Two-step Ligand Exchange Research Articles

Testing a Nanoparticle Reagent for Imaging Mass Cytometry.

Mass cytometry (MC), a powerful single-cell analysis technique, has limitations in detecting low-abundance biomarkers. Nanoparticle (NP) reagents offer the potential for enhancing sensitivity by carrying large numbers of heavy metal isotopes. Here, we report NP reporters for imaging mass cytometry (IMC) based on NaYF4:Yb3+/Er3+ NPs. A two-step ligand exchange was used to coat NP surfaces with either methoxy-PEG2K-neridronate (PEG-Ner) and/or poly(sulfobetaine methacrylate)-neridronate (PSBMA-Ner). Both modifications provided long-term colloidal stability in PBS buffer. IMC measurements on tonsil tissue showed that PSBMA-Ner or a 1:1 mixture of PSBMA-Ner + PEG-Ner effectively suppressed nonspecific binding (NSB) at 2 × 1010 NPs/mL, unlike PEG-Ner alone. However, breast cancer tissue samples showed increased NSB at titers above 2 × 1010 NPs/mL. Reduced NSB with mixed PEG-Ner and PSBMA-Ner coatings opens the door for using heterobifunctional PEGs for the development of NP conjugates with bioaffinity agents, enabling more sensitive and specific MC analyses.

Enable strong electrical coupling between the InZnP@PbS collodial quantum dots in films via the two-step ligand exchange method

Colloidal quantum dots (CQDs) are promising materials for building next-generation solution-processed, high-performance, and low-cost optoelectronic devices. The photoelectric properties of the resulting films are not only determined by the intrinsic characteristics of the CQDs but are also significantly affected by the electrical coupling between them. However, enhancing the electrical coupling in CQD-based films is still a big challenge. In this work, a two-step ligand exchange strategy has been conducted to solve the above issue, where the InZnP@PbS CQDs have been used as the case. First, the Meerwein salt (Et3OBF4) solution in N, N-dimethylformamide (DMF) has been employed to peel off the native ligands that are strongly capped on the surface of oil-soluble CQDs, resulting in a neat surface. Second, iodide ions are linked to the neat surface of the CQDs to narrow the distance between them and passivate their defects, establishing strong electrical coupling. Transient surface photovoltage (TSPV) and photo-conductance tests confirm that the resulting InZnP@PbS–I CQDs films possess good photoelectric properties and stability. In the fabricated solid-state solar cells, 3.1 % of the photoelectric conversion efficiency (PCE) has been achieved under 1 sun. The current results are outstanding for III-V group CQD-based all solid-state solar cells.

Photothermal Actuation of Thick 3D-Printed Liquid Crystalline Elastomer Nanocomposites.

Liquid crystalline elastomers (LCEs) are stimuli-responsive materials that transduce an input energy into a mechanical response. LCE composites prepared with photothermal agents, such as nanoinclusions, are a means to realize wireless, remote, and local control of deformation with light. Amongst photothermal agents, gold nanorods (AuNRs) are highly efficient converters when the irradiation wavelength matches the longitudinal surface plasmon resonance (LSPR) of the AuNRs. However, AuNR aggregation broadens the LSPR which also reduces photothermal efficiency. Here, the surface chemistry of AuNRs is engineered via a well-controlled two-step ligand exchange with a monofunctional poly(ethylene glycol) (PEG) thiol that greatly improves the dispersion of AuNRs in LCEs. Accordingly, LCE-AuNR nanocomposites with very low PEG-AuNR content (0.01wt%) prepared by 3D printing are shown to be highly efficient photothermal actuators with rapid response (>60%strains-1) upon irradiation with near-infrared (NIR; 808nm) light. Because of the excellent dispersion of PEG-AuNR within the LCE, unabsorbed NIR light transmits through the nanocomposites and can actuate a series of samples. Further, the dispersion also allows for the optical deformation of millimeter-thick 3D printed structures without sacrificing actuation speed. The realization of well-dispersed nanoinclusions to maximize the stimulus-response of LCEs can benefit functional implementation in soft robotics or medical devices.

Clickable Polymer Ligand-Functionalized Iron Oxide Nanocubes: A Promising Nanoplatform for 'Local Hot Spots' Magnetically Triggered Drug Release.

