Hydrophilic Ligands Research Articles

Methyl oleate-capped upconverting nanocrystals: a simple and general ligand exchange strategy to render nanocrystals dispersible in aqueous and organic medium.

We report a simple and general ligand exchange strategy to functionalize the nanocrystals with both hydrophobic and hydrophilic ligands. This is achieved by first capping the Er/Yb-doped NaYF4 nanocrystals with a weak ligand such as methyl oleate and subsequently ligand exchanged with various organic ligands which can strongly coordinate to the surface of the nanocrystals. The method involves only a simple stirring or sonication of the nanocrystals dispersion with the ligands of interest. Dicarboxylic acids such as sebacic acid, adipic acid, succinic acid, and malonic acid-functionalized nanocrystals which are difficult to achieve via thermal decomposition method were easily prepared by this ligand exchange strategy. In addition, low boiling point ligands like hexanoic acid can easily be coated over the surface of the Er/Yb-doped NaYF4 nanocrystals. Both size and shape of the nanocrystals were preserved after the ligand exchange process. The methyl oleate-capped Er/Yb-doped NaYF4 nanocrystals display strong upconversion emission after ligand exchanged with hydrophobic and hydrophilic molecules. The high stability of the nanocrystals after ligand exchange process is verified by performing time-dependent luminescent measurements at different pH, buffers, etc.

Nanocomplexes arising from protein-polysaccharide electrostatic interaction as a promising carrier for nutraceutical compounds

The main purpose of the current work was exploring the potential application of the protein–polysaccharide soluble nanocomplexes as delivery systems for nutraceuticals in liquid foods. In this study, the intrinsic transporting property of β-lactoglobulin (BLG) was utilized to develop nanoscale green delivery systems. The binding analysis using fluorescence spectroscopy suggested that the complexation between BLG and four nutraceutical models including β-carotene, folic acid, curcumin and ergocalciferol occurred under all conditions but varied as a function of pH and nutraceutical type. The 1H-NMR study of hydrophilic ligands binding to BLG provided complementary information on the interactions between protein and water soluble ligands. These findings resulted in designing nanoscopic delivery systems for encapsulation of both hydrophobic and hydrophilic bioactives in clear liquid food products of acidic pH. The stability experiments demonstrated that the nutraceuticals of low solubility in water were successfully entrapped within electrostatically stable nanocomplexes arising from BLG-sodium alginate interactions. The electrophoretic mobility analysis showed that soluble nanocomplexes had good stability against aggregation.

Synthesis of Janus-like gold nanoparticles with hydrophilic/hydrophobic faces by surface ligand exchange and their self-assemblies in water.

This study aims at the synthesis of Janus gold nanoparticles (Janus GNPs) with hydrophilic/hydrophobic faces by a simple ligand exchange reaction in an homogeneous system and at the elucidation of the self-assembled structures of the Janus GNPs in water. As hydrophilic surface ligands, we synthesized hexaethylene glycol (E6)-terminated thiolate ligands with C3, C7, or C11 alkyl chains, referred to as E6C3, E6C7, and E6C11, respectively. As a hydrophobic ligand, a butyl-headed thiolate ligand C4-E6C11, in which a C4 alkyl was introduced on the E6C11 terminus, was synthesized. The degree of segregation between the two ligands on the GNPs (5 nm in diameter) was examined by matrix-assisted laser desorption/ionization time-of fright mass spectrometry (MALDI-TOF MS) analysis. We found that the choice of immobilization methods, one-step or two-step addition of the two ligands to the GNP solution, crucially affects the degree of segregation. The two-step addition of a hydrophilic ligand (E6C3) followed by a hydrophobic ligand (C4-E6C11) produced a large degree of segregation on the GNPs, providing Janus-like GNPs. When dispersed in water, these Janus-like GNPs formed assemblies of ∼160 nm in diameter, whereas Domain GNPs, in which the two ligands formed partial domains on the surface, were precipitated even when the molar ratio of the hydrophilic ligand and the hydrophobic ligand on the surface of the NPs was almost 1:1. The assembled structure of the Janus-like GNPs in water was directly observed by pulsed coherent X-ray solution scattering using an X-ray free-electron laser, revealing irregular spherical structures with uneven surfaces.

