Laluk Andrew L D M, Buschmann Dennis A, Takano Shinjiro, Sullivan Angus I, Aminfar Parimah, Stamplecoskie Kevin, Tsukuda Tatsuya, Crudden Cathleen M
Department of Chemistry, Queen's University, Chernoff Hall Kingston Ontario K7L 3N6 Canada
Carbon to Metal Coating Institute, Queen's University Kingston Ontario K7L 3N6 Canada.
Chem Sci. 2025 Jul 31. doi: 10.1039/d5sc02951a.
There is significant potential use for gold nanoclusters in biomedicine owing to their favorable biological and optical properties. To access this potential, there is a need for methods to alter the ligand scaffold of gold nanoclusters to tune their biological properties. Surface modifications to the ligands must occur with molecular precision to generate monodisperse products for the accurate determination of structure activity relationships and eventual translation to clinical practice. Herein, we describe methods for molecularly precise surface modifications to Au nanoclusters amide couplings to -COOH functionalities and their stability to conditions necessary for the removal of protecting groups used in amide coupling chemistry. These clusters were found to be highly stable to basic conditions for the removal of base-labile -Fmoc and -OMe groups but less stable to acidic conditions for the removal of acid-labile -Boc and -O Bu groups. The ligand shell and Au core of such clusters were found to be preserved following modifications to the ligand shell allowing the solubility and biological properties of the cluster to be altered independently of their optical properties. The nature of the protecting ligand was found be instrumental for cluster stability to enable the use of the harsh conditions necessary to yield monodisperse products.
由于金纳米团簇具有良好的生物学和光学性质，它们在生物医学领域具有巨大的潜在应用价值。为了挖掘这种潜力，需要有方法来改变金纳米团簇的配体支架，以调节其生物学性质。对配体的表面修饰必须达到分子精度，以生成单分散产物，用于准确确定结构活性关系，并最终转化为临床应用。在此，我们描述了对金纳米团簇进行分子精确表面修饰的方法——与羧基官能团进行酰胺偶联，以及它们对酰胺偶联化学中用于去除保护基团所需条件的稳定性。发现这些团簇对用于去除碱不稳定的芴甲氧羰基（-Fmoc）和甲氧基（-OMe）基团的碱性条件具有高度稳定性，但对用于去除酸不稳定的叔丁氧羰基（-Boc）和叔丁酯（-O Bu）基团的酸性条件稳定性较差。发现对配体壳层进行修饰后，此类团簇的配体壳层和金核得以保留，从而可以独立于其光学性质改变团簇的溶解性和生物学性质。发现保护配体的性质对团簇稳定性至关重要，以便能够使用产生单分散产物所需的苛刻条件。
