Water-soluble Ligands Research Articles

New series of water-soluble thiosemicarbazones and their copper(II) complexes as potentially promising anticancer compounds

New water soluble thiosemicarbazone ligands, namely 3-(3-{[(aminocarbonothioyl) hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L1Cl), 3-[4-hydroxy-3-({[(methylamino)carbonothioyl]hydrazono}methyl)benzyl]-1-methyl-1H-imidazol-3-ium chloride (H2L2Cl) and 3-(3-{[(anilinocarbonothioyl)hydrazono]methyl}-4-hydroxybenzyl)-1-methyl-1H-imidazol-3-ium chloride (H2L3Cl) were synthesized through 1:1 condensation reaction of thiosemicarbazide derivatives with 3-(3-formyl-4-hydroxybenzyl)-1-methyl-1H-imidazole-3-ium chloride (SalimiCl) and characterized by elemental analysis and spectroscopic methods (UV–Vis, 1H NMR, FTIR). Single crystals of H2L1Cl and H2L2Cl were prepared for crystallographic analysis, which showed similar X-ray structures for both ligands with chiral P212121 space group. The ligands were used for synthesis of the following copper(II) complexes: [Cu(HL1)Cl]Cl, [Cu(HL2)Cl]Cl·H2O, and [Cu(HL3)Cl]Cl. All complexes were characterized by physico-chemical and spectroscopic methods. The X-ray structure of [Cu(HL1)Cl]Cl was orthorhombic with Pcba space group while [Cu(HL2)Cl]Cl·H2O was triclinic with Pī space group. Both complexes were mononuclear, with tridentate ligands in a thione form. All of the studied compounds showed good solubility and stability in water. The measurement of the molar conductance showed the release of Cl− into solution and substitution of water instead of the coordinated chloride. Among the studied complexes, only [Cu(HL3)Cl]Cl shows a quasi-reversible redox behavior with its reduction and oxidation peak potentials separated by a value of about 0.120V (Epc=−0.310V and Epa=−0.190V) indicating one-step and one-electron transfer for CuII/CuI redox couple. The cytotoxic effect of the compounds was measured using the MTT assay on MCF-7 and K562 cell lines and the results showed that [Cu(HL3)Cl]Cl and H2L3Cl had lower IC50 values compared to the other compounds. Flow cytometry analysis on the MCF-7 cells showed the apoptosis cell death after treating with the H2L3Cl and [Cu(HL3)Cl]Cl. Also studies of cell cycles confirmed the cell cycle arrest in G2 phase for H2L3Cl and [Cu(HL3)Cl]Cl.

Toward Smaller Aqueous-Phase Plasmonic Gold Nanoparticles: High-Stability Thiolate-Protected ∼4.5 nm Cores.

Most applications of aqueous plasmonic gold nanoparticles benefit from control of the core size and shape, control of the nature of the ligand shell, and a simple and widely applicable preparation method. Surface functionalization of such nanoparticles is readily achievable but is restricted to water-soluble ligands. Here we have obtained highly monodisperse and stable smaller aqueous gold nanoparticles (core diameter ∼4.5 nm), prepared from citrate-tannate precursors via ligand exchange with each of three distinct thiolates: 11-mercaptoundecanoic acid, α-R-lipoic acid, and para-mercaptobenzoic acid. These are characterized by UV-vis spectroscopy for plasmonic properties; Fourier transform infrared (FTIR) spectroscopy for ligand-exchange confirmation; X-ray diffractometry for structural analysis; and high-resolution transmission electron microscopy for structure and size determination. Chemical reduction induces a blueshift, maximally +0.02 eV, in the localized surface plasmon resonance band; this is interpreted as an electronic (-) charging of the monolayer-protected cluster (MPC) gold core, corresponding to a -0.5 V change in electrochemical potential.

Asymmetric Transfer Hydrogenation in Thermomorphic Microemulsions Based on Ionic Liquids

A thermomorphic ionic-liquid-based microemulsion system was successfully applied for the Ru-catalyzed asymmetric transfer hydrogenation of ketones. On the basis of the temperature-dependent multiphase behavior of the targeted microemulsion, simple product separation as well as catalyst recycling could be realized. The use of water-soluble ligands improved the immobilization of the catalyst in the microemulsion phase and significantly decreased the catalyst leaching into the organic layer upon extraction of the product. Eventually, the optimized microemulsion system could be applied to a wide range of aromatic ketones that were reduced with good isolated yields (up to 98%) and enantioselectivities (up to 97%), while aliphatic ketones were less successful.

