Water-soluble Gold Nanoclusters Research Articles

GraphBNC: Machine Learning-Aided Prediction of Interactions Between Metal Nanoclusters and Blood Proteins.

Hybrid nanostructures between biomolecules and inorganic nanomaterials constitute a largely unexplored field of research, with the potential for novel applications in bioimaging, biosensing, and nanomedicine. Developing such applications relies critically on understanding the dynamical properties of the nano-bio interface. This work introduces and validates a strategy to predict atom-scale interactions between water-soluble gold nanoclusters (AuNCs) and a set of blood proteins (albumin, apolipoprotein, immunoglobulin, and fibrinogen). Graph theory and neural networks are utilized to predict the strengths of interactions in AuNC-protein complexes on a coarse-grained level, which are then optimized in Monte Carlo-based structure search and refined to atomic-scale structures. The training data is based on extensive molecular dynamics (MD) simulations of AuNC-protein complexes, and the validating MD simulations show the robustness of the predictions. This strategy can be generalized to any complexes of inorganic nanostructures and biomolecules provided that one generates enough data about the interactions, and the bioactive parts of the nanostructure can be coarse-grainedrationally.

Enzyme-activatable charge transfer in gold nanoclusters.

Surface-protecting ligands, as a major component of metal nanoclusters (MNCs), can dominate molecular characteristics, performance behaviors, and biological properties of MNCs, which brings diversity and flexibility to the nanoclusters and largely promotes their applications in optics, electricity, magnetism, catalysis, biology, and other fields. We report herein the design of a new kind of water-soluble luminescent gold nanoclusters (AuNCs) for enzyme-activatable charge transfer (CT) based on the ligand engineering of AuNCs with 6-mercaptopurine ribonucleoside (MPR). This elaborately designed cluster, Au5(MPR)2, can form a stable intramolecular CT state after light excitation, and exhibits long-lived color-tunable phosphorescence. After the cleavage by purine nucleoside phosphorylase (PNP), the CT triplet state can be easily directed to a low-lying energy level, leading to a bathochromic shift of the emission band accompanied by weaker and shorter-lived luminescence. Remarkably, these ligand-engineered AuNCs show high affinity towards PNP as well as decent performance for analyzing and visualizing enzyme activity and related drugs. The work of this paper provides a good example for diversifying physicochemical properties and application scenarios of MNCs by rational ligand engineering, which will facilitate future interest and new strategies to precisely engineer solution-based nanocluster materials.

Biomimetic crystallization for long-pursued –COOH-functionalized gold nanocluster with near-infrared phosphorescence

As an interdisciplinary product, water-soluble gold nanoclusters (AuNCs) stabilized by ligands containing carboxyl (–COOH) group have garnered significant attention from synthetic chemists and biologists due to their immense potential for biomedical applications. However, revealing the crystallographic structures of –COOH-functionalized AuNCs remains a bottleneck. Herein, we successfully applied the salting-out method to obtain a series of high-quality single crystals of –COOH-functionalized Au25 nanoclusters and revealed their crystallographic structures. Particularly, K3Au25(2-Hmna)9(mna)6]− (Au25a) protected by 2-mercaptonicotinic acid features an unprecedented tetrameric Au4(SRS)3(SRS,N)2 staple motifs surrounding the icosahedral Au13 kernel, breaking the traditional perception on the structure of Au25(SR)18. Au25a exhibits a distinct near-infrared emission at 970 nm with long lifetime of 8690 ns, which have been studied by transient absorption spectroscopy and time-dependent density functional theory. This work compensates for the research gap in the experimental structure of –COOH-functionalized AuNCs and opens up a new avenue to explore their structure–property correlations.

Atomically Precise Water-Soluble Gold Nanoclusters: Synthesis and Biomedical Application

Atomically precise water-soluble gold nanoclusters (Au NCs) protected by organic ligands have attracted growing attention in serving as unique nanomaterials with the potential to generate theranostic tools (bioimaging, biosensing, and biotherapy), due to their ultrasmall size, superior photoluminescence, good biocompatibility, and nontoxicity. More importantly, Au NCs afford a well-defined atomic packing structure and molecular purity, providing a superior platform to unravel the structure–performance correlations for biodistribution, biological pharmacokinetics, and excretion of Au NCs. In this Review, we mainly survey the synthesis of water-soluble Au NCs and the recent progress in biomedicine of Au NCs, including bioimaging, biosensing, and biotherapy. The effects of ligand and size on the biomedical properties are discussed in detail. We hope that the advances in this research area can expand the applications of Au NCs in biomedicine.

