E–H bond activation by d0 and d10 metal centres

In recent years there has been a drive to study the catalytic dehydrocoupling of various protic and hydridic partners that contain E–H bonds (E = C, N, P, B, Si, Sn). This is in part due to the high atom-efficiency of these reactions as well as their ability to release dihydrogen in a controlled and potentially reversible manner. Transition metal complexes have historically been employed as catalysts for these reactions. Nevertheless, in recent years there has been growing interest in using complexes of the rare earth and main group metals to the same end. For these redox reluctant metals, the lack of multiple stable oxidation states makes -bond metathesis the predominant mechanistic step. This contrasts with the common two-electron and one-electron pathways often observed for transition metals. A diverse selection of mechanistic pathways have emerged with complementary activities and selectivities often reported for transition metal and non-transition metal systems. This thesis describes the activation of various E–H (E = C, Si, N, Al, Zn) bonds by do and d10 metal centres in both catalytic and stoichiometric regimes. The [Y{N(SiMe3)2}3] catalysed C–H silylation of triphenylphosphonium methylide with phenylsilane to give Ph3PCHSiH2Ph is reported. This is the first known example of C–H silylation of an ylide, and was found to be highly dependent on the nature of the pre-catalyst. Whilst exploring the reaction chemistry of the same yttrium complex, the first known example of the catalytic dehydrocoupling of Al–H/N–H bonds was discovered. This latter reaction offers a new synthetic route to form Al–N -bonds from sterically hindered alane and amine partners. The yttrium mediated dehydrocoupling of Si–H/N–H bonds is also documented with an emphasis on the potential for ligand acceleration of catalysis by a cyclometalated phosphonium ylide complex. As part of these studies, the synthesis of a series of structurally diverse aluminium hydride complexes is discussed. These complexes were not only investigated in the aforementioned dehydrocoupling reaction, but also as ligands for transition metals in their own right. The coordination of both Al–H and related Zn–H -bonds to copper(I) was observed in both solution and the solid state and this interaction was characterised by a number of spectroscopic techniques.Open Acces

Synthesis and Properties of Novel Organogold Complexes: Ylide, Allenyl, N-Heterocyclic Carbene and Propargyl Derivatives

La investigación presentada en esta tesis doctoral se centra en la síntesis de complejos organometálicos de oro(I) y oro(III) con ligandos iluro de fosforo, alenilo, carbeno N heterocíclico y propargilo y, también, en el estudio de algunas propiedades de los compuestos como la luminiscencia y la actividad biológica.Se describe la síntesis de derivados de oro(I) y de oro(III) a partir de la sal de fosfonio, cloruro de cianometiltrifenilfosfonio. Estos incluyen complejos mononucleares en los que la sal de fosfonio se ha desprotonado una vez para formar el iluro, permitiendo la coordinación a un centro metálico, y complejos polinucleares en los que la sal de fosfonio se desprotona dos veces para dar la unidad ildiuro que puede formar puente entre dos centros metálicos. También se describen complejos heterometálicos en los que hay un centro metálico adicional coordinado al átomo de nitrógeno del grupo nitrilo, que incluyen dos ejemplos con propiedades luminiscentes que exhiben emisiones fosforescentes a 77 K. Varios de los complejos exhiben actividad antiproliferativa en la línea celular de cáncer de pulmón A549.El bromuro de trifenilpropargilfosfonio sufre una isomerización prototrópica al tautómero alenilo en disolución en varios disolventes, sin embargo, no se observa un tautomerismo análogo en las sales de amonio funcionalizadas con propargilo. Se describe la síntesis de complejos de oro con ligandos alenilo sin precedentes derivados del bromuro de trifenilpropargilfosfonio, en el que se observa una regioselectividad que depende del estado de oxidación del oro. En los complejos de oro(I) se observa una coordinación del átomo de carbono α al centro de oro, mientras que en los derivados de oro(III) una coordinación del átomo de carbono γ al centro metálico da lugar a complejos con una quiralidad axial inusual. También se describen derivados de oro(I) de sales de amonio funcionalizadas con propargilo, sin embargo, en estos complejos, la unidad de propargilo se mantiene y la coordinación al centro de oro se produce a través del átomo de carbono alquino terminal. Los complejos resultantes exhiben actividad antiproliferativa en células A549. Los intentos de preparar un derivado de oro(I) de una sal de sulfonio funcionalizada con propargilo produjeron una mezcla de los complejos propargilo y alenilo de oro.Se describe un nuevo método para la síntesis general de complejos de oro(I) con ligandos NHC. La reacción de sales de imidazolio, con diferentes requerimientos estéricos y electrónicos, con derivados de [AuX(tht)] (tht = tetrahidrotiofeno), en presencia de NBu4(acac), al aire y a temperatura ambiente produce el carbeno de oro con buenos rendimientos y tiempos de reacción muy cortos. Una serie de complejos de oro(I) con ligandos NHC funcionalizados con propargilo se han sintetizado mediante este método, que incluyen los derivados [AuBr(NHC)], [Au(NHC)2]Br, [Au(C6F5)(NHC)] y [Au(NHC)(PR3)]BF4, muchos de estos compuestos se han caracterizado por estudios de difracción de rayos-X de monocristal. Todos los complejos muestran actividad antiproliferativa en células A549, siendo los derivados de fosfina los más potentes. Estos complejos son también luminiscentes y exhiben emisiones fosforescentes a temperatura ambiente y a 77 K. Además, se describe la funcionalización de la unidad propargilo de los complejos oro(I)-NHC en la que se preparan complejos di y trinucleares en los que el carbono terminal alquino coordina a un centro metálico de oro adicional mediante reacción con una base, o complejos en los que el NHC está funcionalizado con una unidad triazol mediante una reacción “click”.Se describe la síntesis de complejos de propargilo oro(I) fosfina por dos métodos diferentes. Los complejos se han caracterizado estructuralmente por difracción de rayos-X de monocristal y en todos los casos se observa la coordinación del carbono alquino terminal de la unidad de propargilo al oro. También se describe derivados heterometálicos luminiscentes dinucleares de oro(I) con cobre(I) o plata(I). Los complejos son activos en células A549 con los derivados heterometálicos dinucleares de oro(I) y plata(I) mostrando la mejor actividad antiproliferativa.<br /