The Ligand-Exchange Reactions of Rod-Like Au25-n Mn (M=Au, Ag, Cu, Pd, Pt) Nanoclusters with Cysteine - A Density Functional Theory Study.

The atomic precision of ultrasmall noble-metal nanoclusters (NMNs) is fundamental for elucidating structure-property relationships and probing their practical applications. So far, the atomic structure of NMNs protected by organic ligands has been widely elucidated, whereas the precise atomic structure of NMNs protected by water-soluble ligands (such as peptides and nucleic acid), has been rarely reported. With the concept of "precision to precision", density functional theory (DFT) calculations were performed to probe the thermodynamic plausibility and inherent determinants for synthesizing atomically precise, water-soluble NMNs via the framework-maintained two-phase ligand-exchange method. A series of rod-like Au25-n Mn (M=Au, Ag, Cu, Pd, Pt) NMNs with the same framework but varied ligands and metal compositions was chosen as the modeling reactants, and cysteine was used as the modeling water-soluble ligand. It was found that the acidity of the reaction remarkably affects the thermodynamic facility of the ligand exchange reactions. Ligand effects (structural distortion and acidity) dominate the overall thermodynamic facility of the ligand-exchange reaction, while the number and type of doped metal atom(s) has little influence.

Sonochemical synthesis of fluorescent 1,4-disubstituted triazoles using l-phenylalanine as an accelerator ligand in aqueous media

A green sonochemical protocol using l-phenylalanine as a water soluble promotor ligand has been developed for the regioselective synthesis of fluorogenic 1,4-disubstituted triazoles (3a-o) via well-known click reaction at 40 °C. l-Phenylalanine is a biocompatible, economical, commercially available and non-toxic ligand which not only serves to stabilize Cu(I) oxidation state but also prevents its disproportion to enhances and modulate the rate of reaction. The designed catalytic system exhibits broad substrate compatibility and can be recycled up to 5 cycles without appreciable loss in the yield of desired product. Gram scale synthesis was successfully accomplished with 92% yield.

Towards Selective Syntheses of Octadienylethers from the Butadiene Palladium‐catalyzed Telomerization with Polyols in Aqueous Biphasic Medium

AbstractThe palladium catalyzed telomerization of butadiene with polyols has been efficiently performed under aqueous and biphasic medium leading to the corresponding octadienylethers. Depending on the choice of the organic co‐solvent and nature of the catalyst employed to promote the reaction, mono‐ to fully substituted ethers could be obtained with high selectivities and yields. Particularly, pentaerythritol was telomerized for the first time allowing the selective synthesis of the corresponding monotelomers by using methylethylketone as organic co‐solvent and the water soluble ligand TPPTS associated to a simple palladium precursor. Polyethers of sorbitol could be efficiently obtained by using a mixture of TPPTS and PPh3 ligands.

Role of the surface composition of the polyethersulfone–TiiP–H2T4 fibers on lead removal: from electrostatic to coordinative binding

The removal of toxic metal ions from water remains an environmental challenge. Promising processes involve formation of metal complexes with appropriate ligands and their successive separation using filtration over membranes. Water-soluble macromolecular ligands are, therefore, important to improve this technology. In this investigation, we have shown that insertion of a Ti-acac-based precursor on non-water-soluble thermoplastic polyethersulfone membranes allows an effective immobilization of the meso-tetra(N-methyl-4-pyridyl)porphine which, in turn, can safely remove Pb2+ ions from water. In particular, it has been demonstrated that the porphyrin readily coordinates Pb2+ thus forming a sitting-atop metal derivative. Moreover, X-ray photoelectron spectroscopy has favored a complete characterization of surfaces of fiber membranes, thus providing evidences of Pb2+ coordination. The efficiency of Pb2+ removal from water has been discussed on the basis of competitive porphyrin deprotonation versus metal complex stability in water, and these data shed light on the role of porphyrin concentration on the fiber surface that can switch the metal absorption from a pure electrostatic interaction to coordinative complexation.

Water-Soluble Sulfonate Schiff-Base Ligands as Fluorescent Detectors for Metal Ions in Drinking Water and Biological Systems

The ability to detect and selectively identify trace amounts of metal ions is of major importance for drinking water identification and biological studies. Herein, we report a series of water-soluble Schiff-base ligands capable of being fluorescent and colorimetric sensors for metal ions. Upon coordination of the metal ion to the ligand, quenching of fluorescence is observed, typically in a 1:1 ratio. The selectivity of metal ions Cu2+, Ni2+, Cr3+, and Co2+ is exhibited via fluorescence quenching accompanied by colorimetric changes, whereas that of Ag+ and Co2+ is observed through colorimetric changes alone. Additionally, pH sensing studies were performed for the potential use of these ligands in biological applications.