Exploiting the local heat on the surface of magnetic nanoparticles (MNPs) upon exposure to an alternating magnetic field (AMF) to cleave thermal labile bonds represents an interesting approach in the context of remotely triggered drug delivery. Here, taking advantages of a simple and scalable two-step ligand exchange reaction, we have prepared iron oxide nanocubes (IONCs) functionalized with a novel multifunctional polymer ligand having multiple catechol moieties, furfuryl pendants, and polyethylene glycol (PEG) side chains. Catechol groups ensure a strong binding of the polymer ligands to the IONCs surface, while the PEG chains provide good colloidal stability to the polymer-coated IONCs. More importantly, furfuryl pendants on the polymer enable to click the molecules of interest (either maleimide-fluorescein or maleimide-doxorubicin) via a thermal labile Diels-Alder adduct. The resulting IONCs functionalized with a fluorescein/doxorubicin-conjugated polymer ligand exhibit good colloidal stability in buffer saline and serum solution along with outstanding heating performance in aqueous solution or even in viscous media (81% glycerol/water) when exposed to the AMF of clinical use. The release of conjugated bioactive molecules such as fluorescein and doxorubicin could be boosted by applying AMF conditions of clinical use (16 kAm-1 and 110 kHz). It is remarkable that the magnetic hyperthermia-mediated release of the dye/drug falls in the concentration range 1.0-5.0 μM at an IONCs dose as low as 0.5 gFe/L and at no macroscopical temperature change. This local release effect makes this magnetic nanoplatform a potential tool for drug delivery with remote magnetic hyperthermia actuation and with a dose-independent action of MNPs.

Fe3O4@Au@Cu2−xS Heterostructures Designed for Tri‐Modal Therapy: Photo‐ Magnetic Hyperthermia and 64Cu Radio‐Insertion

Here, the synthesis and proof of exploitation of three-material inorganic heterostructures made of iron oxide-gold-copper sulfide (Fe3 O4 @Au@Cu2- x S) are reported. Starting with Fe3 O4 -Au dumbbell heterostructure as seeds, a third Cu2- x S domain is selectively grown on the Au domain. The as-synthesized trimers are transferred to water by a two-step ligand exchange procedure exploiting thiol-polyethylene glycol to coordinate Au and Cu2- x S surfaces and polycatechol-polyethylene glycol to bind the Fe3 O4 surface. The saline stable trimers possess multi-functional properties: the Fe3 O4 domain, of appropriate size and crystallinity, guarantees optimal heating losses in magnetic hyperthermia (MHT) under magnetic field conditions of clinical use. These trimers have indeed record values of specific adsorption rate among the inorganic-heterostructures so far reported. The presence of Au and Cu2- x S domains ensures a large adsorption which falls in the first near-infrared (NIR) biological window and is here exploited, under laser excitation at 808nm, to produce photo-thermal heat alone or in combination with MHT obtained from the Fe3 O4 domain. Finally, an intercalation protocol with radioactive 64 Cu ions is developed on the Cu2- x S domain, reaching high radiochemical yield and specific activity making the Fe3 O4 @Au@Cu2- x S trimers suitable as carriers for 64 Cu in internal radiotherapy (iRT) and traceable by positron emission tomography (PET).

Supersensitive photon upconversion based immunoassay for detection of cardiac troponin I in human plasma

Background and aimsUpconverting nanoparticles (UCNPs) are attractive reporters for immunoassays due to their excellent detectability. Assays sensitive enough to measure baseline level of cardiac troponin I cTnI in healthy population could be used to identify patients at risk for cardiovascular disease. Aiming for a cTnI assay of such sensitivity, the surface chemistry of the nanoparticles as well as the assay reagents and the protocol were optimized for monodispersity of the UCNP antibody conjugates (Mab UCNPs) and to minimize their non-specific interactions with the solid support. Materials and methodsUCNPs were coated with poly(acrylic acid) via two-step ligand exchange and conjugated with monoclonal antibodies. The conjugates were applied in a microplate-based sandwich immunoassay using a combination of two capture antibodies to detect cTnI. Assay was evaluated according to guidelines of Clinical & Laboratory Standards Institute. ResultsThe limit of detection and limit of blank of the assay were 0.13 ng/L and 0.01 ng/L cTnI, respectively. The recoveries were >90% in spiked plasma in the linear range. The within- and between-run imprecisions were <10%. ConclusionThe results demonstrate that UCNPs enable quantification of cTnI concentrations expected in plasma of healthy individuals and could be used to identify patients at risk for cardiovascular disease.

