Yes / Electron‐deficient half‐sandwich complexes are a class of under‐studied organometallics with demonstrated potential as metallodrug candidates. The present study investigates the effect of two 16‐electron organoruthenium complexes ([( p‐ cym)Ru(benzene‐1,2‐dithiolato)] ( 1 ) and [( p ‐cym)Ru(maleonitriledithiolate)] ( 2 )) on the cell viability of non‐immortalised human lymphocytes from healthy individuals. The genotoxic effects of 1 and 2 in lymphocytes using the Comet and cytokinesis‐block micronucleus assays is also investigated. Gene expression studies were carried out on a panel of genes involved in apoptosis and DNA damage repair response. Results show that the two 16‐electron complexes do not have significant effect on the cell viability of human lymphocytes from healthy individuals. However, an increase in DNA damage is induced by both compounds, presumably through oxidative stress production. / This project was supported by the Royal Society (University Research Fellowship No. UF150295 to NPEB), the University of Bradford (RDF Award), and by the Academy of Medical Sciences/the Wellcome Trust/ the Government Department of Business, Energy and Industrial Strategy/ the British Heart Foundation Springboard Award [SBF003\1170 to NPEB].

No description available.

Yes / We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(η6-pcymene)( 1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1/2), [Ir(η5-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecarborane- 1,2-dithiolato)] (3), [Os/Ru(η6-p-cymene)(benzene-1, 2-dithiolato)] (4/5) and [Ir(η5-pentamethylcyclopentadiene) (benzene-1,2-dithiolato)] (6)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes 3 and 6 were found to be non-cytotoxic. The anti-inflammatory activity of 1–6 was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes 3 and 6 trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action. / We thank the Royal Society (University Research Fellowship No. UF150295 to NPEB), and the University of Bradford for financial support.

Une étude détaillée a été effectuée sur des composés organométalliques de carbènes N-hétérocycliques (NHC) de nickel(II), et plus particulièrement sur des complexes demi-sandwich nickel(II)−NHC. Ces complexes ont montré des activités sans précédent en catalyse homogène, notamment en α-arylation de cétones acycliques, où des charges en pré-catalyseur de seulement 1 mol% ont pu être utilisées. L' étude mécanistique de cette réaction tend à montrer l'implication d'intermédiaires radicalaires. De plus, ces complexes demi-sandwich se sont révélés être des pré-catalyseurs performants en hydrosilylation de dérivés carbonylés et d'imines. Les méthodologies qui en découlent fournissent de façon efficace et sélective les produits de réduction correspondants, dans des conditions réactionnelles douces. Un intermédiaire réactionnel demi-sandwich de type nickel−hydrure, agissant probablement comme le véritable précurseur catalytique, a en outre pu être isolé. D'autre part, la synthèse de nouveaux complexes Ni−NHC a remarquablement mené à une nouvelle méthodologie de substitution du ligand cyclopentadienyl dans des dérivés demi-sandwich alkyl,NHC−Ni. Enfin, l'utilisation de NHCs moins classiques, comme les NHCs possédant un squelette malonate, ou encore les carbènes (alkyl)(amine) cycliques, a mené à l'isolement de nouveaux complexes carbéniques de nickel(II), dont les premiers résultats catalytiques sont encourageants. / A detailed study has been conducted on organometallic compounds of N-heterocyclic carbenes (NHC) of nickel(II), in particular on half-sandwich nickel(II)−NHC complexes. These complexes showed unprecedented catalytic activity in homogeneous catalysis, especially in the α-arylation of acyclic ketones, where catalyst loadings as low as 1 mol% could be used. Mechanistic experiments suggest that radicals are implied. Furthermore, these half-sandwich complexes proved to be efficient pre-catalysts in the hydrosilylation of carbonyl compounds and imines, allowing the reduction processes to proceed under mild reaction conditions. During the course of these studies, a half-sandwich nickel−hydride intermediate that probably acts as the true pre-catalyst was isolated. Remarkably, the synthesis of new Ni−NHC complexes led to a methodology for cyclopentadienyl ligand substitution in stable 18-electron alkyl,NHC−Ni derivatives. Finally, the use of less common NHC ligands, such as NHCs possessing a malonate backbone, or else, the use of cyclic (alkyl)(amino) carbenes, led to the isolation of new nickel−carbene complexes, which gave encouraging preliminary catalytic results.

