L’oxydation catalytique des liaisons C-H, en condition aérobie est l’une des réactions « phare » de la chimie, aussi bien d’un point de vue fondamental qu’industriel. Le principal défi consiste en l’utilisation de l’oxygène moléculaire comme oxydant « vert » pour l’activation de ces liaisons C-H. De nombreuses métalloprotéines, telles que les mono-oxygénases (Fe, Cu), sont capables de réaliser ces réactions dans des conditions douces. Une stratégie actuelle consiste à développer des systèmes synthétiques capables de reproduire de manière efficace les propriétés catalytiques de ces enzymes. L’objectif principal de nos travaux a été de synthétiser et de caractériser des modèles de mono-oxygénases solubles (sMMO) et membranaires (pMMO). Deux approches ont été développées. La première a consisté à élaborer des ligands ditopiques dissymétriques, dont les deux sites de coordination tris-(2-pyridymethyl)amine “TPA” et pyridinedicarboxamide “PydCA”, sont enclavés dans un seul macrocycle afin de favoriser une distance intermétallique optimale. La seconde stratégie est basée sur la synthèse de ligands ditopiques où les motifs coordinants, tetraazacyclotetradecane “cyclam” et dipicolylamine “DPA”, sont séparés par un espaceur de type phényle. Ces deux approches ont conduit à l’obtention et à la caractérisation, à l’état solide (structure aux rayons X) et en solution (spectroscopie, électrochimie), de nombreux complexes mono et dinucléaires du fer, du cuivre et du cobalt. L’étude de la réactivité de certains complexes mononucléaires vis-à-vis des oxydants tels que O2 et H2O2, en l’absence de substrats organiques, a permis d’identifier des espèces métal-oxygène. L’oxydation catalytique de substrats organiques a également été réalisée. / Catalytic oxydation of C-H bonds using molecular oxygen as ‘green’ oxidant remains a great challenge from both fundamental and industrial point of views. Many metalloproteins, such as copper end iron-based mono-oxygenases are able to perform these reactions under mild conditions. A current strategy is to develop synthetic complexes which can reproduce the efficiency of such enzymes. The main objective of our work has been to synthesize and characterize new models of soluble (sMMO) and particulate (pMMO) mono-oxygenases. Two approaches have been developed. The first strategy was to synthesize unsymmetrical dinucleating ligands bearing two coordination sites, tris-(2-pyridylmethyl)amine “TPA” and pyridinedicarboxamide “PydCA”, which are embedded in a single macrocycle to favor intermetallic interaction. The second strategy is based on the synthesis of dinucleating ligands where coordinating patterns, tetraazacyclotetradecane “cyclam” and dipicolylamine “DPA”, are separated by a phenyl type spacer. These two approaches have led to the formation and characterization in the solid state (X-ray structure) and in solution (spectroscopy, electrochemistry) of many mononuclear and dinuclear iron, copper and cobalt complexes. The study of the reactivity of some mononuclear complexes towards oxidants such as O2 and H2O2, in absence of organic substrates, has led to the identification of metal-oxygen species. Catalytic oxidation of organic substrates was also conducted.

Lanthanide(III) complexes of DOTA derivatives are utilized in the medical imaging techniques such as magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and magnetic resonance spectroscopy (MRS), nuclear imaging (PET and SPECT), or optical methods (luminescence). It has been shown that relaxometric parameters of the Gd(III) complexes of DOTA derivatives with a phosphinic acid pendant arm (Gd-DO3APR ) can reach optimal values (e.g. water residence time, τM, being close to ~10 ns). The relaxometric parameters can be further modified through the phosphorus substituents. It is also known that the complexes possess a high thermodynamic stability and they are kinetically inert. The main goal of this Thesis is an investigation of the effect of pendant amino group protonation in substituents bound to the phosphorus atom on properties of the complexes. Thus in this Thesis, DOTA derivatives with the phosphinic acid pendant arm with an amino group and their complexes were prepared and characterized. The complexes are intended as contrast agents for molecular imaging techniques (mainly for MRI and 31 P MRS). The first part of the Thesis introduces two new versatile "phospha-Mannich" protocols performed under mild conditions. Amino-H-phosphinic acids (AHPAs) were synthesized with excess of...

In recent years, copper radioisotopes have been extensively studied for their suitable coordination and physical properties. Nuclides 61 Cu, 64 Cu and 67 Cu are used in nuclear medicine - in diagnostic as well as in therapeutic applications. The aim of the Thesis is a study of the coordination properties of divalent copper as a stepping stone for the next potential applications. The presented Thesis consists of two thematic parts. The first part deals with the synthesis of cyclam derivatives. Sixteen new macrocyclic ligands with different phosphorus acid coordinating pendant arms (phosphinate, phosphonate, germinal P-C-P) were prepared; an analogous ligand endowed by carboxylic acid pendant arm as well as tetramethylcyclam without coordinating arm were prepared for comparison. The influence of the nature of coordinating acid pendant arms on selectivity and on the rate of copper(II) complexation was studied in detail. The protonation constants of the free ligands and the stability constants of the complexes with selected transition metal ions were determined by potentiometric titrations and by 1 H and 31 P NMR spectroscopy. Kinetic properties - i.e. studies of the formation rate and kinetic inertness of the copper(II) complexes - were performed by UV-Vis spectroscopy. The formation kinetics of the selected...