Light-Driven Ring Slippage in [Re(η7-C7H7)(η5-C7H9)]+ and the Inertness of Its Technetium Homologue.

Here, we present the light-driven reactions of [Re(η7-C7H7)(η5-C7H9)]+ (1+) with nitriles, phosphines, and isocyanides, which are added to 1+ via a ring slippage of the tropylium cation from η7 to η3, forming [Re(η3-C7H7)(η5-C7H9)(L)2]+ (L= acetonitrile 2+; 2-phenylacetonitrile 3+; 1,3,5-triaza-5-phosphoadamantane (PTA) 4+; tert-butyl isocyanide 6+; benzyl isocyanide 7+) and [Re(η3-C7H7)(η5-C7H9)(L)]+ with L = (ethane-1,2-diyl)bis(diphenylphosphane) (dppe) 5+. To compare the reactivities of rhenium and technetium, we also investigated the synthesis of [99Tc(η6-C10H8)2]+, its substitution of naphthalene with cyclohepta-1,3,5-triene to obtain [99Tc(η7-C7H7)(η5-C7H9)]+, and its reactivity (or lack thereof) with light.

Exploring Rhenium Arene Piano-Stool Chemistry with [Re(η6-C6H6)(NCCH3)3]+: A Powerful Semi-Solvated Precursor.

Thermal treatment of the ReIII hydride complex [ReH(η5-C6H7)(η6-C6H6)]+ in CH3CN results in the formation of [Re(η6-C6H6)(NCCH3)3]+. This semi-solvated complex is remarkably stable under an ambient atmosphere and exhibits a fast CH3CN self-exchange, which facilitates substitution reactions. The CH3CN ligands are replaced by σ-donating phosphines such as trimethyl phosphine (PMe3), triphenyl phosphine (PPh3), or the bidentate 1,2-bis(diphenylphosphino)ethane (dppe) to afford [Re(η6-C6H6)(NCCH3)3-x(PR3)x]+ (if R = Me, then x = 2; if R = Ph, then x = 1 or 2) or [Re(η6-C6H6)(dppe)(NCCH3)]+, respectively. [Re(η6-C6H6)(NCCH3)3]+ also reacts with π-acceptors such as 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), or CO (1 atm) to give [Re(η6-C6H6)(L)(NCCH3)]+ (L = bipy or phen) and [Re(η6-C6H6)(CO)(NCCH3)2]+, respectively. The latter does not show any signs of decomposition after being exposed to an ambient atmosphere for multiple days. Additionally, [Re(η6-C6H6)(NCCH3)3]+ reacts with π-donors such as the dienes 2,3-dimethyl-1,3-butadiene (DMBD), norbornadiene (NBD), or 1,5-cyclooctadiene (COD) to give [Re(η6-C6H6)(η4-diene)(NCCH3)]+ (diene = DMBD, NBD, and COD). All three complexes are extremely stable and do not decompose during purification by preparative high-performance liquid chromatography (aqueous acidic gradient). In the presence of 18-crown-6, [Re(η6-C6H6)(NCCH3)3]+ reacts with lithium cyclopentadienyl to give the sandwich complex [Re(η5-C5H5)(η6-C6H6)]. Loss of the coordinated benzene was observed when treating [Re(η6-C6H6)(NCCH3)3]+ with diphenylacetylene (PhC≡CPh), yielding the tetra-coordinated [Re(NCCH3)(η2-PhC≡CPh)3]+.

Binding Small Molecules to a cis-Dicarbonyl 99TcI-PNP Complex via Metal-Ligand Cooperativity.

