Protected Gold Nanoclusters Research Articles

Assembly‐Driven Aggregation‐Induced Emission of Gold Nanoclusters with Excitation Wavelength‐Dependent Emission and Mechanochromic Property

AbstractMetal nanoclusters with aggregation‐induced emission (AIE) characteristics are potential nanomaterial candidates for a wide array of advanced optical applications. In this study, a novel self‐assembly enhanced AIE strategy utilizing 6‐thioguanine (TG)‐protected gold nanoclusters (AuNCs) is fabricated with dual‐stimuli responsive modes of excitation wavelength‐dependent (Ex‐De) emission and mechanochromic properties. The sheetlike structures of AuNCs self‐assembly (AuNC sheets) with typical AIE characteristics are generated in bad solvent owing to the intermolecular hydrogen‐bonds interaction among guanine‐rich moieties of TG ligand. Interestingly, the maximum emission peaks of AuNC sheets are red‐shifted with the increased excitation wavelengths, indicating Ex‐De emission behavior. This phenomenon enables the achievement of wide‐range tunable photoluminescence (PL). In addition, the emission peak of AuNC sheets powders before and after grinding displays the bathochromic shift of 110 nm. The “off–on” switch of Ex‐De emission behavior in AuNC sheets can be manipulated by changing mechanical pressure. It is speculated that the tunable PL behavior of AuNC sheets originates from multiple excited states due to the existence of different Au(I)···Au(I) distances. The self‐assembly‐driven AIE strategy of AuNCs with stimuli‐responsive allochroic modes will facilitate the recording of rewritable information, opening up a new avenue for high‐throughput and multi‐dimensional optical security.

Enhancement of nanozyme activity by second ligand modification on glutathione protected gold nanoclusters for regulation of intracellular oxidative stress

Nanozymes, as an alternative to natural enzymes, have received wide interests in recent years. Here, we have separated two main glutathione protected gold nanoclusters (GSH-Au NCs), namely, high fluorescent species with low peroxidase-like activity, and low fluorescent species with high peroxidase-like activity, from NCs prepared using different ratios of precursors. Additionally, the peroxidase-like activity of the latter species can be regulated by surface modification of a second thiolate ligand. As a representative, L-cysteine (L-Cys) modified GSH-Au NCs may exhibit both enhanced peroxidase-like activity (up to 5-fold) and improved fluorescent properties (∼3.3-fold) compared with GSH-Au NCs. The cytotoxicity and reactive oxygen species (ROS) level detection demonstrate that L-Cys modified NCs may cause effective cytotoxicity on breast cancer cells through the selective ROS generation. This study further expands the peroxidase-like kinetics of surface modified Au NCs and provides a new possibility for regulating the level of oxidative stress in cells.

A gold nanocluster/MIL-100(Fe) bimodal nanovector for the therapy of inflammatory disease through attenuation of Toll-like receptor signaling.

A better understanding of the molecular and cellular events involved in the inflammation process has opened novel perspectives in the treatment of inflammatory diseases, particularly through the development of well-designed nanomedicines. Here we describe the design of a novel class of anti-inflammatory nanomedicine (denoted as Au@MIL) synthesized through a one-pot, cost-effective and green approach by coupling a benchmark mesoporous iron(III) carboxylate metal organic framework (MOF) (i.e. MIL-100(Fe)) and glutathionate protected gold nanoclusters (i.e. Au25SG18 NCs). This nano-carrier exhibits low toxicity and excellent colloidal stability combined with the high loading capacity of the glucocorticoid dexamethasone phosphate (DexP) whose pH-dependent delivery was observed. The drug loaded Au@MIL nanocarrier shows high anti-inflammatory activity due to its capacity to specifically hinder inflammatory cell growth, scavenge intracellular reactive oxygen species (ROS) and downregulate pro-inflammatory cytokine secretion. In addition, this formulation has the capacity to inhibit the Toll-like receptor (TLR) signaling cascade namely the nuclear factor kappa B (NF-κB) and the interferon regulatory factor (IRF) pathways. This not only provides a new avenue for the nanotherapy of inflammatory diseases but also enhances our fundamental knowledge of the role of nanoMOF based nanomedicine in the regulation of innate immune signaling.