DNA as a template for synthesis of fluorescent gold nanoclusters

Water-soluble blue-emitting gold nanoclusters have been synthesized using dsDNA as a template without any additional reducing agent. The features of the formed nanoclusters have been revealed by fluorescence and electronic absorption spectroscopy as well as transmission electron microscopy. The prepared gold nanoclusters have been highly stable at physiological pH without any further modification.

The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation.

Atomically precise gold nanoclusters (AuNCs) are an emerging class of quantum-sized nanomaterials with well-defined molecular structures and unique biophysical properties, rendering them highly attractive for biological applications. We set out to study the impact of different ligand shells of atomically similar nanoclusters on cellular recognition and response. To understand the effects of atomically precise nanoclusters with identical composition on cells, we selected two different water-soluble gold nanoclusters protected with captopril (Capt) and glutathione (GSH): Au25(Capt)18 (CNC) and Au25(GSH)18 (GNC), respectively. We demonstrated that a change of the ligand of the cluster completely changes its biological functions. Whereas both nanoclusters are capable of internalization, only CNC exhibits remarkable cytotoxicity, more specifically on cancer cells. CNC shows enhanced cytotoxicity by inhibiting the OXPHOS of mitochondria, possibly by inhibiting the ATP synthase complex of the electron transport chain (ETC), and by initiating the leakage of electrons into the mitochondrial lumen. The resulting increase in both mitochondrial and total cellular ROS triggers cell death indicated by the appearance of cellular markers of apoptosis. Remarkably, this effect of nanoclusters is independent of any external light source excitation. Our findings point to the prevailing importance of the ligand shell for applications of atomically precise nanoclusters in biology and medicine.

Bis-Schiff base linkage-triggered highly bright luminescence of gold nanoclusters in aqueous solution at the single-cluster level

Metal nanoclusters (NCs) have been developed as a new class of luminescent nanomaterials with potential applications in various fields. However, for most of the metal NCs reported so far, the relatively low photoluminescence quantum yield (QY) in aqueous solution hinders their applications. Here, we describe the utilization of bis-Schiff base linkages to restrict intramolecular motion of surface motifs at the single-cluster level. Based on Au22(SG)18 (SG: glutathione) NCs, an intracluster cross-linking system was constructed with 2,6-pyridinedicarboxaldehyde (PDA), and water-soluble gold NCs with luminescence QY up to 48% were obtained. The proposed approach for achieving high emission efficiency can be extended to other luminescent gold NCs with core-shell structure. Our results also show that the content of surface-bound Au(I)-SG complexes has a significant impact on the PDA-induced luminescence enhancement, and a high ratio of Au(I)-SG will be beneficial to increasing the photoluminescence intensity of gold NCs.

Design of a gold clustering site in an engineered apo-ferritin cage

Water-soluble and biocompatible protein-protected gold nanoclusters (Au NCs) hold great promise for numerous applications. However, design and precise regulation of their structure at an atomic level remain challenging. Herein, we have engineered and constructed a gold clustering site at the 4-fold symmetric axis channel of the apo-ferritin cage. Using a series of X-ray crystal structures, we evaluated the stepwise accumulation process of Au ions into the cage and the formation of a multinuclear Au cluster in our designed cavity. We also disclosed the role of key residues in the metal accumulation process. X-ray crystal structures in combination with quantum chemical (QC) calculation revealed a unique Au clustering site with up to 12 Au atoms positions in the cavity. Moreover, the structure of the gold nanocluster was precisely tuned by the dosage of the Au precursor. As the gold concentration increases, the number of Au atoms position at the clustering site increases from 8 to 12, and a structural rearrangement was observed at a higher Au concentration. Furthermore, the binding affinity order of the four Au binding sites on apo-ferritin was unveiled with a stepwise increase of Au precursor concentration.

Isonicotinamide-Stabilized Gold Nanoclusters as Fluorescent Probes for the Determination of 2,4,6-Trinitrophenol

Water-soluble isonicotinamide-stabilized fluorescent gold nanoclusters (AuNCs) were synthesized in one step and used as fluorescent probes for the sensitive and selective determination of 2,4,6-trinitrophenol (TNP). The AuNCs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The fluorescence of the isonicotinamide-stabilized AuNCs was quenched by TNP that follows a linear relationship with the TNP concentration from 0.2 to 20 µM. The sensor provides a low detection limit of 0.06 µM. By using absorption spectroscopy, fluorescence spectroscopy and fluorescence lifetime, the fluorescence quenching mechanism was demonstrated to be due to the inner filter effect between AuNCs and TNP. The sensor was successfully employed for TNP determination in water samples.