Fluorescent nanosensors for the monitoring of different intracellular reactive oxygen species (ROS)

Reactive oxygen species (ROS) play important roles for the regulation of normal functions such as proliferation, differentiation, migration and cell death. At low doses they participate in the redox balance, but an excess of these species leads to damage to proteins, lipids or DNA. ROS are involved in the onset and progression of several degenerative diseases (e.g., cancer, neurological disorder, etc). Cancer cells are highly susceptible to ROS-mediated damage and several chemotherapy agents achieve cytotoxicity by inducing oxidative stress. Sensing the variations of different intracellular ROS is crucial for real time assessments of anticancer treatment efficiency. Yet, no sensor currently allows simultaneous and independent monitoring of different ROS live cells. Indeed, existing sensors monitor either the total levels of ROS or the levels of single species (i.e., sensors such as diphenylanthracene, peroxy yellow, anthrafluorescein, etc.). The need to optimise and personalise treatment regimens and for unravelling the mechanisms underpinning ROS-induced cell death requires the introduction of a new set of tools able to provide a real-time report of intracellular ROS levels in response to a given intervention. In this project we developed new fluorescent nanosensors able to respond to different ROS. This was achieved through the synthesis of three conjugatable molecular probes able to respond to individual ROS, namely; an anthrafluorescein-based probe for superoxide anion, a dimethylanthracene-based probe for singlet oxygen and a fluorescein-based probe for hydrogen peroxide. The new probes were grafted onto poly(lactic-co-glycolic acid) (PLGA) and formulated as nanoparticles containing either conjugated or encapsulated sensors. We characterised the fluorescent response of the probes, conjugates and nanospecies in the presence of the target ROS analytes. Lastly, we demonstrated the ability of the nanosensors to enter cells and their potential of to be used as intracellular ROS sensors

Organophosphorus Chemistry 2018

Organophosphorus chemistry is an important discipline within organic chemistry. Phosphorus compounds, such as phosphines, trialkyl phosphites, phosphine oxides (chalcogenides), phosphonates, phosphinates and >P(O)H species, etc., may be important starting materials or intermediates in syntheses. Let us mention the Wittig reaction and the related transformations, the Arbuzov- and the Pudovik reactions, the Kabachnik–Fields condensation, the Hirao reaction, the Mitsunobu reaction, etc. Other reactions, e.g., homogeneous catalytic transformations or C-C coupling reactions involve P-ligands in transition metal (Pt, Pd, etc.) complex catalysts. The synthesis of chiral organophosphorus compounds means a continuous challenge. Methods have been elaborated for the resolution of tertiary phosphine oxides and for stereoselective organophosphorus transformations. P-heterocyclic compounds, including aromatic and bridged derivatives, P-functionalized macrocycles, dendrimers and low coordinated P-fragments, are also of interest. An important segment of organophosphorus chemistry is the pool of biologically-active compounds that are searched and used as drugs, or as plant-protecting agents. The natural analogue of P-compounds may also be mentioned. Many new phosphine oxides, phosphinates, phosphonates and phosphoric esters have been described, which may find application on a broad scale. Phase transfer catalysis, ionic liquids and detergents also have connections to phosphorus chemistry. Green chemical aspects of organophosphorus chemistry (e.g., microwave-assisted syntheses, solvent-free accomplishments, optimizations, and atom-efficient syntheses) represent a dynamically developing field. Last, but not least, theoretical approaches and computational chemistry are also a strong sub-discipline within organophosphorus chemistry

Carbon Ligands

Homogeneous catalysis owes its success, in large part, to the development of a wide range of ligands with well-defined electronic and steric properties, which have thus made it possible to adjust the behavior of many organometallic complexes. However, ligands used in catalysis have long been centered on elements of group 15, and it is only more recently that carbon ligands have proved to be valuable alternatives with the emergence of cyclic diaminocarbenes (NHC).This Special Issue aims to provide a contemporary overview of the advances in carbon ligand chemistry from fundamental aspects to applications

Total synthesis of the proposed structure of sclerophytin F and structure re-evaluation

The thesis presents the first enantioselective synthesis of the proposed structure of sclerophytin F and consequently, the first total synthesis of a cladiellin family member having the S-configuration at the C-3 stereocentre. Three novel enantioselective routes are described to access a pivotal intermediate; then, the synthesis follows three key steps: i) radical-mediated cyclisation, ii) oxonium ylide formation and [2,3]-sigmatropic rearrangement, iii) Diels-Alder cycloaddition to deliver the core of the natural product. The novelty of the route relies on the introduction of the C-3 methyl group at an early stage of the synthesis. As anticipated, the presence of this extra methyl had significant influence on many transformations. Finally, the elaboration of the core to meet the proposed structure was completed. Unfortunately, none of the recorded data matched those originally reported for the natural compound. A further three stereoisomers were synthesised but their data also did not match the original