Highly efficient photo-driven generation and elimination of reactive oxygen species in biological environment by gold nanoclusters

Reactive oxygen species (ROS) play an essential role in cell signalling, pathogen defence, and maintaining cellular homeostasis. The photocatalysts are highly desired in the photo-driven in-situ ROS generation and elimination in biological environment. Here, we present the highly efficient photo-driven generation and elimination of ROS in biological environment by glutathione (GSH)-protected gold nanoclusters (AuNCs). In extracellular environment, AuNCs can generate hydrogen peroxide (H2O2) through a two-electron oxygen reduction reaction (ORR) without any additional sacrifices. On the other hand, in intracellular environment, AuNCs are capable of eliminating the ROS in cells under visible light. For the photocatalyst of GSH protected AuNCs, the photogenerated electrons are in response to reduction reactions, and meanwhile photogenerated holes can oxidize the GSH ligands, protecting other biomolecules from oxidation reactions. This work opens a new gate for the concentration manipulation of ROS in the biological environment as well as the real-time regulation of ROS in organisms.

Electrocatalytic regulation of electrochemiluminescence: Mechanisms and sensing strategies

Electrocatalysis (EC) can reduce the overpotential and promote electrochemical reactions, leading to improved energy conversion, and electrochemiluminescence (ECL) is a convenient energy output. However, fundamental understanding of the relationship between EC and ECL performance has been very limited, hindering rational improvement and effective applications. Herein, as a proof of concept, we developed a model system composed of multi-walled carbon nanotubes (MWCNTs) as a catalyst, 6-aza-2-thiothymine protected gold nanoclusters (ATT-AuNCs) as luminophore, and tripropylamine (TPA) as coreactant, to evaluate the electrocatalytic effect on ECL by kinetic analysis of electrocatalytic reactions. A dual EC-mediated ECL enhancement was demonstrated in this system. The catalytically active sites were identified to be the carboxyl groups in the MWCNTs. We also discovered that EC could be tuned by other factors, such as wettability. Our findings were supported by density functional theory and molecular dynamics calculations as well. After understanding the EC mechanism, EC was then used to rationally regulate ECL for biosensor development for the first time. The detection of arginase with a record low limit of detection of 1.6 × 10−7 U mL−1 was achieved. This work not only enriches ECL regulation strategies, but also paves a new avenue for engineering EC guided ECL and devices.

Calixarene-based supramolecular assembly with fluorescent gold-nanoclusters for highly selective determination of perfluorooctane sulfonic acid

The present study developed an efficient fluorescent approach, based on a supramolecular assembly between gold nanoclusters and calix[4]arene derivatives (C4A-Ds), to detect sever pollutant of perfluorooctane sulfonic acid (PFOS). For that, a series of C4A-Ds with different chain lengths and positive charges at the wider rim were designed and synthesized. Cytidine-5′ phosphate protected gold nanoclusters (AuNCs@CMP) were then assembled with calix[4]arene (LC4AP) to form AuNCs/LC4AP assembly, leading to 8-fold luminescence enhancement via the AIEE effect. However, further binding with PFOS reconstituted the as-formed assembly hrough a competitive effect, generating a fluorescence quenching. Particularly, the linear fluorescence response of AuNCs/LC4AP to PFOS realized a highly sensitive determination of the pollutant PFOS in a wide range (2.0–100 μM). In addition, the developed method successfully detected PFOS in pool water near a fire drill field, being good enough for the practical PFOS determination. The calixarene mediated method, based on the fluorescence “on–off” strategy of metal nanoclusters, is sensitive, rapid-responsive, economical, particularly, suitable for the PFOS determination in practice. It takes full advantage of the molecular recognition and self-assembly of artificial macrocyclic host molecules as a promising strategy for the PFOS determination, and will be highlight to develop new detection methods for PFOS and other poisonous compounds in environments.

