Universiẗat, Diss., 2003--Heidelberg.

University, Diss., 2005--Osnabrück. / Erscheinungsjahr an der Haupttitelstelle: 2004.

In the reaction between [Re(CO)5Br] and 2–lithiumthienyl, X–ligand substitution was expected. Li+{C4H3S}¯did not substitute Br¯, but an intermediate negatively charged complex was obtained (non–mobile on silica gel) and it was found that the thienyl had bonded to a carbonyl ligand, producing a dirhenium acylate complex. Such complexes are the precursors to neutral Fischer carbene complexes. After alkylation with Et3OBF4, [Re2 (CO) 9C(OEt)C4H3S] (1) was obtained, instead of a monorhenium monocarbene complex. Greater yields of 1 could be obtained, from reactions with [Re2(CO) 10] instead of [Re(CO) 5Br]. [Re2 (CO) 10] reacted with 5–lithium–2,2'–bithienyl and 2–lithium–3,6– dimethylthieno[3,2–b]thienyl and was then alkylated with Et3OBF4. The reactions proceeded smoothly and [Re2 (CO) 9C(OEt)C8H5S2] (2) and [Re2 (CO) 9C(OEt)C8H7S2] (3) were obtained. The substrates thiophene, 2,2'–bithiophene and 3,6–dimethylthieno[3,2–b]thiophene, can all be doubly lithiated under appropriate reaction conditions. These lithiated species were reacted with two equivalents of [Re2 (CO) 10]. In the case of bithiophene this produced, in good yield, the tetrametal biscarbene complex [Re2 (CO) 9C(OEt)C8H4S2C(OEt)Re2 (CO) 9] (8). In the thiophene and dimethylthieno[3,2–b]thiophene cases [Re2 (CO) 9C(OEt)C4H2SC(OEt)Re2 (CO) 9] (7) and [Re2 (CO) 9C(OEt)C8H6S2C(OEt)Re2 (CO) 9] (9) could be isolated in meagre quantities. This was ascribed to poor double lithiation (also steric hindrance in the case of 7). The carbene ligands reacted with water on the silica gel during column chromatography or in a control experiment with degassed water to produce aldehydes by reductive elimination from the metal. Protonation of the acylrhenate afforded rhenium hydrides which is also a potential precursor to aldehyde formation. This is believed to be a facile process for especially complex 9, isolated in very small quantity. Complexes 7–9 produced monocarbene aldehyde complexes [Re2(CO) 9C(OEt)C4H2SC(O)H] (12), [Re2 (CO) 9C(OEt)C8H4S2C(O)H] (13) and [Re2 (CO) 9C(OEt)C8H6S2C(O)H] (14), as well as dialdehyde compounds. Complexes 2 and 3 also produced aldehyde compounds. The formation of aldehydes from ethoxycarbene complexes is believed to involve hydroxycarbene intermediate species. Experiments were performed on [Re2 (CO) 10] and [Re(CO) 5Br]. They were reacted with 2–lithiumthienyl and then protonated. In the case of [Re2(CO) 10], hydride signals were observed on the 1H NMR spectrum, as well as aldehyde signals. In the case of [Re(CO) 5Br] there was strong NMR evidence indicating the formation of a hydroxycarbene complex. Complexes 1, 2, and 3 were reacted with Br2 (l). The metal–metal bonds were cleaved by the bromine to produce monorhenium carbene complexes [Re(CO) 4{C(OEt)C4H3S}Br] (4), [Re(CO) 4{C(OEt)C8H5S2}Br] (5), and [Re(CO) 4{C(OEt)C8H7S2}Br] 6) and [Re(CO) 5Br]. Complex 8 reacted with bromine to produce a monocleaved complex [Re2 (CO) 9C(OEt)C8H4S2C(OEt)Re(CO) 4Br] (11) and a biscleaved complex [Re(CO) 4Br{C(OEt)C8H4S2C(OEt)}Re2 (CO) 4Br] (10). Unique complexes [Re(CO) 4{C(OH)C4H3S}{μ–H}Re(CO) 4{C(O)C4H3S}] (15) and [Re(CO) 4{C(OH)C8H5S2}{μ–H}Re(CO) 4{C(O) C8H5S2}] (16) were obtained by starting with [Re(CO) 5Br] or [Re2 (CO) 10] and reacting them with 2–lithiumthienyl and 5–lithium–2,2'– bithienyl. These complexes were isolated from the column as very polar compounds after eluation of the aldehyde complexes. The dirhenium complex was obtained with a carbonyl– modified ligand (hydroxycarbene/acyl) on each of the metals. The complexes consist of two fragments held together by a hydrogen atom that bridges the two rhenium atoms (hydrido) and one that bridges the oxygen atoms of the carbene/acyl ligands (protonic). / Thesis (PhD)--University of Pretoria, 2011. / Chemistry / unrestricted