Water-soluble luminescent gold nanoclusters reduced and protected by histidine for sensing of barbaloin and temperature

In terms of the vital functions of barbaloin, it is necessary to develop a selective and sensitive detection means in barbaloin sensing to replace the previous defective analytical methods. Herein, the water-soluble luminescent gold nanoclusters (Au NCs) with good emission character were firstly established for barbaloin detection with high efficiency. The small size and stable probe was synthesized through one-pot way by protecting and reducing of histidine (His). The characterization results revealed that the quenching mechanism was mainly attributed to the inner filter effect (IFE). The His-Au NCs displayed high selectivity to barbaloin against interferes and a good linear relationship existed in the range of 0.5–150 μM. More importantly, the probe was successfully employed to detect barbaloin in bovine serum samples with satisfactory recoveries and the excellent performance was also obtained from temperature sensing. This novel detection platform expanded the analytical methods for barbaloin based on fluorescence properties.

Revealing the etching process of water-soluble Au25 nanoclusters at the molecular level

Etching (often considered as decomposition) is one of the key considerations in the synthesis, storage, and application of metal nanoparticles. However, the underlying chemistry of their etching process still remains elusive. Here, we use real-time electrospray ionization mass spectrometry to study the reaction dynamics and size/structure evolution of all the stable intermediates during the etching of water-soluble thiolate-protected gold nanoclusters (Au NCs), which reveal an unusual “recombination” process in the oxidative reaction environment after the initial decomposition process. Interestingly, the sizes of NC species grow larger and their ligand-to-metal ratios become higher during this recombination process, which are distinctly different from that observed in the reductive growth of Au NCs (e.g., lower ligand-to-metal ratios with increasing sizes). The etching chemistry revealed in this study provides molecular-level understandings on how metal nanoparticles transform under the oxidative reaction environment, providing efficient synthetic strategies for new NC species through the etching reactions.

Synthesis and solution isomerization of water-soluble Au9 nanoclusters prepared by nuclearity conversion of [Au11(PPh3)8Cl2]Cl.

Water-soluble gold nanoclusters (AuNCs) are popular in biomedical applications such as bioimaging, labelling, drug delivery, and biosensing. Despite their widespread applications, the synthesis of water-soluble phosphine-capped AuNCs is not as straightforward as their organic-soluble equivalents. Organic soluble phosphine-passivated [Au9(L)8]3+ are 6-electron closed-shell AuNCs that are generally prepared via the reduction of a phosphine-Au(I) complex by NaBH4. A similar approach attempted for the water-soluble ligand triphenylphosphine monosulfonate (TPPMS) using [AuTPPMS]Cl resulted in a mixture of cluster sizes that required gel electrophoresis or fractional precipitation to isolate the Au9 product. In this work, we report the synthesis of water-soluble [Au9(L)8]3+ nanoclusters in high yield through the biphasic ligand exchange of [Au11(PPh3)8Cl2]Cl with water-soluble phosphines such as TPPMS and 4-(diphenylphosphino)benzoic acid (DPPBA). The small molecule byproducts can be completely removed by size-based separation methods, like size exclusion chromatography or dialysis, as confirmed by 31P and 1H nuclear magnetic resonance (NMR) as well as diffusion ordered spectroscopy (DOSY). Furthermore, [Au9(DPPBA)8]Cl3 underwent a visible pH- and temperature-induced isomerization in ethanol between the 'crown' and 'butterfly' isomers of [Au9(L)8]3+ which has not been previously reported. Cytotoxicity evaluation of these water-soluble nanoclusters gave CC50 values of 36 μg mL-1 and 70 μg mL-1 against A549 human alveolar epithelial cells, and 30 μg mL-1 and 40 μg mL-1 against NIH/3T3 mouse fibroblast cells for [Au9(TPPMS)8]Cl3 and [Au9(DPPBA)8]Cl3, respectively. For comparison, auranofin, an FDA-approved gold drug, is more than an order of magnitude more toxic with a CC50 value of 7.7 μg mL-1 against A549 cells.

Effect of subtle changes of isomeric ligands on the synthesis of atomically precise water-soluble gold nanoclusters.

