†Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306, United States.
‡Department of Chemistry and Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, United States.
J Am Chem Soc. 2015 Apr 29;137(16):5438-51. doi: 10.1021/jacs.5b00671. Epub 2015 Apr 14.
We introduce a new set of multicoordinating polymers as ligands that combine two distinct metal-chelating groups, lipoic acid and imidazole, for the surface functionalization of QDs. These ligands combine the benefits of thiol and imidazole coordination to reduce issues of thiol oxidation and weak binding affinity of imidazole. The ligand design relies on the introduction of controllable numbers of lipoic acid and histamine anchors, along with hydrophilic moieties and reactive functionalities, onto a poly(isobutylene-alt-maleic anhydride) chain via a one-step nucleophilic addition reaction. We further demonstrate that this design is fully compatible with a novel and mild photoligation strategy to promote the in situ ligand exchange and phase transfer of hydrophobic QDs to aqueous media under borohydride-free conditions. Ligation with these polymers provides highly fluorescent QDs that exhibit great long-term colloidal stability over a wide range of conditions, including a broad pH range (3-13), storage at nanomolar concentration, under ambient conditions, in 100% growth media, and in the presence of competing agents with strong reducing property. We further show that incorporating reactive groups in the ligands permits covalent conjugation of fluorescent dye and redox-active dopamine to the QDs, producing fluorescent platforms where emission is controlled/tuned by Förster Resonance Energy Transfer (FRET) or pH-dependent charge transfer (CT) interactions. Finally, the polymer-coated QDs have been coupled to cell-penetrating peptides to facilitate intracellular uptake, while subsequent cytotoxicity tests show no apparent decrease in cell viability.
我们引入了一组新的多配位聚合物作为配体，它们结合了两种不同的金属螯合基团，即硫辛酸和咪唑，用于 QD 的表面功能化。这些配体结合了硫醇和咪唑配位的优点，可以减少硫醇氧化和咪唑结合亲和力弱的问题。配体设计依赖于可控数量的硫辛酸和组氨酸锚定，以及亲水部分和反应性官能团，通过一步亲核加成反应接枝到聚（异丁烯-alt-马来酸酐）链上。我们进一步证明，这种设计与一种新的温和光交联策略完全兼容，可在无硼氢化条件下促进疏水性 QD 的原位配体交换和相转移到水相。用这些聚合物进行键合可提供高荧光 QD，在包括宽 pH 范围（3-13）、在纳摩尔浓度下储存、在环境条件下、在 100%生长培养基中和在具有强还原性质的竞争试剂存在下，具有出色的长期胶体稳定性。我们进一步表明，在配体中引入反应性基团可以使荧光染料和氧化还原活性多巴胺共价偶联到 QD 上，产生荧光平台，其中发射通过Förster 共振能量转移（FRET）或 pH 依赖性电荷转移（CT）相互作用来控制/调谐。最后，聚合物包覆的 QD 已与穿透细胞的肽偶联，以促进细胞内摄取，而随后的细胞毒性测试表明细胞活力没有明显下降。
