Towards the Preparation of Novel Re/99mTc Tricarbonyl-Containing Peptide Nucleic Acid Bioconjugates

Abstract

A novel azido derivative of the di-(2-picolyl)amide (Dpam) ligand, namely 3-azido-N,N-bis-pyridin-2-ylmethyl-propionamide (3), was prepared from 3-bromo-N,N-bis(pyridin-2-ylmethyl)propanamide (2) with an excess of sodium azide in DMSO. 3 was then reacted, by CuI-catalyzed [3 + 2] cycloaddition (often referred to as ‘Click Chemistry’), with the previously reported alkyne-containing peptide nucleic acid (PNA) monomer Fmoc-1-OtBu to give the Dpam-containing PNA monomer (Fmoc-4-OtBu) in 44% yield. It was also demonstrated that 3 could be reacted by Click Chemistry, on the solid phase, to an alkyne-containing PNA oligomer (Alkyne-PNA) to yield Dpam-PNA. Our attempts to complex Dpam-PNA with [NEt4]2[ReBr3(CO)3] and [99mTc(CO)3(H2O)3]+ are also discussed in detail.