Functionalization of platinum nanoparticles with L-proline: simultaneous enhancements of catalytic activity and selectivity.

In this work we present the successful application of functionalizing Pt nanoparticles (NPs) with hydrophilic organic ligands as a strategy for enhancing their catalytic activity and selectivity. In the first step, Pt NPs were prepared by a colloidal approach and subsequently functionalized in a separate synthesis step with L-proline (PRO). The functionalized NPs were supported onto Al2O3 and investigated as heterogeneous catalysts for the selective hydrogenation of acetophenone. Whereas significant amounts of side products are formed by supported, "unprotected" (ligand-free) NPs, the PRO-functionalized Pt NPs are highly chemoselective even at 100% conversion. Experiments under kinetically controlled conditions reveal that this high chemoselectivity is not accompanied by a loss of catalytic activity. In contrast, an enhanced rate toward the desired product was found for PRO-Pt in comparison to the "unprotected" Pt NPs. This finding demonstrates that the use of ligands in heterogeneous catalysis allows for simultaneous enhancements of activity and selectivity.

Monitoring pattern formation in drying and wetting dispersions of gold nanoparticles by ESEM.

We report an investigation of the self-assembly of patterns from functionalized gold nanoparticles (GNPs) by monitoring the process in situ by environmental scanning electron microscopy (ESEM) during both evaporation and condensation of the dispersant. As this method limits the choice of dispersants to water, GNPs functionalized with hydrophilic thiol ligands, containing poly(ethylene)glycol (PEG) groups, were used on a variety of substrates including pre-patterned ones. Particular emphasis was given to early stage deposition of GNPs, as well as redispersion and lift-off upon condensation of water droplets. ESEM presents a unique opportunity of directly imaging such events in situ. It was found that attractive interactions between the substrate and the GNPs are often stronger than expected once the particles have been deposited. The role of nickel perchlorate as a highly water-soluble additive was studied. It was found that entropically driven deposition of particles and decoration of surface features was enhanced in its presence, as expected.

Membrane partitioning of anionic, ligand-coated nanoparticles is accompanied by ligand snorkeling, local disordering, and cholesterol depletion.

Intracellular uptake of nanoparticles (NPs) may induce phase transitions, restructuring, stretching, or even complete disruption of the cell membrane. Therefore, NP cytotoxicity assessment requires a thorough understanding of the mechanisms by which these engineered nanostructures interact with the cell membrane. In this study, extensive Coarse-Grained Molecular Dynamics (MD) simulations are performed to investigate the partitioning of an anionic, ligand-decorated NP in model membranes containing dipalmitoylphosphatidylcholine (DPPC) phospholipids and different concentrations of cholesterol. Spontaneous fusion and translocation of the anionic NP is not observed in any of the 10-µs unbiased MD simulations, indicating that longer timescales may be required for such phenomena to occur. This picture is supported by the free energy analysis, revealing a considerable free energy barrier for NP translocation across the lipid bilayer. 5-µs unbiased MD simulations with the NP inserted in the bilayer core reveal that the hydrophobic and hydrophilic ligands of the NP surface rearrange to form optimal contacts with the lipid bilayer, leading to the so-called snorkeling effect. Inside cholesterol-containing bilayers, the NP induces rearrangement of the structure of the lipid bilayer in its vicinity from the liquid-ordered to the liquid phase spanning a distance almost twice its core radius (8–10 nm). Based on the physical insights obtained in this study, we propose a mechanism of cellular anionic NPpartitioning, which requires structural rearrangements of both the NP and the bilayer, and conclude that the translocation of anionic NPs through cholesterol-rich membranes must be accompanied by formation of cholesterol-lean regions in the proximity of NPs.

