Ultrasmall Copper Nanoclusters Research Articles

NIR-II emissive anionic copper nanoclusters with intrinsic photoredox activity in single-electron transfer

Ultrasmall copper nanoclusters have recently emerged as promising photocatalysts for organic synthesis, owing to their exceptional light absorption ability and large surface areas for efficient interactions with substrates. Despite significant advances in cluster-based visible-light photocatalysis, the types of organic transformations that copper nanoclusters can catalyze remain limited to date. Herein, we report a structurally well-defined anionic Cu40 nanocluster that emits in the second near-infrared region (NIR-II, 1000−1700 nm) after photoexcitation and can conduct single-electron transfer with fluoroalkyl iodides without the need for external ligand activation. This photoredox-active copper nanocluster efficiently catalyzes the three-component radical couplings of alkenes, fluoroalkyl iodides, and trimethylsilyl cyanide under blue-LED irradiation at room temperature. A variety of fluorine-containing electrophiles and a cyanide nucleophile can be added onto an array of alkenes, including styrenes and aliphatic olefins. Our current work demonstrates the viability of using readily accessible metal nanoclusters to establish photocatalytic systems with a high degree of practicality and reaction complexity.

Serum albumin-embedding copper nanoclusters inhibit Alzheimer’s β-amyloid fibrillogenesis and neuroinflammation

Increasing evidence suggests that the accumulations of reactive oxygen species (ROS), β-amyloid (Aβ), and neuroinflammation are crucial pathological hallmarks for the onset of Alzheimer’s disease (AD), yet there are few effective treatment strategies. Therefore, design of nanomaterials capable of simultaneously elimination of ROS and inhibition of Aβ aggregation and neuroinflammation is urgently needed for AD treatment. Herein, we designed human serum albumin (HSA)-embedded ultrasmall copper nanoclusters (CuNCs@HSA) via an HSA-mediated fabrication strategy. The as-prepared CuNCs@HSA exhibited outstanding multiple enzyme-like properties, including superoxide dismutase (>5000 U/mg), catalase, and glutathione peroxidase activities as well as hydroxyl radicals scavenging ability. Besides, CuNCs@HSA prominently inhibited Aβ fibrillization, and its inhibitory potency was 2.5-fold higher than native HSA. Moreover, CuNCs@HSA could significantly increase the viability of Aβ-treated cells from 60 % to over 96 % at 40 μg/mL and mitigate Aβ-induced oxidative stresses. The secretion of neuroinflammatory cytokines by lipopolysaccharide-induced BV-2 cells, including tumor necrosis factor-α and interleukin-6, was alleviated by CuNCs@HSA. In vivo studies manifested that CuNCs@HSA effectively suppressed the formation of plaques in transgenic C. elegans, reduced ROS levels, and extended C. elegans lifespan by 5 d. This work, using HSA as a template to mediate the fabrication of copper nanoclusters with robust ROS scavenging capability, exhibited promising potentials in inhibiting Aβ aggregation and neuroinflammation for AD treatment.

Ultrasmall copper nanoclusters as an efficient antibacterial agent for primary peritonitis therapy.

The urgent need to develop biocompatible, non-resistant antibacterial agents to effectively combat Gram-negative bacterial infections, particularly for the treatment of peritonitis, presents a significant challenge. In this study, we introduce our water-soluble Cu30 nanoclusters (NCs) as a potent and versatile antibacterial agent tailored for addressing peritonitis. The as-synthesized atomically precise Cu30 NCs demonstrate exceptional broad-spectrum antibacterial performance, and especially outstanding bactericidal activity of 100% against Gram-negative Escherichia coli (E. coli). Our in vivo experimental findings indicate that the Cu30 NCs exhibit remarkable therapeutic efficacy against primary peritonitis caused by E. coli infection. Specifically, the treatment leads to a profound reduction of drug-resistant bacteria in the peritoneal cavity of mice with peritonitis by more than 5 orders of magnitude, along with the resolution of pathological features in the peritoneum and spleen. Additionally, comprehensive in vivo biosafety assessment underscores the remarkable biocompatibility, low biotoxicity, as well as efficient hepatic and renal clearance of Cu30 NCs, emphasizing their potential for in vivo application. This investigation is poised to advance the development of novel Cu NC-based antibacterial agents for in vivo antibacterial treatment and the elimination of abdominal inflammation.

