Date of Award
Master of Science (MSc)
Chemistry and Chemical Biology
The synthesis of new macromolecular diagnostic imaging agents has been a growing field in polymeric chemistry research. Dendrimers provide a viable scaffold for such applications due to their unique, defined macromolecular architecture. The precise structural control afforded via the step-wise synthesis of dendrimers yields exceptional and precise macromolecules that can be functionalized to include necessary imaging moieties with the same degree of precision.
We have herein contributed to this growing field by attempting the synthesis of a series of PEGylated poly(2,2-bis[hydroxymethyl]propanoic acid) PMPA dendrons using thiol-ene "click" chemistry. The series consisted of three dendritic architectures peripherally functionalized with poly(ethylene glycol) (PEG) chains of varying length (n= 3, 8, 16), with the goal of determining the effect of PEG chain length on blood circulation times. Synthesis of these conjugates began first with functionalization of the dendron periphery to incorporate alkene functionalities using anhydride-mediated esterification chemistry.
The core of the alkene PMPA dendrons was then modified to introduce a metal chelating bis-pyridyl functionality, which has been observed to chelate the radionuclide technetium-99m (99mTc) with high binding affinity. 99mTc is the most widely used diagnostic radioisotope in diagnostic medicine due to its ideal isotopic properties, widespread availability, low cost, and its ability to be traced, in real time, in vivo using Single Photon Emission Computed Tomography (SPECT).
PEGylation at the periphery was performed by thiol-ene “click” chemistry using thiol-terminated PEG chains. Metallation of the core of each PEGylated dendron was then attempted according to literature procedures for 99mTc radiolabeling with the bis-pyridyl chelate.
Knight, Spencer D., "The Synthesis of Dendrimer-based Radioimaging Agents" (2012). Open Access Dissertations and Theses. Paper 7328.
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