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

Abstract

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‐MCCu(II)Glyha‐5](Cl)3 (1(Gd)), Gd(H2O)4[15‐MCCu(II)Alaha‐5](Cl)3 (2(Gd)), Gd(H2O)3[15‐MCCu(II)Phalaha‐5](Cl)3 (3(Gd)) and Gd(H2O)3[15‐MCCu(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‐MCCu(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.

pH‐Responsive Switching Properties of a Water‐Soluble Metallamacrocyclic Phenylalaninehydroximate La(III)–Cu(II) Complex: Insight into Tuning Protonation Ligand States

“…In the visible region of the spectra a broad band with a maximum at 575 nm ( ε = 406 M –1 cm –1 ) is attributed to Cu(II) d‐d transition band. This broad band is responsible for the characteristic dark blue color of 1 , that is observed in all previously reported water‐soluble Cu(II)‐Ln(III) aminohydroximate complexes , , , . Note, that the broad bands in the region above 600 nm are quite common for copper(II) complexes with square pyramidal or distorted square pyramidal geometries .…”

“…Nowadays, the popularity of water‐soluble polynuclear metallamacrocyclic Cu(II)‐Ln(III) complexes is largely due to their rich coordination chemistry, diverse properties and ease of synthesis . The remarkable feature of Cu(II)‐Ln(III) 15‐MC‐5 complexes is the deep color .…”

Synthesis and Molecular Structure of the First Metallamacrocyclic Bi(III)-Cu(II) 15-MC-5 Complex Derived from Pyrazinohydroxamic Acid

“…[4] The first planar 15-MC-5 uranyl complex was obtained by self assembly of picolinehydroxamic acid with Cu 2+ and UO 2 2+ ions. [15] A number of MCs were prepared in a similar way in the following few years, leading to the isolation of 15-MC-5 of copper and aminohydroxamic acids encapsulating Ln 3+ , [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Y 3+ , [31][32][33] and non-transition metals Ca 2+ , [33][34][35] Na + , [31] Ag + , [31] Pb 2+ , [31] and Hg 2+ . [31] Following our interest in Ln(III)-Cu(II) 15-MC-5 metallacrowns with aminohydroxamic ligands, we report now on a metallamacrocyclic complex constructed from Cu 2+ and Bi 3+ metal centers and aminohydroxamic moieties.…”

Water-Soluble Bismuth(III) Polynuclear Tyrosinehydroximate Metallamacrocyclic Complex: Structural Parallels to Lanthanide Metallacrowns

“…Following a previously described synthetic procedure for water-soluble Ln(III)-Cu(II) 15-MC-5 metallacrowns [ 30 , 31 ] we employed the most frequently used two-step methodology with some modification. In the first step, α-tyrosinehydroxamic acid and Cu(CH 3 COO) 2 were mixed in water and, in the second step, Bi(NO 3 ) 3 was added to this solution ( Scheme 2 ).…”

“…The Bi 3+ ion is located at the center of the 15-MC-5 ring consisting of five [Cu(II)-N-O] repeating units. Following our interest in water-soluble Ln(III)-Cu(II) 15-MC-5 metallacrowns with aminohydroximate ligands [ 30 , 31 , 32 , 33 , 34 ], we describe here a general synthetic approach and comparable characterization of a new water-soluble metallamacrocyclic Bi(III)-Cu(II) 15-MC-5 complex derived from tyrosinehydroxamic acid.…”