Recent Advances in Bioorthogonal Click Chemistry for Efficient Synthesis of Radiotracers and Radiopharmaceuticals.

In recent years, several catalyst-free site-specific reactions have been investigated for the efficient conjugation of biomolecules, nanomaterials, and living cells. Representative functional group pairs for these reactions include the following: (1) azide and cyclooctyne for strain-promoted cycloaddition reaction, (2) tetrazine and trans-alkene for inverse-electron-demand-Diels-Alder reaction, and (3) electrophilic heterocycles and cysteine for rapid condensation/addition reaction. Due to their excellent specificities and high reaction rates, these conjugation methods have been utilized for the labeling of radioisotopes (e.g., radiohalogens, radiometals) to various target molecules. The radiolabeled products prepared by these methods have been applied to preclinical research, such as in vivo molecular imaging, pharmacokinetic studies, and radiation therapy of cancer cells. In this review, we explain the basics of these chemical reactions and introduce their recent applications in the field of radiopharmacy and chemical biology. In addition, we discuss the significance, current challenges, and prospects of using bioorthogonal conjugation reactions.

Crystal structure of 2,3-bis-(4-methyl-phen-yl)benzo[g]quinoxaline.

The title compound, C26H20N2, was obtained during a search for new π-extended ligands with the potential to generate efficient phosphors with iridium(III) for organic light-emitting devices (OLEDs). The benzoquinoxaline ring system is almost planar (r.m.s. deviation = 0.076 Å). A pseudo-twofold rotation axis runs through the midpoints of the C2-C3 and C9-C10 bonds. The two phenyl rings are twisted relative to the benzoquinoxaline ring system, making dihedral angles of 53.91 (4) and 36.86 (6)°. In the crystal, C-H⋯π (arene) inter-actions link the mol-ecules, but no π-π inter-actions between aromatic rings are observed.

Radiolabeling and preliminary biodistribution study of 99mTc-labeled antibody-mimetic scaffold protein repebody for initial clearance properties.

Antibody-mimetic proteins are intensively being developed for biomedical applications including tumor imaging and therapy. Among them, repebody is a new class of protein that consists of highly diverse leucine-rich repeat (LRR) modules. Although all possible biomedical applications with repebody are ongoing, it's in vivo biodistribution and excretion pathway has not yet been explored. In this study, hexahistidine (His6)-tag bearing repebody (rEgH9) was labeled with [99mTc]-tricarbonyl, and biodistribution was performed following intravenous (I.V.) or intraperitoneal (I.P.) injection. Repebody protein was radiolabeled with high radiolabeling efficiency (>90%) and radiolabeled compound was more than 99% pure after purification. Biodistribution data indicates radiotracer has a rapid clearance from blood and excreted through the kidneys for intravenous (I.V.) injection, but comparatively slow clearance for an intraperitoneal (I.P.) injection. SPECT-CT images were found to be in agreement with biodistribution data, high activity was found inside kidneys. The observed result for rapid blood clearance and renal excretion of repebody (rEgH9) provide useful information for the further development of therapeutic strategy.

Efficient bioremediation of radioactive iodine using biogenic gold nanomaterial-containing radiation-resistant bacterium, Deinococcus radiodurans R1.

We herein report a new bioremediation method using a radiation-resistant bacterium. Biogenic gold nanomaterial-containing Deinococcus radiodurans R1 showed excellent capability for the removal of radioactive iodine (>99%) in several aqueous solutions. These observations demonstrated that our remediation system would be efficiently applied to the treatment of radioactive wastes.

Gold-Nanoparticle-Immobilized Desalting Columns for Highly Efficient and Specific Removal of Radioactive Iodine in Aqueous Media.

There has been worldwide attention on the efficient removal of radioactive iodine, because it is commonly released in nuclear plant accidents. Increasing concerns on environmental problems due to the radioactive iodine are leading us to develop stable and sustainable technology for remediation of radioelement contaminants. In this work, we report a highly efficient chromatographic method for specific and rapid capture of radioactive iodine. The gold nanoparticles immobilized dextran gel columns showed excellent removal capabilities of radioactive iodine in various conditions. These results suggested that our platform technology can be a promising method for the desalination of radioactive iodines in water.

Highly efficient method for 125I-radiolabeling of biomolecules using inverse-electron-demand Diels-Alder reaction.

In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels-Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give 125I-labeled azide ([125I]1) with high radiochemical yield (65±8%) and radiochemical purity (>99%). For radiolabeling application of [125I]1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrated were reacted with [125I]1 under mild condition to provide the radiolabeled products [125I]6 and [125I]8, respectively, with excellent radiochemical yields. The biodistribution study of [125I]8 in normal ICR mice showed significantly lower thyroid uptake values than that of 125I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore [125I]8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that [125I]1 will be used as a valuable prosthetic group for radiolabeling of biomolecules.

Bis[2-(1,3-benzo-thia-zol-2-yl)phenyl-κ(2) C (1),N][1,3-bis-(4-bromo-phen-yl)propane-1,3-dionato-κ(2) O,O']iridium(III).

The title complex, [Ir(C15H9Br2O2)(C13H8NS)2], lies about a crystallographic twofold rotation axis passing through the Ir(III) atom and the central C atom of the bis-(bromo-phen-yl)propane-1,3-dionate ligand. The Ir(III) atom adopts a distorted octa-hedral geometry coordinated by two N atoms in the axial positions, and two C and two O atoms in the equatorial plane. The dihedral angle between the two thia-zole ring systems in the complex is 77.45 (10)°.

Bis[3,5-difluoro-2-(4-methyl-pyridin-2-yl)phenyl-κC,N](picolinato-κN,O)iridium(III) chloro-form monosolvate.

In the title complex, [Ir(C(12)H(8)F(2)N)(2)(C(6)H(4)NO(2))]·CHCl(3), two similar mol-ecules of each component comprise the asymmetric unit. The independent complex mol-ecules are linked by inter-molecular π-π inter-actions [centroid-centroid distance = 3.830 (4) Å]. The Ir(III) ion adopts a distorted octa-hedral geometry, being coordinated by three N atoms, two C atoms, and one O atom of three bidentate ligands, with the N atoms arranged meridionally.

Di-µ-chlorido-bis-{[2-(benzyl-imino-meth-yl)pyridine-κN,N']chloridomercury(II)} dichloridomercury(II).

The Hg(II) ion in the title centrosymmetric dinuclear complex, [Hg(2)Cl(4)(C(13)H(12)N(2))(2)]·[HgCl(2)], adopts a distorted square-pyramidal geometry, being coordinated by the bis-chelating N-heterocyclic ligand, two bridging Cl atoms and one terminal Cl atom. One of the bridging Hg-Cl bonds [2.8428 (11) Å] is significantly longer than the other [2.5327 (10) Å]. In the crystal, there are weak π-π inter-actions [centroid-centroid distance = 3.630 (3) Å] between the aromatic rings of the discrete units. The HgCl(2) adduct molecule is located on an inversion centre and has an Hg-Cl bond length of 2.2875 (11) Å.