Benjamin P. Burton-Pye

Lanthanide Complexes for Luminescence Imaging Applications

Abstract In this article, imaging applications of luminescent complexes and recent advances in the design and photophysical behaviour of near‐IR responsive complexes are reviewed. Various properties of the luminescent lanthanide complexes are also discussed in detail.

p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for 89Zr ImmunoPET

Zirconium-89 has an ideal half-life for use in antibody-based PET imaging; however, when used with the chelator DFO, there is an accumulation of radioactivity in the bone, suggesting that the (89)Zr(4+) cation is being released in vivo. Therefore, a more robust chelator for (89)Zr could reduce the in vivo release and the dose to nontarget tissues. Evaluation of the ligand 3,4,3-(LI-1,2-HOPO) demonstrated efficient binding of (89)Zr(4+) and high stability; therefore, we developed a bifunctional derivative, p-SCN-Bn-HOPO, for conjugation to an antibody. A Zr-HOPO crystal structure was obtained showing that the Zr is fully coordinated by the octadentate HOPO ligand, as expected, forming a stable complex. p-SCN-Bn-HOPO was synthesized through a novel pathway. Both p-SCN-Bn-HOPO and p-SCN-Bn-DFO were conjugated to trastuzumab and radiolabeled with (89)Zr. Both complexes labeled efficiently and achieved specific activities of approximately 2 mCi/mg. PET imaging studies in nude mice with BT474 tumors (n = 4) showed good tumor uptake for both compounds, but with a marked decrease in bone uptake for the (89)Zr-HOPO-trastuzumab images. Biodistribution data confirmed the lower bone activity, measuring 17.0%ID/g in the bone at 336 h for (89)Zr-DFO-trastuzumab while (89)Zr-HOPO-trastuzumab only had 2.4%ID/g. We successfully synthesized p-SCN-Bn-HOPO, a bifunctional derivative of 3,4,3-(LI-1,2-HOPO) as a potential chelator for (89)Zr. In vivo studies demonstrate the successful use of (89)Zr-HOPO-trastuzumab to image BT474 breast cancer with low background, good tumor to organ contrast, and, importantly, very low bone uptake. The reduced bone uptake seen with (89)Zr-HOPO-trastuzumab suggests superior stability of the (89)Zr-HOPO complex.

Europium(III) Reduction and Speciation within a Wells−Dawson Heteropolytungstate

The redox speciation of Eu(III) in the 1:1 stoichiometric complex with the alpha-1 isomer of the Wells-Dawson anion, [alpha-1-P 2W 17O 61] (10-), was studied by electrochemical techniques (cyclic voltammetry and bulk electrolysis), in situ XAFS (X-ray absorption fine structure) spectroelectrochemistry, NMR spectroscopy ( (31)P), and optical luminescence. Solutions of K 7[(H 2O) 4Eu(alpha-1-P 2W 17O 61)] in a 0.2 M Li 2SO 4 aqueous electrolyte (pH 3.0) show a pronounced concentration dependence to the voltammetric response. The fully oxidized anion and its reduced forms were probed by Eu L 3-edge XANES (X-ray absorption near edge structure) measurements in simultaneous combination with controlled potential electrolysis, demonstrating that Eu(III) in the original complex is reduced to Eu(II) in conjunction with the reduction of polyoxometalate (POM) ligand. After exhaustive reduction, the heteropoly blue species with Eu(II) is unstable with respect to cluster isomerization, fragmentation, and recombination to form three other Eu-POMs as well as the parent Wells-Dawson anion, alpha-[P 2W 18O 62] (6-). EXAFS data obtained for the reduced, metastable Eu(II)-POM before the onset of Eu(II) autoxidation provides an average Eu-O bond length of 2.55(4) A, which is 0.17 A longer than that for the oxidized anion, and consistent with the 0.184 A difference between the Eu(II) and Eu(III) ionic radii. The reduction of Eu(III) is unusual among POM complexes with Lindqvist and alpha-2 isomers of Wells-Dawson anions, that is, [Eu(W 5O 18) 2] (9-) and [Eu(alpha-2-As 2W 17O 61) 2] (17-), but not to the Preyssler complex anion, [EuP 5W 30O 110] (12-), and fundamental studies of materials based on coupling Eu and POM redox properties are still needed to address new avenues of research in europium hydrometallurgy, separations, and catalysis sciences.

