A macrocyclic quinol-containing ligand enables high catalase activity even with a redox-inactive metal at the expense of the ability to mimic superoxide dismutase.

Previously, we found that linear quinol-containing ligands could allow manganese complexes to act as functional mimics of superoxide dismutase (SOD). The redox activity of the quinol enables even Zn(ii) complexes with these ligands to catalyze superoxide degradation. As we were investigating the abilities of manganese and iron complexes with 1,8-bis(2,5-dihydroxybenzyl)-1,4,8,11-tetraazacyclotetradecane (Hqp4) to act as redox-responsive contrast agents for magnetic resonance imaging (MRI), we found evidence that they could also catalyze the dismutation of HO.

Diquinol Functionality Boosts the Superoxide Dismutase Mimicry of a Zn(II) Complex with a Redox-Active Ligand while Maintaining Catalyst Stability and Enhanced Activity in Phosphate Solution.

In the current work, we demonstrate ligand design concepts that significantly improve the superoxide dismutase (SOD) activity of a zinc complex; the catalysis is enhanced when two quinol groups are present in the polydentate ligand. We investigate the mechanism through which the quinols influence the catalysis and determine the impact of entirely removing a chelating group from the original hexadentate ligand. Our results suggest that SOD mimicry with these compounds requires a ligand that coordinates Zn(II) strongly in both its oxidized and reduced forms and that the activity proceeds through Zn(II)-semiquinone complexes.

A Highly Water- and Air-Stable Iron-Containing MRI Contrast Agent Sensor for H O.

A highly water- and air-stable Fe(II) complex with the quinol-containing macrocyclic ligand H qp4 reacts with H O to yield Fe(III) complexes with less highly chelating forms of the ligand that have either one or two para-quinones. The reaction increases the T -weighted relaxivity over four-fold, enabling the complex to detect H O using clinical MRI technology. The iron-containing sensor differs from its recently characterized manganese analog, which also detects H O , in that it is the oxidation of the metal center, rather than the ligand, that primarily enhances the relaxivity.

Recent advances in the preclinical development of responsive MRI contrast agents capable of detecting hydrogen peroxide.

In this review, we focus on the preclinical development and study of coordination complexes that act as magnetic resonance imaging (MRI) contrast agent sensors for hydrogen peroxide. Redox-responsive probes have been developed that provide signals that can be detected through traditional T-weighted H, F, and Chemical Exchange Saturation Transfer MRI. The sensors can also be classified with respect to whether the change in the signal corresponds to the oxidation of the metal ion or the organic ligand.

A Macrocyclic Ligand Framework That Improves Both the Stability and -Weighted MRI Response of Quinol-Containing HO Sensors.

Previously prepared Mn(II)- and quinol-containing magnetic resonance imaging (MRI) contrast agent sensors for HO relied on linear polydentate ligands to keep the redox-activatable quinols in close proximity to the manganese. Although these provide positive -weighted relaxivity responses to HO that result from oxidation of the quinol groups to -quinones, these reactions weaken the binding affinity of the ligands, promoting dissociation of Mn(II) from the contrast agent in aqueous solution. Here, we report a new ligand, 1,8-bis(2,5-dihydroxybenzyl)-1,4,8,11-tetraazacyclotetradecane, that consists of two quinols covalently tethered to a cyclam macrocycle.