The subtle structural change of hydrophilic ligands on the size control of metal nanoclusters (NCs) is unclear but critically important for fundamental understanding. Herein, we report our findings that subtle changes of isomeric ligands lead to a dramatic difference in the size of water-soluble Au NCs. By using isomeric para-mercaptobenzoic acid (p-MBA), m-MBA, and o-MBA as model ligands, it was found that both the steric hindrance and the electronic effect of isomeric ligands significantly influences the size of Au NCs, resulting in the formation of different sized Au44(p-MBA)26 NCs, Au25(m-MBA)18 NCs, and Au37/43(o-MBA)22/26 NCs. Besides this, by collocating any two of the isomeric MBAs as ligand pairs to compare their protecting capability for Au NCs, the protecting abilities of such ligands were found to follow the trend: m-MBA > o-MBA > p-MBA. In addition, the growth process of Au44(p-/o-MBA)26 NCs from Au(i)-MBA complexes in the NaBH4 reduction system was also monitored by real-time UV-vis absorption spectroscopy and ESI mass spectrometry, which complies with the 2e- hopping growth principle, indicating the universal applicability of this principle in the synthesis of thiolated metal NCs. This study provides a fundamental understanding of the effect of ligands' steric hindrance and electronic factors on the size control of water-soluble metal NCs and sheds light on the formation of metal NCs in the NaBH4 reduction system.

Synthesis of folic acid functionalized gold nanoclusters for targeting folate receptor-positive cells

We report on the synthesis of water-soluble gold nanoclusters capped with polyethylene glycol (PEG)-based ligands and further functionalized with folic acid for specific cellular uptake. The dihydrolipoic acid-PEG-based ligands terminated with –OMe, –NH2 and –COOH functional groups are produced and used for surface passivation of Au nanoclusters (NCs) with diameters <2 nm. The produced sub 2 nm Au NCs possess long-shelf life and are stable in physiologically relevant environments (temperature and pH), are paramagnetic and biocompatible. The paramagnetism of Au NCs in solution is also reported. The functional groups on the capping ligands are used for direct conjugation of targeting molecules onto Au NCs without the need for post synthesis modification. Folic acid (FA) is attached via an amide group and effectively target cells expressing the folate receptor. The combination of targeting ability, biocompatibility and paramagnetism in FA-functionalized Au NCs is of relevance for their exploitation in nanomedicine for targeted imaging.

Highly orange fluorescence emission by water soluble gold nanoclusters for “turn off” sensing of Hg2+ ion

Herein, a simple, facile and biocompatible fluorescent sensor using L-cysteine assisted chitosan reduced gold nanocluster (L-cys/CS-AuNC) is prepared by “one pot” synthetic protocol for ultrasensitive detection of Hg2+ ion which produces a strong orange fluorescence emission at 575 nm. The quantum yield of L-cys/CS-AuNC is calculated to be 5.2%. The surface functionality and morphology of nanocomposites are studied by Fourier transform infrared spectroscopy and transmission electron microscopy respectively. Zeta potential measurement shows the stability of as-synthesized L-cys/CS-AuNC. With addition of Hg2+ ion to the gold nanoclusters, the orange fluorescence emission is quenched which is due to the strong metallophilic interactions i.e. interaction of 5d10 of Hg2+ and 5d10 of Au+ on the gold surface. High selectivity and sensitivity for sensing of Hg2+ are achieved through present fluorescent assay and a linear correlation is obtained with correlation coefficient of 0.99 by plotting the graph between the relative fluorescent intensity and concentration of Hg2+ ion (0–1000 nM). Further, the detection limit (LOD) for mercury (II) is found to be 3 nM. Moreover, the L-cys/CS-AuNC can be applied to real water samples such as pond, river and tap water for detection of Hg2+ ion.

Structural and optical properties of penicillamine-protected gold nanocluster fractions separated by sequential size-selective fractionation