>Magister Scientiae - MSc / Herein we report the successful synthesis of a class of stable and flexible Schiff-base chelators capable of coordinating both ruthenium (II) and rhenium (VII) and which would be catalytically active for oxo-transfer reactions. The synthesis of bidentate (L1), tetradentate (L2-L3), and multidendate ligands (DL1-DL4) of nitrogen was a result of a reaction of primary amine with 2-pyridinecarboxaldehyde. Ligand (L3) is reported herein for the first time. The amines (n-propylamine, ethylenediamine, butanediamine, diaminobutane, propylene iminopyridyl (DAB-PPI) dendrimer) were varied as to afford metal complexes that exhibit different physical and chemical properties. The ligands were isolated and fully characterized by IR, NMR spectroscopy and elemental (H, C, N) analysis.The Schiff-base complexes of methyltrioxorhenium (MTO): Methyl(n-pyridin-2-yl)methylene)propan-1-amine)trioxorhenium (C1), Methyl([bis(pyridin-2- yl)formylidene]butane-1,4-diamine)trioxorhenium (C2), Methyl(diaminobutane propylene imonopyridyl)trioxorhenium G1(DC1) and G2(DC2) have exhibited sensitivity to water than MTO itself. Rapid ligand-exchange reactions in solution are observed at elevated temperatures. The MTO Schiff-base complexes are also slightly sensitive to light and slowly decompose as they are exposes to air. These complexes were isolated and fully characterized by IR, NMR, UV-Vis, EA and MS. In the ESI mass spectra of compound C1-C2 and DC1-DC2 show the peaks of the Schiff-base ligand and the MTO moiety separately, without a traceable fragmentation pattern. The isotopic cluster and the molecular ion peak were observed.The mononuclear ruthenium compounds (B1 and B3) were prepared from dichlorotetrakis(dimethyl sulfoxide)ruthenium (II) metal precursor by reacting the synthesized ligands (L2 and L3) with the metal precursor. Compounds (B2 and B4) were obtained by subsequently stabilizing the neutral compounds (B1 and B2) as hexaflourophosphate salts via metathesis employing thallium (I) hexafluorophosphate (V).The homobimetallic cationic compound (B5) was synthesized by reacting the dinuclear complex [(p-cymene)2RuCl2]2 with ligand (L4).The neutral tetranuclear (V1 and V3) and octanuclear (V2 and V4) (N,N) ruthenium(II) metallodendrimers were synthesized mimicking the same route as for the neutral mononuclear compounds (B1 and B3). The compounds (V1-V4) were prepared from the dichlotetrakis(dimethyl sulfoxide)ruthenium(II) based on the synthesized dendritic scaffolds (DL1-DL4). Compounds (V5 and V6) were fashioned in a similar manner to compound (B5),by reacting the iminopyridyl dendritic scaffolds (DL1 and DL3) with the dinuclear precursor[(p-cymene)2RuCl2]2 to afford two complexes of the type [{(p-cymene)RuCl2}4G1, V5] and [{p-cymene)RuCl2}8G2, V6]. Electronic spectra of the prepared complexes were obtained (in a Sharpless Biphasic solvent system: CCl4:MeCN:H2O) in order to understand the nature of the active species in the catalytic cycle and to propose a mechanism for the catalytic cycle .Confirmation of the prepared complexes (B1-V6) was done using several spectroscopic techniques (IR, NMR, UV-Vis, ESI-MS) in conjuction with elemental analysis.The compounds C1-DC2 were then tested towards the epoxidation of selected cyclic alkenesi.e cyclohexene and cis-cyclooctene, respectively and straight chain alkenes. The catalyzed epoxidation reactions were carried out at room temperature employing using Urea hydrogen peroxide adduct (UHP) as the oxidant and dichlomethane (DCM) as the solvent. The complexes displayed high catalytic activity and selectivity when applied to the epoxidation of cyclohexene and cis-cyclooctene with urea hydrogen peroxide adduct (UHP) as oxidant in dicholoromethane. The epoxidation reaction was quantified using gas chromatography.Conversions reached 100% for all the complexes within 6 hours. The catalytic activity of complex C1 and C2 was relatively low compared to the catalytic activity of complex DC1 and DC2.