One more step to fast and efficient short-wavelength infrared photodetection

Ligand exchanges play a crucial role in development of high-quality colloidal quantum dot (CQD) solids for fast and sensitive short-wavelength infrared photodetection. Sargent et al. report a two-step ligand exchange route to tailor efficient passivation, remove unwanted organics, and enhance charge transport, leading to a CQD photodetector with an EQE > 80% at 1550 nm, a measured detectivity of 8 × 10¹¹ Jones, and a 10-ns response time.

Effect of Zwitterionic Surfactant Ligand Monolayer on Magnetic Hyperthermia Properties of Monosize Fe3O4 Nanoparticles

Here Brown relaxation time was altered to enhance magnetic hyperthermia value. Narrow size distributed, hydrophobic Fe3O4 nanoparticles were synthesized by solvothermal reflux method. It is reported that the existing both single step and two-step ligand exchange protocols could not replace hydrophobic surfactant ligand completely. Hence, as-synthesized samples were transferred into hydrophilic by completely removing the hydrophobic surfactant on the nanoparticles by high polar ionic liquids and ligated short-chain bidentate zwitterionic dopamine sulfonate on nanoparticles surface. The short molecules will fast up the Brown relaxation time compared to long molecule surfactant such as polyethylene glycol (PEG). The resultant sample shows magnetic hyperthermia value of 558 Js− 1g− 1 of Fe content at 316 kHz and 35.33 kA/m, at 2 mg/mL. The obtained hyperthermia is very high compared to long-chain PEG ligated Fe3O4 nanoparticles. It is attributed to relaxation time difference of long-chain PEG ligated Fe3O4 and short molecule zwitterion surfactant stabilized Fe3O4. Present hyperthermia results are the first report on zwitterionic dopamine sulfonate anchored Fe3O4 superparamagnetic nanoparticles.

Lead Sulfide Quantum Dot Photodetector with Enhanced Responsivity through a Two-Step Ligand-Exchange Method

Recently, lead sulfide (PbS) quantum dots (QDs) have demonstrated great potential in becoming one of the most promising next-generation photoelectrical materials for photodetectors. PbS QDs provide fascinating properties including size-controllable spectral sensitivity, a wide and tunable absorption range, cost-efficient solution processability, and flexible substrate compatibility. One of the key problems that limit the performance of PbS QDs-based photodetectors is inefficient carrier transfer. Long ligands decorating the outside surface of PbS QDs to protect them against degeneration inhibit the transfer of electrical charge carriers and thereby limit the device performance. To overcome this problem, the long ligands need to be effectively exchanged. Here, a two-step ligand-exchange method is demonstrated. The QDs are pretreated using methylammonium iodide in solution as the first step ligand exchange before the layer-by-layer deposition process and solid-state ligand exchange. The grazing-incidence small-angle X-ray scattering and X-ray photoelectron spectroscopy analyses prove a smaller spacing among the QDs and an increased ligand-exchange ratio by adopting the two-step method. This strongly indicates a better capability of charge transfer than the traditional one-step solid-state ligand-exchange technology. Devices fabricated using the two-step method present an enhancement of the charge-transfer capability with a larger current. The efficient charge transfer is further demonstrated by a significant 94% increase of the responsivity and a 57% enhancement of the detectivity of the PbS QDs-based photodetector, reaching 3302 mA/W and 5.06 × 1012 J, respectively.

Reversible end-to-end assembly of selectively functionalized gold nanorods by light-responsive arylazopyrazole-cyclodextrin interaction.

We propose a two-step ligand exchange for the selective end-functionalization of gold nanorods (AuNR) by thiolated cyclodextrin (CD) host molecules. As a result of the complete removal of the precursor capping agent cetyltrimethylammonium bromide (CTAB) by a tetraethylene glycol derivative, competitive binding to the host cavity was prevented, and reversible, light-responsive assembly and disassembly of the AuNR could be induced by host–guest interaction of CD on the nanorods and a photoswitchable arylazopyrazole cross-linker in aqueous solution. The end-to-end assembly of AuNR could be effectively controlled by irradiation with UV and visible light, respectively, over four cycles. By the introduction of AAP, previous disassembly limitations based on the photostationary states of azobenzenes could be solved. The combination photoresponsive interaction and selectively end-functionalized nanoparticles shows significant potential in the reversible self-assembly of inorganic–organic hybrid nanomaterials.