Die vorliegende Dissertation beschäftigt sich mit der Synthese und Charakterisierung von Übergangsmetallkomplexen und deren Anwendungen in der MOCVD (= metal-organic chemical vapor deposition), sowie als Precursoren zur Darstellung von Nanopartikeln und Nanokompositen. Ein Schwerpunkt dieser wissenschaftlichen Arbeit liegt dabei in der Entwicklung von Me-, tBu- und SiMe3-substituierten Manganhalbsandwichkomplexen für die Generierung dünner Mangan-basierter Schichten mittels MOCVD-Technik. Die gezielte strukturelle Veränderung des Cyclopentadienyl-Liganden beeinflusst die physikalischen und chemischen Eigenschaften dieser Verbindungen, welche systematisch untersucht werden. Ein weiteres zentrales Thema dieser Arbeit ist die Entwicklung von Bis(β-diketonato)- und Allyl-(β-diketonato)-palladium(II) Verbindungen als MOCVD-Precursoren. Hierbei dienen asymmetrische β-Diketonate des Typs CH3COCCO(CH2)n (n = 3, 4) als Liganden. Zudem wird durch Substitutionsreaktionen mit Me- und tBu-Gruppen am η3-Allyl-Liganden Einfluss auf die Stabilität der Verbindungen genommen. Die Abscheidung dieser Precursoren führt, in Abhängigkeit des verwendeten Reaktivgases, zur Bildung von Palladium- bzw. Palladiumoxid-Schichten. Zudem wird die Synthese und Charakterisierung von Co(II)-Carboxylaten des Typs [Co(CO2CRR´(OC2H4)nOMe)2] (n = 1, 2; R = H, R´ = Me; R = H, R´ = Ph) beschrieben. Stellvertretend wird eine Verbindung als Single-Source Precursor zur Darstellung von Co3O4-Nanopartikeln eingesetzt. Darüber hinaus wird die Inkorporation von Co3O4-Nanopartikel in organisch-anorganische Hybridmaterialien mittels Zwillingspolymerisation vorgestellt.

Significant developments have been made in the field of C–H activation. However, various disadvantages, mainly low reactivity and selectivity, limit their usage in large-scale synthesis. It is crucial to understand the mechanisms and the nature of the transient species involved in the C–H activation paths to develop effective catalytic routes for homogeneous C–H functionalization reactions. Computational techniques are employed in this study to throw light on these processes. Chapter 1 briefly introduces C–H activation and functionalization reactions. After classifying the reactions on the basis of mechanisms, computational studies on the mechanisms of C–H activation reactions are described. The challenges involved in the discovery of efficient homogeneous C–H functionalization catalysts and progress made in the field are discussed. The insights provided to overcome the problems associated with the catalytic C–H functionalization reactions in a few examples are highlighted. In Chapter 2, DFT model studies are carried out to estimate the affinity and selectivity of 16-electron half-sandwich d6-metal fragments (η5–C5H5)Re(CO)2 and (η6–C6H6)W(CO)2 for binding with alkane C–H bonds. Different C–H binding sites of pentane, at the M06 level of theory have been evaluated. The effects of ancillary ligand variations on the metal–pentane binding strength are studied by substituting different ligands such as N-heterocyclic carbene (NHC), PF3 and NO+ for one of the carbonyl ligands. Isomers of the metal-pentane C–H σ-complexes studied in this chapter are shown in Scheme 1. Binding energies of the terminal methyl C–H bonds (C1 and C5) are significantly lower than those of the methylene C–H bonds (C2, C3 and C4) in all the cases. The metal–pentane binding interactions of the rhenium complexes are significantly stronger than those of the corresponding tungsten analogs. The PF3 complexes have slightly greater binding energies compared to the CO complexes, in both Re(I) and W(0) analogs. These results are in conformity with the