A responsive particulate MRI contrast agent for copper(i): A cautionary tale

A responsive MION-based MRI contrast agent for the detection of copper(i) is presented. Induced agglomeration of azide and acetylene-functionalized magnetite nanoparticles via Cu(i)-catalysed Huisgen cycloaddition leads to significant decrease in longitudinal relaxivity due to the slow exchange of water molecules trapped within the cluster with bulk solvent. Agglomeration leads to an initial two-fold increase followed by a sharp and almost complete loss in transverse relaxivity for clusters larger than 200 nm in size. The decrease in r ₂ for clusters reaching the static dephasing regime has two significant implications for particulate responsive MRI contrast agents. First, the maximum increase in r ₂ is barely two-fold, second, since r ₂ does not increase continuously with increasing cluster size, the r ₁/r ₂ ratio cannot be used to determine the concentration of an analyte ratiometrically.