Control of Protein Self-Assembly with Water-Soluble Porphyrins

Interactions between charged porphyrins and complimentary or similarly charged proteins provide important models systems for studies of electron transfer processes, artificial photosynthesis, and control of protein-protein interactions. Typically, the experimental results are analyzed and discussed assuming that the proteins exist in a monodisperse state. Here, we explored interaction of wild-type and 12 mutants of PpcA, a 3-heme c-type cytochrome (cyt) from Geobacter sulfurreducenswith several anionic water-soluble derivatives of tetraphenylporphyrin. Combined small- and wide-angle X-ray scattering experiments revealed formation of multimers with a wide range of complex sizes. Thermodynamic interaction parameters and complex binding stoichiometries were established with isothermal calorimetry. All-atom molecular dynamics simulations revealed quick complex formation with binding sites well matching the areas identified in our experimental work. The obtained results demonstrate that multimerization of solution-state proteins by large water-soluble ligands can be tuned to control shape and size of the formed complexes. Molecular level mapping of the binding sites allows us to build a theory explaining the size of the formed complexes and provides opportunities for targeted design and assembly of multi-subunit protein complexes.

Cytoprotective effects of imidazole-based [S1] and [S2]-donor ligands against mercury toxicity: a bioinorganic approach.

Here we report the coordination behaviour of an imidazole-based [S1]-donor ligand, 1,3-dimethyl-imidazole-2(3H)-thione (L1), and [S2]-donor ligand, 3,3'-methylenebis(1-methyl-imidazole-2(3H)-thione) (L2) or 4,4'-(3,3'-methylenebis-(2-thioxo-2,3-dihydro-imidazole-3,1-diyl))dibutanoic acid (L3), with HgX2 (X = Cl, Br or I) in solution and the solid state. NMR, UV-Vis spectroscopic, and single crystal X-ray studies demonstrated that L1 or L2 coordinated rapidly and reversibly to the mercury center of HgX2 through the thione moiety. Treatment of L2 with HgCl2 or HgBr2 afforded 16-membered metallacycle k1-(L2)2Hg2Cl4 or k1-(L2)2Hg2Br4 where two Cl or Br atoms are located inside the ring. In contrast, treatment of L2 with HgI2 afforded a chain-like structure of k1-[L2Hgl2]n, possibly due to the large size of the iodine atom. Interestingly, [S1] and [S2]-donor ligands (L1, L2, and L3) showed an excellent efficacy to protect liver cells against HgCl2 induced toxicity and the strength of their efficacy is in the order of L3 > L2 > L1. 30% decrease of ROS production was observed when liver cells were co-treated with HgCl2 and L1 in comparison to those cells treated with HgCl2 only. In contrast, 45% and 60% decrease of ROS production was observed in the case of cells co-treated with HgCl2 and thiones L2 and L3, respectively, indicating that [S2]-donor ligands L2 and L3 have better cytoprotective effects against oxidative stress induced by HgCl2 than [S1]-donor ligand L1. Water-soluble ligand L3 with N-(CH2)3CO2H substituents showed a better cytoprotective effect against HgCl2 toxicity than L2 in liver cells.

Water Soluble Mixed Ligand Complexes Spectral, antioxidant, antimicrobial and DNA interaction studies

A new series of water soluble mixed ligand complexes [MII(L)(bpy)AcO].nH2O M = Cu, (n=1) (1); Co (2), Mn (3), Ni (4) (n=4) and Zn (5) (n=2) have been synthesized from 2-(2-Morpholinoethylimino)methyl)phenol Schiff base ligand (HL) and 2,2�-bipyridine in a 1:1:1 molar ratio. The resulting complexes were characterized by spectral techniques. The spectral data of these complexes suggest an octahedral geometry. In vitro antioxidant activity results of DPPH assay, hydroxyl radical, super oxide and nitric oxide for complexes (1-5) were compared with ligand (HL) and in vitro antimicrobial activities of all compounds were examined against selected bacterial and fungal strains which indicate that the complexes exhibit higher antimicrobial activity than free ligand (HL). Gel electrophoresis results indicated that, complexes (1) and (2) have exhibited more DNA cleavage efficiency than others. The intrinsic binding constant (Kb) values for the complexes (1-5) observed by electronic absorption technique were in the order of (1) ] (4) ] (5) ] (2) ] (3) and DNA binding affinity values for these complexes obtained by viscosity measurements were in the order of ethidium bromide ] (1) ] (2) ] (3) ] (4) ] (5).

