New insights into water-soluble and water-coordinated copper 15-metallacrown-5 gadolinium complexes designed for high-field magnetic resonance imaging applications

The development of contrast agents specifically designed for high‐field magnetic resonance imaging (MRI) is required because the relaxation efficiency of classic Gd(III) contrast agents significantly decreases with increasing magnetic field strengths. With an idea of exploring the unique structure of lanthanide (Ln) 15‐MC‐5 metallacrowns, we developed a series of water‐soluble Gd(III) aqua‐complexes, bearing aminohydroxamate (glycine, α‐alanine, α‐phenylalanine and α‐tyrosine) ligands, with increasing number of water molecules directly coordinated to the Gd(III) ion: Gd(H₂O)₄[15‐MC_Cu(II)Glyha‐5](Cl)₃ (1(Gd)), Gd(H₂O)₄[15‐MC_Cu(II)Alaha‐5](Cl)₃ (2(Gd)), Gd(H₂O)₃[15‐MC_{Cu(II)Phalaha}‐5](Cl)₃ (3(Gd)) and Gd(H₂O)₃[15‐MC_Cu(II)Tyrha‐5](Cl)₃ (4(Gd)). In these systems, the Ln(III) central ion is coordinated by five oxygen donor atoms of the ligands and three or four inner‐sphere water molecules. The X‐ray crystal structure of metallacrown Ln(H₂O)_3,4[15‐MC_Cu(II)Rha‐5]³⁺ agrees with density functional theory predictions. The calculations demonstrate that the exchange of coordinated water molecules can proceed easily, resulting in increased relaxivity parameters. The longitudinal relaxivities (r₁) of 1(Gd)–4(Gd) in water at ultrahigh magnetic field of 9.4 T were determined to be 11.5, 14.8, 13.9 and 12.2 mM⁻¹ s⁻¹, respectively. The ability to increase the number of Ln(III) inner‐sphere water molecules up to four, the planar metallacrown structure and the rich hydration shell due to strong hydrogen bonds between the [15‐MC‐5] moiety and bulk water molecules provide new opportunities for potential MRI applications.