Molecular Sensors Operating by a Spin‐State Change in Solution: Application to Magnetic Resonance Imaging

Abstract

Recent proposals for molecular switches are reviewed that adopt a different spin state before and after the encounter with an analyte (metabolite) or physical stimulus (light). Spin‐state switching has significant potential to provide molecular MRI with a first line of probes operating by an off/on mode. Past efforts to design MRI sensors relied on strategies other than spin‐switching and thus mostly comprised probes only modulating the signal before and after encounter with the analyte (X%‐on/Y%‐on). The article thus essentially treats small‐molecule metal ion chelates, i.e. coordination compounds. Initially, a comprehensive treatment of design considerations for optimal spin‐state switches is furnished. The article then enters into a treatment of reported examples of spin‐state switches according to three response mechanisms: 1) changes in the redox state of the metal center; 2) changes in coordination geometry; and 3) modification of the surrounding ligand field, either by peripheral interaction with the analyte, or by replacement of a coordinating ligand by another.

Bioimaging agents based on redox-active transition metal complexes

“…1). [48][49][74][75][76][77][78][79] The small pH changes in living systems may result in serious diseases, which makes it meaningful to develop pH-responsive probes detecting pH changes at physiological ranges. Gale's group developed a pH-responsive Fe(III)-based MR imaging probe (14, Fig.…”

“…76 Hasserodt's group also published some interesting studies using the spin switchable iron complexes. 77 They designed two binary Fe(II) complexes (19-20, Fig. 1) of a large ring hexadentate N6 ligand with two picolyl pendent arms with high stability and low-spin diamagnetic state.…”

Low-Molecular-Weight Fe(III) Complexes for MRI Contrast Agents

“…Generally, changing the third ancillary group into a coordination group such as the above triazole groups or the hydroxypropyl (Fe(III)-NOHP) [55], phosphonate (Fe(III)-NOTP) [56], carboxylate (Fe(III)-NOTA) [56], or amides (Fe(III)-TOCs or Fe(III)-TOCO151) [57] pendants produces coordinatively saturated Fe(III) complexes without the inner-sphere water ligands, and therefore giving rise to lower relaxivities of the Fe(III) complexes (Table 2). Fe(III) macrocyclic complexes with switching spin-states upon stimulus have significant potential to provide molecular MRI contrast agents that respond by a change in their relaxivity [58]. One of example is the hydrogen bonding interaction-triggered spin-state switching of a five-coordinate iron-(III) octaethyltetraarylporphyrin chloride reported by de Visser and Prasad Rath [59].…”

“…In contrast, the cis isomer does not bind to the iron porphyrin due to the sterical hindrance. It can be replaced by Fe(III) macrocyclic complexes with switching spin-states upon stimulus have significant potential to provide molecular MRI contrast agents that respond by a change in their relaxivity [58]. One of example is the hydrogen bonding interaction-triggered spin-state switching of a five-coordinate iron-(III) octaethyltetraarylporphyrin chloride reported by de Visser and Prasad Rath [59].…”

“…This study provided a beautiful example of weak external perturbations to switch the spin states of Fe(III) macrocyclic complexes, but the experiments were conducted in organic solution instead of aqueous solution, and the relaxivities of these two states were not reported. Fe(III) macrocyclic complexes with switching spin-states upon stimulus have significant potential to provide molecular MRI contrast agents that respond by a change in their relaxivity [58]. One of example is the hydrogen bonding interaction-triggered spin-state switching of a five-coordinate iron-(III) octaethyltetraarylporphyrin chloride reported by de Visser and Prasad Rath [59].…”