The aromatic peptide protected gold nanoclusters with significant Stokes shift: Ligand-mediated two-step FRET

The aromatic peptide protected gold nanoclusters with significant Stokes shift: Ligand-mediated two-step FRET

Fluorescence Evolution of Gold Nanoclusters in the Presence of Shapely Silver Nanoparticles and UV-Vis Light

Gold nanoclusters (Au NCs) belong to a class of materials that is highly fluorescent and biocompatible. Bovine serum albumin (BSA) protected gold nanoclusters (BSA-Au NCs) have been extensively used in biological applications due to their easy synthesis and relatively high quantum yield. Therefore, understanding the behavior of BSA-Au NCs in different chemical and physical environments is essential to enhance their application in biological systems. In this study, we investigated the effect of plasmonic nanostructures with different localized surface plasmon resonance (LSPR) wavelengths on the behavior of BSA-Au NCs by recording time-dependent fluorescence spectra in the presence of silver nanoparticles (AgNPs) with various shapes. However, we did not observe any conclusive LSPR-wavelength-dependent fluorescent behavior. Additionally, the fluorescence intensity of BSA-Au NCs exhibited gradual decay under light excitation, even at several hundred μW/cm2 in a fluorescence spectrometer, indicating that they are not as photostable as previously assumed. We found further that the photostability of BSA-Au NCs is affected by the wavelength of the incident light (370, 420, 480, and 550 nm), which can be accurately described using bi-exponential decay functions. Our study provides an easy in situ method to evaluate the photostability of Au NCs under different-wavelength light irradiation using a commercial fluorescence spectrometer.

Green synthesis of R-phycoerythrin protected gold nanoclusters for sensitive detection of mercury(II) ions and their antibacterial properties

Green synthesis of R-phycoerythrin protected gold nanoclusters for sensitive detection of mercury(II) ions and their antibacterial properties

A novel ratiometric fluorescence probe for the detection of copper (II) and silver(I) based on assembling dye-doped silica core-shell nanoparticles with gold nanoclusters.

Acreatively designed and constructed a multifunctional ratiometric fluorescence probe is reportedby assembling glutathione (GSH)-protected gold nanoclusters (AuNCs) with fluorescein-doped mesoporous silica nanoparticle (FS) for the detection of Cu2+ and Ag+ ions, which could eliminate most interferences by self-calibration. Under the excitation at 450 nm, the fluorescence connected with AuNCs can rapidly respond by quenching or enhancement, respectively, for Cu2+ and Ag+ ions, while the fluorescein isothiocyante (FITC) fluorescence served as reference with negligible change. The fluorescence intensity ratio showed good linear relationships with Cu2+ and Ag+ concentrations in the range 0.5-10 μM and 0.1-8 μM, respectively. The detection limits were as low as 140 nM and 60 nM for Cu2+ and Ag+ ions, respectively. The color change induced by fluorescent intensity ratio variation could also beemployed for visual discrimination. TheAuNC-embedded FS (FS-Au) nanoprobe was successfully used for Cu2+ and Ag+ ion determination in drinking water and intracellular Cu2+ imaging, which exhibits promising prospects in cost-effective and rapid determination of both Cu2+ and Ag+ with good sensitivity and selectivity.

Kinetically Controlled Synthesis of Highly Emissive Au18SG14 Clusters and Their Phase Transfer: Tips and Tricks.

