Technetium-99 (99Tc) is important to the nuclear fuel cycle as a long-lived radionuclide produced in ∼6% fission yield from 235U or 239Pu. In its most common chemical form, namely, pertechnetate (99TcO4–), it is environmentally mobile. In situ hydrogen sulfide reduction of pertechnetate has been proposed as a potential method to immobilize environmental 99TcO4– that has entered the environment. Reactions of 99TcO4– with sulfide in solution result in the precipitation of Tc2S7 except when olefinic acids, specifically fumaric or maleic acid, are present; a water-soluble 99Tc species forms. NMR (1H, 13C, and 2D methods) and X-ray absorption spectroscopy [XAS; near-edge (XANES) and extended fine structure (EXAFS)] studies indicate that sulfide adds across the olefinic bond to generate mercaptosuccinic acid (H3MSA) and/or dimercaptosuccinic acid (H4DMSA), which then chelate(s) the 99Tc to form [99TcO(MSA)2]3–, [99TcO(DMSA)2]5–, or potentially [99TcO(MSA)(DMSA)]4–. 2D NMR methods allowed identification of the products by comparison to 99Tc and nonradioactive rhenium standards. The rhenium standards allowed further identification by electrospray ionization mass spectrometry. 99TcO4– is essential to the reaction because no sulfide addition occurs in its absence, as determined by NMR. Computational studies were performed to investigate the structures and stabilities of the potential products. Because olefinic acid is a component of the naturally occurring humic and fulvic acids found in soils and groundwater, the viability of in situ hydrogen sulfide reduction of environmental 99TcO4– as an immobilization method is evaluated.

The chemistry and radiochemistry of high specific activity radioisotopes of arsenic, rhenium and rhodium are reviewed with emphasis on University of Missouri activities over the past several decades, and includes recent results. The nuclear facilities at the University of Missouri (10 MW research reactor and 16.5 MeV GE PETtrace cyclotron) allow research and development into novel theranostic radionuclides. The production, separation, enriched target recovery, radiochemistry, and chelation chemistry of 72,77As, 186,188Re and 105Rh are discussed.

Radiolabeled proteolytic degradation-resistant somatostatin analogues have been of long-standing interest as cancer imaging and radiotherapy agents for targeting somatostatin receptor-positive tumors. Our interest in developing 186Re- and 188Re-based therapeutic radiopharmaceuticals led to investigation of a new Re(V)-cyclized octreotide analogue, Re(V)-cyclized, thiolated-DPhe1-Cys2-Tyr3-DTrp4-Lys5-Thr6-Cys7-Thr(OH)8 (Re-SDPhe-TATE) using both experimental and quantum chemical methods. The metal is directly coordinated to SDPhe-TATE through cyclization of the peptide around the [ReO]3+ core. Upon complexation, four isomers were observed; the isolated/semi-isolated isomers exhibited different somatostatin receptor (sstr) binding affinities, 0.13 to 1.5 μM, in rat pancreatic tumor cells. Two-dimensional NMR experiments and electronic structure calculations were employed to elucidate the structural differences among the different isomers. According to NMR studies, the metal is coordinated to three thiolates and the backbone amide of Cys2 in isomers 1 and 4, whereas the metal is coordinated to three thiolates and the backbone amide of Tyr3 in isomer 2. Quantum chemical methods clarified the stereochemistry of Re-SDPhe-TATE and the possible peptide arrangements around the [ReO]3+ core. The re-cyclization reaction was translated to the 99mTc radiotracer level with four isomers observed on complexation with comparable HPLC retention times as the Re-SDPhe-TATE isomers. About 85% total 99mTc labeling yield was achieved by ligand exchange from 99mTc-glucoheptonate at 60 °C for an hour. About 100% and 51% of 99mTc(V)-cyclized SDPhe-TATE remained intact in phosphate buffered saline and 1 mM cysteine solution under physiological conditions at 6 h, respectively.

Arsenic-72 (72As) and 77As have nuclear properties useful for positron emission tomography (PET) and radiotherapy, respectively. The thiophilic nature of arsenic led to the evaluation of dithioarylarsines for potential use in radiopharmaceuticals. Several dithioarylarsines were synthesized from their arylarsonic acids and dithiols and were fully characterized by NMR, ESI-MS, and X-ray crystallography. This chemistry was translated to the no-carrier-added (nca) 77As level. Because arsenic was available at the nca nanomolar level only as [77As]arsenate, this required addition of an aryl group directly to the As to form the [77As]arylarsonic acid. The [77As]arsenate was reduced from 77As (V) to 77As (III), and a modified Bart reaction was used to incorporate the aryl ring onto the 77As, which was followed by dithiol addition. Various modifications and optimizations resulted in 95% radiochemical yield of nca [77As]p-ethoxyphenyl-1,2-ethanedithiolatoarsine.

