Multi-dentate ligands enabling a quick and high yield water transfer of inorganic nanocrystals (NCs) via a ligand exchange process is of great interest to promote the applications of NCs in the biomedical field. Here, we describe a facile two-step protocol for the synthesis of polymeric multi-dentate ligands that are suitable for the water transfer of hydrophobic colloidal inorganic nanocrystals (NCs). This protocol first exploits the photo-induced atom transfer radical (photo-ATRP) copolymerization of ester-activated N-succinimidyl methacrylate and oligoethylene glycol methyl ether methacrylate. A high monomer conversion rate along with a fair control over the polymerization is confirmed by size exclusion chromatography and nuclear magnetic resonance spectroscopy. In the second step, the activated carboxyl moieties of the copolymers are reacted with nucleophilic agents such as 2-aminoethylphosphonic acid or histamine dihydrochloride via a post-polymerization reaction to generate phosphonic- or amino-based multi-dentate ligands, respectively. As shown here, polymers comprising poly-phosphonic acid moieties are suitable as multi-dentate ligands for water transfer of multiple varieties of NCs with distinct compositions including iron oxide nanoparticles, CdSe@CdS quantum dots (QDs) and up-converting nanoparticles (UCNPs). Meanwhile the polymers containing histamine groups are also able to strongly coordinate to the surface of semiconductor QDs, thus enabling their water transfer. Notably, the NCs exhibit long-term stability in physiological media (saline) upon water transfer, while their size, shape, magnetic properties, and optical properties were also maintained. The UCNPs could be imaged when excited under an infrared laser while the QDs show a bright fluorescence signal under UV irradiation. QDs coated with a poly-phosphonic acid-based ligand resulted in a more homogeneous coating as demonstrated by the narrow band on gel electrophoresis, along with a higher quantum yield (QY ∼48%) in comparison with the polyimidazole-based ones (QY ∼31%). The aqueous IONPs instead were proven to provide a transversal relaxation making them useful as contrast agents in magnetic resonance imaging. The water transfer procedure is straightforward thanks to the full solubility of the amphiphilic polymer in the NC chloroform solution. This enables the right interaction between the anchoring moieties on the polymer chains and the surface of NCs, thus replacing the surfactant molecules. The gram scale production of the polymer together with the very simple steps of the water transfer protocol enables a quick translation of the protocol for large scale production of aqueous stabilized nanoparticles.

中文翻译：

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活化酯甲基丙烯酸酯聚合物的光诱导铜介导共聚及其作为反应性前体来制备用于无机纳米颗粒水转移的多齿配体的用途

能够通过配体交换过程实现无机纳米晶体（NCs）的快速，高产率的水转移的多齿配体，对于促进NCs在生物医学领域的应用具有极大的兴趣。在这里，我们描述了一种适用于疏水性胶体无机纳米晶体（NCs）的水转移的聚合多齿配体合成的简便两步协议。该协议首先利用了酯活化N的光诱导原子转移自由基（photo-ATRP）共聚-甲基丙烯酸琥珀酰亚胺基酯和低聚乙二醇甲基醚甲基丙烯酸酯。通过尺寸排阻色谱法和核磁共振波谱证实了高单体转化率以及对聚合的合理控制。在第二步中，使共聚物的活化羧基与亲核试剂（例如2-氨基乙基膦酸或组胺二盐酸盐）通过后聚合反应分别生成基于膦酸或氨基的多齿配体。如此处所示，包含多膦酸部分的聚合物适合作为多齿配体，用于水转移具有不同成分的多种NC分子，包括氧化铁纳米粒子，CdSe @ CdS量子点（QD）和上转换纳米粒子（UCNP） 。同时，含有组胺基团的聚合物还能够与半导体量子点的表面强烈配位，从而实现水的转移。值得注意的是，NCs在水转移后在生理介质（盐水）中显示出长期稳定性，同时它们的尺寸，形状，磁性能和光学性能也得以保持。当在红外激光下激发时，UCNP可以成像，而QD在UV辐射下显示出明亮的荧光信号。凝胶电泳上的窄带表明，涂有多膦酸基配体的量子点产生了更均匀的涂层，与基于聚咪唑的量子点相比，量子产率更高（QY〜48％） 31％）。相反，已证明水性IONP提供横向松弛，使其在磁共振成像中可用作造影剂。由于两亲聚合物在NC氯仿溶液中的完全溶解性，水的转移过程非常简单。这使聚合物链上的锚定部分与NC的表面之间实现正确的相互作用，从而取代了表面活性剂分子。