Metal-ligand cooperativity is a powerful tool for the activation of various bonds but has rarely, if ever, been studied with the radioactive transition metal 99Tc. In this work, we explore this bond activation pathway with the dearomatized PNP complex cis-[99TcI(PyrPNPtBu*)(CO)2] (4), which was synthesized by deprotonation of trans-[99TcI(PyrPNPtBu)(CO)2Cl] with KOtBu. Analogous to its rhenium congener, the dearomatized compound reacts with CO2 to form the carboxy complex cis-[99TcI(PyrPNPtBu-COO)(CO)2] and with H2 to form the mono-hydride complex cis-[99TcI(PyrPNPtBu)(CO)2H] (7). Substrates with weakly acidic protons are deprotonated by the Brønsted basic pincer backbone of 4, yielding a variety of intriguing complexes. Reactions with terminal alkynes enable the isolation of acetylide complexes. The deprotonation of an imidazolium salt results in the in situ formation and coordination of a carbene ligand. Furthermore, a study with heterocyclic substrates allowed for the isolation of pyrrolide and pyrazolide complexes, which is uncommon for Tc. The spectroscopic analyses and their solid-state structures are reported.

One Electron Changes Everything: Synthesis, Characterization, and Reactivity Studies of [Re(NCCH3)6]3.

Oxidation of [Re(NCCH3)6]2+ with the thianthrene radical cation results in the formation of [Re(NCCH3)6]3+, one of the very rare cases of a fully solvated +3 complex. It was fully characterized by spectroscopy and X-ray structure analysis. In contrast to its reduced analogue, [Re(NCCH3)6]3+ exhibits a much faster CH3CN exchange. Hence, substitution reactions proceed at 20 °C within minutes. Its potential as a versatile precursor for ReIII chemistry was examined with a series of substitution reactions. The more lipophilic analogue [Re(NCPh)6]3+ was synthesized by nitrile exchange in benzonitrile (NCPh). The Re(II) analogue of [Re(NCPh)6]3+, [Re(NCPh)6]2+, forms by AgI-mediated oxidation of in situ formed [Re(η6-C6H6)(NCPh3)3]+ in NCPh. The same synthetic strategy is feasible for the synthesis of [Re(NCCH3)6]2+ as well. [Re(NCCH3)6]3+ reacts with 1,4,7-trithiacyclononane (C6H12S3) to yield sevenfold-coordinated [Re(κ3-C6H12S3)2(NCCH3)]3+. The reaction of [Re(NCCH3)6]3+ with 1 equiv of (NBu4)X produces the ReIII monohalide complexes [ReX(NCCH3)5]2+ (X = Cl, Br, I). Mixed ReIII dihalides (trans-[ReXY(NCCH3)4]+) were obtained by treating [ReX(NCCH3)5]2+ with a second equivalent of (NBu4)Y (if X = Cl, Y = Br, I; if X = Br, Y = I). Because of this fast CH3CN exchange, [Re(NCCH3)6]3+ is a very suitable precursor for new ReIII complexes.

Watching Hydrogens Migrate: Step by Step from [ReI(η6-C6H6)2]+ to [ReIII(η3-C6H9)(η6-C6H6)(NCCH3)2]2.

Arene substitution reactions in [M(η6-arene)2]0/2+ are well documented for Groups 6 and 8 but are essentially unknown for the manganese triad. Aiming to replace benzene in [ReI(η6-C6H6)2]+, we altered the hapticity of one coordinated benzene, which we found to be tunable stepwise from an η6 to an η3-allyl coordination mode. Reduction of [ReI(η6-C6H6)2]+ with hydrides gives [ReI(η5-C6H7)(η6-C6H6)]. Subsequent addition of acid yields [ReIIIH(η5-C6H7)(η6-C6H6)]+, which converts to [ReI(η4-C6H8)(η6-C6H6)NCCH3]+ in acetonitrile. Further protonation gives the title complex [ReIII(η3-C6H9)(η6-C6H6)(NCCH3)2]2+ by a rhenium-mediated, intramolecular hydride shift. Herein, we present a full mechanistic elucidation of these transformations based on NMR studies, isolation of reaction intermediates, and their full characterizations. The structural feature {ReIII(η6-C6H6)} is unprecedented. Direct arene exchange from [ReI(η6-C6H6)2]+ to [ReI(η6-arene)(η6-C6H6)]+ was found only under strongly acidic conditions in neat arene. The analogous chemistry of the lighter homologue technetium (99Tc) is distinctly different. Treatment of [TcI(η5-C6H7)(η6-C6H6)] with acid in acetonitrile yields only mixtures of [TcI(η6-C6H6)2]+ and [TcII(NCCH3)6]2+.

