Amphiphilic Ligands Research Articles

Design and Applications of an Efficient Amphiphilic “Click” CuI Catalyst in Water

The copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) using the conventional Sharpless–Fokin catalyst that consists of CuSO4 + Na ascorbate, the most well-known and used “click” reaction, is considerably accelerated by the addition of a tris(triazolyl)-poly(ethylene glycol) (tris-trz-PEG) amphiphilic ligand in water under ambient conditions. Only parts per million amount of CuI were necessary to reach quantitative yields with TONs up to 86000 and TOFs of 3600 h–1. The ligand was fully recycled, and the catalyst was reused at least six times without decomposition. Large-scale syntheses were also successfully achieved with 93% yield. The catalyst was applied to the efficient synthesis of various useful functional products with medicinal, catalytic, targeting, and labeling properties.

Solvent Extraction: Structure of the Liquid–Liquid Interface Containing a Diamide Ligand

AbstractKnowledge of the (supra)molecular structure of an interface that contains amphiphilic ligand molecules is necessary for a full understanding of ion transfer during solvent extraction. Even if molecular dynamics already yield some insight in the molecular configurations in solution, hardly any experimental data giving access to distributions of both extractant molecules and ions at the liquid–liquid interface exist. Here, the combined application of X‐ray and neutron reflectivity measurements represents a key milestone in the deduction of the interfacial structure and potential with respect to two different lipophilic ligands. Indeed, we show for the first time that hard trivalent cations can be repelled or attracted by the extractant‐enriched interface according to the nature of the ligand.

Solvent Extraction: Structure of the Liquid-Liquid Interface Containing a Diamide Ligand.

Knowledge of the (supra)molecular structure of an interface that contains amphiphilic ligand molecules is necessary for a full understanding of ion transfer during solvent extraction. Even if molecular dynamics already yield some insight in the molecular configurations in solution, hardly any experimental data giving access to distributions of both extractant molecules and ions at the liquid-liquid interface exist. Here, the combined application of X-ray and neutron reflectivity measurements represents a key milestone in the deduction of the interfacial structure and potential with respect to two different lipophilic ligands. Indeed, we show for the first time that hard trivalent cations can be repelled or attracted by the extractant-enriched interface according to the nature of the ligand.

ChemInform Abstract: Highly Efficient Transition Metal Nanoparticle Catalysts in Aqueous Solutions.

AbstractA tris(triazolyl)‐polyethylene glycol amphiphilic ligand is designed and successfully used as highly efficient catalyst in combination with various transition metal nanoparticles in click reactions, Suzuki—Miyaura couplings, as well as transfer hydrogenation reactions.

Design of pyridyl-modified amphiphilic polymeric ligands: Towards better passivation of water-soluble colloidal quantum dots for improved optical performance

HypothesisAn effective surface passivation is crucial to obtain quantum dots (QDs) with good photoluminescence response. Whereas the encapsulation of QDs inside amphiphilic polymers provides colloidal stability, a decrease in the quantum yield (QY) is observed. Pyridyl motifs are known to bind strongly to the ZnS on core/shell QD and increase the structure rigidity. Hence, the incorporation of pyridyl groups into the polymer could make it more compact in order to improve the optical behavior of the QDs. ExperimentsPyridyl-modified amphiphilic polymeric ligands were synthesized based on a poly(isobutylene-alt-maleic anhydride) backbone with pyridyl and alkyl end-groups as anchoring groups. The proportion of both ligands was optimized. The resulting QDs were characterized using complementary techniques such as absorption spectroscopy, static and time-resolved photoluminescence spectroscopy, transmission electron microscopy, and dynamic light scattering. FindingsCoating with the designed polymer maintains the high QY of the QDs after being transferred to water and provides them colloidal stability under relevant biological conditions (i.e. wide range of pH and ionic strength, biological buffers and stability over time). The significant improvements of such ligand may be attributed to the synergistic effect of two anchoring groups (pyridyl and alkyl groups) which establish different types of interaction with the QD.

