Multifunctional ligands based on dihydrolipoic acid and polyethylene glycol to promote biocompatibility of quantum dots

One of the common strategies to promote the transfer of quantum dots (QDs) to buffer media and to couple them to biological molecules has relied on cap exchange. We have shown previously that dihydrolipoic acid (DHLA) and polyethylene glycol (PEG)-appended DHLA can effectively replace the native ligands on CdSe-ZnS QDs. Here we explain in detail the synthesis of a series of modular ligands made of the DHLA-PEG motif appended with terminal functional groups. This design allows easy coupling of biomolecules and dyes to the QDs. The ligands are modular and each is comprised of three units: a potential biological functional group (biotin, carboxylic acid and amine) and a DHLA appended at the ends of a short PEG chain, where PEG promotes water solubility and DHLA provides anchoring onto the QD. The resulting QDs are stable over a broad pH range and accessible to simple bioconjugation techniques, such as avidin-biotin binding.