Dataset Information

Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine.

ABSTRACT: The Zr⁴⁺ complexes with desferrioxamine (H₃DFO) and its derivatives are the only ⁸⁹Zr-based imaging agents for proton emission tomography (PET) that have been used so far in clinical trials. Nevertheless, a complete speciation of the Zr⁴⁺/H₃DFO system in solution has never been performed and the stability constants of the relevant complexes are still unknown. Here we report, for the first time, the speciation of this system in water, performed by potentiometric titrations, and the determination of the stability constants of all complexes formed in the pH range 2.5-11.5. Surprisingly, although desferrioxamine gives rise to very stable 1:1 complexes with Zr⁴⁺ (logK = 36.14 for Zr⁴⁺ + DFO^3- = [ZrDFO]⁺), 2:2 and 2:3 ones are also formed in solution. Depending on the conditions, these binuclear complexes can be main species in solution. These results were corroborated by small-angle X-ray scattering (SAXS) and MALDI mass spectrometry analyses of complex solutions. Information on complex structures was obtained by means of density functional theory (DFT) calculations.

SUBMITTER: Savastano M

PROVIDER: S-EPMC6600682 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine.

Savastano Matteo M Bazzicalupi Carla C Ferraro Giovanni G Fratini Emiliano E Gratteri Paola P Bianchi Antonio A

Molecules (Basel, Switzerland) 20190602 11

The Zr4+ complexes with desferrioxamine (H3DFO) and its derivatives are the only 89Zr-based imaging agents for proton emission tomography (PET) that have been used so far in clinical trials. Nevertheless, a complete speciation of the Zr4+/H3DFO system in solution has never been performed and the stability constants of the relevant complexes are still unknown. Here we report, for the first time, the speciation of this system in water, perform ...[more]

PMID: 31159506

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Project description:Metalloporphyrin and metallophthalocyanine dyes ligating Hf(IV) and Zr(IV) ions bind to semiconductor oxide surfaces such as TiO(2) via the protruding group IV metal ions. The use of oxophylic metal ions with large ionic radii that protrude from the macrocycle is a unique mode of attaching chromophores to oxide surfaces in the design of dye-sensitized solar cells (DSSCs). Our previous report on the structure and physical properties of ternary complexes wherein the Hf(IV) and Zr(IV) ions are ligated to both a porphyrinoid and to a defect site on a polyoxometalate (POM) represents a model for this new way of binding dyes to oxide surfaces. The Zr(IV) and Hf(IV) complexes of 5,10,15,20-tetraphenylporphyrin (TPP) with two ligated acetates, (TPP)Hf(OAc)(2) and (TPP)Zr(OAc)(2), and the corresponding metallophthalocyanine (Pc) diacetate complexes, (Pc)Hf(OAc)(2) and (Pc)Zr(OAc)(2), were evaluated as novel dyes for the fabrication of dye-sensitized solar cells. Similarly to the ternary complexes with the POM, the oxide surface replaces the acetates to affect binding. In DSSCs the Zr(IV) phthalocyanine dye performs better than the Zr(IV) porphyrin dye, and reaches an overall efficiency of ~ 1.0%. The Hf(IV) dyes are less efficient. The photophysical properties of these complexes in solution suggested energetically favorable injection of electrons into the conduction band of TiO(2) semiconductor nanoparticles, as well as a good band gap match with I(3) (-)/I(-) pair in liquid 1-butyl-3-methyl imidazolium iodide. The combination of blue absorbing TPP with the red absorbing Pc complexes can increase the absorbance of solar light in the device; however, the overall conversion efficiency of DSSCs using TiO(2) nanoparticles treated with a mixture of both Zr(IV) complexes is comparable, but not greater than, the single (Pc)Zr. Thus, surface bound (TPP)Zr increases the absorbance in blue region of the spectra, but at the cost of diminished absorbance in the red in this DSSC architecture.

Project description:Herein we report a new high-denticity chelator based on the iron siderophore desferrioxamine (DFO). Our new chelator-DFO2-is acyclic and was designed and synthesized with the purpose of improving the coordination chemistry and radiolabeling performance with radioactive zirconium-89. The radionuclide zirconium-89 ([89Zr]Zr4+) has found wide use for positron emission tomography (PET) imaging when it is coupled with proteins, antibodies, and nanoparticles. DFO2 has a potential coordination number of 12, which uniquely positions this chelator for binding large, high-valent, and oxophilic metal ions. Following synthesis of the DFO2 chelator and the [natZr]Zr-(DFO2) complex we performed density functional theory calculations to study its coordination sphere, followed by zirconium-89 radiolabeling experiments for comparisons with the "gold standard" chelator DFO. DFO (CN 6) can coordinate with zirconium in a hexadentate fashion, leaving two open coordination sites where water is thought to coordinate (total CN 8). DFO2 (potential CN 12, dodecadentate) can saturate the coordination sphere of zirconium with four hydroxamate groups (CN 8), with no room left for water to directly coordinate, and only binds a single atom of zirconium per chelate. Following quantitative radiolabeling with zirconium-89, the preformed [89Zr]Zr-(DFO) and [89Zr]Zr-(DFO2) radiometal-chelate complexes were subjected to a battery of in vitro stability challenges, including human blood serum, apo-transferrin, serum albumin, iron, hydroxyapatite, and EDTA. One objective of these stability challenges was to determine if the increased denticity of DFO2 over that of DFO imparted improved complex stability, and another was to determine which of these assays is most relevant to perform with future chelators. In all of the assays DFO2 showed superior stability with zirconium-89, except for the iron challenge, where both DFO2 and DFO were identical. Substantial differences in stability were observed for human blood serum using a precipitation method of analysis, apo-transferrin, hydroxyapatite, and EDTA challenges. These results suggest that DFO2 is a promising next-generation scaffold for zirconium-89 chelators and holds promise for radiochemistry with even larger radionuclides, which we anticipate will expand the utility of DFO2 into theranostic applications.

Dataset Information

Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine.

Publications

Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine.

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