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.

A Single-chain Antibody for One-pot Fabrication of Luminescent Gold Nanoclusters and Rabies Virus Imaging in Cells

The fragile antibody leads to a great challenge as a scaffold to fabricate the luminescent metal nanoclusters using one-pot method.This study presents a stable single-chain anti-body(scFv57R-ATS)for the fabrication of luminescent gold nanoclusters(AuNCs@scFv57R-ATS)and a quick,sensitive rabies virus detection in living cells.In this paper,AuNCs@scFv57R-ATS was designed to specifically recognize antigen RV in modified HeLa cells,which promoted the demonstration of metal nanocluster fluorescent probes for antigen targeting and therapy.

Ratiometric Fluorescence Detection of 6-Mercaptopurine Based on the Nanohybrid of Fluorescence Carbon Dots and Gold Nanoclusters

The development of a simple and accurate quantitative method for the determination of 6-mercaptopurine (6-MP) is of great importance because of its serious side effects. Ratiometric fluorescence (RF) sensors are not subject to interference from environmental factors, and exhibit enhanced precision and accuracy. Therefore, a novel RF sensor for the selective detection of 6-MP was developed. The present work reports a sensitive and selective RF sensor for the detection of 6-mercaptopurine, by hybridizing carbon nanodots (CDots) and gold nanoclusters (AuNCs) capped with bovine serum albumin (BSA). The CDots serve as the reference signal and the AuNCs as the reporter. On addition of the 6-MP, AuNCs formed aggregates, because the existing cross-links within the AuNCs and BSA structure were broken in favour of the Au-S bonds, which can enhance the fluorescence of AuNCs, while the fluorescence of CDots is stable against 6-MP, leading to distinct ratiometric fluorescence changes when exposed to 6-MP. 6-MP could be detected in the range of 0 - 30.22 μM with a detection limit of 54 nM. The developed sensor was applied for the determination of 6-MP in human serum samples and satisfactory results were obtained.

Structural Evolution Patterns of FCC-Type Gold Nanoclusters

Recent progress in the research of atomically-precise metal nanoclusters has identified a series of exceptionally stable nanoclusters with specific chemical compositions. Structural determination on such "magic size" nanoclusters revealed a variety of unique structures such as decahedron, icosahedron, as well as hexagonal close packing(hcp) and body-centered cubic(bcc) packing arrangements in gold nanoclusters, which are largely different from the face-centered cubic(fcc) structure in conventional gold nanoparticles. The characteristic geometrical structures enable the nanoclusters to exhibit interesting properties, and these properties are in close correlation with their atomic structures according to the recent studies. Experimental and theoretical analyses have been applied in the structural identification aiming to clarify the universal principle in the structural evolution of nanoclusters. In this mini-review, we summarize recent studies on periodic structural evolution of fcc-based gold nanoclusters protected by thiolates. A series of nanoclusters exhibit one-dimensional growth along the [001] direction in a layer-by-layer manner from Au_(23)(TBBT)_(20) to Au_(36)(TBBT)_(24),Au_(44)(TBBT)_(28), and to Au_(52)(TBBT)_(32)(TBBT: 4-tert-butylbenzenethiolate). The optical properties of these nanoclusters also evolve periodically based on steady-state and ultrafast spectroscopy. In addition, two-dimensional growth from Au_(44)(TBBT)_(28) toward both [100] and [010] directions leads to the Au_(92)(TBBT)_(44) nanocluster, and the recently reported Au_(52)(PET)_(32)(PET: 2-phenylethanethiol) also follows this growth pattern with partial removal of the layer. Theoretical predictions of relevant fcc nanoclusters include Au_(60)(SCH_3)_(36), Au_(68)(SCH_3)_(40), Au_(76)(SCH_3)_(44), etc, for the continuation of 1 D growth pattern, as well as Au_(68)(SR)_(38)mediating the 2 D growth pattern from Au_(44)(TBBT)_(28) to Au_(92)(TBBT)_(44). Overall, this mini-review provides guidelines on the rules of structural evolution of fcc gold nanoclusters based on 1 D, 2 D and 3 D growth patterns.