<p> The products of the reaction between oxomethoxodichlorobistriphenylphosphinerhenium(V) and acetylacetone are determined, characterized and correlated in terms of a reaction scheme. A series of rhenium(III) compounds, characteristic of reactions analogous to the one mentioned above, with other β-ketoenols is prepared and characterized. The syntheses and properties of tris-1,1,1-5,5,5-hexafluoropentane-2,4-dionatorhenium(III) and trispentane-2,4-dionatorhenium(III) are described. A new nitrido-rhenium complex, nitridochloro-1,1,1-5,5,5-hexafluoropentane-2,4-dionatobistriphenylphosphinerhenium(V) complex is prepared and characterized. A synthetic route to pyridine-acetylacetonate complexes of rhenium is described. </p> / Thesis / Doctor of Philosophy (PhD)

<p> The structure of one of the complexes of rhenium (V) is discussed in this work, namely,[ReOOH(en) 2] (ClO4)2. Chapter I, the Introduction, surveys some of the recent work on rhenium complexes and introduces the basic problems. Chapter II contains a summary of most of the relevant theory for crystal structure determinations. The partial solution of the structure is given in Chapter III entitled Experimental. This section concludes with a discussion of the ambiguity of the actual space group, the ambiguity being whether the space group is P1, or P1. Chapter IV summarizes and discusses the results obtained and compares them with other known results. Anomolous dispersion and neutron diffraction are suggested as possible means for complete solution.</p> / Thesis / Master of Science (MSc)

This thesis describes the synthesis and complexation of amino acid based chelants for technetium and rhenium. All of the chelates were of the NxSy type. An initial N2S2 diamido dithiol peptide of the type mercaptoacetic acid-serine-cysteine was synthesized and coordinated with both rhenium and technetium. The complexes were analysed by NMR spectroscopy and found to retain the benzyl moieties. Syn and anti diastereoemers were produced with one conformation preferred over the other. This was not true of another chelant RP294 supplied by Resolution Pharmaceuticals. The N2N1'S1 chelant consisted of dimethyl-glycine-serine-cysteineglycine and was a novel variation of the N2S2 tripeptide used initially. The coordination of this N3S chelant to technetium resulted in the formation of equal 1:1 quantities of diastereomers. Analysis was done by NMR spectroscopy and electrospray mass spectrometry. The two diastereomers were found to slowly interconvert and a mechanism for the interconversion proposed. The radiopharmaceutical RP128 (dimethylglycineserine-cysteine-glycine-threonine-lysine-proline-proline-arginine), of which the RP294 is the chelating portion, was coordinated to technetium. Analysis of the bifunctional chelant and its coordination complex by NMR spectroscopy demonstrated that the targeting portion of the molecule was unaffected by the technetium. Two diastereomers of the TcO(RP128) complex were found, as seen for the chelating portion of the molecule, TcO(RP294). / Thesis / Master of Science (MS)

