Authors: Anna Gonzàlez‐Rosell | Stacy M. Copp
Source: Accounts of Chemical Research (review, 2024-07-12)
Field: Materials Science — Materials Chemistry

An Atom-Precise Understanding of DNA-Stabilized Silver Nanoclusters DNA-stabilized silver nanoclusters (Ag<sub>N</sub>-DNAs) are sequence-encoded fluorophores. Like other noble metal nanoclusters, the optical properties of Ag<sub>N</sub>-DNAs are dictated by their atomically precise sizes and shapes. What makes Ag<sub>N</sub>-DNAs unique is that nanocluster size and shape are controlled by nucleobase sequence of the templating DNA oligomer. By choice of DNA sequence, it is possible to synthesize a wide range of Ag<sub>N</sub>-DNAs with diverse emission colors and other intriguing photophysical properties. Ag<sub>N</sub>-DNAs hold significant potential as "programmable" emitters for biological imaging due to their combination of small molecular-like sizes, bright and sequence-tuned fluorescence, low toxicities, and cost-effective synthesis. In particular, the potential to extend Ag<sub>N</sub>-DNAs into the second near-infrared region (NIR-II) is promising for deep tissue imaging, which is a major area of interest for advancing biomedical imaging. Achieving this goal requires a deep understanding of the structure-property relationships that govern Ag<sub>N</sub>-DNAs in order to design Ag<sub>N</sub>-DNA emitters with sizes and geometries that support NIR-II emission. In recent years, major advances have been made in understanding the structure and composition of Ag<sub>N</sub>-DNAs, enabling new insights into the correlation of nanocluster structure and photophysical properties. These advances have hinged on combined innovations in mass characterization and crystallography of compositionally pure Ag<sub>N</sub>-DNAs, together with combinatorial experiments and machine learning-guided design. A combined approach is essential due to the major challenge of growing suitable Ag<sub>N</sub>-DNA crystals for diffraction and to the labor-intensive nature of preparing and solving the molecular formulas of atomically precise Ag<sub>N</sub>-DNAs by mass spectrometry. These approaches alone are not feasibly scaled to explore the large sequence space of DNA oligomer templates for Ag<sub>N</sub>-DNAs. This account describes recent fundamental advances in Ag<sub>N</sub>-DNA science that have been enabled by high throughput synthesis and fluorimetry together with detailed analytical studies of purified Ag<sub>N</sub>-DNAs. First, short introductions to nanocluster chemistry and Ag<sub>N</sub>-DNA basics are presented. Then, we review recent large-scale studies that have screened thousands of DNA templates for Ag<sub>N</sub>-DNAs, leading to discovery of distinct classes of these emitters with unique cluster core compositions and ligand chemistries. In particular, the discovery of a new class of chloride-stabilized Ag<sub>N</sub>-DNAs enabled the first <i>ab initio</i> calculations of Ag<sub>N</sub>-DNA electronic structure and present new approaches to stabilize these emitters in biologically relevant conditions. Near-infrared (NIR) emissive Ag<sub>N</sub>-DNAs are also found to exhibit diverse structures and properties. Finally, we conclude by highlighting recent proof-of-principle demonstrations of NIR Ag<sub>N</sub>-DNAs for targeted fluorescence imaging. Continued efforts may future push Ag<sub>N</sub>-DNAs into the tissue transparency window for fluorescence imaging in the NIR-II tissue transparency window. Nanoclusters ; Atom (system on chip) ; Nanotechnology ; Chemistry ; Chemical physics ; Materials science ; Crystallography ; Computer science Nanocluster Synthesis and Applications ; Gold and Silver Nanoparticles Synthesis and Applications ; Advanced Nanomaterials in Catalysis