Redox-Responsive MRI Probes Based on First-Row Transition-Metal Complexes

Abstract

The presence of multiple oxidation and spin states of first-row transition-metal complexes facilitates the development of switchable MRI probes. Redox-responsive probes capitalize on a change in the magnetic properties of the different oxidation states of the paramagnetic metal ion center upon exposure to biological oxidants and reductants. Transition-metal complexes that are useful for MRI can be categorized according to whether they accelerate water proton relaxation (T 1 or T 2 agents), induce paramagnetic shifts of 1 H or 19 F resonances (paraSHIFT agents), or are chemical exchange saturation transfer (CEST) agents. The various oxidation state couples and their properties as MRI probes are summarized with a focus on Co(II)/Co(III) or Fe(II)/Fe(III) complexes as small molecules or as liposomal agents. Solution studies of these MRI probes are reviewed with an emphasis on redox changes upon treatment with oxidants or with enzymes that are physiologically important in inflammation and disease. Finally, we outline the challenges of developing these probes further for in vivo MRI applications.

Copper(ii) complexes of cyclams withN-(2,2,2-trifluoroethyl)-aminoalkyl pendant arms as potential probes for19F magnetic resonance imaging

“…fat), or utilization of responsive ("smart") contrast agents which change their response according to the surrounding conditions. [8][9][10][11][12][13][14][15] Alternatively, NMR spectra of different tissues could be acquired in a method called magnetic resonance spectroscopy imaging (MRSI). 16,17 With increasing magnetic fields used in modern scanners, other NMR active nuclei such as 13 C (often hyperpolarized), 17,18 19 F, 23 Na, 31 P can be easily detected by MRI as well.…”

“…fat), or utilization of responsive (“smart”) contrast agents which change their response according to the surrounding conditions. 8–15 Alternatively, NMR spectra of different tissues could be acquired in a method called magnetic resonance spectroscopy imaging (MRSI). 16,17…”

Encapsulated or amphiphilic liposomal Fe(III) coordination complexes for MRI studies of tumor uptake and clearance

“…9 While Gd(III)-based probes show promise in molecular imaging through the incorporation of targeting moieties or activatable ligands, 10 paramagnetic transition metal complexes bring another level of responsiveness to molecular imaging through their ability to change oxidation states, spin states and their unique solution chemistry. [11][12][13] Moreover, transition metal complexes, especially those of Mn(II) and Fe(III) are of interest as alternatives for Gd(III) agents given that both metals are biocompatible. 11,12,14 Fe(III) agents in particular are of interest for further development in light of the body's ability to sequester, store and recycle iron.…”

“…11,12,14 Fe(III) agents in particular are of interest for further development in light of the body's ability to sequester, store and recycle iron. 15 Our laboratory focuses on the development of transition metal MRI probes, including CEST agents (Fe(II), Co(II) and Ni(II)), 13,16 liposomal CEST agents 17 and relaxivity agents such as high-spin Fe(III) complexes. 12 The development of Fe(III) based agents has many challenges 3 including overcoming low water solubility and lowered relaxivity 12,[18][19][20] and complicated solution chemistry.…”

“…This yielded N,N-distearyl-2-chloro-acetamide as white solid (98-99%). The product was characterized using 1 H NMR and 13 C NMR (Figure S1a and S2a).…”