Oxygen Electroreduction Performance of Ultrasmall Gold Nanoclusters

Ultrasmall gold nanoclusters consisting of 2-4 Au atoms were synthesized and their per- formance in electrocatalytic oxygen reduction reactions （ORR） was examined. These clus- ters were synthesized by exposing AuPPh3Cl to the aqueous ammonia medium for one week. Electrospray ionization mass spectrometry （ESI-MS）, X-ray absorption fihe struc- ture （XAFS）, and X-ray photoelectron spectroscopy （XPS） analyses indicate that the as- synthesized gold clusters （abbreviated as Aux） consist of 2-4 Au atoms coordinated by the triphenylphosphine, hydroxyl, and adsorbed oxygen ligands. A glassy carbon disk electrode loaded with the Aux clusters （Aux/GC） was characterized by the cyclic and linear-sweep voltammetry for ORR. The cyclic voltammogram vs. RHE shows the onset potential of 0.87 V, and the kinetic parameters of JK at 0.47 V and the electron-transfer mmlber per oxygen molecule were calculated to be 14.28 mA/cm2 and 3.96 via the Koutecky-Levich equations, respectively.

Atomically precise gold nanoclusters for healthcare applications

The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commercial drug molecules.The emergence of atomically precise gold nanoclusters(APGNCs)provides the opportunity to address the puzzle due to their ultrasmall size,defined molecular formula,editable surface engineering,available structures and unique physicochemical properties including excellent biocompatibility,strong luminescence,enzyme-like activity and efficient renal clearance,et al.Recently,these advantages of APGNCs also endow them promising performances in healthcare such as bioimaging,drug delivery,antibacterial and cancer therapy.Especially,their clear composition and structures like the commercial drug molecules facilitate the study of their functions and the structure-activity relationship in healthcare,which is essential for the guided design of APGNC nanomedicine.Therefore,this review will focus the advantages and recent progress of APGNCs in health care and envision their prospects for the future.

Fabrication of High Color Rendering Index White Light Emitting Diodes from Gold Nanoclusters

We demonstrated gold nanoclusters as color tunable emissive light converters for the application of white light emitting diodes (WLEDs). A blue LED providing 460 nm to excite gold nanoclusters mixed with UV curable material generates broad bandwidth emission at the visible range. Increasing the amount of gold nanoclusters, the correlated color temperature of WLEDs tuned from cold white to warm white, and also results in the variation of color rendering index (CRI). The highest CRI in the experiment is 92.

Controllably partial removal of thiolate ligands from unsupported Au_(25) nanoclusters by rapid thermal treatments for electrochemical CO_(2)reduction

Colloidal synthesis of metal nanoclusters will inevitably lead to the blockage of catalytically active sites by organic ligands.Here,taking[Au_(25)(PET)_(18)]-(PET=2-phenylethanethiol)nanocluster as a model catalyst,this work reports a feasible procedure to achieve the controllably partial removal of thiolate ligands from unsupported[Au_(25)(PET)_(18)]-nanoclusters with the preservation of the core structure.This procedure shortens the processing duration by rapid heating and cooling on the basis of traditional annealing treatment,avoiding the reconfiguration or agglomeration of Au_(25)nanoclusters,where the degree of dethiolation can be regulated by the control of duration.This work finds that a moderate degree of dethiolation can expose the Au active sites while maintaining the suppression of the competing hydrogen evolution reaction.Consequently,the activity and selectivity towards CO formation in electrochemical CO_(2)reduction reaction of Au_(25)nanoclusters can be promoted.This work provides a new approach for the removal of thiolate ligands from atomically precise gold nanoclusters.

Coherent Vibrational Dynamics of[Au_(25)(SR)_(18)]^(-) Nanoclusters

Coherent vibrational dynamics can be observed in atomically precise gold nanoclusters using femtosecond time-resolved pump-probe spectroscopy.It can not only reveal the coupling between electrons and vibrations,but also reflect the mechanical and electronic properties of metal nanoclusters,which holds potential applications in biological sensing and mass detection.Here,we investigated the coherent vibrational dynamics of[Au_(25)(SR)_(18)]^(-)nanoclusters by ultrafast spectroscopy and revealed the origins of thesecoherent vibrations by analyzing their frequency,phase and probe wavelength distributions.Strong coherent oscillations with frequency of 40 cm^(-1) and 80 cm^(-1) can be reproduced in the excited state dynamics of[Au_(25)(SR)_(18)]^(-),which should originate from acoustic vibrations of the Au13 metal core.Phase analysis on the oscillations indicates that the 80 cm^(-1) mode should arise from the frequency modulation of the electronic states while the 40 cm^(-1) mode should originate from the amplitude modulation of the dynamic spectrum.Moreover,it is found that the vibration frequencies of[Au_(25)(SR)_(18)]^(-)obtained in pump-probe measurements are independent of the surface ligands so that they are intrinsic properties of the metal core.These results are of great value to understand the electron-vibration coupling of metal nanoclusters.

