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

Abstract

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 r2 for clusters reaching the static dephasing regime has two significant implications for particulate responsive MRI contrast agents. First, the maximum increase in r2 is barely two fold, second, since r2 does not increase continuously with increasing cluster size, the r1/r2 ratio cannot be used to determine the concentration of an analyte ratiometrically.

Scaling laws at the nanosize: the effect of particle size and shape on the magnetism and relaxivity of iron oxide nanoparticle contrast agents

“…The contribution of each mechanism to the longitudinal relaxivity varies with both the strength of the applied magnetic field and the anisotropy of the maghemite or magnetite crystals, the latter being in turn a function of the size of the crystals 5 with larger iron oxide crystals being characterized by high crystal anisotropy. 12 For large nanoparticles, at low applied magnetic field, the magnetic moment is free to flip from one anisotropy direction to another and both the Néel relaxation and the Curie relaxation contribute to the longitudinal relaxivity which follows the Freed spectral density. 21 At high magnetic field, however, the magnetic moment is locked with the magnetic field direction and Néel relaxation is no longer possible.…”

Magnetoluminescent Light Switches – Dual Modality in DNA Detection

“…Unlike for longitudinal relaxation, the effects observed for transverse relaxivity arise from changes in the global structure of the cluster and the magnetic field surrounding it. As demonstrated by Gillis 47–48 and ourselves 41 , increase in transverse relaxivity with clustering of nanoparticles is only observed for small substrates and, most importantly, small clusters that maintain the motional averaging condition. 47–48 In these cases, the cluster itself behaves as a large magnetized sphere whose total magnetic moment increases according to Langevin’s law.…”

“…Such aggregation is known to affect both the longitudinal and the transverse relaxivity of superparamagnetic iron oxide nanoparticles, and is the basis for responsive particulate MRI contrast agents. 35–41 As such, the response of both probes to DNA was expected to be observable not only by luminescence but also by MRI.…”

A Magnetoplasmonic Imaging Agent for Copper(I) with Dual Response by MRI and Dark Field Microscopy

“…5 The thiol and acetyl terminated polymer was synthesized in a similar fashion from the commercial NHS-activated and BOC-protected PEG according to Scheme 1. In a first step, the acetylene functionality was added upon reaction with propargylamine.…”