Fragment-based solid-phase assembly of oligonucleotide conjugates with peptide and polyethylene glycol ligands

Ligand conjugation to oligonucleotides is an attractive strategy for enhancing the therapeutic potential of antisense and siRNA agents by inferring properties such as improved cellular uptake or better pharmacokinetic properties. Disulfide linkages enable dissociation of ligands and oligonucleotides in reducing environments found in endosomal compartments after cellular uptake. Solution-phase fragment coupling procedures for producing oligonucleotide conjugates are often tedious, produce moderate yields and reaction byproducts are frequently difficult to remove. We have developed an improved method for solid-phase coupling of ligands to oligonucleotides via disulfides directly after solid-phase synthesis. A 2′-thiol introduced using a modified nucleotide building block was orthogonally deprotected on the controlled pore glass solid support with N-butylphosphine. Oligolysine peptides and a short monodisperse ethylene glycol chain were successfully coupled to the deprotected thiol. Cleavage from the resin and full removal of oligonucleotide protection groups were achieved using methanolic ammonia. After standard desalting, and without further purification, homogenous conjugates were obtained as demonstrated by HPLC, gel electrophoresis, and mass spectrometry. The attachment of both amphiphilic and cationic ligands proves the versatility of the conjugation procedure. An antisense oligonucleotide conjugate with hexalysine showed pronounced gene silencing in a cell culture tumor model in the absence of a transfection reagent and the corresponding ethylene glycol conjugate resulted in down regulation of the target gene to nearly 50% after naked application.

A small molecule nanodrug consisting of amphiphilic targeting ligand–chemotherapy drug conjugate for targeted cancer therapy

Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy.

Synthesis and Characterization of a Novel Series of Amphiphilic Mercapto‐1,2,4‐Triazole Schiff Base Ligands: Investigation of their Behavior in Hydro‐Organic Solutions

AbstractA novel series of four Schiff base amphiphiles derived from 3‐mercapto‐1,2,4‐triazole and different alkyl chains were successfully prepared by a new synthetic three‐step method. The chemical structures of the different ligands were characterized by elemental analysis, FT‐IR spectroscopy, 1H‐NMR and 13C‐NMR spectra. The effect of the chain length on the solution behavior of the amphiphilic ligands were studied, in both homogeneous and heterogeneous systems, using pH‐metric and spectrophotometric methods. Based on the electronic spectroscopy data, some parameters governing their surfactant properties, such as the critical micelle concentration (CMC), the micellization free energy (ΔGmic) and the hydrophilic‐lipophilic balance (HLB) were evaluated in chloroform and discussed. The behavior of the four Schiff bases in the heterogeneous chloroform‐water mixture was then explored through the establishment of their acidity (pKA) and distribution (Log Kd) constants in 1 M chloride medium and the acidity constants in aqueous medium (pKa) were deduced. Results showed that an increase of the alkyl chain decreases the distribution of the ligands and increases their acidity. The extractive performance of the Schiff base amphiphiles were investigated towards Ni(II) from a chloride medium at 30 °C. The analysis of extraction data revealed that the synthesized Schiff bases exhibit a better and faster extractability than many ligands reported in the literature.

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity.

Bioresponsive MRI contrast agents sensitive to Ca(II) fluctuations may play a critical role in the development of functional molecular imaging methods to study brain physiology or abnormalities in muscle contraction. A great challenge in their chemistry is the preparation of probes capable of inducing a strong signal variation that could be detected in a robust way. To this end, the incorporation of small molecular weight bioresponsive agents into nanocarriers can improve the overall properties in a few ways: (i) the agent can be delivered into the tissue of interest, increasing the local concentration; (ii) its biokinetic properties and retention time will improve; (iii) the high molecular weight and size of the nanocarrier may cause additional changes in the MRI signal and raise the chances for their detection in functional experiments. In this work, we report the preparation of the new class of liposome-based, Ca-sensitive MRI agents. We synthesized a novel amphiphilic ligand which was incorporated into the liposome bilayer. A remarkable increase of ∼420% in longitudinal relaxivity r1, from 7.3 mM(-1) s(-1) to 38.1 mM(-1) s(-1) at 25 °C and 21.5 MHz in the absence and presence of Ca(II), respectively, was achieved by the most active liposomal formulation. To the best of our knowledge, this is the highest change in r1 observed for Ca-sensitive agents at physiological pH and can be explained by simultaneous Ca-triggered increase in hydration and reduction of local motion of Gd(III) complex, which can be followed at low magnetic fields.

