Synthesis and Characterization of the Actinium Aquo Ion

Abstract

Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H2O)x3+) is critical for current efforts to develop 225Ac [t1/2 = 10.0(1) d] as a targeted anticancer therapeutic agent. However, given the limited amount of actinium available for study and its high radioactivity, many aspects of actinium chemistry remain poorly defined. We overcame these challenges using the longer-lived 227Ac [t1/2 = 21.772(3) y] isotope and report the first characterization of this fundamentally important Ac-aquo coordination complex. Our X-ray absorption fine structure study revealed 10.9 ± 0.5 water molecules directly coordinated to the AcIII cation with an Ac–OH2O distance of 2.63(1) Å. This experimentally determined distance was consistent with molecular dynamics density functional theory results that showed (over the course of 8 ps) that AcIII was coordinated by 9 water molecules with Ac–OH2O distances ranging from 2.61 to 2.76 Å. The data is presented in the context of other actinide(III) and lanthanide(III) aquo ions characterized by XAFS and highlights the uniqueness of the large AcIII coordination numbers and long Ac–OH2O bond distances.

An Eighteen‐Membered Macrocyclic Ligand for Actinium‐225 Targeted Alpha Therapy

“…In contrast, the larger La 3+ ion forms an 11-coordinate complex by the incorporation of an inner-sphere water molecule which penetrates the macrocycle.This structural motif was also observed in acrystal structure of the La 3+ complex of ar elated ligand, ppa18c6. [29,30] An interesting difference between the La 3+ and Lu 3+ structures is that one of the picolinate arms in the La 3+ complex is protonated, thus giving ac ationic formula of [La(Hmacropa)(H 2 O)] 2+ .This hydrogen atom was located directly on the difference Fourier map and refined semi-freely.Aclose intermolecular contact (2.468 ) between O6 and O8 in neighboring molecules in the crystal lattice also supports the presence of ahydrogen atom, which mediates this short hydrogen bond. [29,30] An interesting difference between the La 3+ and Lu 3+ structures is that one of the picolinate arms in the La 3+ complex is protonated, thus giving ac ationic formula of [La(Hmacropa)(H 2 O)] 2+ .This hydrogen atom was located directly on the difference Fourier map and refined semi-freely.Aclose intermolecular contact (2.468 ) between O6 and O8 in neighboring molecules in the crystal lattice also supports the presence of ahydrogen atom, which mediates this short hydrogen bond.…”

Chemical aspects of metal ion chelation in the synthesis and application antibody‐based radiotracers

“…65 131 I is a reactor-produced isotope, conveniently accessible from 235 U fission products. 66 However, 123 I and 125 I have also become of interest due to their potential for either imaging or Auger therapy applications, respectively. The photon energy of 125 I is considered too low for optimal imaging, especially for quantitative imaging, and its half-life is undesirably long.…”

“…The photon energy of 125 I is considered too low for optimal imaging, especially for quantitative imaging, and its half-life is undesirably long. Thus, 125 I is typically used for in vitro applications and radioactive binding assays. 67 124 I (t 1/2 = 4.2 days) has a relatively low ratio of disintegration resulting in positrons (22.7%) and a complex decay scheme that includes high-energy gamma emissions (highest about 1.7 MeV).…”

“…complex revealed a coordination number of 10-11, predicting a need for polydentate chelators beyond the usual octadentate DTPA and DOTA-type chelators. 124,125 Limited studies have been carried out on the development of novel chelators for this radionuclide, but reported work includes extended polyaza-macrocycle systems HEHA and PEPA. 126 However, radiolabeling properties and in vivo stability did not significantly improve when compared with DOTA, underscoring the need for novel, custom bifunctional chelators for Ac 3+ .…”

The Actinium Aqua Ion: A Century in the Making

“…This same team is now reporting for the first time the characterization of the Ac(III) aqua ion, a study that provides much-needed, fundamental data that will be useful in the development of chelating agents tailored to the specific size, shape, and Lewis acidity of Ac(III). 11 …”