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. 2024 Dec 23;63(51):24049-24053.
doi: 10.1021/acs.inorgchem.4c04136. Epub 2024 Dec 9.

Zn(II)-Responsive MRI Probe Based on an Fe(III) Macrocyclic Complex

Roy Cineus  1 , Aruni Dissanayake  1 , Janet R Morrow  1
Affiliations

Zn(II)-Responsive MRI Probe Based on an Fe(III) Macrocyclic Complex

Roy Cineus et al. Inorg Chem. .

Abstract

The development of responsive MRI contrast agents to detect fluctuations in Zn(II) is a growing area of research. Here we describe a high-spin Fe(III) coordination complex, Fe(ADAPT), as one of the first examples of an Fe(III) MRI probe that is responsive to Zn(II). The six-coordinate Fe(ADAPT) contains a phenolate-appended 1,4,7-triazacyclononane (TACN) ligand framework, with the phenolate groups linked to a Zn(II) binding moiety. Fe(ADAPT) lacks an exchangeable inner-sphere water and thus relies on second- and outer-sphere water interactions for proton relaxation. Fe(ADAPT) is highly kinetically inert under physiological conditions at pH 7.4 and 37 °C and to excess Zn(II) over 72 h. In the presence of 2 equiv of Zn(II) with a 200 μM Fe(III) probe, an increase in relaxivity of ∼80% is observed. A ternary complex among Fe(ADAPT), Zn(II), and human serum albumin leads to a nearly 200% increase in relaxivity.

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Conflict of interest statement

Notes

The authors declare the following competing financial interest(s): J.R.M. is a cofounder of Ferric Contrast, a company that develops iron contrast agents.

Figures

Figure 1.
Figure 1.
ITC binding isotherm of 0.050 mM Fe(ADAPT) with Zn(II) in 0.10 M NaCl and 50 mM HEPES at pH 7.4.
Figure 2.
Figure 2.
(A) Plot of 1/T1 of Fe(ADAPT) as a function of the probe concentration to give r1. (B) r1 with variable Zn(II) titrated into 0.20 mM Fe(ADAPT). (C) r1 in the presence of Zn(II), Cu(II), Fe(II), Ca(II), and Mg(II) with 0.20 mM Fe(ADAPT). All solutions contained 0.10 M NaCl and 50 mM HEPES at pH 7.4 and 33 °C. (D) Zn(II) titration into 0.20 mM Fe(ADAPT) containing 0.60 mM HSA.
Scheme 1.
Scheme 1.. MRI Probes Based on Gd(III) or Fe(III)
Scheme 2.
Scheme 2.. Model for Zn(II)-Responsive Probe: (A) Zn(II), HSA Binding and (B) Probe and Zn(II) to Give a Zn–Probe–HSA Complex
See this image and copyright information in PMC

References

    1. Khalighinejad P; Parrott D; Sherry AD Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents. Pharmaceuticals 2020, 13, 268. - PMC - PubMed
    1. Malikidogo KP; Martin H; Bonnet CS From Zn(II) to Cu(II) Detection by MRI Using Metal-Based Probes: Current Progress and Challenges. Pharmaceuticals 2020, 13, 436. - PMC - PubMed
    1. Clavijo Jordan MV; Lo S-T; Chen S; Preihs C; Chirayil S; Zhang S; Kapur P; Li W-H; De Leon-Rodriguez LM; Lubag AJM; Rofsky NM; Sherry AD Zinc-sensitive MRI contrast agent detects differential release of Zn(II) ions from the healthy vs. malignant mouse prostate. Proc. Nat. Acad. Sci. USA 2016, 113, E5464–E5471. - PMC - PubMed
    1. Martins AF; Clavijo Jordan V; Bochner F; Chirayil S; Paranawithana N; Zhang S; Lo S-T; Wen X; Zhao P; Neeman M; et al. Imaging Insulin Secretion from Mouse Pancreas by MRI Is Improved by Use of a Zinc-Responsive MRI Sensor with Lower Affinity for Zn2+ Ions. J. Am. Chem. Soc. 2018, 140, 17456–17464. - PMC - PubMed
    1. Myers SA; Nield A; Myers M Zinc Transporters, Mechanisms of Action and Therapeutic Utility: Implications for Type 2 Diabetes Mellitus. J. Nutrition Metab. 2012, 2012, No. 173712. - PMC - PubMed

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