As depicted in Scheme 1, the multidentate polymer was synthesized by covalently modifying about 35% of the carboxylic acids of polyacrylic acid (PAA, MW ∼1800) with cysteamine and N-Fmocethylenediamine using diisopropylcarbodiimide (DIC) and N-hydroxysuccinimide (NHS). After deprotection of the amine with piperidine and purification, each polymer molecule contained approximately 3.5 active thiols and 3.0 active amines, as determined via Ellman's reagent and fluorescamine assays (see Supporting Information). For coating QDs, this balanced composition of amines and thiols was found to provide superior monodispersity, photostability, and fluorescence quantum yield compared to either amines or thiols alone. These multifunctional, multidentate polymers are soluble only in strongly polar solvents such as water, DMSO, and DMF. Because the CdTe QDs were prepared in a high temperature organic solvent using hydrophobic ligands (alkylamines, see Supporting Information), it is necessary to first exchange the native ligands with thioglycerol (Scheme 2). These polar monovalent ligands are then replaced with the multidentate ligand. A surprising finding is that stable, compactly coated QDs are produced only after heating (60−70°C) for 1−2 hours in DMSO under inert conditions. It is energetically favorable for the linear multidentate polymer to wrap around the QD in a closed configuration, but this highly ordered structure is kinetically slow to form at room temperature (see Scheme 2), so elevated temperatures are needed to speed up ligand exchange and loop closure.

Comparison of optical and hydrodynamic properties of CdTe QDs (2.5 nm) solubilized in water with an amphiphilic polymer (octylamine-modified polyacrylic acid) or a multidentate polymer ligand. (a) Absorption (blue curves) and fluorescence emission (red curves) spectra of CdTe QDs with amphiphilic polymer (upper) or multidentate polymer (lower) coatings. (b) Dynamic light scattering size data of QDs with amphiphilic polymer (blue curve) and multidentate polymer (green curve) coatings. PL = photoluminescence, AU = arbitrary units. All samples were dissolved in phosphate buffered saline.

Effects of polymer capping ratios on QD properties. (a) QD (2.5 nm) fluorescence quantum yield (blue curve) and polydispersity index (red curve) as a function of molar capping ratio, and (b) photostability data at various capping ratios (MCR = 1.5, 1.0, or 0.5) and in the absence of polymer (MCR = 0). See text for details.

(a) Gel filtration chromatograms of multidentate polymer coated CdTe QDs showing direct size comparison with protein standards (29, 43, 158, 440 kDa). (b) Fluorescence emission spectra from the corresponding QDs. The QD hydrodynamic sizes are 5.6 nm (2.5 nm core, blue), 6.6 nm (3.1 nm core, green), 7.8 nm (4.0 nm core, red), and 9.7 nm (6.0 nm core, brown).