Engineering Fluorescent Gold Nanoclusters Using Xanthate-Functionalized Hydrophilic Polymers: Toward Enhanced Monodispersity and Stability

Abstract

We introduce xanthate-functionalized poly(cyclic imino ethers)s (PCIEs), specifically poly(2-ethyl-2-oxazoline) and poly(2-ethyl-2oxazine) given their stealth characteristics, as an attractive alternative to conventional thiol-based ligands for the synthesis of highly monodisperse and fluorescent gold nanoclusters (AuNCs). The xanthate in the PCIEs interacts with Au ions, acting as a well-controlled template for the direct formation of PCIE-AuNCs. This method yields red-emitting AuNCs with a narrow emission peak (λ em = 645 nm), good quantum yield (4.3−4.8%), long fluorescence decay time (∼722−844 ns), and unprecedented product yield (>98%). The PCIE-AuNCs exhibit long-term colloidal stability, biocompatibility, and antifouling properties, enabling a prolonged blood circulation, lower nonspecific accumulation in major organs, and better renal clearance when compared with AuNCs without polymer coating. The advances made here in the synthesis of metal nanoclusters using xanthate-functionalized PCIEs could propel the production of highly monodisperse, biocompatible, and renally clearable nanoprobes in large-scale for different theranostic applications.

Bright Future of Gold Nanoclusters in Theranostics

“…We recently developed a method aiming to overcome these challenges by employing a xanthate-functionalized polymer as a ligand to template and stabilize AuNCs. 6 Poly(cyclic imino ether)s (PCIEs) were designed and synthesized with a xanthate terminal group which served as an attractive alternative to thiolated ligands. The new method yielded a highly monodispersed PCIEs-AuNCs with excellent optical properties such as narrow emission (λ em = 645 nm), long fluorescence decay time (∼722−844 ns), and good quantum yield (4.3−4.8%).…”

“…While proteins provide certain advantages such as allowing a one-pot synthesis approach in aqueous solution–mostly advantageous for biomedical applications–protein-protected AuNCs are a complex marriage hard to structurally characterize, making their structure–property relationship difficult to predict or elucidate . This is why the use of other ligands such as polymers, , including dendrimers, peptides, , including single amino acids, and DNA to synthesize AuNCs is emerging in the literature (Figure E,F), as they offer a higher degree of programmability. For example, by manipulating the nature of the polymer, peptide, or DNA, the metal–ligand charge transfer can be optimized toward a maximized photoluminescence …”

“…The size, composition, and atomic packing of the Au core and Au-ligand interface will be key to the AuNC structure–property relationship. The size, length, and charge of the ligand also define certain physicochemical properties of AuNCs such as structural and colloidal stability, symmetry, and interaction with biological barriers, such as the ability to penetrate deeper within tumors or be renally cleared. − For examples, AuNCs have been shown to have high stability in serum and urine without affecting their size or catalytic activity, which is a clear advantage over commonly used enzymes as they are prone to be degraded . Moreover, the intrinsic chirality of AuNCs given their asymmetry in metal atomic packing or surface ligand arrangement could be further harnessed for catalytic purposes .…”

Lysozyme-Functionalized 5-Methyl-2-thiouracil Gold/Silver Nanoclusters for Luminescence Assay of Alkaline Phosphatase

“…4 Meanwhile, the monodisperse NCs are easily obtained via various synthesis strategies (microwave-assisted methods, 5 hydrothermal, 6 heating and stirring method, 7 etc.) and numerous ligands (thiolates, 8 peptides, 9 proteins, 10 polymers, 11 and phosphines 12 ). However, inhomogeneous and low quantum yields (QYs) of NCs greatly restrict their optical applications.…”

pH and Redox Dual-Response Disulfide Bond-Functionalized Red-Emitting Gold Nanoclusters for Monitoring the Contamination of Organophosphorus Pesticides in Foods

“…Still, studies of AuNCs on OP screening are scarcely reported. To the best of our knowledge, only 12 related works have been reported. − However, most of them (10) detect OPs through the unique response of signalers to thiocholine and require additional quenchers, and the other two sensors are built based on OPs’ depression on trypsin or alkaline phosphatase activity, which might not like AChE to be specifically inhibited by OPs. , In addition, most of the AuNCs are prepared using monothiol compounds, BSA, and polyethyleneimine as reductants and only have −OH, −NH 2 , and −COOH groups; thus, developing AuNCs with new functionalized groups is in high demand.…”