The influence of selected ω-mercaptocarboxylate ligands on physicochemical properties and biological activity of Cd-free, zinc‑copper‑indium sulfide colloidal nanocrystals

In this work core/shell cadmium-free zinc‑copper‑indium sulfide ZnCuInS/ZnS quantum dots (QDs) originally stabilized with hydrophilic alkanethiol were modified with 3-mercaptopropionic acid (MPA) or 6-mercaptohexanoic acid (MHA) via two-step ligand exchange method. The obtained QDs were further characterized by TEM, UV Vis, and fluorescence spectroscopy. Both types of QDs were non-toxic in a wide range of concentrations. To our knowledge, our studies are the first attempt to determine the type of cell death and reactive oxygen species production level as a result of incubation of cell cultures with ZnCuInS/ZnS QDs. Furthermore, the accumulation of QDs in vitro was examined on three human cell lines by fluorescence intensity measurements and visualized by confocal microscopy. The modification of QDs with a ligand characterized by slightly longer aliphatic chain (MHA), instead of typically used MPA turns out to be beneficial both from the point of colloidal stability, preservation of optical properties during ligand exchange as well as reflects in a higher cellular uptake. This contribution can be beneficial from the point of view of the selection of the optimal ligands and concentrations in the case of ZnCuInS/ZnS core-shell QDs for biological applications.

Controlled Exchange of Achiral Linkers with Chiral Linkers in Zr-Based UiO-68 Metal-Organic Framework.

The development of highly robust heterogeneous catalysts for broad asymmetric reactions has always been a subject of interest, but it remains a synthetic challenge. Here we demonstrated that highly stable metal-organic frameworks (MOFs) with potentially acid-labile chiral catalysts can be synthesized via postsynthetic exchange. Through a one- or two-step ligand exchange, a series of asymmetric metallosalen catalysts with the same or different metal centers are incorporated into a Zr-based UiO-68 MOF to form single- and mixed-M(salen) linker crystals, which cannot be accomplished by direct solvothermal synthesis. The resulting MOFs have been characterized by a variety of techniques including single-crystal X-ray diffraction,N2 sorption, CD, and SEM/TEM-EDS mapping. The single-M(salen) linker MOFs are active and efficient catalysts for asymmetric cyanosilylation of aldehydes, ring-opening of epoxides, oxidative kinetic resolution of secondary alcohols, and aminolysis of stilbene oxide, and the mixed-M(salen) linker variants are active for sequential asymmetric alkene epoxidation/epoxide ring-opening reactions. The chiral MOF catalysts are highly enantioselective and completely heterogeneous and recyclable, making them attractive catalysts for eco-friendly synthesis of fine chemicals. This work not only advances UiO-type MOFs as a new platform for heterogeneous asymmetric catalysis in a variety of syntheses but also provides an attractive strategy for designing robust and versatile heterogeneous catalysts.

Mechanism of Cp2ZrCl2-Catalyzed Olefin Cycloalumination with AlEt3: Quantum Chemical Approach

A mechanism of α-olefin cycloalumination by AlEt3 in the presence of Cp2ZrCl2 catalyst was proposed, based on theoretical estimation of the thermodynamic and activation parameters of the possible reaction pathways calculated at the DFT level using the PBE/3ζ and M06-2X/cc-pVDZ quantum chemical methods. The reaction steps to bimetallic Zr,Al- and Zr,Zr-complexes, [Cp2Zr(μ-Cl)CH2CH2AlEt2], [Cp2Zr(μ-H)CH2CH2AlEt2], and [Cp2Zr(Cl)CH2CH2Zr(Cl)Cp2], observable on the NMR time scale were considered. Among the possible intermediates, zirconacyclopropane was proposed as the catalyst species most active toward the alkenes, whose formation goes via two-step ligand exchange between Cp2ZrCl2 and AlEt3, and subsequent ethane elimination from the Cp2ZrEt2. The reaction of zirconacyclopropane with the alkene gives the zirconacyclopentane intermediate, in which transmetalation by ClAlEt2 and AlEt3 gives 1-ethyl-3-alkylalumolanes via 2-substituted dialuminobutane.