Highly Efficient Transition Metal Nanoparticle Catalysts in Aqueous Solutions

AbstractA ligand design is proposed for transition metal nanoparticle (TMNP) catalysts in aqueous solution. Thus, a tris(triazolyl)‐polyethylene glycol (tris‐trz‐PEG) amphiphilic ligand, 2, is used for the synthesis of very small TMNPs with Fe, Co, Ni, Cu, Ru, Pd, Ag, Pt, and Au. These TMNP‐2 catalysts were evaluated and compared for the model 4‐nitrophenol reduction, and proved to be extremely efficient. High catalytic efficiencies involving the use of only a few ppm metal of PdNPs, RuNPs, and CuNPs were also exemplified in Suzuki–Miyaura, transfer hydrogenation, and click reactions, respectively.

Highly Efficient Transition Metal Nanoparticle Catalysts in Aqueous Solutions.

A ligand design is proposed for transition metal nanoparticle (TMNP) catalysts in aqueous solution. Thus, a tris(triazolyl)-polyethylene glycol (tris-trz-PEG) amphiphilic ligand, 2, is used for the synthesis of very small TMNPs with Fe, Co, Ni, Cu, Ru, Pd, Ag, Pt, and Au. These TMNP-2 catalysts were evaluated and compared for the model 4-nitrophenol reduction, and proved to be extremely efficient. High catalytic efficiencies involving the use of only a few ppm metal of PdNPs, RuNPs, and CuNPs were also exemplified in Suzuki-Miyaura, transfer hydrogenation, and click reactions, respectively.

Tunable dynamic hydrophobic attachment of guest molecules in amphiphilic core–shell polymers

In this study, synthesis and dynamic properties of amphiphilic core–shell polymers are reported as monitored through their interaction with small amphiphilic ligands. Our findings point to a most complex self-assembling nature of those host and guest molecules.

Preparing a highly dispersed catalyst supported on mesoporous microspheres via the self-assembly of amphiphilic ligands for the recovery of ultrahigh concentration wastewater

Highly dispersed catalysts supported on mesoporous microspheres were prepared and displayed significant recovery properties for ultrahigh concentration wastewater.

A simple approach to the synthesis of eccentric Au@SiO2 Janus nanostructures and their catalytic applications

In this paper, we present a simple method to synthesize eccentric Au@SiO2 Janus nanoparticles. By simply tuning the concentration of poly(vinyl pyrrolidone) (PVP), the surface of gold nanoparticle can be partially or fully wrapped with the amphiphilic ligand. As a result, Janus nanoparticle or concentric core-shell nanostructures can be obtained, respectively. A systematic study has been carried out to confirm the function of PVP molecules. The as-prepared Janus nanoparticle can act as a catalyst to catalyze the reduction of 4-nitrophenol, while the core-shell nanostructure is not active due to the coverage of dense silica shell. This work provides a robust and scalable method to produce Au@SiO2 Janus nanoparticles.

Magnetofluorescent Nanoaggregates Incorporating Terbium(III) Complexes as Potential Bimodal Agents for Magnetic Resonance and Optical Imaging

AbstractTerbium(III) ions were coordinated to two diethylenetriaminepentaacetic acid (DTPA) amphiphilic bisamide ligands, and the complexes were assembled into micellar nanoaggregates. The magnetic and optical properties of the resulting nanoaggregates were examined in detail. Upon excitation into the ligand levels at 265 nm, the complexes show characteristic TbIII emission at 546 nm with quantum yields of up to 7.6 %. Nuclear magnetic relaxation dispersion (NMRD) measurements have shown that the transverse relaxivity r2 at 500 MHz and 310 K reaches a maximum value of 9.4 s–1 mM–1. The efficient T2 relaxivity at high magnetic field strengths is sustained by the increased rotational correlation time of the nanoaggregates and high magnetic moment of the terbium ion.

