Over the past decade, quantum dots (QDs) and gold nanoparticles (AuNPs) have attracted significant attention for biological sensing applications. Such interest is driven by their unique spectroscopic properties, including tunable emission and large extinction coefficients. Among the major challenges when designing QDs and AuNPs for use in biology is to design surface-functionalization strategies that provide long term stability over a broad range of biologically relevant conditions and are compatible with common bioconjugation techniques.

We have previously developed a series of compact and modular dihydrolipoic acid appended poly(ethylene glycol) (DHLA-PEG-OH) ligands, which can render QDs (via cap exchange strategy) water-soluble and functional (J. Am. Chem. Soc., 2005, 127: 3870-8). We report here the design of a new series of ligands that feature a more robust linkage group between the DHLA and PEG; the new ligands use an amide bond while the previously reported featured an ester bond. We have also developed a series of ligands with a variety of functional end groups, including biotin and carboxyl groups. Each of these ligands has a bidentate anchoring group, a variable length PEG to promote hydrophilicity, and a terminal group for bioconjugation.

Cap exchange of nanoparticles, both QDs and AuNPs, with the new ligands enabled their dispersion in aqueous buffer solutions. The dispersions were homogeneous and stable over a broad pH range (from 3 to 13 for CdSe/ZnS QDs and 2-13 for AuNPs) and in high ion concentration. Using DHLA-PEG-OCH3 either neat or mixed with amine- or carboxyl-terminated ligands (DHLA-PEG-NH2 or DHLA-PEG-COOH) allowed tuning of the surface functionalities of these nanoparticles, hence tailoring their interaction with their environment.