Ultra-small water-soluble fluorescent copper nanoclusters for p-nitrophenol detection.

Due to the widespread application of p-nitrophenol (p-NP) across various industries, particularly in the pharmaceutical and chemical sectors, it has emerged as a significant environmental contaminant in both soil and water ecosystems. The development of swift and sensitive detection platforms for p-NP is therefore demanding. Herein, a fluorescence sensor based on ultra-small copper nanoclusters with exterior glutathione ligands determined by electrospray ionization mass spectrometry (ESI-MS) as [Cu14(SG)12]+ (denoted as Cu-SG NCs) has been prepared in high efficiency, and shown high selectivity for p-NP detection. The Cu-SG NCs, synthesized via a facile one-pot chemical reduction technique, exhibit emission maxima at 620 nm. Notably, the introduction of p-NP into the nanocluster system causes a significant quenching of the Cu-SG NCs fluorescence. The quenching phenomenon arises predominantly as a result of the inner filter effect (IFE), which stems from the substantial overlap between the UV-Vis absorption spectrum of p-NP and the excitation wavelength of Cu-SG NCs. The developed fluorescence sensor platform demonstrates a wide determination range for p-NP, ranging from 0.04 to 2000 µM, with a detection limit of 30 nM. Additionally, the sensor efficacy was successfully validated in the analysis of actual water samples. The ease of synthesis, excellent optical properties, and low toxicity of Cu-SG NCs represent significant advantages over the reported noble metal nanomaterials and is highly promising for future practical applications.

Enhancing Fenton-like Degradation of Organic Pollutants at Neutral pH by Multivalent Cu NCs/HAp Nanocatalysts.

Heterogeneous Fenton-like catalysis is a widely used method for the degradation of organic pollutants. However, it still has some limitations such as low activity in the neutral condition, low conversion rates of metals with different valence states, and potential secondary metal pollution. In this study, a Fenton-like nanocatalyst was first created by generating ultrasmall copper nanoclusters (Cu NCs) on the surface of hydroxyapatite (HAp) through a process of doping followed by modification. This resulted in the formation of a composite nanocatalyst known as Cu NCs/HAp. With the help of hydrogen peroxide (H2O2), Cu NCs/HAp exhibits an outstanding Fenton-like catalytic performance by efficiently degrading organic dyes such as methylene blue under mild neutral conditions. The removal rate can reach over 83% within just 30 min, demonstrating ideal catalytic universality and stability. The improved Fenton-like catalytic performance of Cu NCs/HAp can be ascribed to the synergistic effect of the multivalent Cu species through two simultaneous reaction pathways. During route I, the embedded Cu NCs with a core-shell Cu0/Cu+ structure can undergo sequential oxidation to form Cu2+, which continuously activates H2O2 to generate hydroxyl radicals (•OH) and singlet oxygen (1O2). In route II, Cu2+ produced from route I and initially adsorbed on the surface of HAp can be reduced by H2O2, thus regenerating Cu+ species for route I and achieving a closed-loop reaction. This work has confirmed that Cu NCs loaded on HAp may be an alternative Fenton-like catalyst for degradation of organic pollutants and environmental remediation, opening up new avenues for potential applications of other Cu NCs in future water pollution control.

Pyridyl-containing graphdiyne stabilizes sub-2 nm ultrasmall copper nanoclusters for the electrochemical reduction of CO2

Pyridyl-containing graphdiyne provides well-defined sites for stabilizing sub-2 nm copper nanoclusters, which show an optimum CH4faradaic efficiency of 58% in the electrochemical CO2reduction reaction.

Ultrasmall copper nanoclusters with multi-enzyme activities.

Reactive oxygen species (ROS) as a key messenger of signal transduction mediate physiological activities, however, oxidative stress produced by excessive ROS can cause the destruction of cell homeostasis, which will result in a series of diseases. Therefore, effective control of ROS level is critical to the homeostasis of the cell. Here, we reported that glutathione (GSH)-stabilized copper nanoclusters (CuNCs) with about 9 Cu atoms can functionally mimic three major antioxidant enzymes, namely catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). The rate of H2O2 decomposition was calculated to be ∼0.23 mg L−1 s−1 when the concentration of CuNCs was 100 μg mL−1. The SOD-like activity by catalyzing the disproportionation of superoxide to H2O2 and O2 reached 25.6 U mg−1 when the effective inhibition rate was ∼55.4%. Intracellular ROS scavenging studies further identified that CuNCs can obviously protect cells from oxidative stress and the cell viability recovered to above 90%. Hence, we expect that ultrasmall CuNCs will provide good therapeutic potential in the future treatment of ROS-related diseases.