Glutathione (GSH) protected gold nanoclusters (Au n SG m NCs) have been attractive because of their novel properties such as enhanced luminescence and band gap tunability at their quantum confinement region (below ∼2 nm). Initial synthetic routes of mixed-size clusters and size-based separation techniques had latter evolved toward atomically precise nanoclusters via thermodynamic and kinetic control routes. One such exemplary synthesis taking the advantages of a kinetically controlled approach is producing highly red-emissive Au18SG14 NCs (where SG = thiolate of glutathione), thanks to the slow reduction kinetics provided by the mild reducing agent NaBH3CN. Despite the developments in the direct synthesis of Au18SG14, several meticulous reaction conditions still need to be understood for the highly adaptable synthesis of atomically pure NCs irrespective of the laboratory conditions. Herein, we have systematically studied a series of reaction steps involved in this kinetically controlled approach starting from the role of the antisolvent, formation of precursors to Au-SG thiolates, growth of Au-SG thiolates as a function of aging time, and exploring an optimal reaction temperature to optimize the desired nucleation under slow reduction kinetics. The crucial parameters derived in our studies guide the successful and large-scale production of Au18SG14 at any laboratory condition. Next, we investigated the effect of pH on the NCs to study the stability and the best suitable condition for the phase transfer of Au18SG14 clusters. The commonly implemented method of phase transfer at the basic conditions (pH > 9) is not successful in this case. However, we developed a feasible method for the phase transfer by diluting the aqueous NC solution to enhance the negative charges on the NCs' surface by increasing the degree of dissociation at the carboxylic acid group. It is interesting to note that after the phase transfer, the Au18SG14-TOA NCs in toluene as well as in other organic solvents exhibited enhanced luminescence quantum yields from 9 to 3 times and increased average photoluminescence lifetimes by 1.5-2.5 times, respectively.

A Simple Schiff Base as Fluorescent Probe for Detection of Al3+ in Aqueous Media and its Application in Cells Imaging.

A novel fluorescence probe for the detection of Al3+ was developed based on methionine protected gold nanoclusters (Met-AuNCs). A fluorescent Schiff base (an aldimine) is formed between the aldehyde group of salicylaldehyde (SA) and the amino groups of Met on the AuNCs, and developed for selective detection of Al3+ in aqueous solution. Al3+ can strongly bind with the Schiff base ligands, accompanied by the blue-shift and an obvious fluorescence emission enhancement at 455nm. The limits of detection (LODs) of the probe are 2pmol L-1 for Al3+. Moreover, the probe can successfully be used in fluorescence imaging of Al3+ in living cells (SHSY5Y cells), suggesting that the simple fluorescent probe has great potential use in biological imaging.

Hydrophilic Cyclodextrin Derivative Directed Lateral Recombination of 1-D Dipeptide Protected Gold Nanoclusters Assembly for Lysosomal Localization

Hydrophilic Cyclodextrin Derivative Directed Lateral Recombination of 1-D Dipeptide Protected Gold Nanoclusters Assembly for Lysosomal Localization

Atomically precise thiolate‐protected gold nanoclusters: Current status of designability of the structure and physicochemical properties

AbstractThiolate (SR)‐protected gold nanoclusters (Aun(SR)m NCs) are a rare type of material capable of simultaneously exhibiting multiple physicochemical properties well‐suited to specific applications, including photoluminescence, thermocatalysis, electrocatalysis, photocatalysis, magnetism, and optical activity. Over the past several decades, there has been tremendous progress in our understanding of the structure and physicochemical properties of Aun(SR)m NCs, resulting in the ability to fine‐tune the characteristics of these materials. It is therefore helpful to examine the extent to which the properties of Aun(SR)m and related metal NCs can now be adjusted based on design. This review presents representative examples of previous studies concerning the geometry, electronic structure, luminescence properties, catalysis, magnetism and optical activity of Aun(SR)m and related metal NCs and discusses the current status of the designability of these NCs to impart specific structural and physicochemical characteristics. This information is expected to accelerate the fabrication of highly functional materials based on Aun(SR)m and related metal NCs.