Expanding the Cyclopentadienyl Framework: 99mTc/Re Complexes with Orthogonal Functions for Bioconjugation.

A series of bifunctional cyclopentadienes of the type 1,3-EtOCO-HCp-linker-NH2 were synthesized. In this series, the linker length (distance between the amine functionalities and the cyclopentadiene) has been systematically varied (CH2)n (n = 1-3). The corresponding Re complexes [(η5-C5H3RR')Re(CO)3] (R = -COOEt, R' = -linker-NH2) were synthesized and structurally characterized. They exhibit extraordinary stability toward water and air. All bifunctional cyclopentadienes have been labeled with the [99mTc(CO)3]+ moiety. Whereas the reactions with ethylene and propylene linked cyclopentadiene under mild reaction conditions led to the products in high radiochemical purity (>96%) without applying further purification protocols, harsher reaction conditions were required for the synthesis of the methylene-linked cyclopentadiene compound. Masking the amine in the methylene-linked cyclopentadiene by an amide bond bypasses this problem. The very hydrophilic characters of these complexes were assessed by KOW analysis. The reported cyclopentadienes and their complexes offer a robust and versatile platform for (radio)metal incorporation into biologically active lead structures.

Relativity as a Synthesis Design Principle: A Comparative Study of [3 + 2] Cycloaddition of Technetium(VII) and Rhenium(VII) Trioxo Complexes with Olefins.

The difference in [3 + 2] cycloaddition reactivity between fac-[MO3(tacn)]+ (M = Re, 99Tc; tacn = 1,4,7-triazacyclononane) complexes has been reexamined with a selection of unsaturated substrates including sodium 4-vinylbenzenesulfonate, norbornene, 2-butyne, and 2-methyl-3-butyn-2-ol (2MByOH). None of the substrates was found to react with the Re cation in water at room temperature, whereas the 99Tc reagent cleanly yielded the [3 + 2] cycloadducts. Interestingly, a bis-adduct was obtained as the sole product for 2MByOH, reflecting the high reactivity of a 99TcO-enediolato monoadduct. On the basis of scalar relativistic and nonrelativistic density functional theory calculations of the reaction pathways, the dramatic difference in reactivity between the two metals has now been substantially attributed to differences in relativistic effects, which are much larger for the 5d metal. Furthermore, scalar-relativistic ΔG values were found to decrease along the series propene > norbornene > 2-butyne > dimethylketene, indicating major variations in the thermodynamic driving force as a function of the unsaturated substrate. The suggestion is made that scalar-relativistic effects, consisting of greater destabilization of the valence electrons of the 5d elements compared with those of the 4d elements, be viewed as a new design principle for novel 99mTc/Re radiopharmaceuticals, as well as more generally in heavy-element coordination chemistry.

Exploring the Coordination Chemistry of N2 with Technetium PNP Pincer-Type Complexes.

Dinitrogen (N2) complexes of technetium (99Tc) are rare, and only two examples have been reported. To complement this important class of complexes also for 99Tc, two different pincer-type complexes of 99Tc were studied to assess their abilities for coordinating dinitrogen. The reactions of the 99TcIII complex [99TcCl3(PPh3)2(NCCH3)] with the pincer ligands PNPtBu and PyrPNPtBu respectively gave [99Tc(PNPtBu)Cl2] and [99Tc(PyrPNPtBu)Cl3], the first structurally characterized 99Tc complexes with mer-coordinated pincer ligands. Reductions with [Co(Cp*)2] under N2 gave the mononuclear bis-dinitrogen complex [99TcI(PNPtBu)(N2)2] and the dinuclear complex [99TcI(PyrPNPtBu)(N2)Cl]2(µ-N2) with both a bridging and a terminal N2 ligand. Spectroscopy and crystal structures confirm their identities. The complexes are stable under a dinitrogen atmosphere, and the N2 ligands are tightly bound. The results for the complexes with the PNPtBu pincer allow a comparison to its rhenium homologue, which has recently been shown to split the N2 ligand with the formation of a nitrido complex.