Stable Graphene-Two-Dimensional Multiphase Perovskite Heterostructure Phototransistors with High Gain.

Recently, two-dimensional (2D) organic-inorganic perovskites emerged as an alternative material for their three-dimensional (3D) counterparts in photovoltaic applications with improved moisture resistance. Here, we report a stable, high-gain phototransistor consisting of a monolayer graphene on hexagonal boron nitride (hBN) covered by a 2D multiphase perovskite heterostructure, which was realized using a newly developed two-step ligand exchange method. In this phototransistor, the multiple phases with varying bandgap in 2D perovskite thin films are aligned for the efficient electron-hole pair separation, leading to a high responsivity of ∼105 A W-1 at 532 nm. Moreover, the designed phase alignment method aggregates more hydrophobic butylammonium cations close to the upper surface of the 2D perovskite thin film, preventing the permeation of moisture and enhancing the device stability dramatically. In addition, faster photoresponse and smaller 1/f noise observed in the 2D perovskite phototransistors indicate a smaller density of deep hole traps in the 2D perovskite thin film compared with their 3D counterparts. These desirable properties not only improve the performance of the phototransistor, but also provide a new direction for the future enhancement of the efficiency of 2D perovskite photovoltaics.

Broadband dye-sensitized upconverting nanocrystals enabled near-infrared planar perovskite solar cells

Extending the spectral absorption of perovskite solar cells (PSCs) from visible into near-infrared (NIR) range is a promising strategy to minimize non-absorption loss of solar photons and enhance the cell photovoltaic performance. Herein, we report on for the first time a viable strategy of incorporating IR806 dye-sensitized upconversion nanocrystals (IR806-UCNCs) into planar PSC for broadband upconversion of NIR light (800–1000 nm) into perovskite absorber-responsive visible emissions. A smart trick is firstly adopted to prepare hydrophilic IR806-UCNCs via a NOBF4 assisted two-step ligand-exchange that allows incorporating with perovskite precursor for in-situ growth of upconverting planar perovskite film. Unlike typically reported upconverting nanoparticles with narrow NIR absorption, the as-prepared IR806-UCNCs are able to harvest NIR light broadly and then transfer the captured energy to the UCNCs for an efficient visible upconversion. The IR806-UCNCs-incorporated cell exhibits a power conversion efficiency of 17.49%, corresponding to 29% increment from that of the pristine cell (13.52%). This strategy provides a feasible way to enable the most efficient harvesting of NIR sunlight for solar cells and other optoelectric devices.

Effects of surface modification of upconversion nanoparticles on cellular uptake and cytotoxicity

Lanthanide-doped upconversion nanoparticles(UCNPs) are great promising to apply to biomedical imaging and therapy. We prepared NaYF4:Yb3+,Er3+ nanoparticles with different surface ligands, i.e., without any ligands(bare), coordinated with 2-aminoethyl dihydrogen phosphate(AEP), polyacrylic acid(PAA) or polyallylamine (PAAm), via a simple two-step ligand exchange of oleic acid capped NaYF4:Yb3+,Er3+ nanoparticles. Although the surface modification retained the crystal structure and transimission electron microscope(TEM) size distribution of the nanoparticles, and good dispersibility in aqueous solution and did not significantly change the upconversion luminescence, distinct differences were observed in the surface charge and hydrodynamic diameter. The cellular uptake and cytotoxicity of the nanoparticles were studied on two different cell lines, breast cancer MCF-7 and fibroblast 3T3. Confocal microscopy images demonstrate that PAAm-coordinated UCNPs can enhance the cellular uptake and endocytosis, whereas AEP- and PAA-coordinated UCNPs show a very low level of nonspecific adsorption. Biocompatibility studies based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, however, indicate that PAAm-coordinated UCNPs are more toxic than the other two, and thus need further modifiaction(like PEG coordinating) to improve their biocompatibility. These results are important to the knowledge base required for the biomedical application of the UCNPs.

Functional PEG-PAMAM-tetraphosphonate capped NaLnF₄ nanoparticles and their colloidal stability in phosphate buffer.

