Rational Ligand Design Enables pH Control Over Aqueous Iron Magnetostructural Dynamics and Relaxometric Properties
| Autor: | Peter Caravan, Hannah S. Shafaat, Eric M. Gale, Huan Wang, Veronica Clavijo Jordan, Jeffrey W. Bacon, Genevieve R Nemeth, Luke C. Lewis, Alison Wong |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Aqueous solution
Absorption spectroscopy 010405 organic chemistry Dimer 010402 general chemistry 01 natural sciences Article 0104 chemical sciences Inorganic Chemistry Crystallography chemistry.chemical_compound Monomer Deprotonation chemistry Molecule Titration Physical and Theoretical Chemistry Ternary complex |
| Zdroj: | Inorg Chem |
| Popis: | Complexes of Fe(3+) engage in rich aqueous solution speciation chemistry in which discrete molecules can react with solvent water to form multinuclear μ-oxo and μ-hydroxide bridged species. Here we demonstrate how pH- and concentration-dependent equilibration between monomeric and μ-oxo-bridged dimeric Fe(3+) complexes can be controlled through judicious ligand design. We purposed this chemistry to develop a first-in-class Fe(3+)-based MR imaging probe, Fe-PyCy2AI, that undergoes relaxivity change via pH-mediated control of monomer vs. dimer speciation. The monomeric complex exists in a S=5/2 configuration capable of inducing efficient T(1)-relaxation, whereas the antiferromagnetically coupled dimeric complex is a much weaker relaxation agent. The mechanisms underpinning the pH dependence on relaxivity were interrogated using a combination of pH-potentiometry, (1)H and (17)O relaxometry, electronic absorption spectroscopy, bulk magnetic susceptibility, electron paramagnetic resonance spectroscopy, and X-ray crystallography measurements. Taken together, the data demonstrate that PyCy2AI forms a ternary complex with high-spin Fe(3+) and a rapidly exchanging water co-ligand, [Fe(PyCy2AI)(H(2)O)](+) (ML), which can deprotonate to form the high-spin complex [Fe(PyCy2AI)(OH)] (ML(OH)). Under titration conditions of 7 mM Fe complex, water co-ligand deprotonation occurs with apparent pK(a) 6.46. Complex ML(OH) dimerizes to form the antiferromagnetically coupled dimeric complex [(Fe(PyCy2AI))(2)O] ((ML)(2)O) with an association constant (K(a)) of 5.3 ± 2.2 mM(-1). The relaxivity of the monomeric complexes are between 7- to 18-fold greater than the antiferromagnetically coupled dimer at applied field strengths ranging between 1.4T and 11.7T. ML(OH) and (ML)(2)O interconvert rapidly within the pH 6.0–7.4 range that is relevant to human pathophysiology, resulting in substantial observed relaxivity change. Controlling Fe(3+) μ-oxo bridging interactions through rational ligand design and in response to local chemical environment offers a robust mechanism for biochemically responsive MR signal modulation. |
| Databáze: | OpenAIRE |
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