Fluorescence dual “turn-on” detection of acid phosphatase via fluorescence resonance energy transfer and dual quenching strategy to improve sensitivity

A fluorescent dual “turn-on” method is utilized to detect acid phosphatase (ACP) via dual quenching and fluorescence resonance energy transfer (FRET) strategy to improve sensitivity for the first time. Bovine serum albumin protected gold nanoclusters (BSA-AuNCs) are utilized as fluorescence probe and peroxidase-mimicking catalyst. BSA-AuNCs oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) to TMB (oxTMB) with the absorbance peak at 652 nm. Fluorescence spectrum of BSA-AuNCs with emission peak at 635 nm is largely overlapped with absorption spectrum of oxTMB, which brings FRET from BSA-AuNCs to oxTMB and fluorescence is quenched. When Ce3+ is added, BSA-AuNCs catalyze the oxidation of Ce3+ to Ce4+ by H2O2. Ce4+ has oxidizing properties, which can oxidize TMB into oxTMB and enhance FRET. It achieves the fluorescence is quenched further more. This dual fluorescence quenching effect brings a low background for ACP detection. ACP catalyzes ascorbic acid 2-phosphate (AA2P) hydrolysis into phosphate ion (PO43−) and ascorbic acid (AA). Owing to high coordination between Ce3+ and PO43−, TMB oxidation is prevented and fluorescent is turned-on. AA reduces oxTMB into TMB, which makes FRET be prevented and fluorescence is also increased. Therefore it is utilized in ACP detection from 0.01 to 2 U/L with high selectivity and accuracy.

Folic acid-modified lysozyme protected gold nanoclusters as an effective anti-inflammatory drug for rapid relief of gout flares in hyperuricemic rats

BackgroundGout normally occurs when excess urate crystals accumulate in the joints that induce inflammation. The inflammations further result in gout flares, causing serious pain. Some anti-inflammatory drugs can relieve pain, but they have various side effects. Nanomedicines can reduce side effects but are mostly based on the delivery of additional organic drugs, which adds complexity and may cause other health problems. We developed folic acid (FA)-modified lysozyme (Lys)-protected gold nanoclusters (AuNCs) (i.e., FLA) by a one-pot method, and successfully used FLA as an effective anti-inflammatory drug for relief of gout flares in hyperuricemic rats. MethodsThe morphological changes of the cells were studied by Transmission electron microscopy (TEM) and fluorescence microscopy. Western blot was conducted to understand the inflammation factors. AutoDock Vina was used for molecular docking of FLA. ResultsFLA reduced the inflammation, oxidative stress level in vitro. By injecting FLA into gout rat models, inflammations, cartilage destructions and pain during gout flares were also significantly relieved. ConclusionCompared with complicated nano-delivery systems, FLA directly exhibits exciting therapeutic efficiency against gout flares, which will have considerable prospects in the clinic.

Development of cytidine 5′-monophosphate-protected gold-nanoclusters to be a direct luminescent substrate via aggregation-induced emission enhancement for ratiometric determination of alkaline phosphatase and inhibitor evaluation

The cytidine 5′-monophosphate (CMP)-protected gold nanoclusters (AuNCs@CMP) was developed to be a fluorescent nanosubstrate for direct ratiometric determination of alkaline phosphatase (ALP). The binding mode investigations revealed that the ligand CMP binds to the gold core via two oxygen atoms of ribose and cytosine and leaves the phosphate group freely outside, promoting AuNCs@CMP to be the direct nanosubstrate of ALP. AuNCs@CMP emits at 570 nm while the hydrolysis product of AuNCs@Cyt emits at 485 nm; the large emission gap between them provided a ratiometric approach for ALP determination. Moreover, a natural and biofunctional oligomer, chitosan oligosaccharide (COS), was introduced to the system, which significantly amplified the fluorescence signals of AuNCs@Cyt and improved the limit of detection (LOD) down to 0.00026 U·L−1. Furthermore, the intrinsic mechanism of AuNCs@CMP hydrolysis by ALP and the COS amplification on AuNCs@Cyt were studied in-depth, which indicated the emission enhancement was attributed to the aggregation-induced emission enhancement (AIEE) property of the produced AuNCs@Cyt. Finally, the developed approach was successfully applied to determine ALP in human serum and the evaluation of ALP inhibitors. Therefore, the present study develops a novel nanosubstrate for ALP determination in a range of 0.0050–0.25 U·L−1 and provides a straightforward way to amplify the fluorescence signal by employing available polymer. The work will stimulate and encourage the structural promotion of metal nanoclusters, and extend their biological applications broadly.