Developing surface coatings for NaLnF4 nanoparticles (NPs) that provide long-term stability in solutions containing competitive ions such as phosphate remains challenging. An amine-functional polyamidoamine tetraphosphonate (NH2-PAMAM-4P) as a multidentate ligand for these NPs has been synthesized and characterized as a ligand for the surface of NaGdF4 and NaTbF4 nanoparticles. A two-step ligand exchange protocol was developed for introduction of the NH2-PAMAM-4P ligand on oleate-capped NaLnF4 NPs. The NPs were first treated with methoxy-poly(ethylene glycol)-monophosphoric acid (Mn = 750) in tetrahydrofuran. The mPEG750-OPO3-capped NPs were stable colloidal solutions in water, where they could be ligand-exchanged with NH2-PAMAM-4P. The surface amine groups on the NPs were available for derivatization to attach methoxy-PEG (Mn = 2000) and biotin-terminated PEG (Mn = 2000) chains. The surface coverage of ligands on the NPs was examined by thermal gravimetric analysis, and by a HABA analysis for biotin-containing NPs. Colloidal stability of the NPs was examined by dynamic light scattering. NaGdF4 and NaTbF4 NPs capped with mPEG2000–PAMAM-4P showed colloidal stability in DI water and in phosphate buffer (10 mM, pH 7.4). A direct comparison with NaTbF4 NPs capped with a mPEG2000-lysine-based tetradentate ligand that we reported previously (Langmuir2012, 28, 12861−1287022906305) showed that both ligands provided long-term stability in phosphate buffer, but that the lysine-based ligand provided better stability in phosphate-buffered saline.

Double-sided coordination assembly: superparamagnetic composite microspheres with layer-by-layer structure for protein separation

Double-sided coordination assembly via a two-step ligand exchange reaction was introduced to synthesize superparamagnetic poly(styrene-co-acrylic acid)/Fe3O4/polyacrylic acid (P(St-AA)/Fe3O4/PAA) composite microspheres for the first time. In the two-step ligand exchange reaction, the coordination interaction of carboxyl groups with the iron replaced the hydrogen bonding between triethylene glycol (TEG) and the Fe3O4 nanoparticles, resulting in the attachment of the Fe3O4 nanoparticles onto the surface of P(St-AA) colloidal template and the coating of monomeric AA onto the surface of Fe3O4 nanoparticles. The obtained P(St-AA)/Fe3O4/PAA composite microspheres showed excellent uniformity, high saturation magnetization, stability and efficient protein separation capacity. The equilibrium adsorption capacity of P(St-AA)/Fe3O4/PAA microspheres for lysozyme was as high as 1800 mg g−1. Functionalized with nitrilotriacetate-Ni2+ (NTA-Ni2+), such composite microspheres could efficiently and selectively capture polyhistidine-tagged glutathione-S-transferase (His-tagged-GST) from cell lysate.

Charge reversible gold nanoparticles for high efficient absorption and desorption of DNA

Mercaptoundecylamine and mercaptoundecanoic acid co-modified Au nanoparticles were prepared by two-step ligand exchange of 6-mercaptohexanoic acid modified gold nanoparticles. Such particles terminated by appropriate ratios of the amine and carboxyl groups (R N/C) were identified to show reversible charge on their surface, which were switchable by pH of the solution. The isoelectric point (IEP) of the particles is tunable by changing the ratios of the amine and carboxyl groups on the particle surfaces. The particles can absorb DNA effectively at pH lower than the IEP driven by the direct electrostatic interactions between DNA and the particle surface. When pH of the solutions was elevated to be higher than the IEP, the absorbed DNA can be released almost completely due to the electrostatic repulsion between the particle surface and DNA. With appropriate R N/C ratios of 0.8, the absorption and desorption efficiencies of DNA were 97 and 98 %, respectively, corresponding an extraction efficiency of 95 %. Such particles with reversible surface charges allow the high efficient extraction of DNA by simply changing pH instead of by changing salt concentration in the conventional salt bridge method.

Synthesis of cationic quantum dots via a two-step ligand exchange process

A new class of quaternary ammonium derivatives has been used to synthesize cationic CdSe/ZnS quantum dots with exceptional stability in water as well as in biological media.