Photoligation combined with zwitterion-modified lipoic acid ligands provides compact and biocompatible quantum dots.

We describe the design and synthesis of a series of compact ligands made of lipoic acid (LA)-based coordinating anchors and hydrophilic zwitterion groups. This ligand design is combined with a novel photoligation strategy to promote the transfer of QDs to polar and buffer media. This approach has provided hydrophilic QDs that exhibit great colloidal stability over a broad range of pHs and in the presence of cell culture media. Our photoligation strategy drastically improves previous phase transfer methods by eliminating the need for chemical reduction of the dithiolane ring using NaBH4 prior to the cap exchange, and it is adapted to several LA-based ligands. We also found that QDs stabilized with these compact zwitterionic ligands are fully compatible with metal-histidine-driven self-assembly where the protein activity is maintained after forming conjugation with the QDs.