Preparation of tea polyphenol-modified copper nanoclusters to promote the proliferation of MC3T3-E1 in high glucose microenvironment

Monodisperse, ultra-small copper nanoclusters (ca. 1.8 nm) were prepared by using tea polyphenols (TP) as both the reducing and capping reagent.

Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst.

Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst.

Surface Plasmon Tunability and Emission Sensitivity of Ultrasmall Fluorescent Copper Nanoclusters

Ultrasmall copper nanoparticles have been synthesized using copper(II) salt as precursor by hydrazine reduction in the presence of citric acid and cetyltrimethylammonium bromide facilitating the growth of stable copper nanoparticles with an average diameter of <2 nm. The corresponding surface plasmon resonances were monitored under variable microenvironments, and it is seen that these tiny copper nanoparticles form aggregates under stipulated reaction conditions. It is noted that ultrasmall copper nanoparticles do not exhibit any characteristic surface plasmon band in the visible region; rather, a continuous absorption is seen over the entire UV–vis region. However, a well-defined plasmon absorption band makes its appearance while the particles are aggregated in close-packed assembly. These results demonstrate that the maximum of surface plasmon resonance is red-shifted from that of isolated particles because of electromagnetic interaction between the particles. The aggregation process is manifested upon changes of pH, anionic surfactant, etc. and is not reversible, i.e., the aggregates could not be re-dispersed into ultrasmall particles. The effect of addition of electrolyte has been monitored to study the surface plasmon damping of the copper nanoparticles. The plasmonic sensitivity of the copper nanoparticle aggregates has been elicited by the determination of amino acid chain length with exquisite sensitivity because of enormous electromagnetic field at the junction of the particles in the aggregates. Interestingly, the as-synthesized ultrasmall copper nanoclusters exhibit excellent fluorescence properties with a narrow emission profile. The emission properties of these copper nanoclusters have been utilized as an indicator for selective and ultrasensitive detection of highly toxic HgII ions in water in the nanomolar detection limit.

Millifluidics: Developing a Millifluidic Platform for the Synthesis of Ultrasmall Nanoclusters: Ultrasmall Copper Nanoclusters as a Case Study (Small 5/2012)

The image features the concept of a millifluidic platform for the controlled synthesis of nanomaterials–an alternative to difficult-to-fabricate, expensive, and complex microfluidic reactors. The millifluidic platform offers a transformative approach, which should jump-start the commercialization of lab-on-a-chip devices for the large-scale production of nanomaterials; it enables better control over size and the ability to probe reactions in situ. Ultrasmall copper nanoclusters are synthesized with the help of ligands in the system, and X-ray absorption near-edge structure (XANES) investigations confirm the possibility of atomically precise control.

Developing a Millifluidic Platform for the Synthesis of Ultrasmall Nanoclusters: Ultrasmall Copper Nanoclusters as a Case Study

The future of lab-on-a-chip devices for the synthesis of nanomaterials hinges on the successful development of high-throughput methods with better control over their size. While significant effort in this direction mainly focuses on developing "difficult to fabricate" complex microfluidic reactors, scant attention has been paid to the "easy to fabricate" and simple millifluidic systems that could provide the required control as well as high throughput. By utilizing numerical simulation of fluids within the millifluidic space at different flow rates, the results presented here show velocity profiles and residence time distributions similar to the case of microfluidics. By significantly reducing the residence time and residence time distribution, a continuous flow synthesis of ultrasmall copper nanoclusters (UCNCs) with exceptional colloidal stability is achieved. In-situ synchrotron-radiation-based X-ray absorption spectroscopy (XAS) reveal that the as-prepared clusters are about 1 nm, which is further supported by transmission electron microscopy and UV-vis spectroscopy studies. The clusters reported here are the smallest ever produced using a lab-on-a-chip platform. When supported on silica, they are found to efficiently catalyze C-H oxidation reactions, hitherto unknown to be catalyzed by Cu. This work suggests that a millifluidic platform can be an inexpensive, versatile, easy-to-use, and powerful tool for nanoparticle synthesis in general, and more specifically for ultrasmall nanoclusters (UNCs).