•Simple, rapid 77As/76,77Ge separation developed.•No carrier added 77As was separated from neutron irradiated 76Ge using silica gel.•∼74% arsenate eluted with methanol with minimal to no Ge breakthrough.•>80–90% arsenate eluted with 12 M HCl:EtOH (1:1200) without Ge breakthrough.•98% 76Ge recovered by elution with 3 mL of aqueous solution (pH ≥ 7).A simple column chromatographic method was developed to isolate 77As (94 ± 6% (EtOH/HCl); 74 ± 11 (MeOH)) from germanium for potential use in radioimmunotherapy. The separation of arsenic from germanium was based on their relative affinities for different chromatographic materials in aqueous and organic environments. Using an organic or mixed mobile phase, germanium was selectively retained on a silica gel column as germanate, while arsenic was eluted from the column as arsenate. Subsequently, enriched 76Ge (98 ± 2) was recovered for reuse by elution with aqueous solution (neutral to basic). Greater than 98% radiolabeling yield of a 77As-trithiol was observed from methanol separated [77As]arsenate [17].

Reaction of (Bu4N)[ReOCl4] with the tetradentate Schiff base ligand α,α′-[(1,1-dimethylethylene)dinitrilo]di-o-cresol (sal2ibnH2) yields cis-[ReVOCl(sal2ibn)], which quickly forms trans-[μ-O(ReVO(sal2ibn))2] in solution. The dinuclear complex can also be isolated by the addition of base (Et3N) to the reaction mixture. Conversely, the mononuclear complex can be trapped as cis-[ReVO(NCS)(sal2ibn)] by addition of (Bu4N)SCN to the reaction mixture. Reduction of cis-[ReVO(NCS)sal2ibn] with triphenylphosphine gives the rare trans-[ReIII(NCS)(PPh3)(sal2ibn)] and unique μ-oxo Re(IV) dimer trans-[μ-O(ReIV(NCS)(sal2ibn))2]. All of the complexes were characterized by 1H and 13C NMR, FT-IR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), cyclic voltammetry and single crystal X-ray diffraction.

A laboratory discussion worksheet and its answer key provide instructors and students a discussion model to further the students’ understanding of chemical kinetics. This discussion worksheet includes a section for students to augment their previous knowledge about chemical kinetics measurements, an initial check on students’ understanding of basic concepts, a group participation model where students work on solving complex-conceptual problems, and a conclusion to help students connect this discussion to their laboratory or lecture class. Additionally, the worksheet has a detailed solution to a more advanced problem to help students understand how the concepts they have put together relate to problems they will encounter during later formal assessments.Keywords: First-Year Undergraduate/General; High School/Introductory Chemistry; Inquiry-Based/Discovery Learning; Kinetics; Problem Solving/Decision Making;

2-[2-benzothiazoylmethyl)thio]-benzenamine, which was first reported in 1898, was isolated from the reaction of bromoacetyl bromide and 2-aminothiophenol [1]. The product crystallized from an aqueous methanol solution of the reaction mixture to which nickel(II) acetate had been added. 2-[(2-benzothiazolylmethyl)thio]-benzenamine crystallized in the monoclinic system, in space group C2/c, with cell dimensions of a = 27.392 (19) Å, b = 4.730 (3) Å, and c = 23.686 (16) Å, β = 122.465 (6)°, V = 2589(3) Å3, Z = 8 and refined to R = 0.0343 and Rw = 0.0844. Crystallization from methanol yielded the product as the hydrobromide salt in the monoclinic space group Cc, with cell dimensions of a = 10.488 (3) Å, b = 33.404 (9) Å, c = 5.2578 (14) Å, β = 116.769(2)°, V = 1644.7(8) Å3, Z = 4 and refined to R = 0.0296 and Rw = 0.0600. Mass spectral and NMR analyses confirmed that the bulk and crystalline compound were all 2-[(2-benzothiazolylmethyl)thio]-benzenamine.

Reactions of ReV, tetradentate Schiff base complexes with tertiary phosphines have previously yielded both rearranged ReV and reduced ReIII complexes. To further understand this chemistry, the rigid diiminediphenol (N2O2) Schiff base ligand sal2phen (N,N′-o-phenylenebis(salicylaldimine)) was reacted with (n-Bu4N)[ReOCl4] to yield trans-[ReOCl(sal2phen)] (1). On reaction with triphenylphosphine (PPh3), a rearranged ReV product cis-[ReO(PPh3)(sal2phen*)]PF6 (2), in which one of the imines was reduced to an amine during the reaction, and the reduced ReIII products trans-[ReCl(PPh3)(sal2phen)] (4) and trans-[Re(PPh3)2(sal2phen)]+ (5) were isolated. Reaction of sal2phen with [ReCl3(PPh3)2(CH3CN)] resulted in the isolation of [ReCl2(PPh3)2(salphen)] (3). The compounds were characterized using standard spectroscopic methods, elemental analyses and single crystal X-ray crystallography.

