Richard Whalley

Massachusetts Institute of Technology

Ting Laboratory
Mentors: Peng Zhou and Dan Liu

Summer 2008

Synthesis of a Quantum Dot with Smaller and More Robust Tetravalent Ligands Specialized for Cell Imaging

Quantum Dots (QD) are fluorescent nanoparticles with extremely bright and narrow emission bandwidth. These properties make QDs an ideal candidate for live cell imaging. The structure of QDs consists of an inorganic, semiconductive crystal core of cadmium selenide (CdSe), a zinc sulfide coating and, often, a second organic ligand coating to make it suitable for live cell imaging.

The goal of my project is to develop a novel, strong-binding ligand for QD surfaces, which will stabilize them in an aqueous environment and hence render them suitable for cellular labeling and imaging. By further conjugating each QD to one monovalent streptavidin molecule, I hope to develop these new QDs for labeling mammalian cell surface receptors via a biotin ligase-based targeting approach, previously developed in the Ting Lab.   The new QD ligands are designed to have four thiol functionalities on one end for QD surface coordination and a polyethylene glycol (PEG) tail for aqueous solubilization.   The PEG tail is functionalized with a carboxylate on the other end, allowing for electrophoretic isolation of monovalent streptavidin conjugated QDs.  

My ligand synthesis began with the reduction of lipoamide to lipoamine, (A), followed by conjugation to the carboxyl groups of aspartic acid to form (C). The aspartate amine was then conjugated to a di-carboxyl polyethylene glycol molecule, (B), which was derived from PEG 400 via oxidation, to form (D). A final reduction of the two dithiolane moieties of lipoamine will give the thiol groups to be used for chelation, shown as compound (E). The Bawendi research group has previously synthesized and utilized divalent ligands.   With the creation of this new, tetravalent ligand, I hope to demonstrate increased stability and biological utility.