In the present thesis, the potential of functionalized Re(CO)3 complexes as thiol-specific probes, luminescent markers for microscopy, and non-radioactive congeners for 99mTc and 186/188Re radiopharmaceuticals was explored. In the first section, three different routes to alkyne-based thiol probes were investigated. Initially, a mixed 2-picolyl/triazole ligand (pictz), with the aim of directly introducing the required peripheral thiol-specific alkyne group to the ligand periphery, was prepared from 2 (azidomethyl)pyridine and 1,4-Bis(ethinyl)benzene. However, the resulting complexes showed likely due to the significant flexibility introduced by the methylene linker connecting the triazole and pyridyl groups, unfavorable luminescence properties. A second attempt was based on a mixed pyridyl/NHC ligand, for which the non-functionalized parent compound was synthesized, but also shows a low emission, which led to the route being abandoned. In the end, a Sonogashira coupling of 4-brom-2,2’-bipyridine with trimethylsilylacetylene gave the desired complex [ReBr(bpyCCH)(CO)3], which showed the desired bright orange luminescence centered around 570–590 nm upon excitation at 380 nm. NMR studies in the presence of L cysteine under different conditions (no additive, addition of morpholine as base, and 2,2 dimethoxy-2-phenylacetophenone as a radical initiator) showed that the cysteine thiol group has to be either deprotonated or oxidized to the thiyl state for a reaction to take place. Only in the latter two cases, the typical spectral signature of a trans-alkene moiety from sulfur addition to the CC triple bond was observed in the 1H NMR spectra of the respective reaction mixtures. In the second chapter, axial ligand modification in [Re(N3)(bpy)(CO)3] by iClick reaction with different alkynes was explored. In addition to dimethyl acetylene dicarboxylate (DMAD), a number of other terminal and internal alkynes was also investigated and the iClick reaction also extended to strained and “masked” alkynes in the form of cyclooctyne and oxanorbornadiene derivatives. While bulky phenyl groups in internal alkynes of the general formula C6H5CCR with R = COCH3 or COOCH3 did, likely due to steric hinderance, not lead to formation of any triazolato product, other internal and terminal alkynes showed iClick reactions to proceed with reaction rate constants in the range of 10 5 to 101 M-1 s-1, with two strongly electron-withdrawing groups like ester or trifluoromethyl generally leading to the fastest reactions and strained or masked alkynes in the 10-4 to 10-2 M-1 s-1 range. Some of the title complexes were internalized by bacterial cells, as demonstrated by luminescence microscopy, but overall the quantum yields were too low for general suitability as emissive markers and the compounds will require further optimization of their photophysical properties for future and more universal use. In the last section, a one-pot synthesis of [Re(triazolatoCOOCH3,COOCH3)(bpy)(CO)3] by sequential addition of 2,2’-bipyridine (bpy), sodium azide, and DMAD to [ReBr3(CO)3]2- was based on HPLC detection, developed. By careful optimization of the HPLC gradient and reaction times after each of the consecutive additions, the title compound could indeed be isolated and authenticated by matching of retention time and UV/Vis spectral signature to that of an authentic sample separately synthesized on a preparative scale, paving the way to transfer the method to radioactive 99mTc complexes. Overall, this work shows the great utility of the [ReX(N^N)(CO)3] moiety for both, small molecule reporters and biological molecules such as thiols, in luminescence spectroscopy, as well as models for radioactive Tc analogues. / In der vorliegenden Arbeit wurde das Potential von funktionalisierten Re(CO)3-Komplexen als thiolspezifische Sonden, Lumineszenzmarker für Mikroskopie und nicht radioaktive Kongenere für 