Rapid and Large-Scale Synthesis of Chiral Fluorescent Sulfur Quantum Dots for Intracellular Temperature Monitoring

Academic Background

Fluorescent nanomaterials have broad application potential in fields such as energy harvesting, lighting displays, communication and information technology, biology, and medicine. Among them, sulfur quantum dots (SQDs), as a novel type of metal-free quantum dots, have attracted increasing attention in recent years due to their environmental friendliness, excellent biocompatibility, and tunable surface chemistry. However, the large-scale preparation of SQDs and their application in consumer markets still face challenges, particularly due to the time-consuming nature of their synthesis and the difficulty in obtaining high-quality products in a short time. Therefore, developing a rapid, large-scale synthesis method for SQDs and exploring their applications in biomedicine have become a current research focus.

This study aims to address the time-consuming issues in the preparation of SQDs and proposes a universal strategy for rapid, large-scale synthesis. By leveraging the ability of sulfide species’ empty 3d orbitals to bind with lone-pair π electrons of nitrogen- or oxygen-containing groups, the researchers developed a method to prepare SQDs with blue fluorescence and chiral properties within 10 minutes. Additionally, the study explores the application of SQDs in intracellular temperature monitoring, providing a new tool for the diagnosis of inflammation-related diseases.

Source of the Paper

This paper was co-authored by Li Zhao, Tianjian Sha, Yufu Liu, Qingsong Mei, Haibin Li, Pinghua Sun, Haibo Zhou, and Huaihong Cai from the College of Pharmacy, School of Medicine, and College of Chemistry and Materials Science at Jinan University. The paper was published on September 20, 2024, in the journal Chemical & Biomedical Imaging, titled “Rapid and Large-Scale Synthesis of Chiral and Fluorescent Sulfur Quantum Dots for Intracellular Temperature Monitoring.”

Research Process and Results

1. Rapid Synthesis of Sulfur Quantum Dots

The researchers developed a rapid reaction strategy based on sulfur powder, sodium hydroxide, and amino-group-containing compounds (such as amino acids or polyethyleneimine). The specific steps are as follows:

• Precursor Preparation: Sulfur powder, sodium hydroxide, and amino-group-containing compounds (e.g., L-cysteine) were dissolved in water and stirred at 90°C for 10 minutes to form a transparent orange precursor solution.
• Oxidation Reaction: Hydrogen peroxide (H₂O₂) was added to the precursor solution, causing the solution color to rapidly change from orange to colorless. Under 365 nm UV light irradiation, the solution emitted blue fluorescence, forming SQDs.

This method allows the preparation of SQDs within 10 minutes, with a yield of up to 16.844 grams per batch, significantly improving production efficiency.

2. Structural Characterization of SQDs

Transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM) observations revealed that SQDs exhibit an inhomogeneous spherical structure with a diameter of approximately 4 nm. HRTEM images showed clear lattice fringes with a spacing of 0.21 nm, consistent with literature reports. Additionally, Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses indicated that SQDs contain sulfur elements, sulfonate groups, and cysteine molecules on their surfaces, further validating the structural model.

3. Optical Properties and Chirality Study

SQDs exhibited a distinct absorption peak at 215 nm in the UV-visible absorption spectrum, attributed to n → σ* transitions. Under 370 nm excitation, SQDs emitted blue fluorescence at 460 nm, with fluorescence intensity varying depending on the excitation wavelength, demonstrating excitation-dependent photoluminescence properties. Furthermore, circular dichroism (CD) spectroscopy confirmed the chiral properties of SQDs, indicating that their chirality originates from cysteine molecules.

4. Temperature-Dependent Fluorescence Properties

SQDs exhibited reversible temperature-dependent fluorescence properties, with fluorescence intensity gradually decreasing as temperature increased. Within the range of 20-50°C, the change in fluorescence intensity showed a linear relationship with temperature, with a sensitivity of 0.72%/°C. This property enables SQDs to serve as nanothermometers for intracellular temperature monitoring, aiding in the diagnosis of inflammation-related diseases.

5. Application in Intracellular Temperature Monitoring

Through MTT assays, the researchers verified the excellent biocompatibility of SQDs, with Hela cell viability exceeding 85% even at a concentration of 200 μg/mL. Using confocal laser scanning microscopy (CLSM), the researchers successfully monitored changes in fluorescence intensity in Hela cells under different temperature conditions, demonstrating the potential of SQDs for intracellular temperature monitoring.

Conclusions and Significance

This study developed a rapid, large-scale synthesis strategy for SQDs, significantly improving production efficiency and successfully applying them to intracellular temperature monitoring. The research not only lays the foundation for the commercial application of SQDs but also provides a new tool for the diagnosis of inflammation-related diseases. Additionally, the chiral properties of SQDs open up new possibilities for their application in chiral recognition, chiral detection, and asymmetric catalysis.

Research Highlights

1. Rapid Large-Scale Synthesis: This study proposes a method to prepare high-quality SQDs within 10 minutes, with a yield of up to 16.844 grams per batch, significantly improving production efficiency.
2. Chiral Properties: By using chiral amino acids (e.g., L-cysteine), the researchers successfully endowed SQDs with chiral properties, providing new insights for their application in chiral-related fields.
3. Temperature Monitoring Application: SQDs exhibited excellent temperature-dependent fluorescence properties, with a sensitivity of 0.72%/°C, enabling their use in intracellular temperature monitoring and offering a new tool for diagnosing inflammation-related diseases.

Additional Valuable Information

This study also explored the effects of different nitrogen- or oxygen-containing ligands (e.g., tyrosine, serine, tryptophan, and polyethyleneimine) on the fluorescence properties of SQDs. It was found that aromatic amino acid ligands could induce SQDs to emit longer-wavelength fluorescence. This discovery provides new insights for tuning the fluorescence color of SQDs, with potential for further optimization of their optical properties in future research.

This study not only addresses the time-consuming issues in the preparation of SQDs but also provides new possibilities for their application in biomedicine and chiral-related fields, holding significant scientific and practical value.