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A biocompatible redox MRI probe based on a Mn()/Mn() porphyrin
For the development of redox responsive MRI probes based on the Mn III /Mn II couple, stable complexation of both reduced and oxidized forms of the metal ion and appropriate tuning of the redox potential in the biologically relevant range are key elements. The water soluble fluorinated Mn-porphyrin...
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Published in: | Dalton transactions : an international journal of inorganic chemistry 2019-03, Vol.48 (1), p.3249-3262 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | For the development of redox responsive MRI probes based on the Mn
III
/Mn
II
couple, stable complexation of both reduced and oxidized forms of the metal ion and appropriate tuning of the redox potential in the biologically relevant range are key elements. The water soluble fluorinated Mn-porphyrin derivative Mn-
3
satisfies both requirements. In aqueous solutions, it can reversibly switch between Mn
III
/Mn
II
oxidation states. In the presence of ascorbic acid or β-mercaptoethanol, the Mn
III
form undergoes reduction, which is slowly but fully reversed in the presence of air oxygen. A UV-Vis kinetic study of Mn
III
/Mn
II
reduction under oxygen-free conditions yielded second-order rate constants,
k
2
, of 46.1 M
−1
s
−1
and 13.8 M
−1
s
−1
for the reaction with ascorbic acid and β-mercaptoethanol, respectively. This could correspond, in the absence of oxygen, to a half-life of a few minutes in blood plasma and a few seconds in circulating immune cells where ascorbic acid reaches 20-40 μM and a few mM concentrations, respectively. In contrast to expectations based on the redox potential, reduction with glutathione or cysteine does not occur. It is prevented by the coordination of the glutathione carboxylate group(s) to Mn
III
in the axial position, as was evidenced by NMR data. Therefore, Mn
III
-
3
acts as an ascorbate specific turn-on MRI probe, which in turn can be re-oxidized by oxygen. The relaxivity increase from the oxidized to the reduced form is considerably improved at medium frequencies (up to 80 MHz) with respect to the previously studied Mn-TPPS
4
analogues; at 20 MHz, it amounts to 150%. No
in vitro
cytotoxicity is detectable for Mn-
3
in the typical MRI concentration range. Finally,
19
F NMR resonances of Mn
III
-
3
are relatively sharp which could open further opportunities to exploit such complexes as paramagnetic
19
F NMR probes.
A water-soluble fluorinated Mn
III/II
porphyrin responds reversibly to ascorbate redox state as a turn-on MRI probe. |
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ISSN: | 1477-9226 1477-9234 |
DOI: | 10.1039/c8dt04775h |