Fully Solvated, Monomeric ReII Complexes: Insights into the Chemistry of [Re(NCCH3)6]2.

The oxidation of [Re(η6-C10H8)2]+ with AgI in acetonitrile yields [Re(NCCH3)6]2+. This fully solvated ReII compound was characterized by spectroscopic methods and X-ray structure analyses. We show that [Re(NCCH3)6]2+ acts as a precursor complex for a variety of substitution reactions. Treatment with monodentate triphenylphosphine (PPh3) and bidentate 1,2-bis(diphenylphosphino)ethane (dppe) yields the complexes [trans-Re(PPh3)2(NCCH3)4]2+ and [trans-Re(dppe)2(NCCH3)2]+, respectively. [trans-Re(dppe)2(NCCH3)2]+ is oxidized under mild conditions by AgI to its ReII analogue [trans-Re(dppe)2(NCCH3)2]2+. Reactions of [Re(NCCH3)6]2+ with a halide mixture consisting of NaX and AgX (X = Cl, I) result in the formation of the corresponding ReIII complexes [trans-ReX2(NCCH3)4]+. [trans-ReBr2(NCCH3)4]+ can be obtained directly from [Re(η6-C10H8)2]+ by oxidation with FeBr3 in acetonitrile. The title compound is thus a convenient starting material for ReII and ReIII complexes by simple solvent exchange, which are otherwise difficult to access.

Bioorganometallic Technetium and Rhenium Chemistry: Fundamentals for Applications.

Due to its long half-life of 2.111×105 y, technetium, i.e. 99Tc, offers the excellent opportunity of combining fundamental and ' classical ' organometallic or coordination chemistry with all methodologies of radiochemistry. Technetium chemistry is inspired by the applications of its short-lived metastable isomer 99mTc in molecular imaging and radiopharmacy. We present in this article examples about these contexts and the impact of purely basic oriented research on practical applications. This review shows how the chemistry of this element in the middle of the periodic system inspires the chemistry of neighboring elements such as rhenium. Reasons are given for the frequent observation that the chemistries of 99Tc and 99mTc are often not identical, i.e. compounds accessible for 99mTc, under certain conditions, are not accessible for 99Tc. The article emphasizes the importance of macroscopic technetium chemistry not only for research but also for advanced education in the general fields of radiochemistry.

To Sandwich Technetium: Highly Functionalized Bis-Arene Complexes [99m Tc(η6 -arene)2 ]+ Directly from Water and [99m TcO4 ].

The labeling of (bio)molecules with metallic radionuclides such as 99m Tc demands conjugated, multidentate chelators. However, this is not always necessary since phenyl rings can directly serve as integrated, organometallic ligands. Bis-arene sandwich complexes are generally prepared by the Fischer-Hafner reaction. In extension of this, we show that [99m Tc(η6 -C6 R6 )2 ]+ -type complexes are directly accessible from water and [99m TcO4 ]- , even using arenes incompatible with Fischer-Hafner conditions. To unambiguously confirm the nature of these unprecedented 99m Tc complexes, their rhenium homologous have been prepared by substituting naphthalene ligands in [Re(η6 -C10 H8 )2 ]+ with the corresponding phenyl groups. The ease with which highly stable [99m Tc(η6 -C6 R6 )2 ]+ complexes are formed under standard labeling conditions enables a multitude of new potential imaging agents based on commercial pharmaceuticals or lead structures.

Chemistry at High Dilution: Dinuclear 99 m Tc Complexes.

The formation of di- or polynuclear complexes at nanomolar concentrations is generally too slow to be observed with 99m Tc. It is reported in this communication that an appropriate choice of potentially bridging ligands, herein thiols HS-R, accelerates the dimerization reaction to an extent that dinuclear complexes are formed at very high dilution. The dinuclear nature of [99m Tc2 (µ2 -SR)3 (CO)6 ]- is shown by chromatographic comparison, not only with its rhenium homologue as commonly done, but also with the true 99 Tc analogue.

Self-Assembled Multinuclear Complexes Incorporating 99m Tc.