experimental results. The electron-deficient nitrosyl complexes have the highest binding energies. These results illustrate that by proper tuning of the electronic factors of the transition-metal fragments with different ancillary ligands, the alkane C–H binding affinity can be controlled. Energy decomposition analyses (EDA) are carried out to determine the nature of the interaction between the metal fragments and pentane C–H bonds. Scheme 1. Formation of pentane C–H σ-complexes Chapter 3 addresses the energetics of various intramolecular site-exchange (chain walking) processes and C–H oxidative addition reactions (Scheme 2) of the pentane C–H σ-complexes studied in Chapter 2. Four possible site-exchange processes such as 1,2-, 1,3-, 1,4- and 1,5-migration processes are studied using DFT/M06 level of theory. η2-(H,H)···M type transition states are located for these migrations (Scheme 2). The 1,3-migration is the most favorable process. Two different pentyl hydride isomers, as shown in Scheme 2, are obtained for oxidative addition of methyl and methylene C–H bonds of pentane for all systems, at same level of theory. Oxidative insertion of metal into the methyl C–H bonds is more favorable than insertion into the methylene C–H bonds for all complexes. The activation energies of all site-exchange and C–H oxidative addition processes of the Re(I) complexes are significantly greater than those of the corresponding W(0) complexes. For all these processes, the activation barriers of the electron-deficient NO+ complexes are the greatest among all ligand systems studied, in both Re(I) and W(0) systems. These results are consistent with the experimental results and suggest that the experimentally observed pentyl hydride isomer [(η5–C5H5)Re(CO)(PF3)H(C5H11)] might be Isomer B and not Isomer A (Scheme 2). The C–H oxidative addition reactions are less favorable than dynamic site-exchange processes in all complexes. These results imply that the metal fragments migrate along the pentane chain more easily than insert into the pentane C–H bonds. Scheme 2. Alkane chain walking and C–H oxidative addition reactions Chapter 4 deals with the mechanisms and energetics of a unique metal migration process of an olefin complex that proceeds via olefinic (C–H)···Metal interaction. Migration of the Re(I) fragment from one π face of the olefin to the opposite π face in [(η5–C5H5)Re(NO)(PPh3)(PhCH═CH2)]+ has been documented experimentally by Gladysz and coworkers. The experimental results provide evidences for an intramolecular mechanism for this process (i.e., without styrene dissociation from Re(I)) and based on kinetic isotope effects (KIE), the involvement of a trans C–H bond is indicated. Either oxidative addition or a vinylic (C–H)···Re interaction could account for the experimentally observed kinetic isotope effect. In this study, the free energy of activation for the migration of Re from one enantioface of the olefin to the other through various pathways is computed using DFT calculations at the B3LYP and M06 levels. Two pathways, one that involves migration of Re through a trans (C–H)···Re interaction and another that involves oxidative addition of Re into the trans C–H bond, are identified as possible paths (Scheme 3) at the B3LYP level. Surprisingly, at the M06 level, DFT computes a lower energy path for the conducted tour mechanism that is not consistent with the experimental KIE. But the computed energy profiles for the reaction are consistent with the experiment when computations are carried out at the B3LYP level. Scheme 3. Mechanisms of olefin π face exchange reaction In Chapter 5, the mechanistic studies of C–H metathesis of d6 half-sandwich complex [(η5–C5Me5)Ru(CH3)(CO)(C6H6)] are discussed. A 1-step mechanism that proceeds via a four-center transition state and a 2-step Oxidative Addition and Reductive Coupling mechanism (OA/RC) are identified as possible mechanisms (Scheme 4) using DFT/M06 level of theory. The 1-step mechanism is more favorable than the 2-step mechanism. As in the oxidative addition intermediate, metal–hydrogen bond is observed in the four-center transition state of the 1-step mechanism. This mechanism is referred to as Oxidative Hydrogen Migration (OHM) rather than σ-Bond Metathesis (σ-BM) which proceeds via a transition state without M−H bonding. The effects of metal (M = Fe(II), Ru(II) or Os(II)) and ancillary ligand (L = H–, NHC, CO or NO+) variations on the mechanisms and energetics of the model Cp complex [(η5–C5H5)M(CH3)(L)(C6H6)] are also studied (Scheme 4). Scheme 4. Oxidative hydrogen migration vs Oxidative addition/reductive coupling Increase in the electron-density on the metal center, using electron-donating ligands such as H−, favors the formation of the oxidative species (intermediate or transition state) and reduces the activation barriers of the C–H metathesis reaction. Similarly, the electron-withdrawing NO+ ligand, which reduces the electron density on the metal center, increases the activation energies of the C–H metathesis reaction or disfavors the formation of the oxidative species. Factor affecting the choice of the mechanism of the C–H metathesis reaction is found to be the net charge transfer between the two fragments [(η5–C5H5)M(CH3)(L)] and benzene in [(η5–C5H5)M(CH3)(L)(C6H6)]. The computational studies reported in this thesis provide valuable insight into the mechanisms and energetics of C–H binding, activation and fluxional processes of the (C–H)···Metal σ alkane and alkene complexes. These studies will be helpful in solving problems associated with the C–H activation reactions. Reference Thenraj, M.; Samuelson, A. G. Organometallics 2013, 32, 7141. (For structural formula and figures pl see the abstract pdf file.)

Die vorliegende Dissertation beschäftigt sich mit der Synthese und Charakterisierung von Übergangsmetallkomplexen und deren Anwendungen in der MOCVD (= metal-organic chemical vapor deposition), sowie als Precursoren zur Darstellung von Nanopartikeln und Nanokompositen. Ein Schwerpunkt dieser wissenschaftlichen Arbeit liegt dabei in der Entwicklung von Me-, tBu- und SiMe3-substituierten Manganhalbsandwichkomplexen für die Generierung dünner Mangan-basierter Schichten mittels MOCVD-Technik. Die gezielte strukturelle Veränderung des Cyclopentadienyl-Liganden beeinflusst die physikalischen und chemischen Eigenschaften dieser Verbindungen, welche systematisch untersucht werden. Ein weiteres zentrales Thema dieser Arbeit ist die Entwicklung von Bis(β-diketonato)- und Allyl-(β-diketonato)-palladium(II) Verbindungen als MOCVD-Precursoren. Hierbei dienen asymmetrische β-Diketonate des Typs CH3COCCO(CH2)n (n = 3, 4) als Liganden. Zudem wird durch Substitutionsreaktionen mit Me- und tBu-Gruppen am η3-Allyl-Liganden Einfluss auf die Stabilität der Verbindungen genommen. Die Abscheidung dieser Precursoren führt, in Abhängigkeit des verwendeten Reaktivgases, zur Bildung von Palladium- bzw. Palladiumoxid-Schichten. Zudem wird die Synthese und Charakterisierung von Co(II)-Carboxylaten des Typs [Co(CO2CRR´(OC2H4)nOMe)2] (n = 1, 2; R = H, R´ = Me; R = H, R´ = Ph) beschrieben. Stellvertretend wird eine Verbindung als Single-Source Precursor zur Darstellung von Co3O4-Nanopartikeln eingesetzt. Darüber hinaus wird die Inkorporation von Co3O4-Nanopartikel in organisch-anorganische Hybridmaterialien mittels Zwillingspolymerisation vorgestellt.

