Thioctic Acid-Based Compact Hydrophilic Ligands for Biocompatible Quantum Dots and Gold Nanoparticles: Facile Synthesis and Improved Utility

We describe the facile synthesis of three different classes of nanoparticle (NP) surface ligands that are particularly useful to prepare hydrophilic, biocompatible semiconductor quantum dots (QDs) and gold nanoparticles (AuNPs). The ligands consist of a bidentate thioctic acid (TA) or dihydrolipoic acid anchor group, allowing for high-affinity NP attachment, and are synthesized in a simple manner without compromising the hydrophilicity and utility for further applications. First, we applied a trifluoroacetamide protecting group to amine-terminated TA-based ligands to suppress irreversible gelation, which is common with amine-appended TA-based ligands. Both the protection and deprotection steps were straightforward, and the successful in situ deprotection was demonstrated by gel electrophoresis and dye conjugation assays. Second, our TA-based zwitterionic ligands with a bis(carboxyethyl)amino group were integrated with oligo(ethylene glycol) or poly(ethylene glycol) (PEG) groups to enhance the biocompatibility. Their antifouling properties were examined by a gel electrophoresis assay with bovine serum albumin. Lastly, hydroxy-terminated branched TA-based ligands were synthesized using a minimum number of steps as alternatives to hydroxy-terminated TA-based PEG ligands, which require laborious purification steps. The utility of the compact hydroxy-terminated ligands was further demonstrated by (i) gel electrophoresis assays to explore their antifouling properties and (ii) photoluminescence wavelength tuning during the direct aqueous synthesis of luminescent gold nanoclusters. Inherent benefits of the ligand design were demonstrated beyond QDs as AuNPs functionalized with the same compact ligand series showed similar colloidal properties. The simple designs along with a variety of proven utilities highlight the strong potential of these ligands to expand NP capabilities in many biological applications.