Fluorescent polymeric aggregates induced by Eu3+ ions and their surface morphologies

A novel method to prepare fluorescent polymeric aggregates via Eu3+-induced self-assembly is described in this research contribution. The amphiphilic polymeric ligand, polystyrene-block-poly(N-vinylpyrrolidone) (PS-b-PNVP) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Eu3+ ions that function as coordination crosslinking agents were added to the reactive solution to induce self-assembly within the PNVP block. Eu3+ ions preferentially coordinate to PNVP segments, yielding coordinatively cross-linked networks with reduced solubility in the solvent. Polystyrene segments retain their solubility in solution due to the amphiphilic character of the block copolymer. Mechanisms for self-assembly and reversible network formation are discussed. Due to the unique optical properties of Eu3+ ions, in-depth analysis of fluorescent data was performed. These aggregates were drip-coated onto the surface of silicon wafers, with subsequent investigation of polymer morphology near the interface with silicon. This represents the initial step in the development of opto-electronic and photovoltaic applications for these self-assembled fluorescent polymeric aggregates.

Chiral surfactant-type catalyst: enantioselective reduction of long-chain aliphatic ketoesters in water.

A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst 2. The CH/π interaction and the strong hydrophobic interaction of long aliphatic chains between the catalyst and the substrate in the metallomicelle core played a key role in the catalytic transition state. Synergistic effects between the metal-catalyzed site and the hydrophobic microenvironment of the core in the micelle contributed to high stereoselectivity.

Magnetofluorescent micellar complexes of terbium(III) as potential bimodal contrast agents for magnetic resonance and optical imaging.

Terbium(III) was coordinated to four novel 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) amphiphilic bisamide ligands. The complexes were assembled into mono-disperse micellar nano-aggregates and for the first time Tb(III) has been evaluated as a single lanthanide negative bimodal contrast agent for MRI/OI. The complexes show characteristic Tb(III) emission with quantum yields reaching 7.3% and transverse relaxivity r2 per Tb(III) micelle at 500 MHz and 310 K reaches maximum values up to 60 s(-1) micelle(-1). The efficient T2 relaxation at high magnetic field strengths is sustained by the increased rotational correlation time of the nano-aggregates and high magnetic moment of the terbium ion.

Surface-promoted aggregation of amphiphilic quadruplex ligands drives their selectivity for alternative DNA structures.

Scientists are currently truly committed to enhance the specificity of chemotherapeutics that target DNA. To this end, sequence-specific drugs have progressively given way to structure-specific therapeutics. However, while numerous strategies have been implemented to design high-affinity candidates, strategies devoted to the design of high-selectivity ligands are still rare. Here we report on such an approach via the study of an amphiphilic compound, TEGPy, that self-assembles at a liquid/solid interface to provide nanosized objects that are stable in water. The resulting aggregates, identified through atomic force microscopy measurements, were found to disassemble upon interaction with DNA in a structure-specific manner (quadruplex- versus duplex-DNA). Our results provide a fertile ground for devising new strategies aiming at concomitantly enhancing DNA structural specificity and the water-solubility of aggregation-prone ligands.

A versatile 'click chemistry' route to size-restricted, robust, and functionalizable hydrophilic nanocrystals.

A versatile addition-crosslinking route is developed to transfer various hydrophobic nanocrystals into water. By assembling amphiphilic ligands and then crosslinking through 'click chemistry', a monolayer of polymer forms on the nanocrystal surface, leading to excellent stability and limited increase in hydrodynamic diameter. These nanocrystals can also be further functionalized easily for various applications such as catalysis, bioimaging, and medical therapy.