Hydrophilic 1,10-phenanthroline derivatives for selective Am(III) stripping into aqueous solutions

The novel and fully combustible hydrophilic 1,10-phenanthroline-2,9-dicarboxamide (1) was synthesized and investigated as Am(III) stripping agent in a simulated advanced hydrometallurgical process, in comparison with two other 1,10-phenanthroline-based ligands 2 and 3. The stripping efficiency and the Am(III)/lanthanides(III) selectivity of the TODGA (org)/phen-derivative (aq) extracting system were studied under several experimental conditions by liquid–liquid extraction tests. The results obtained clarify the main limitations of these ligands in the scope of the hydrometallurgical reprocessing but also enable to get indications to steer future investigations in the domain of the selective An(III) recovery for the advanced reprocessing of Spent Nuclear Fuel by hydrophilic ligands.

Self-assembly of nanoparticle amphiphiles with adaptive surface chemistry.

We investigate the self-assembly of amphiphilic nanoparticles (NPs) functionalized with mixed monolayers of hydrophobic and hydrophilic ligands in water. Unlike typical amphiphilic particles with "fixed" surface chemistries, the ligands used here are not bound irreversibly but can rearrange dynamically on the particles' surface during their assembly from solution. Depending on the assembly conditions, these adaptive amphiphiles form compact micellar clusters or extended chain-like assemblies in aqueous solution. By controlling the amount of hydrophobic ligands on the particles' surface, the average number of nearest neighbors--that is, the preferred coordination number--can be varied systematically from ∼ 1 (dimers) to ∼ 2 (linear chains) to ∼ 3 (extended clusters). To explain these experimental findings, we present an assembly mechanism in which hydrophobic ligands organize dynamically to form discrete patches between proximal NPs to minimize contact with their aqueous surroundings. Monte Carlo simulations incorporating these adaptive hydrophobic interactions reproduce the three-dimensional assemblies observed in experiment. These results suggest a general strategy based on reconfigurable "sticky" patches that may allow for tunable control over particle coordination number within self-assembled structures.

Carboxylic acid effects on the size and catalytic activity of magnetite nanoparticles

Magnetite nanoparticles (Fe3O4-NPs) were successfully synthesized in diethylene glycol in the presence of carboxylic acids. They were characterized using XRD, SEM and FTIR. Carboxylic acid plays a critical role in determining the morphology, particle size and size distribution of the resulting particles. The results show that as-prepared magnetite nanoparticles are monodisperse and highly crystalline. The nanoparticles can be easily dispersed in aqueous media and other polar solvents due to coated by a layer of hydrophilic polyol and carboxylic acid ligands in situ. Easily prepared Fe3O4-NPs have been shown to be an active, recyclable, and highly selective catalyst for the epoxidation of cyclic olefins with aqueous 30% H2O2.

A New Family of Pyridine-Appended Multidentate Polymers As Hydrophilic Surface Ligands for Preparing Stable Biocompatible Quantum Dots

The growing utility of semiconductor quantum dots (QDs) in biochemical and cellular research necessitates, in turn, continuous development of surface functionalizing ligands to optimize their performance for ever more challenging and diverse biological applications. Here, we describe a new class of multifunctional polymeric ligands as a stable, compact and high affinity alternative to multidentate thiolated molecules. The polymeric ligands are designed with a poly(acrylic acid) backbone where pyridines are used as anchoring groups that are not sensitive to degradation by air and light, along with short poly(ethylene glycol) (PEG) pendant groups which are coincorporated for aqueous solubility, biocompatibility and colloidal stability. The percentages of each of the latter functional groups are controlled during initial synthesis along with incorporation of carboxyl groups which serve as chemical handles for subsequent covalent modification of the QD surface. A detailed physicochemical characterization indi...

Quantitative Measurement of Ligand Exchange on Iron Oxides via Radiolabeled Oleic Acid

