Copolymerization and Synthesis of Multiply Binding Histamine Ligands for the Robust Functionalization of Quantum Dots

Abstract

The polymeric functionalization of quantum dots via ligand exchange is a robust method for the preparation of stable fluorescent particles with high quantum yields. For most biological applications of quantum dots, water solubility is a key requirement; to achieve biocompatibility, polymeric ligand systems that can provide water solubility as well as effective anchoring groups are advantageous. In this work, histamine functional polymers bearing poly(ethylene glycol) (PEG) side chains were prepared using RAFT polymerization. A versatile postmodification strategy using activated ester units of Nmethacryloxysuccinimide (NMS) and poly(ethylene glycol) methacrylate in the polymer chain afforded copolymers ranging from 6K to 50K with low polydispersities, along with tailored composition of each monomer along the copolymer chain. By controlling the monomer ratio, PEGMA molecular weight, time, and temperature, the composition could be tuned to study its effect on quantum dot functionalization. Representative oleate-capped CdSe/Cd x Zn 1−x S QDs purified by a recently established gel permeation chromatography (GPC) method were used to test the effectiveness of the histamine-bearing polymers for preparation of water-soluble QDs. Successful ligand exchange of the QDs was characterized by good dispersions in water, lack of aggregation between QDs, and good quantum yields in water. Overall, the synthetic method demonstrates a facile and robust postmodification strategy for the formation of multiply binding, histamine-bearing copolymers, which can be applied to nanomaterials for fundamental investigations and bioimaging/biodistribution studies. ■ INTRODUCTIONIn the past decade, considerable progress has been seen in applications of semiconductor nanocrystals (quantum dots, QDs) in areas such as light-emitting diodes, 1 solar cells, 2 and bioimaging applications. 3,4 Based on the size and choice of material, the emission and absorption wavelengths of quantum dots can be tuned, allowing for narrow emission bands and high quantum yields. 5,6 The right choice of surface functional groups prevents aggregation of the quantum dots, allows for good dispersions in its environment, passivates the quantum dot surface, and maintains high fluorescence quantum yield. 7 This in turn allows for its successful implementation in various high performance applications.Hence, the need for soft functional materials that allow for quantum dots to be well dispersed in a variety of environments and facilitate stability over extended periods of time is essential. In the case of well-represented II−VI, III−V, and IV−VI compound semiconductors, colloidal quantum dots are synthesized with hydrophobic ligands such as oleic acid and trioctylphosphine; these ligands are necessary to manage precursor reactivity and colloidal stability during high-temperature growth but lead to QDs with low solubility in polar solvents. 7 Encapsulation with surfactants, silica shells, or amphiphilic copolymers can yield stable and water-soluble QDs but adds considerably to hy...

Photoligation of an Amphiphilic Polymer with Mixed Coordination Provides Compact and Reactive Quantum Dots

“…To address some of these limitations, polymer ligands presenting 3 multiple imidazole (or pyridine) groups have been developed as an alternative to thiol groups for coordination on the nanocrystal. 42,[44][45][46][47] Imidazole is not affected by this oxidation problem and has been found to potentially enhance the QD emission. 48 However, imidazole and pyridine exhibit weaker coordination affinity to the nanocrystal surfaces than thiols.…”

A methacrylate-based polymeric imidazole ligand yields quantum dots with low cytotoxicity and low nonspecific binding

“…The MA-PIL ligand includes multiple imidazole binding groups that could participate in a multidentate binding mode to the QD surface, poly(ethylene glycol) (PEG) chains to promote water solubility, and a methacrylate backbone [20]. Previous approaches to polymeric, multiply-binding ligands include modification of commercially available polyacrylic acid [18] and poly(maleic anhydrides) [17,19] with mixtures of thiols and/or imidazole binding groups, PEGs for water solubility, and/or functional handles; free-radical co-polymerization of thiol-functionalized methacrylates [16], and RAFT-mediated co-polymerization of functionalized acrylate monomers [15].…”

“…Wurtzite CdSe/CdZnS core/shell quantum dots and MA-PIL ligands were synthesized as described previously [20], PEG side-chains were incorporated using poly(ethylene glycol) methyl ether methacrylate 500 from Sigma–Aldrich. Bio-Beads S-X1 GPC medium was obtained from Bio-Rad Laboratories.…”

“…Multiply-binding polymeric ligands are designed to provide biocompatible QDs with increased stability compared to those terminated with small molecules bearing the same chelating groups, as well as a high degree of tunability on the basis of polymer composition and length. We recently described the synthesis of a series of polymeric imidazole ligands with a methacrylate backbone (MA-PILs) and their use in preparing water-soluble QDs [20]. The methacrylate monomers exhibit increased stability compared to acrylate monomers, facilitating the control of polymer ligand properties through RAFT polymerization kinetics.…”

Application of functional quantum dot nanoparticles as fluorescence probes in cell labeling and tumor diagnostic imaging

“…Compared with conventional organic fluorescent probes, QDs have shown great potential to be fluorescent probes and images in biology because of their unique optical properties [7][8][9][10][11][12][13][14][15]. Alivisatos and Nie employed QDs as fluorescent probes in biological staining and diagnostics that provided a novel study to display QDs as labels for cell and tissue research [16,17].…”