Chapter 1.<br />1-Ethynyl-2-phenyltetramethyldisilanes HCºCSiMe2SiMe2C6H4-p-X [X = NMe2(1.1), Me (1.2), H (1.3), Br (1.4), CF3 (1.5)] are accessible from ClSiMe2SiMe2Cl, BrMgC6H4X and HCºCMgBr in a two step Grignard reaction. The crystal structure of 1.1 as determined by single crystal X-ray crystallography exhibits a nearly planar PhNMe2 moiety and an unusual gauche array of the phenyl and the acetylene group with respect to rotation around the Si-Si-bond. Full geometry optimization (B3LYP/6- 31+G**) of the gas phase structures of 1.1 and 1.3 affords minima for the gauche and the trans rotational isomers, both being very close in energy with a rotational barrier of only 3 – 5 kJ/mol. Experimental and calculated (time-dependent DFT B3LYP/TZVP) UV absorption data of 1.1 – 1.5 show pronounced electronic interactions of the HCºC- and the C6H4X p-systems with the central Si-Si bond.<br /><br />Chapter 2.<br />A family of [( 5-Cp*)Ru( 6-arene)]+ (Cp* = C5Me5) sandwich complexes of 1- and 1,4-substituted phenyl and naphthyl systems are described along with the regioselectivities of the reactions under various conditions. Finally, the (h 5-Cp*) Ru+ arenophile was found to act as a gate to the flow of electrons between para-substituted termini. When it is complexed onto the phenyl or A naphthyl ring, the gate is closed. On the contrary, when it is complexed onto the B naphthyl ring, the gate is open.<br /><br />Chapter 3.<br />Regioselective complexation reactions of the organoiron acetylide derivatives (h 2- dppe)(h 5-Cp*)Fe-C C-Ar (Ar = phenyl, 1-naphthyl; dppe = 1,2- bis(diphenylphosphino)ethane) with [(h 5-Cp*Ru(CH3CN)3][PF6] to afford heterobimetallic complexes formulated as [(h 2-dppe)(h 5-Cp*)Fe-C C-{(h 6-Ar)Ru(h 5- Cp*)}][PF6], were achieved. In the case of the FeII-RuII 1-naphthyl derivative, the (h 5-Cp*)Ru+ arenophile was complexed both onto the substituted ring and free rings of the acetylide 1-naphthyl linker. The first redox-driven h 6-h 6 inter-ring haptotropic migration of the (h 5-Cp*)Ru+ moeity was shown to occur. Crystal structures of all of the seven new iron acetylenes were resolved, including both haptotropomers of the naphthyl compound.<br /><br />Chapter 4.<br />The diorganoiron [{(h2-dpppe)(h5-Cp*)Fe-CC-}2(1,4-naphthyl)] (4.12) was synthesized in good yield in two steps via the vinylidene, and oxidation led to the mixed valence (MV) and iron(III)-iron(III) species in good to excellent yields. This exhaustive empirical study on the family of complexes 4.12[PF6]n (n = 0,1,2) includes a crystal structure for the case in which n = 2. This work clearly establishes good electronic and magnetic communication between the iron centers across the bis(ethynyl)naphthalene bridge. All empirical measurements of these naphthyl compounds reveal that their properties fall between those of known phenyl and anthracenyl derivatives. In some cases, the naphthyl derivative behaves as an average of the phenyl and anthracenyl complexes. For example, the comproportionation constant of the naphthyl species falls at the midpoint between those for the phenyl and anthracenyl compounds. The same is true for the UV absorption maxima in all three oxidation states (Fe[II]- Fe[II], MV, and Fe[III]- Fe[III]). The large electronic (2043 cm-1) and magnetic (-526 cm-1) coupling constants were determined via NIR spectroscopy and SQUID magnetometry, respectively. As for the heterotrinuclear species, the iron(II) acetylene, 4.14B[PF6] [{Cp*(dppe)Fe-C C}2-(h 6 – [1,4-napthyl])RuCp*](PF6), [Cp* = h 5 - C5Me5; Fe = FeII] was prepared in high yields with an adapted, regioselective synthesis via the trinuclear vinylidene. Complete characterization, including a crystal structure, of this sandwich complex reveals that the arenophile perturbs the organoiron ligand more in the bis(iron) than in the previously reported mono(iron) case.