Carbohydrate Functionalization of Few-Layer Graphene through Microwave-Assisted Reaction of Perfluorophenyl Azide.

The excellent physical and chemical properties of graphene make it an attractive nanomaterial and a component in high-performance nanocomposite materials. To prepare graphene-based nanocomposite materials, chemical functionalization is often necessary. Water-soluble ligands such as carbohydrates not only make the functionalized graphene compatible with aqueous media, but also introduce biorecognition, which is important for graphene to be used in biotechnology. In this study, we report the derivatization of few-layer graphene (FLG) with carbohydrates through microwave-assisted reaction of perfluorophenyl azide (PFPA). FLG was first treated with PFPA under microwave radiation. Subsequent conjugation with glycosyl amine gave carbohydrate-presenting FLG. Thermogravimetric analysis showed that microwave radiation gave a higher degree of functionalization compared to conventional heating, with higher weight losses for both PFPA and Man ligands. The carbohydrates (mannose and galactose) retained their bioactivity, as demonstrated by the lectin binding assays. Higher degree of binding toward lectins was obtained for the carbohydrate-functionalized FLG prepared by microwave radiation than the conventional heating.

Density functional theory molecular modelling, DNA interactions, antioxidant, antimicrobial, anticancer and biothermodynamic studies of bioactive water soluble mixed ligand complexes

A novel series of bioactive water soluble mixed ligand complexes (1–5) [MII(L)(phen)AcO]. nH2O {where M = Cu (1) n = 2; Co (2), Mn (3), Ni (4), n = 4 and Zn (5) n = 2} were synthesized from 2-(2-Morpholinoethylimino) methyl)phenol Schiff base ligand (LH), 1, 10-phenanthroline and metal(II) acetate salt in a 1:1:1 stoichiometric ratio and characterized by several spectral techniques. The obtained analytical and spectral data suggest the octahedral geometry around the central metal ion. Density functional theory calculations have been further supportive to explore the optimized structure and chemical reactivity of these complexes from their frontier molecular orbitals. Gel electrophoresis result indicates that complex (1) manifested an excellent DNA cleavage property than others. The observed binding constants with free energy changes by electronic absorption technique and DNA binding affinity values by viscosity measurements for all compounds were found in the following order (1) > (2) > (4) > (5) > (3) > (LH). The binding results and thermodynamic parameters are described the intercalation mode. In vitro antioxidant properties disclose that complex (1) divulges high scavenging activity against DPPH•, •OH, O2−• NO•, and Fe3+. The antimicrobial reports illustrate that the complexes (1–5) were exhibited well defined inhibitory effect than ligand (LH) against the selected different pathogenic species. The observed percentage growth inhibition against A549, HepG2, MCF-7, and NHDF cell lines suggest that complex (1) has exhibited superior anticancer potency than others. Thus, the complex (1) may contribute as potential anticancer agent due to its unique interaction mode with DNA.GRAPHICAL ABSTRACTCommunicated by Ramaswamy H. Sarma

Aqueous biphasic hydroformylation of olefins: From classical phosphine-containing systems to emerging strategies based on water-soluble nonphosphine ligands

ABSTRACTThis review provides an overview of recent developments in the area of aqueous biphasic hydroformylation of higher olefins using metal catalysts and surfactants, cosolvents, thermoregulated ligands, cyclodextrins, and most importantly emerging water-soluble nonphosphine ligands. Water-soluble phosphine ligands have been widely explored for aqueous biphasic hydroformylation; however, phosphines are generally expensive and are prone to oxidation hence the recent interest in exploring other ligands. Various approaches have been used to introduce hydrophilicity to the ligands. The catalytic activity of monometallic and heterobimetallic systems containing nonphosphine ligands in aqueous biphasic media is emphasized in this review.