Gold nanoclusters encapsulated microneedle patches with antibacterial and self-monitoring capacities for wound management

The management of infected wounds is always of great significance and urgency in clinical and biomedicalfields.Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial,drug delivery,and sensor properties.Here,we present novel hyaluronic acid(HA)microneedle patches with these features by encapsulating aminobenzeneboronic acid-modified gold nanoclusters(A-GNCs)for infected wound management.The A-GNCs loaded microneedle patches were derived from negative-mold replication and showed high mechanical strength to penetrate the skin.The release of the A-GNCs was realized by the degradation of HA,and the self-monitor of the released actives was based on the dynamic bright orangefluorescence emitted from A-GNCs under ultravio-let radiation.As the A-GNCs could destroy bacteria membranes,the microneedle patches were with excellent in vitro antibiosis ability.Based on these features,we have demonstrated the bacteria inhibition,residual drug self-monitoring,and wound healing promotion abilities of the microneedle patches in Escherichia coli-or Staphylococcus aureus-infected wound management.These results indicated the great potential of such A-GNCs loaded microneedle patches for clinical applications.

Producing of cinnamyl alcohol from cinnamaldehyde over supported gold nanocatalyst

Chemoselective hydrogenation of unsaturated aldehyde to unsaturated alcohol has attracted growing interests in recent years due to its widespread applications in fine chemicals.However,the hydrogenation of the C=O bond was thermodynamically and kinetically unfavorable over the hydrogenation of the C=C bond.Thus,to obtain the unsaturated alcohol from the unsaturated aldehyde is very difficult in most of the catalytic systems.In this work,ZnAl-hydrotalcite-supported cysteine-capped Au25 nanoclusters were used as the precatalysts for chemoselective hydrogenation of cinnamaldehyde to cinnamyl alcohol.The catalyst showed stable high selectivity(~95%)at prolonged reaction time and complete conversion of the substrate.According to the results of the control experiments,the in-situ DRIFTS of the substrate under high pressure of hydrogen and the 27Al MAS-NMR spectroscopy,we proposed that the difference of the preferential adsorption of the C=O bond to that of the C=C bond was derived from the nature of the support of the gold catalysts.

ZIF-8封装AuNCs荧光传感器用于铁离子的检测

介绍一个适合于本科教学使用的综合创新实验,设计合成了一种荧光传感器Au NCs@ZIF-8,并将其用于铁离子(Fe^(3+))的检测。MOFs具有高效吸附、聚集检测物的特点,因此选择将Au NCs封装到ZIF-8中,从而实现目标物的定量检测。封装后,由于Au NCs具有AIE特性,所以Au NCs@ZIF-8的荧光强度明显增强。ZIF-8是一种多孔材料,加入Fe^(3+)后,Fe^(3+)能够进入ZIF-8内部,导致Au NCs的荧光被Fe^(3+)猝灭,成功用于实际水样中Fe^(3+)的检测。尽管该实验步骤复杂并涉及新型纳米材料的合成和表征,但它成功地整合了无机化学、分析化学以及材料化学的相关知识,且操作难度适宜。这为提升学生的动手能力和科技前沿理解提供了一次宝贵的机会。

Transition metal-mediated catalytic properties of gold nanoclusters in aerobic alcohol oxidation

Heteroatom dopants can greatly modify the electronic and physical properties and catalytic performance of gold nanoclusters. In this study, we investigate the catalytic activity of [Au25-x（PET）18-xM]NH3 （PET = 2-phenylethanethiolate, and M = Cu, Co, Ni, and Zn） nanoclusters in aerobic alcohol oxidation. The [Au25-xPET）18-xM]NH3 nanoclusters are thoroughly characterized by matrix assisted laser desorption ionization （MALDI） mass spectrometry, X-ray photoelectron spectroscopy （XPS）, Fourier transform infrared spectroscopy （FT-IR）, and inductively coupled plasma-mass spectrometry （ICP-MS）. The XPS analyses suggest that the transition metals strongly interact with the gold atoms of the nanoclusters. The CeO2-supported nanoclusters show catalytic activity, based on the conversion of benzyl alcohol, in the order, [Au25-x（PET）18-xNi] 〉 [Au25-x（PET）18-xCu] 〉 [Au25-x（PET）18-xZn] 〉 [Au25-x（PET）18-xCo]. Regarding product selectivity, the [Au25-xPET）18-xZn] and [Au25-x（PET）18-xCo] catalysts preferably yield benzaldehyde, [Au25-x（PET）18-xCu] yields benzaldehyde and benzyl acid, and [Au25-x（PET）18-xNi] yields benzyl acid. The exposed metal atoms are considered as the catalytic active sites. Also, the catalytic performance （including activity and selectivity） of the [Au25-x（PET）18-xM] catalysts is greatly turned and mediated by the transition metal type.