Multinuclear complexes or clusters are rarely investigated in medicinal inorganic chemistry although they represent structural intermediates between molecules and nanomaterials. We present in this report two strategies towards 99m Tc-containing clusters. In a pre-assembly approach, the preformed but incomplete cluster fragment [Re3 (µ2 -OH)3 (µ3 -OH)(CO)9 ]- reacts with [99m Tc(CO)3 ]+ to the highly stable [99m TcRe3 (µ3 -OH)4 (CO)12 ] cube. The same structure self-assembles when reacting the mononuclear Re and 99m Tc precursors in one pot. Integrating the coordinating OH groups from Schiff bases in this concept leads straight to dinuclear, mixed-metal complexes of the type [99m TcRe(µ2 -O^N-R1 )2 (CO)6 ] in quantitative yields. Both strategies are unprecedented and open a future path towards clusters, incorporating a 99m Tc radiolabel while being decorated with targeting or cytotoxic moieties.

A Mixed-Ring Sandwich Complex from Unexpected Ring Contraction in [Re(η6-C6H5Br)(η6-C6R6)](PF6).

The contraction of coordinated aromatic hydrocarbons is a rare reactivity pattern in organometallic chemistry. We describe the conversion of a bromobenzene coordinated to a ReI center into a cyclopentadienyl aldehyde. Under mildly alkaline conditions, the expected phenol complex is formed with Re and 99Tc but under strong basic conditions; ring contraction occurs in close to quantitative yields for Re only. A mechanism for this unprecedented reaction is proposed based on 1H and 2H NMR spectra and density functional theory calculations.

Synthesis and Molecular Structure of 99 Tc Corroles.

The first 99 Tc corroles have been synthesized and fully characterized. A single-crystal X-ray structure of a 99 TcO triarylcorrole revealed nearly identical geometry parameters as the corresponding ReO structure. A significant spectral shift between the Soret maxima of TcO (410-413 nm) and ReO (438-441 nm) corroles was observed and, based on two-component spin-orbit ZORA TDDFT calculations, ascribed to relativistic effects in the Re case. The syntheses reported herein potentially pave the way toward 99m Tc-porphyrinoid-based radiopharmaceuticals.

Bis-Arene Complexes [Re(η6-arene)2]+ as Highly Stable Bioorganometallic Scaffolds.

The synthesis of mono- and difunctionalized [Re(η6-C6H5R)(η6-C6H6-nRn)]+ (n = 0, 1; R = COOH, Br) complexes starting from [Re(η6-benzene)2]+ is described. The lithiation of [Re(η6-benzene)2]+ with n-BuLi leads preferentially to the neutral, alkylated product [Re(η6-C6H6)(η5-C6H6-Bu)] but not to the expected deprotonation of the arene ring. Deprotonation/lithiation with LDA gave the mono- and the dilithiated products in situ. Their reactions with 1,1,2,2-tetra-bromoethane (TBE) or with CO2, respectively, gave [Re(η6-C6H5Br)(η6-C6H6)]+, [Re(η6-C6H5Br)2]+, or [Re(η6-C6H5COOH)(η6-C6H6)]+, [Re(η6-C6H5COOH)2]+. These functionalized derivatives of [Re(η6-benzene)2]+ represent novel precursors for the synthesis of bioconjugates to bioactive structures, comparable to [Co(Cp)2]+ or [Fe(Cp)2]. Different model compounds [Re(η6-C6H5R)(η6-C6H6-nRn)]+ (n = 0, 1; R = -SCH2Ph, -NHPh, -CONHCH2Ph, -C6H5-COdpa) were synthesized via amide bond formation and nucleophilic aromatic substitution. These conjugates were fully characterized including X-ray structure analyses of most products. For all complexes, the 1H NMR arene proton signals are strongly upfield-shifted as compared to those of the noncoordinated arenes. The electrochemical analyses show an irreversible, probably substituent-centered oxidation, which contrasts the cyclic voltammetry of the underivatized complexes where oxidation is fully reversible. The stability of the core and the reactivity of the substituents make these bis-arene complexes useful precursors in medicinal inorganic chemistry, comparable to cobaltocenium or ferrocene.

Kinetics and Mechanism of CO Exchange in fac-[MBr2(solvent)(CO)3](-) (M = Re, (99)Tc).

The self-exchange kinetics of CO ligands in the solvated forms of the commonly used complex [MBr3(CO)3](2-) (M = Re, (99)Tc) were investigated in-depth by (13)C NMR spectroscopy in organic solvents such as dimethylformamide and methanol. The two homologues exhibit surprisingly different chemical behavior. In the case of rhenium, the stable intermediate [NEt4][ReBr2(CO)4] was isolated and characterized by (13)C NMR and IR spectroscopy as well as by single-crystal X-ray diffraction. For technetium, no such intermediate could be identified. The activation parameters (ΔH(⧧) = 110 ± 7 kJ mol(-1) and ΔS(⧧) = 127 ± 22 J mol(-1) K(-1)) and the observed influences of different ligands and solvents suggest a dissociative-interchange-type mechanism with a second-order rate constant for the formation of [NEt4][ReBr2(CO)4], k1 = 0.039 ± 0.001 M(-1) s(-1) at 274 K. On the basis of variable-temperature NMR experiments, kinetic simulations, and density functional theory calculations, a complete model for the CO self-exchange, including all respective rate constants, is reported.

Ditechnetium Heptoxide Revisited: Solid-State, Gas-Phase, and Theoretical Studies.

Ditechnetium heptoxide was synthesized from the oxidation of TcO2 with O2 at 450 °C and characterized by single-crystal X-ray diffraction, electron-impact mass spectrometry (EI-MS), and theoretical methods. Refinement of the structure at 100 K indicates that Tc2O7 crystallizes as a molecular solid in the orthorhombic space group Pbca [a = 7.312(3) Å, b = 5.562(2) Å, c = 13.707(5) Å, and V = 557.5(3) Å3]. The Tc2O7 molecule can be described as corner-sharing TcO4 tetrahedron [Tc---Tc = 3.698(1) Å and Tc-OBri-Tc = 180.0°]. The EI-MS spectrum of Tc2O7 consists of both mononuclear and dinuclear species. The main dinuclear species in the gas-phase are Tc2O7 (100%) and Tc2O5 (56%), while the main mononuclear species are TcO3 (33.9%) and TcO2 (42.8%). The difference in the relative intensities of the M2O5 (M = Tc, Re) fragments (1.7% for Re) indicates that these group 7 elements exhibit different gas-phase chemistry. The solid-state structure of Tc2O7 was investigated by density functional theory methods. The optimized structure of the Tc2O7 molecule is in good agreement with the experimental one. Simulations indicate that the more favorable geometry for the Tc2O7 molecule in the gas-phase is bent (Tc-OBri-Tc = 156.5°), while a linear geometry (Tc-OBri-Tc = 180.0°) is favored in the solid-state.

High--valent technetium chemistry-new opportunities for radiopharmaceutical developments.

The rich coordination chemistry of (99m) Tc distinguishes this radiometal from other radiolabels applied for single-photon emission computed tomography (SPECT) or positron emission tomography (PET). This potential should be used to create novel opportunities for the development of effective imaging probes. In this context, the field of high-valent technetium chemistry has received much interest. It has been shown that fac-{(99m) TcO3 }(+) complexes are potential new synthons for radiopharmaceutical developments, due to their unique physicochemical properties and unprecedented reactivity. In this article, recent developments and the 'state of the art' in this field of technetium chemistry will be reviewed comprehensively.

Induced fac-mer rearrangements in {M(CO)3}+ complexes (M = Re, 99(m)Tc) by a PNP ligand.

The fac-mer rearrangements in [MX3(CO)3]2- (M = Re, 99Tc) induced by a pincer-type ligand (PNP) and a "halide scavenger" are reported. The reactions of fac-[99mTc(CO)3(OH2)3]+ or [99mTcO4]- in saline both yield mer-[99mTc(PNP)(CO)3]+, the first example of a mer-{99mTc(CO)3}+ type complex. In contrast, reactions with terpyridine (terpy) only gave the facial κ2-terpy complexes with Re and 99Tc.