Are Bidentate Ligands Really Better than Monodentate Ligands For Nanoparticles?

Abstract

Coordinating ligands are widely used to vary the solubility and reactivity of nanoparticles for subsequent bioconjugation. Although long-term colloidal stability is enhanced by using bidentate coordinating ligands over monodentate ones, other properties such as non-specific adsorption of target molecules and ligand exchange have not been quantified. In this study, we modified a near infrared dye to serve as a highly-sensitive reporter for non-specific binding of thiolated target molecules to nanoparticle surfaces that are functionalized with monodentate or bidentate coordinated ligands. Specifically, we analyzed non-specific binding mechanisms to quantum dots (QDs) by fitting the adsorption profiles to the Hill equation and the parameters are used to provide a microscopic picture of how ligand density and lability control non-specific adsorption. Surprisingly, bidentate ligands are worse at inhibiting adsorption to QD surfaces at low target:QD ratios, although they become better as the ratio increases, but only if the nanoparticle surface area is large enough to overcome steric effects. This result highlights that a balance between ligand density and lability depends on the dentate nature of the ligands and controls how molecules in solution can coordinate to the nanoparticle surface. These results will have major implications for a range of applications in nanobiomedicine, bioconjugation, single molecule spectroscopy, self-assembly and nano(photo)catalysis where both non-specific and specific surface interactions play important roles. As an example, we tested the ability of monodentate and bidentate functionalized nanoparticles to resist non-specific adsorption of IgG antibodies that contained free thiol groups at a 1:1 QD:IgG ratio and found that QDs with monodentate ligands did indeed result in lower non-specific adsorption.

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“…These forces can be produced by introducing charge or steric repulsion (Takeuchi et al, 2013) on the surface of the particle. Salts are one of the major components of biological fluids.…”