2,6-Bis(1-alkyl-1H-1,2,3-triazol-4-yl)-pyridines: selective lipophilic chelating ligands for minor actinides

Starting from the promising minor actinides (MA) affinity showed by the water-soluble ligands (PyTri-polyols) with the 2,6-bis[1H-1,2,3-triazol-4-yl]-pyridine chelating unit, different attempts were made to functionalize the same N3-donor set with alkyl chains in the 1-position of triazole nuclei to obtain novel lipophilic extractants endowed with comparable MA selectivity. Solubility in organic diluents was found to be the main limitation to the development of efficient lipophilic ligands, thus resulting in less efficient extractants with respect to their hydrophilic analogues and sometimes impairing the selectivity evaluation. Interestingly, the ethyl hexyl derivative (PTEH) showed adequate extraction capability and a MA selectivity comparable to that of the hydrophilic PyTri family.

Synthesis and Properties of Water-Soluble Branched Polyester Poly{3-[3-(morpholin-4-yl)propyl]amino}propionate and Its Copper(II) Complex

A new water-soluble multidentate ligand based on a second-generation hyperbranched polyester containing 3-(morpholin-4-yl)propionate fragments in the terminal position has been synthesized, and its complex with copper(II) has been obtained. The degree of polyester functionalization with aminopropylmorpholine is 56%.

Pd/PTABS: An Efficient Water-Soluble Catalytic System for the Amination of 6-Chloropurine Ribonucleoside and Synthesis of Alogliptin.

The synthesis and catalytic applications of the highly water-soluble ligand 7-phospha-1,3,5-triaza-admantane butane sultonate (PTABS) has been described. The synthesized PTABS ligand along with palladium acetate exhibits excellent reactivity towards the amination reaction of 6-chloro-9-(β-D-ribofuranosyl)-9H-purine at ambient temperature. This protocol offers an advantage over the previously published procedures for the amination of 6-chloropurine nucleoside furnishing 6-N-substituted adenosine analogues. The validation of the present strategy has been demonstrated via synthesis of a uracil-based, anti-diabetic drug alogliptin. © 2018 by John Wiley & Sons, Inc.

Robust Removal of Ligands from Noble Metal Nanoparticles by Electrochemical Strategies

Ligand-stabilized metal nanoparticles (MNPs) have attracted much attention due to their promising catalytic applications. Fully/partially removing these ligands is critical to realize their proper functions. The traditional ligand-removing approaches (e.g., thermal annealing) focus on the ligand side. Herein, we demonstrate an electrochemical method that pays attention to the MNPs side. By rationally regulating the potential (oxidizing Pt and hydrogen evolution) to construct robust Pt–O or Pt–H covalent bond to displace Pt–ligand coordination bond, the approach could effectively remove almost all kinds of ligands from Pt NPs. For the oxidizing Pt method, up potential > 1.3 V and cycling number (n) > 20 are preferred to completely remove the ligands. The water-soluble ligands (such as poly(vinylpyrrolidone), cetyltrimethylammonium bromide, sodium acetate) can be removed by just one cycle after thoroughly being washed by water to remove the unattached ligands. However, the oil-soluble ligands (such as oleyl...

Synthesis of Rh(I) alkylated-PTA complexes as catalyst precursors in the aqueous-biphasic hydroformylation of 1-octene

A series of mono- and multivalent phosphorus-based ligands was synthesised by the lower-rim benzylation of the water-soluble ligand, 1,3,5-triaza-7-phosphaadamantane (PTA). These ligands were used to prepare mono-, bi- and trinuclear Rh(I) complexes whose catalytic activity, product selectivity and recyclability were evaluated in the aqueous biphasic hydroformylation of 1-octene.

New water-soluble Schiff base ligands based on β-cyclodextrin for aqueous biphasic hydroformylation reaction

Abstract The synthesis of water-soluble rhodium(I) salicylaldiminato and salicylhydrazonic complexes has been achieved employing two preparative routes. Schiff base condensation between 6A-deoxy-6A-amino-β-CD or 6A-deoxy-6A-hydrazino-β-CD and 5-sodiosulfonato-2-hydroxybenzaldehyde (sulfonated salicylaldehyde) (1) or 5-sodiosulfonato-3-tert-butyl-2-hydroxybenzaldehyde (sulfonated t Bu-salicylaldehyde) (2) led to the formation of the corresponding imine or hydrazone ligands (3, 4, 5 and 6). Reaction of [Rh(COD)2 +BF4 −] with these new ligands in an alkaline solution formed the corresponding rhodium complexes quantitatively. These rhodium(I) complexes could also be prepared in one-pot by mixing, in stoichiometric proportions, the modified β-CDs with the sulfonated salicylaldehyde and with the rhodium precursor in an alkaline solution at room temperature. These rhodium complexes were applied as catalysts in the aqueous biphasic hydroformylation of 1-decene as a model reaction.