Ligand exchange of hydrophilic molecules on the surface of hydrophobic iron oxide nanoparticles produced via thermal decomposition of chelated iron precursors is a common method for producing aqueous suspensions of particles for biomedical applications. Despite the wide use, relatively little is understood about the efficiency of ligand exchange on the surface of iron oxide nanoparticles and how much of the hydrophobic ligand is removed. To address this issue, we utilized a radiotracer technique to track the exchange of a radiolabeled (14)C-oleic acid ligand with hydrophilic ligands on the surface of magnetite nanoparticles. Iron oxide nanoparticles functionalized with (14)C-oleic acid were modified with poly(ethylene glycol) with terminal functional groups including, L-3,4-dihydroxyphenylalanine, a nitrated L-3,4-dihydroxyphenylalanine, carboxylic acid, a phosphonate, and an amine. Following ligand exchange, the nanoparticles and byproducts were analyzed using liquid scintillation counting and inductively coupled plasma mass spectroscopy. The labeled and unlabeled particles were further characterized by transmission electron microscopy and dynamic light scattering to determine particle size, hydrodynamic diameter, and zeta potential. The unlabeled particles were characterized via thermogravimetric analysis and vibrating sample magnetometry. Radioanalytical determination of the (14)C from (14)C-oleic acid was used to calculate the amount of oleic acid remaining on the surface of the particles after purification and ligand exchange. There was a significant loss of oleic acid on the surface of the particles after ligand exchange with amounts varying for the different functional binding groups on the poly(ethylene glycol). Nonetheless, all samples demonstrated some residual oleic acid associated with the particles. Quantification of the oleic acid remaining after ligand exchange reveals a binding hierarchy in which catechol derived anchor groups displace oleic acid on the surface of the nanoparticles better than the phosphonate, followed by the amine and carboxylic acid groups. Furthermore, the results show that these ligand exchange reactions do not necessarily occur to completion as is often assumed, thus leaving a residual amount of oleic acid on the surface of the particles. A thorough analysis of ligand exchange is required to develop nanoparticles that are suitable for their desired application.

Separation of Am and Cm by using TODGA and DOODA(C8) adsorbents with hydrophilic ligand-nitric acid solution

Extraction chromatographic separation of trivalent minor actinides (MA: Am and Cm) was investigated by using solid adsorbents impregnating the lipophilic diamide-type ligands, TODGA (N,N,N′,N′-tetraoctyl-3-oxapentane-1,5-diamide) and DOODA(C8) (N,N,N′,N′-tetraoctyl-3,6-dioxaoctane-1,8-diamide). In nitric acid eluents, hydrophilic diamide-type ligands, DOODA(C2) (N,N,N′,N′-tetraethyl-3,6-dioxaoctanediamide) and TEDGA (N,N,N’,N’-tetraethyl-diglycolamide) were included for the respective adsorbents as masking agents in order to produce a synergistic effect in mutual separation of Am and Cm. The adsorption tendency of Am and Cm for the adsorbents was opposite each other, that was similar to the case of lanthanides.

Fluorogen-peptide conjugates with tunable aggregation-induced emission characteristics for bioprobe design.

Fluorogens with aggregation-induced emission (AIE) characteristics are attracting intense research interest, and an AIE-peptide conjugate strategy has been reported for developing turn-on probes based on hydrophilic peptide ligands. To build a model also suitable for hydrophobic ligands, we propose to fine-tune the AIE characteristics for probe design. In this work, an iconic AIE fluorogen tetraphenylethene (TPE) was designed to conjugate with peptide fragments containing different numbers of aspartic acid (D) units. Relationships between the numbers of D and the hydrophilicity, optical properties, and aggregate sizes and the AIE characteristics of TPE-peptide conjugates were investigated carefully. Five carboxyl groups were found to be the threshold to "turn off" the fluorescence of TPE. As a proof-of-concept, TPE-SS-D5 containing a cleavable disulfide bond was synthesized for thiol turn-on detection. The validated tunable AIE characteristic offers new opportunities to design fluorescence turn-on probes based on hydrophobic recognition elements and AIE fluorogens.