Atomistic Molecular Dynamics Simulation Study on the Interaction between Atomically Precise Thiolate-Protected Gold Nanoclusters and Phospholipid Membranes

The interaction of atomically precise monolayer thiolate (SR) protected gold nanoclusters (Au NCs) with the phospholipid membranes has been studied by the all-atom molecular dynamics (AAMD) simulations. The effect of cluster size, type, and the surface charge density of protection ligand was studied. The simulation results show gold nanoclusters with different size and surface modifications have much different transmembrane behaviors. The Au25(SR)18 cluster was found to possess the best affinity to the phospholipid membranes among six atomically accurate clusters Au25(SR)18, Au36(SR)24, Au44(SR)28, Au68(SR)32, Au144(SR)60, and Au314(SR)96. Using the Au25 NC as a model, this work also found that the aggregation mode of the surface ligands and the surface charge density are the important factors affecting the interaction between the gold nanoclusters and the phospholipid membranes. Moreover, the balance of hydrophilic and hydrophobic ligands on the surface of Au NCs is beneficial to the high permeability.

Comparative Toxicity, Biodistribution and Excretion of Ultra-Small Gold Nanoclusters with Different Emission Wavelengths.

The exponentially increased use of gold nanoclusters in diagnosis and treatment has raised serious concern about their potential threat to living organisms. However, the mechanisms of toxicity of gold nanoclusters in vitro and in vivo remain poorly understood. In this work, comparative toxicity studies, including biodistribution and excretion, were carried out with mildly and chemically synthesized ultra-small L-histidine-protected and bovine serum albumin (BSA)-protected gold nanoclusters in an all-aqueous process. These nanoclusters did not induce a remarkable impact on cell viability, even at relatively high concentrations (100 μg/mL). The haemolytic assay demonstrated that the gold nanoclusters could not destroy blood cell at 600 μg/mL. After intravenous injection with mice, the biocompatibility, biodistribution, and excretion were determined. Quantitative analysis results showed that accumulation varied in the liver, spleen, kidney, and lung, though primarily in the liver and spleen. They were excreted in urine and faeces, but mainly excreted through urine. In our study, no obvious abnormalities were found in body weight, behavioral changes, blood and serum biochemical indicators, and histopathology. These findings suggested that both gold nanoclusters showed similar effects in vivo and were safe and biocompatible, laying the foundation for safe biomedical application in the future.

Correlating structural rules with electronic properties of ligand-protected alloy nanoclusters.

Thiolate protected gold nanoclusters (TPNCs) are a unique class of nanomaterials finding applications in various fields, such as biomedicine, optics, and catalysis. The atomic precision of their structure, characterized through single crystal x-ray diffraction, enables the accurate investigation of their physicochemical properties through electronic structure calculations. Recent experimental efforts have led to the successful heterometal doping of TPNCs, potentially unlocking a large domain of bimetallic TPNCs for targeted applications. However, how TPNC size, bimetallic composition, and location of dopants influence electronic structure is unknown. To this end, we introduce novel structure-property relationships (SPRs) that predict electronic properties such as ionization potential (IP) and electron affinity (EA) of AgAu TPNCs based on physically relevant descriptors. The models are constructed by first generating a hypothetical AgAu TPNC dataset of 368 structures with sizes varying from 36 to 279 metal atoms. Using our dataset calculated with density functional theory (DFT), we employed systematic analyses to unravel size, composition, and, importantly, core-shell effects on TPNC EA and IP behavior. We develop generalized SPRs that are able to predict electronic properties across the AgAu TPNC materials space. The models leverage the same three fundamental descriptors (i.e., size, composition, and core-shell makeup) that do not require DFT calculations and rely only on simple atom counting, opening avenues for high throughput bimetallic TPNC screening for targeted applications. This work is a first step toward finely controlling TPNC electronic properties through heterometal doping using high throughput computational means.