The structure–activity relationships of a series of rhenium (Re)-cyclized octreotide derivatives are described. The effects of changes in the peptide sequence, N-terminus, and C-terminus on metal cyclization, as well as binding to the somatostatin receptor, were investigated. Each peptide complex was found to have an integrated Re(V) core with a single metal oxo group, two coordination sites filled by the cysteine sulfhydryls, and another by the amide nitrogen of Phe3/Tyr3. The final coordination site was determined by the peptide N-terminus: the N-terminal amine coordinated for N-NH2 peptides and the amide nitrogen of Thr6 for peptides with acetylated N-termini. Re-cyclization of the octreotide derivatives led to structural perturbations of the somatostatin receptor-binding sequence relative to the Re−free disulfide analogues, resulting in reduced binding affinities. The findings presented herein demonstrate the importance of understanding the consequences of structural modifications when designing metal−peptide complexes for somatostatin receptor targeting.

IntroductionTargeted radiotherapy using the bifunctional chelate approach with 186/188Re(V) is challenging because of the susceptibility of monooxorhenium(V)-based complexes to oxidize in vivo at high dilution. A monoamine–monoamide dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium and technetium to determine its utility for in vivo applications.MethodsA 222-MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222-MAMA(N-6-Ahx-BBN(7–14)NH2) were synthesized, complexed with rhenium, radiolabeled with 99mTc and 186Re (carrier added and no carrier added), and evaluated in initial biological distribution studies.ResultsAn IC50 value of 2.0 ± 0.7 nM for natReO-222-MAMA(N-6-Ahx-BBN(7–14)NH2) compared to [125I]-Tyr4-BBN(NH2) was determined through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation of the no-carrier added 99mTc-222-N2S2(N-6-Ahx-BBN(7–14)NH2) complex showed little gastric uptake and blockable pancreatic uptake in normal mice.ConclusionsThe 186ReO-222-N2S2(N-6-Ahx-BBN(7–14)NH2) complex showed stability in biological media, which indicates that the 222-N2S2 chelator is appropriate for chelating 186/188Re in radiopharmaceuticals involving peptides. Additionally, the in vitro cell studies showed that the ReO-222-N2S2(N-6-Ahx-BBN(7–14)NH2) complex (macroscopically) bound to PC3-tumor cell surface receptors with high affinity. The 99mTc analog was stable in vivo and exhibited pancreatic uptake in mice that was blockable, indicating BB2r targeting.

•99mTc and 186Re production via proton bombardment of MoS2, WS2, and OsS2 reported.•OsS2 synthesized in high yield (93%) via simple distillation and precipitation method.•Disulfide targets easily pressed for irradiation.•186Re produced via 186W(p, n) and 189Os(p, α) or 192Os(p, α3n) reactions.•WS2 and OsS2 targets easily dissolved, and recovered for reuse.Novel, natural abundance metal disulfide targets were irradiated for 1 h with a 10 µA proton beam in a small, medical cyclotron. Osmium disulfide was synthesized by simple distillation and precipitation methods while MoS2 and WS2 were commercially available. The targets dissolved under mild conditions and were analyzed by γ-spectroscopy. Production rates and potential applications are discussed, including target recovery and recycling schemes for OsS2 and WS2.

Reactions of ReV, tetradentate Schiff base complexes with tertiary phosphines have previously yielded both rearranged ReV and reduced ReIII complexes. To further understand this chemistry, the rigid diiminediphenol (N2O2) Schiff base ligand sal2phen (N,N′-o-phenylenebis(salicylaldimine)) was reacted with (n-Bu4N)[ReOCl4] to yield trans-[ReOCl(sal2phen)] (1). On reaction with triphenylphosphine (PPh3), a rearranged ReV product cis-[ReO(PPh3)(sal2phen*)]PF6 (2), in which one of the imines was reduced to an amine during the reaction, and the reduced ReIII products trans-[ReCl(PPh3)(sal2phen)] (4) and trans-[Re(PPh3)2(sal2phen)]+ (5) were isolated. Reaction of sal2phen with [ReCl3(PPh3)2(CH3CN)] resulted in the isolation of [ReCl2(PPh3)2(salphen)] (3). The compounds were characterized using standard spectroscopic methods, elemental analyses and single crystal X-ray crystallography.

Reaction of (Bu4N)[ReOCl4] with the tetradentate Schiff base ligand α,α′-[(1,1-dimethylethylene)dinitrilo]di-o-cresol (sal2ibnH2) yields cis-[ReVOCl(sal2ibn)], which quickly forms trans-[μ-O(ReVO(sal2ibn))2] in solution. The dinuclear complex can also be isolated by the addition of base (Et3N) to the reaction mixture. Conversely, the mononuclear complex can be trapped as cis-[ReVO(NCS)(sal2ibn)] by addition of (Bu4N)SCN to the reaction mixture. Reduction of cis-[ReVO(NCS)sal2ibn] with triphenylphosphine gives the rare trans-[ReIII(NCS)(PPh3)(sal2ibn)] and unique μ-oxo Re(IV) dimer trans-[μ-O(ReIV(NCS)(sal2ibn))2]. All of the complexes were characterized by 1H and 13C NMR, FT-IR spectroscopy, electrospray ionization mass spectrometry (ESI-MS), cyclic voltammetry and single crystal X-ray diffraction.