Nanoparticle tracers in calcium carbonate porous media

Tracers are perhaps the most direct way of diagnosing subsurface fluid flow pathways for ground water decontamination and for natural gas and oil production. Nanoparticle tracers could be particularly effective because they do not diffuse away from the fractures or channels where flow occurs and thus take much less time to travel between two points. In combination with a chemical tracer they can measure the degree of flow concentration. A prerequisite for tracer applications is that the particles are not retained in the porous media as the result of aggregation or sticking to mineral surfaces. By screening eight nanoparticles (3–100 nm in diameter) for retention when passed through calcium carbonate packed laboratory columns in artificial oil field brine solutions of variable ionic strength we show that the nanoparticles with the least retention are 3 nm in diameter, nearly uncharged, and decorated with highly hydrophilic polymeric ligands. The details of these column experiments and the tri-modal distribution of zeta potential of the calcite sand particles in the brine used in our tests suggests that parts of the calcite surface have positive zeta potential and the retention of negatively charged nanoparticles occurs at these sites. Only neutral nanoparticles are immune to at least some retention.

Arene-ruthenium(II) complexes with hydrophilic P-donor ligands: versatile catalysts in aqueous media.

In the last few years there has been increasing interest in the use of water as a reaction medium for catalysis, and therefore in designing water-soluble transition-metal catalysts. Half-sandwich (η(6)-arene)-ruthenium(ii) complexes are a versatile and well-known family of ruthenium compounds that exhibit a rich catalytic and coordination chemistry. This Perspective article focuses on the catalytic applications in aqueous media of (η(6)-arene)-ruthenium(ii) complexes containing water-soluble phosphines, and related hydrophilic P-donor ligands.

"Click" synthesis of nona-PEG-branched triazole dendrimers and stabilization of gold nanoparticles that efficiently catalyze p-nitrophenol reduction.

Two new water-soluble 1,2,3-triazole-containing nona-PEG-branched dendrimers are obtained with nine intradendritic 1,2,3-triazoles (trz). Addition of HAuCl4 in water to these dendrimers quantitatively leads to the intradendritic formation of AuCl3(trz) moieties subsequent to complete Cl(-) substitution by trz on Au(III), whereas the analogous complexation reaction of AuCl3 with a linear PEG trz ligand forms only an equilibrium between trz-coordinated Au(III) and Au(III) that is not coordinated to trz. Reduction of the dendrimer-Au(III) complexes to Au(0) by NaBH4 then leads to stabilization of gold nanoparticles (AuNPs) in water. The sizes of the AuNPs stabilized by the dendritic macromolecules are further controlled between 1.8 and 12 nm upon selecting the stoichiometry of Au(III) addition per dendritic trz followed by NaBH4 reduction. With a 1:1 Au/trz stoichiometry, the AuNP size depends on the length of the PEG tether of the dendrimer; small dendrimer-encapsulated AuNPs are formed with PEG2000, whereas large AuNPs are formed with PEG550. With Au/trz stoichiometries larger than unity, Au(III) is reduced outside the macromolecule, resulting in the formation of large interdendritically stabilized AuNPs. The formation of very small and only mildly stabilized AuNPs by neutral hydrophilic triazole ligands offers an opportunity for very efficient p-nitrophenol reduction by NaBH4 in water at the AuNP surface.

Amphiphilic polyvinyl alcohol adsorbent for the removal of low-density lipoprotein

Spacer can effectively reduce the steric hindrance and synergistic effect of the hydrophilic and hydrophobic ligands immobilized in adsorbents can improve the specific adsorption for low-density lipoprotein (LDL). In this paper, in order to improve the adsorption capacity for the Low-density lipoprotein-cholesterol (LDL-C), specifically, amphiphilic adsorbent based on polyvinyl alcohol (PVA) containing cholesterol ligand and sulfonic dextran ligands was synthesized. All kinds of factors affecting the synthesis yield and adsorption properties were studied in detail. Results showed that the amphiphilic PVA adsorbent has higher adsorption capacity for total cholesterol (TC), (LDL-C), triglyceride (TG), and lower adsorption capacity, and percentage for high-density lipoprotein-cholesterol (HDL-C), while the ligand ratio of cholesterol to sulfonic ligands is 1.57:1, the adsorption percentage and adsorption capacity for TC, LDL-C, TG, and HDL-C were 54.4%, 67.6%, 42.5%, 10.4% and 4.02, 3.612, 2.154, 0.168 mg/g, respectively.