99mTc and 186/188Re Pharmazeutika untersucht. Im ersten Abschnitt wurden drei verschiedene Routen zu alkinbasierten Thiolsonden untersucht. Zuerst, ein gemischter 2-Picolyl/Triazolligand (pictz), welcher die unmittelbare Einführung des benötigten thiolspezifischen Alkin in der Ligandenperipherie als Ziel hatte und aus 2‑(Azidomethyl)pyridin und 1,4-Bis(ethinyl)benzol hergestellt wurde. Allerdings zeigten die Komplexe, wahrscheinlich wegen der zusätzlichen Flexibilität durch den Methylenlinker zwischen Triazol und Pyridin unvorteilhafte Lumineszenzeigenschaften. Ein zweiter Ansatz basierte auf der Synthese eines Pyridyl/NHC-Liganden, für welchen die nicht-funktionalisierte Stammverbindung synthetisiert wurde, jedoch ebenfalls eine schwache Emission zeigte, weshalb diese Route eingestellt wurde. Zuletzt wurde der gewünschten Komplex [ReBr(bpyCºCH)(CO)3] über eine Sonogashira-Kupplung von 4‑Brom‑2,2’-bipyridin mit Trimethylsilylacetylen hergestellt, welcher nach Anregung bei 380 nm eine intensive orangene Lumineszenz im Bereich von 570–590 nm zeigte. NMR‑Studien mit L-Cystein unter verschiedenen Bedingungen (Keine Additive, Zugabe von Morpholin als Base und 2,2‑Dimethoxy-2-phenylacetophenon als Radikalstarter) zeigten, dass das Thiol von Cystein entweder deprotoniert oder zur Thiyl species oxidiert werden muss, sodass eine Reaktion stattfindet. Nur in diesen zwei Fällen wurde die typische spektrale Signatur des Transalkens, welches durch Schwefeladdition an die CºC‑Dreifachbindung entsteht, im 1H NMR der beiden Reaktionsmischungen beobachtet. Im zweiten Kapitel wurde die Modifizierung des axialen Liganden von [Re(N3)(bpy)(CO)3] durch iClick Reaktion mit verschiedenen Alkinen untersucht. Neben Dimethylacetylendicarboxylat (DMAD), wurden auch eine Reihe anderer terminaler und interner Alkine untersucht sowie die iClick Reaktion hierbei auch auf gespannte und maskierte Alkine in Form von Cyclooktin- und Oxanorbornadien-Derivate erweitert. Während räumlich anspruchsvolle phenylsubstituierte interne Alkine der allgemeinen Formel C6H5CºCR mit R = COCH3 oder COOCH3 wahrscheinlich aufgrund von sterischer Hinderung und +M-Effekt nicht zum gewünschten Triazolat führten, zeigten andere interne und terminale Alkine iClick Reaktionen mit Ratenkonstanten im Bereich von 10‑5 to 101 M‑1 s‑1, wobei stark elektronenziehende Gruppen wie beispielsweise Ester oder Trifluormethyl generell zu den schnellsten Reaktionen führen und Reaktionen von gespannten oder maskierten Alkinen im Bereich von 10-4 to 10-2 M-1 s-1 liegen. Einige der Komplexe wurde von den Bakterienzellen aufgenommen wie anhand von Lumineszenzmikrospkopie gezeigt, insgesamt waren die Quantenausbeuten zu gering für die generelle Eignung als Fluoreszenzfarbstoff und die Verbindungen erfordern weitere Optimierung ihrer photophysikalischen Eigenschaften für eine zukünftige und breitere Anwendung. Im letzten Abschnitt wurde eine Eintopfsynthese von [Re(triazolatoCOOCH3,COOCH3)(bpy)(CO)3] durch schrittweise Zugabe von 2,2’-Bipyridin (bpy), Natriumazid und DMAD zu [ReBr3(CO)3]2- basierend auf der Detektion von HPLC entwickelt. Durch sorgfältige Optimierung des HPLC‑Gradienten und der Reaktionszeit nach jeder der aufeinanderfolgenden Zugaben, konnte die jeweilige Verbindung in der Tat isoliert und durch Vergleich der Retentionszeiten und der UV/Vis spektralen Signatur, mit der einer separat im präparativen Maßstab synthetisierten Probe authentifiziert werden und somit den Weg zum Transfer der Methode auf die radioaktiven 99mTc‑Komplexe ebnet. Zusammenfassend zeigt diese Arbeit den großen Nutzen der [ReX(N^N)(CO)3] Einheit für einerseits kleine Molekülreporter und biologische Moleküle wie beispielsweise Thiole, in Lumineszenzspektroskopie und andererseits auch als Modellkomplexe für radioaktive Tc Analoga.

Call number: LD2668 .T4 1965 C45 / Master of Science

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy