Water-stable fac-{TcO₃}⁺ complexes - a new field of technetium chemistry

The development of technetium chemistry has been lagging behind that of its heavier congener rhenium, primarily because the inherent radioactivity of all Tc isotopes has limited the number of laboratories that can study the chemistry of this fascinating element. Although technetium is an artificial element, it is not rare. Significant amounts of the isotope (99)Tc are produced every day as a fission byproduct in nuclear power plants. Therefore, a fundamental understanding of the chemistry of (99)Tc is essential to avoid its release into the environment. In this article the chemistry of technetium at its highest oxidation state (+VII) is reviewed with a special focus on recent developments which make water-stable complexes of the general type [TcO(3)(tacn-R)](+) (tacn-R = 1,4,7-triazacyclononane or derivatives) accessible. Complexes containing the fac-{TcO(3)}(+) core display a unique reactivity. In analogy to [OsO(4)] and [RuO(4)], complexes containing the fac-{TcO(3)}(+) core undergo with alkenes metal-mediated, vicinal cis-dihydroxylation reactions (alkene-glycol interconversion) in water via a (3+2)-cycloaddition reaction. Therefore, water-stable fac-{(99m)TcO(3)}(+) complexes pave the way for a new labeling strategy for radiopharmaceutical applications, based on (3+2)-cycloaddition reactions. This new concept for the labeling of biomolecules with small [(99m)TcO(3)(tacn-R)](+)-type complexes by way of a (3+2)-cycloaddition with alkenes is discussed in detail. The herein reported developments in high-valent technetium chemistry create a new field of research with this artificial element. This demonstrates the potential of fundamental research to provide new impetus of innovation for the development of new methods for radiopharmaceutical applications

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

Binding Small Molecules to a cis-Dicarbonyl 99^{\text{99}}TcITc^{\text{I}}-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 $^{\text{99}}$Tc. 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

Induced fac−merfac-mer rearrangements in {M(CO)3_3}+^{+} complexes (M = Re, 99(m)^{99(m)}Tc) by a PNP ligand

The fac–mer isomerisation in [MX$_{3}$(CO)$_{3}$]$^{2−}$ (M = Re, $^{99}$Tc) is induced by a PNP pincer-type ligand in the presence of a halide scavenger. The adaptation to the aqueous and saline chemistry of $^{99m}$Tc yields mer-[$^{99m}$Tc(PNP)(CO)$_{3}$]$^{+}$

To Sandwich Technetium: Highly Functionalized Bis‐Arene Complexes [99mTc(η6‐arene)2]+ Directly from Water and [99mTcO4]−

The labeling of (bio)molecules with metallic radionuclides such as 99mTc 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 [99mTc(η6‐C6R6)2]+‐type complexes are directly accessible from water and [99mTcO4]−, even using arenes incompatible with Fischer–Hafner conditions. To unambiguously confirm the nature of these unprecedented 99mTc complexes, their rhenium homologous have been prepared by substituting naphthalene ligands in [Re(η6‐C10H8)2]+ with the corresponding phenyl groups. The ease with which highly stable [99mTc(η6‐C6R6)2]+ complexes are formed under standard labeling conditions enables a multitude of new potential imaging agents based on commercial pharmaceuticals or lead structures

Towards 99mTc- and Re-based multifunctional silica platforms for theranostic applications

Taking advantage of the radiation properties of 99mTc and 186/188Re and the photophysical characteristics of the {M(CO)3}+ moiety (M = Re), we developed a multifunctional silica platform with the theranostic pair 99mTc/Re with high potential for (nano)medical applications. Starting with a general screening to evaluate the most suitable mesoporous silica construct and the development of appropriate chelate systems, multifunctional mesoporous silica microparticles (SBA-15) were synthesized. These particles act as a model towards the synthesis of the corresponding nanoconstructs. The particles can be modified at the external surface with a targeting function and labeled with the {M(CO)3}+ moiety (M = 99mTc, Re) at the pore surface. Thus, a silica platform is realized, whose bioprofile is not altered by the loaded modalities. The described synthetic procedures can be applied to establish a target-specific theranostic nanoplatform, which enables the combination of fluorescence and radio imaging, with the possibility of radio- and chemotherapy

Novel organometallic rhenium and technetium complexes

0\. Titelblatt und Inhaltsverzeichnis 1\. Einleitung 1 2\. Ergebnisse und Diskussion Teil I 3 2.1. Re- und Tc-Komplexe mit 1,4,7-Trithiacyclononan 4 2.2. 6 Ergebnisse und Diskussion Teil II 19 3.1. N-Heterocyclische Carbene 19 3.2. Re(V)- und Tc(V)-Komplexe mit N-heterocyclischen Carbenen 23 4\. Experimenteller Teil 117 4.1. Ausgangsverbindungen 117 4.2. Untersuchungsmethoden 118 4.3. Röntgenkristallstrukturanalyse 118 4.4. Synthesen 121 5\. Zusammenfassung und Ausblick 137 6\. Kristallographischer Anhang 151 6.1. Tc-Komplexe 153 6.2. Re-Komplexe 118 6.3. Imidazoliumsalz 240 6.4. Hinterlegungsdaten 242 7\. Literaturverzeichnis 243Gegenstand dieser Arbeit ist die Synthese, Charakterisierung und Strukturaufklärung neuer metallorganischer Rhenium und Technetiumkomplexe. Im ersten Teil wird das Koordinationsverhalten von Technetium mit 1,4,7-Triazacyclononan beschrieben und die Ergebnisse mit denen der schon bekannten Rheniumanaloga verglichen. Im zweiten Teil der Arbeit wird das Koordinationsverhalten von Rhenium- und Technetium-startverbindungen mit Oxo-, Nitrido- und Phenylimidozentren mit N-heterocyclischen Carbenen des Imidazolyliden- und Triazolyliden-Typs behandelt. Bei diesen Untersuchungen wurden sehr differenzierte Reaktionsmuster gefunden und es konnten erste Modellverbindungen, die Aussagen über die Stabilität der gebildeten Komplexe und das Koordinationsverhalten der eingesetzten Liganden erlauben, synthetisiert werden.In this thesis, the synthesis, characterization and structure elucidation of new organometallic rhenium and technetium complexes are discussed. In the first section, the coordination behavior of technetium with 1,4,7-triazacyclononane is be described and the results are compared with the known rhenium analogs. The second section of this thesis deals with the coordination behavior of rhenium and technetium starting materials with oxo, nitrido, and phenylimido centers with imidizolylidene and triazolylidene based N-heterocyclic carbenes. In the course of these investigations, clearly differentiated reaction patterns were found. It was possible to synthesize the first model compounds, which allow conclusions to be drawn about the stability of the complexes as well as about the coordination behavior of the applied ligands

Synthesis and reactivity of the rhenium fulvene sandwich complex [Re(η6-C5H4CH2)(η6-C6H6)]+

We present the synthesis of the first mixed-ring rhenium fulvene sandwich complex, [Re(η6-C5H4CH2)(η6-C6H6)]+, from the respective carbinol precursor [Re(η5-C5H4CH2OH)(η6-C6H6)]. The demanding preparation on the basis of the reactive cross-conjugated π system of the fulvene ligand restricts the synthetic accessibility for such fulvene complexes, and the only pathways elaborated originate from the respective carbinols. In contrast to related systems, a suitable rhenium-containing precursor did not exist hitherto. Recently, we described the synthesis of the mixed-aromatic complex [Re(η5-C5H4CHO)(η6-C6H6)] which gave access to the carbinol complex [Re(η5-C5H4CH2OH)(η6-C6H6)] and the title compound, both described herein. With [Re(η6-C5H4CH2)(η6-C6H6)]+ in hand, the susceptibility of the exocyclic methylidene group of the coordinated pentafulvene to nucleophilic attacks was investigated with a variety of Lewis bases (hydride, cyanide, amide, alkoxide, thiolate, and phosphine moieties). The characteristic NMR pattern and X-ray crystal structures of [Re(η6-C5H4CH2)(η6-C6H6)]+ and postfunctionalized [Re(η5-C5H4CH2R)(η6-C6H6)] complexes are presented to confirm their authenticities