NIR-II light activated photodynamic therapy with proteincapped gold nanoclusters

The use of near-infrared （NIR） light for photodynamic therapy （PDT） is a promising strategy to circumvent the limitations of current PDT, in which visible light with limited tissue penetration depth is usually used. In the present stud~ alkyl thiolated gold nanoclusters （AuNCs） were co-modified with human serum albumin （HSA） and catalase （CAT）, and then employed as a multifunctional, optical, theranostic nano-agent. In the AuNC@HSA/CAT system, the AuNCs were able to produce singlet oxygen under excitation by a 1,064-nm laser, which locates in the second NIR window （NIR-II）, and featured much lower tissue absorption and scattering, enabling NIR-II-triggered PDT. The HSA coating greatly improved the physiological stability of the nanoparticles, which showed efficient tumor retention after intravenous injection, as revealed by detecting the AuNC fluorescence. Moreover, the presence of CAT in the nanoparticles triggered decomposition of tumor endogenous H202 to generate oxygen, thereby enhancing the efficacy of PDT by relieving tumor hypoxia. Compared with conventional PDT using visible light, NIR-II-triggered PDT exhibits remarkably increased tissue penetration. Thus, we developed a new type of photosensitizing nano-agent that simultaneously enables in vivo fluorescence imaging, tumor hypoxia relief, and NIR-II light-induced in vivo PDT in the treatment of cancer.

Theoretical Investigations of the Catalytic Role of Water in Propene Epoxidation on Gold Nanoclusters： A Hydroperoxyl- Mediated Pathway

We report a comprehensive theoretical investigation of the catalytic reaction mechanisms of propene epoxidation on gold nanoclusters using density functional theory （DFT）. We have shown that water acts as a catalytic promoter for propene epoxidation on gold catalysts. Even without reducible supports, hydroperoxyl （OOH） and hydroxyl （OH） radicals are readily formed on small-size gold clusters from co-adsorbed H20 and 02, with energy barriers as low as 4-6 kcal/mol （1 cal = 4.186 J）. Propene epoxidation occurs easily through reactions between C3H6 and the weakened O-O bond of the OOH radicals on the surfaces of gold clusters.

酪蛋白-金银合金纳米簇的制备及其对金霉素的荧光检测

以酪蛋白为保护剂和还原剂,采用优化的一锅加热合成方法,成功制备一种新型金银合金纳米簇(Au-AgNCs@casein)。产物在325 nm最佳激发波长下有双荧光发射峰,通过红外光谱、透射电子显微镜等方法对其进行结构表征。在常见离子或氨基酸存在下,金霉素(CTC)可明显增强比率型探针Au-AgNCs@casein的荧光,其结构类似物却无明显影响。因此,本研究中制备的纳米簇可快速、灵敏、选择性检测CTC。

Green synthesis of gold nanoclusters using papayajuice for detection of L-lysine

Gold nanoclusters were rapid synthesized within 3 min at 120 ℃ by using papaya juice as a capping and reducing agent(P-AuNCs). The properties of the fluorescent probe were characterized by fluorescent spectroscopy, UV-vis spectroscopy, dynamic light scattering and transmission electron microscope.Based on the surface electron density increase-induced fluorescence enhancing principle, a high selective method for detection of L-lysine was developed with the as-prepared P-AuNCs coupling the fluorescence emission at 440 nm. The fluorescent probe showed high stability and good biocompatibility. Its fluorescence intensity was found to be linearly dependent on the L-lysine concentration in the range of 10.0μmol/L to 1000.0 μmol/L(R^2=0.969) with a limit of detection of 6.0μmol/L. Furthermore, the PAuNCs based approach was applied for monitoring the urine L-lysine contents, demonstrating great potential of fluorescent probes in real samples analysis.

Metal–Organic Frameworks-Mediated Assembly of Gold Nanoclusters for Sensing Applications

Gold nanoclusters(AuNCs)are an emerging type of ultrasmall nanomaterials possessing unique physicochemical characteristics.Metal–organic frameworks(MOFs),a singular kind of porous solid and crystalline material,have attracted tremendous attention in recent years.The combination of AuNCs and MOFs can integrate and improve the prominent properties of both components,such as high catalytic activities,tunable optical properties,good biocompatibility,surface functionality and stability,which make the composites of MOFs and AuNCs promising for sensing applications.This review systematically summarizes the recent progress on the sensing of various analytes via MOFs-mediated AuNCs assemblies based on strategies of luminescence sensing,colorimetric sensing,electrochemiluminescence sensing,and electrochemical and photoelectrochemical sensing.A brief outlook regarding the future development of MOFs-mediated AuNCs assemblies for sensing application is presented as well.