Polydisperse water-soluble gold nanoclusters (AuNCs) protected by penicillamine have been synthesized in this work. The sequential size-selective precipitation (SSSP) technique has been applied for the size fractionation and purification of the monolayer-protected AuNCs. Through continuously adding acetone to a crude AuNC aqueous solution and controlling the volume percentage of acetone, we successfully separated the polydisperse AuNCs with diameters ranging from 0.5 to 5.4 nm into four different fractions sequentially. High-resolution transmission electron microscopy (HRTEM) shows that the four fractions are well-dispersed spherical particles of diameter 3.0 ± 0.6, 2.3 ± 0.5, 1.7 ± 0.4, and 1.2 ± 0.4 nm. Proton nuclear magnetic resonance spectroscopy suggests that disulfide, excess ligands and gold(I) complexes were removed from the AuNCs fractions. These results demonstrate the considerable potential of the SSSP technique for size-based separation and purification of AuNCs, achieving not only the isolation of larger nanoclusters (NCs) from small NCs in a continuous fashion, but also for the removal of small-molecule impurities. Based on the results from the mass spectrometry and thermogravimetric analysis, the average composition of the four fractions can be represented by Au38(SR)18, Au28(SR)15, Au18(SR)12, and Au11(SR)8, respectively. This indicates that the SSSP separation is mainly dependent on the core size and the ratio of Au atoms to ligands of AuNCs. X-ray photoelectron spectroscopy (XPS) has also been applied to observe the molecular dependence on the gold and sulfur chemical state of organosulfur monolayers of the fractions. The photoluminescence spectra of these AuNCs in the range of 900–790 nm was investigated at room temperature. The results show that the peak emission energy of the size-selected AuNCs undergoes a blue shift when the size is decreased, which can be attributed to the quantum confinement effect.

Synthesis of water-soluble fluorescent gold nanoclusters

In this paper, we explored the preparation process of gold nanoclusters (AuNCs). AuNCs was synthesized by micro-reaction process and compared with the traditional one-pot strategy. The water-soluble AuNCs was prepared by reducing hydrogen tetrachloroaurate hydrate (HAuCl4) in aqueous solution with 11-mercaptoundecanoic acid (MUA) as ligand and reducing agent. The effect of NaBH4 and reactant concentration ratio on the experimental results was investigated systematically, and it was found that NaBH4 had little effect on the fluorescence intensity of synthesized AuNCs. When the ratio of MUA to Au3+ ion concentration was 4:1, the AuNCs reached the highest fluorescence intensity. The synthesized water-soluble AuNCs were characterized by ultraviolet spectrophotometer, fluorescence spectrophotometer and high resolution transmission electron microscopy (HRTEM). The average particles of AuNCs prepared by one-pot strategy and the micro-reaction method were 1.8nm ± 0.5nm, 1.7nm ± 0.4nm, respectively. The quantum yield of AuNCs prepared by micro-reaction method was improved to 9.1% comparing with the one-pot strategy of 6.9%.

Size-dependent electrophoretic migration and separation of water-soluble gold nanoclusters by capillary electrophoresis.

Recently, water-soluble gold nanoclusters (AuNCs) have attracted more and more attention due to their unique properties. In this study, penicillamine-protected gold nanoclusters (Pen-AuNCs) were synthesized and initially fractionated by sequential size-selective precipitation (SSSP). The crude Pen-AuNCs and SSSP fractions were separated by capillary zone electrophoresis (CZE) with a diode array detector. The effects of key parameters, including the concentration of phosphate buffer, pH value and the ethanol content were systematically investigated. The separation of water-soluble poly-disperse AuNCs were well achieved at 30 mM phosphate buffer with 7.5% EtOH, pH 12.0, and applied voltage of 15 kV. The linear correlation between AuNCs diameter and mobility was observed. This finding provides an important reference for CE separation and product purification of water-soluble AuNCs or other nanomaterials.

Towards Controlled Synthesis of Water-Soluble Gold Nanoclusters: Synthesis and Analysis

Water-soluble gold nanoclusters with well-defined molecular structures and stability possess particular biophysical properties making them excellent candidates for biological applications as well a...

Amplified vibrational circular dichroism as a manifestation of the interaction between a water soluble gold nanocluster and cobalt salt.

Vibrational circular dichroism (VCD) is a powerful tool for the structure determination of dissolved molecules. However, the application of VCD to nanostructures is limited up to now due to the weakness of the effect and hence the low signal intensities. Here we show that the addition of a small amount of cobalt(ii) drastically enhances the VCD signals of a thiolate-protected gold cluster Au25(Capt)18 (Capt = captopril) in aqueous solution. An increase of VCD signal intensity of at least one order of magnitude is observed. The enhancement depends on the amount of CoCl2 added but almost an order of magnitude enhancement is already observed at a cluster : CoCl2 ratio of 1 : 1. In contrast, circular dichroism (CD) and infrared spectra hardly change. The increase in VCD intensity goes along with a qualitative change of the spectrum and the enhancement increases with time reaching a stable state only after several hours. The enhancement is due to an interaction between the cobalt(ii) and the cluster, which also leads to quenching of its fluorescence. The behaviour is completely different for free captopril, where the addition of cobalt(ii) salt does not affect the VCD spectrum.