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study

Herein, we report the synthesis of eight new mononuclear and binuclear Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn²⁺-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co²⁺, Ni²⁺, Cu²⁺, and Zn²⁺) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu²⁺ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.     

Synthesis,structural and spectroscopic properties of asymmetric Schiff bases derived from 2,3-diaminopyridine

Two Schiff base derivatives, 4-(2-amino-3-pyridyliminomethyl)phenol (I) and 3-(2-amino-3-pyridyliminomethyl)nitrobenzene (II), were synthesised and characterised by spectroscopy. The structure of I was determined by single crystal X-ray diffraction studies. The asymmetric Schiff base derived from 2,3-diaminopyridine selectively recognise transition and heavy metal cations, and some anion. Ligands I and II form stable complexes with Cu²⁺, Zn²⁺, Pb²⁺, Al³⁺ whereas ligand I also binds F~ ions. The stoichiometry for the host: cation is 1: 1 and 2: 1. The addition of F~ ion in CH₃CN to ligand I causes a colour change of the solution from colourless to yellow. The binding behaviour of ligand I towards several ions was investigated using density functional theory calculations.     

Naphthalene and pyrrole substituted guanidine in selective sensing of Cu2+, Hg2+, Pb2+ and CN− ions under different conditions

Naphthalene and pyrrole substituted guanidine 1 has been designed and synthesised. Compound 1 efficiently distinguishes Cu²⁺, Hg²⁺ and Pb²⁺ ions by exhibiting different responses in fluorescence. While compound 1 exhibited turn-on emission selectively in the presence of Hg²⁺ and Pb²⁺ ions in CH₃CN and CH₃CN–H₂O (1:1, v/v), respectively, it showed decrease in emission upon interaction with Cu²⁺ ion in CH₃CN. Furthermore, the Cu-1 ensemble has been established as a potential probe for selective detection of CN^? ion over a series of other anions involving colour change (in ordinary light: colourless to light yellow and under UV light: colourless to sky blue). Theoretical insight has been invoked to understand the mode of metal–ligand interaction.     

A SPECTRAL STUDY OF Cu2+ AND Cd2+ WITH A SUBSTITUTED PYRAZINE LIGAND

Abstract

We wish to report a novel ligand that forms an intense blue to purple color when complexed with various non-transition as well as transition metals. This color appears when Cd²⁺, Zn²⁺, Ag¹⁺, Mg²⁺ Fe²⁺, Fe³⁺, Cu²⁺, Co²⁺, Ni²⁺, or Mn²⁺ is added to N,N′-bis(4-N″,N″-dimethylanilinyl)-2,5-bis(methylenimino)pyrazine (Figure 1) which is dissolved in dimethylformamide (DMF). The ligand is capable of being multidentate; therefore, spectro-photometric titration experiments were performed using Cd²⁺ in one experiment and Cu²⁺ in another experiment. If these ions can be considered as being representative of the non-transition and transition complexes respectively, then the stoichiometry is 1:1 and 2:1 (metal:ligand). Whether this sampling is truly representative is under further investigation.     

Synthesis and Characterization of a Mg2+-Selective Probe Based on Benzoyl Hydrazine Derivative and Its Application in Cell Imaging

A simple benzoyl hydrazine derivative P was successfully synthesized and characterized as Mg²⁺-selective fluorescent probe. The binding of P with Mg²⁺ caused an obvious fluorescence enhancement at 482 nm. The fluorescent, UV-vis spectra, ¹H-NMR, and IR spectra confirmed the formation of P-Mg²⁺ complex, and the formation of a 1:1 stoichiometry complex was proved by Job’s plot and mass spectrometry. The recognition mechanism of P to Mg²⁺ was owing to the photoinduced electron transfer effect (PET). The fluorescent response was linear in the range of 0.9–4.0 µM with the detection limit of 0.3 µM Mg²⁺ in water–ethanol solution (1:9, v:v, pH10.0, 20 mM HEPES). In addition, the results of cell imaging of Mg²⁺ in Hl-7701 cells was satisfying.     

Characterization of rhodamine B hydroxylamide as a highly selective and sensitive fluorescence probe for copper(II)

Rhodamine B hydroxylamide (1) is characterized as a highly selective and sensitive fluorescence probe for Cu²⁺. Under the optimized conditions, the probe exhibits specific absorbance-on and fluorescence-on responses to Cu²⁺ only. This remarkable property may allow Cu²⁺ to be detected directly in the presence of the other transition metal ions, and such an application has been demonstrated to human serum. The reaction mechanism is also investigated and proposed as that the hydroxylamide group of 1 binds Cu²⁺, and the subsequent complexation of Cu²⁺ displays a high catalytic activity for the hydrolytic cleavage of the amide bond, causing the release of fluorophore (rhodamine B) and thereby the retrievement of absorbance and fluorescence. The recovered fluorescence intensity is proportional to the concentration of Cu²⁺ in the range 1-20 μM. The detection limit for Cu²⁺ is 33 nM (k = 3). The reaction mechanism described here may be useful for developing excellent spectroscopic probes with cleavable active bonds for other analytes.     

Out-cage metal ion coordination by novel benzoazacrown bisamides with carboxyl,pyridyl and picolinate pendant arms

A new series of macrocyclic diamides with carboxyl, pyridyl and picolinate pendant arms have been synthesized and the stability constants of their complexes with Ni²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Pb²⁺ in water were determined. Complexes with a stoichiometry of 1 : 1 (M: L) were found for all ligands with the exception of 15-membered crown ethers with one pendant carboxyl or pyridine group. The ligand containing two picolinate backbone groups exhibits the highest values of the stability constants for all studied cations (logβ_ML?=?12.5–15.7). X-ray study of free ligands showed that the introduction of benzene and amide fragments into the macrocyclic moiety provides a flatten open structure of the ligand. The crystallographic analysis of Cu²⁺ and Zn²⁺ complexes revealed the external coordination of the metal atom by amine N atoms of the macrocycle and heteroatoms of the pendant groups.