Synthesis and luminescence properties of lanthanide complexes incorporating a hydralazine-derived chromophore

Reaction of 1-hydrazinophthalazine with chloroacetyl chloride yields 3-chloromethyl-1,2,4-triazolo-phthalazine. Reaction of this product with the tris tert-butyl ester of DO3A yields a triazolophthalazine appended macrocycle. Hydrolysis and complexation with lanthanide ions gives access to a series of lanthanide complexes (Ln = Nd, Eu, Yb, Er); these are all luminescent and exhibit sensitisation of the lanthanide centre by the chromophore.

Interaction between tetrathiafulvalene carboxylic acid and ytterbium DO3A: solution state self-assembly of a ternary complex which is luminescent in the near IR

Tetrathiafulvalene carboxylate associates with the charge neutral complex, Yb.DO3A, in methanolic solution to give rise to a novel ternary species; the tetrathiafulvalene unit transfers energy to the lanthanide, causing luminescence from the Yb metal, indicating for the first time that an electron donor chromophore can act as an efficient sensitiser in a self-assembled system containing a lanthanide acceptor.

Ternary phthalocyanato Hf(IV) and Zr(IV) polyoxometalate complexes

Ternary phthalocyanine–metal–polyoxometalate (Pc–M–POM) complexes were synthesized and characterized. Group (IV) Hf or Zr ions reside outside the plane of the macrocycle and are coordinated to both the phthalocyanine and the lacunary polyoxometalate. The metal ions mediate the electronic communication between the Pc and the POM.

Speciation and reactivity of heptavalent technetium in strong acids

Technetium is the workhorse of the radiopharmaceutical imaging agents; it is also an important byproduct of the nuclear industry. Studies of the chemistry of Tc in strong acids are relevant to nuclear applications, environmental remediation and fundamental chemistry. Nitric acid is used at the industrial level for spent fuel reprocessing while H2SO4 and HClO4 are used at the laboratory scale for Tc separation from Mo or U. During reprocessing activities, radiolysis products from nitric acid (e.g., H2O2) and from organics extracting agents (e.g., alcohols) are formed and these might interact with Tc(VII). An understanding of Tc(VII) chemistry in the presence of H2O2 and/or organics in acidic solution is important to predict its behavior in separation processes. Concerning environmental remediation, sulfur has been proposed to immobilize “Tc2S7”. Technetium heptasulfide can be obtained from the reaction of Tc(VII) with H2S gas in acidic solutions. A better understanding of “Tc2S7” formation could give information to predict its formation and behavior in the environment. Under oxidizing conditions, the aqueous chemistry of Tc(VII) is dominated by TcO4−. In high acid concentrations, pertechnetic acid can be formed and control the reactivity of Tc. Speciation data on Tc(VII) in concentrated acids are still parse, and the structure and reactivity of pertechnetic acid are unknown. Here, the speciation of Tc(VII) in sulfuric, nitric and perchloric acids and its reactivity with H2O2, methanol and H2S is reviewed. Experimental results and density functional calculations show the formation of TcO3(OH)(H2O)2 in concentrated H2SO4 and HClO4. In 12–13 M H2SO4, Tc(V) species and Tc(IV) polymeric species were respectively detected in the presence of methanol and H2S. Finally, peroxo pertechnetic acid was identified in nitric and sulfuric acid in the presence of H2O2.

CCDC 1485446: Experimental Crystal Structure Determination

Related Article: Melissa A. Deri, Shashikanth Ponnala, Paul Kozlowski, Benjamin P. Burton-Pye, Huseyin T. Cicek, Chunhua Hu, Jason S. Lewis, and Lynn C. Francesconi|2015|Bioconjugate Chem.|26|2579|doi:10.1021/acs.bioconjchem.5b00572

Hafnium (IV) and zirconium (IV) porphyrinoid diacetate complexes as new dyes for solar cells

New concepts in the design and function of organic dyes as sensitizers for solar energy harvesting are needed. Simple porphyrin dyes offer cost effective synthesis and long-term stability, but new modes of incorporation into devices are needed to increase the efficiency of charge separation that drives any photonic device designed to harvest light. We are developing a new strategy to couple dyes to oxide surfaces using hafnium and zirconium metalloporphyrins. The formation of ternary complexes of Hf(IV) and Zr(IV) porphyrins with a Keggin polyoxometalate (POM), PW11O397− suggested that one way to self-organize porphyrinoids onto oxide surfaces is to use oxophilic group IV metals Hf and Zr. The 3–4 open metal coordination sites of Hf(Por)2+ and Zr(Por)2+ are bound primarily to surface defect sites by displacement of the auxiliary acetate ligands.