Microwave-assisted synthesis of water soluble thiol capped CdSe/ZnS quantum dots and its interaction with sulfonylurea herbicides

A simple and fast procedure for water solubilization of CdSe/ZnS quantum dots (QDs) using microwave irradiation (MW) has been optimized. The CdSe/ZnS QDs were synthesized in organic media and water solubilization was achieved by replacing the initial hydrophobic ligands (TOPO and TOP) with hydrophilic heterobifunctional thiol ligands, such as l-cysteine (l-Cys), 3-mercaptopropionic acid (3-MPA) and cysteamine (CTAM). The use of MW irradiation allowed carrying out the modification of the surface thiol of QDs in a simple and fast way (only 40 s was required). Different optimization studies based on activation-time, irradiation-time, concentration of ligands, pH and lifetime fluorescent properties were carried out in order to obtain the best results for the solubilization of QDs. By the proposed method, the resulting water-soluble QDs exhibit a strong fluorescence emission at about 590nm, with a high and reproducible photostability and acceptable yields. With the aim of contributing to exploiting the advantages of synthetized QDs from an analytical point of view, the different behavior with sulfonylurea herbicides (SUHs) were studied.

“Click” Synthesis of Intrinsically Hydrophilic Dendrons and Dendrimers Containing Metal Binding Moieties at Each Branching Unit

A new family of water-soluble triazole dendrimers composed of tri(ethylene glycol) (TrEG) and bis(methylol)propionic acid (bis-MPA) was created through Cu(I)-catalyzed alkyne–azide cycloaddition (CuAAC) between specifically designed complementary building blocks. Dendrimers up to generation three were synthesized by CuAAC to a trifunctional core with yields ranging from 72% for generation one, through 67% for generation two, and 64% for third generation dendrimer. The two triazole rings at each bis-MPA branching site could serve as efficient chelating pockets for some VIIIA group elements. As proof-of-principle, the [PdCl2(PhCN)2] coordination chemistry of these hydrophilic dendritic ligands was studied by 1H NMR, dynamic light scattering, transmission electron microscopy, and DFT calculations. The results showed that the complexation is completed within 5 min. The novel hydrophilic dendritic Pd complexes were able to catalyze Suzuki–Miyaura coupling reactions in water within 3 h at 100 °C, at 60 °C, and even at 50 °C with practically quantitative conversion.

Clickable, Hydrophilic Ligand forfac-[MI(CO)3]+(M = Re/99mTc) Applied in anS-Functionalized α-MSH Peptide

The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[MI(CO)3]+ (M = Re/99mTc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[99mTcI(CO)3]+ complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[ReI(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[99mTcI(OH2)3(CO)3]+. The corresponding 99mTc complex (4a) was obtained in high radiochemical yields, was stable in vitro for 24 h during amino acid challenge and serum stability assays, and showed increased hydrophilicity by log P analysis compared to an analogous complex with nonfunctionalized pyridine rings (2a). An α-MSH peptide functionalized with an azide was labeled with fac-[MI(CO)3]+ using both click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation) and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the peptide) strategies to assess the effects of CuAAC conditions on fac-[MI(CO)3]+ complexation within a peptide framework. The peptides from the click, then chelate strategy had different HPLC tR’s and in vitro stabilities compared to those from the chelate, then click strategy, suggesting nonspecific coordination of fac-[MI(CO)3]+ using this synthetic route. The fac-[MI(CO)3]+-complexed peptides from the chelate, then click strategy showed >90% stability during in vitro challenge conditions for 6 h, demonstrated high affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses, and led to moderately high uptake in B16F10 melanoma cells. Log P analysis of the 99mTc-labeled peptides confirmed the enhanced hydrophilicity of the peptide bearing the novel, carboxylate-functionalized DPA chelate (10a′) compared to the peptide with the unmodified DPA chelate (9a′). In vivo biodistribution analysis of 9a′ and 10a′ showed moderate tumor uptake in a B16F10 melanoma xenograft mouse model with enhanced renal uptake and surprising intestinal uptake for 10a′ compared to predominantly hepatic accumulation for 9a′. These results, coupled with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be incorporated into numerous biomolecules containing azides for generating targeted fac-[MI(CO)3]+ complexes in future studies.