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Radiopharmaceuticals containing copper isotopes can be used as diagnostic tools (methods PET, SPECT) or agents for tumour treatment. Copper radionuclides must be applied into the organism in the form of a coordination compound with suitable ligand. Derivatives of 1,4,8,11-tetraazacyclotetradecane (cyclam) are some of the most suitable ligands for Cu (II). A coordination compound must be thermodynamically stable and kinetically inert, the ligand must coordinate the metal ion as quickly as possible. In this Diploma thesis, one of the first unsymmetrically substituted derivatives of cyclam has been synthesized using two methods of orthogonal protection. The synthesized ligand contains one phosphonate and one methylene bis(phosphinate) pendant arm. Copper complex of the ligand was prepared, and its acid assisted dissociation kinetics were studied.

Copper radionuclides have a potential in nuclear medicine as diagnostic or therapeutic agents. Copper isotopes are used in the form of coordination compounds with various ligands, such as derivatives of 1,4,8,11-tetraazacyclotetradecane (cyclam). Properties of such complexes can be modified by pendant arms introduced on amino groups of cyclam. This thesis is aimed on the synthesis of asymmetrically substituted cyclam derivative with derivatives of phosphorous acids in 1,8- position. In spite of the fact, that the target ligand has not been successfully synthesised, various possibilities of substitution on diprotected cyclam were investigated. New possibilities of orthogonal protection of cyclam were found as well. Keywords: PET, SPECT, copper complexes, cyclam protection, phosphonic acids

19 F MRI contrast agents are relatively new, developing field of medical and chemical sciences. In this Theses, based on previous results in this area, new type of Ni2+ complex with possible 19 F MRI applications was synthesized and characterized by relaxometric measurements.

Lanthanides have several specific properties which cannot be found for other elements in the periodic table. Among various applications of lanthanides, complexes of LnIII ions are used in medicine, e.g., as contrast agents in MRI, as luminescent probes or as radiopharmaceuticals, where their specific properties are important. These complexes must be kinetically inert to prevent release of highly toxic "free" LnIII ions. This requirement is fulfilled with pre-organized ligands such as analogues of H4dota (1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid). Many of important properties of LnIII complexes of H4dota, such as relaxivity, isomerism and fluxionality, depend on the solution dynamics of the complexes. However, the knowledge of this solution dynamics is limited for LnIII complexes of H4dota derivatives with phosphonate or phosphinate pendant arms. Recently, a new dynamical process where phosphonate oxygen atoms interchange through a bidentate phosphonate intermediate ("a phosphonate rotation") has been proposed by DFT calculations but unconfirmed experimentally. To prove the process experimentally, solution dynamics of LnIII complexes of monophosphonate and monophosphinate derivatives of H4dota was investigated. Especially, to examine the "P-rotation", 17 O NMR spectroscopy was used...

Macrocyclic ligands are compounds well-known and studied for their ability to bind metal ions into complexes possessing high kinetic inertness and thermodynamic stability. These properties make such compounds useful in medicine. This thesis focuses on ligand cis- DO2A2P, which belongs to a series of ligands based on cyclen skeleton with mixed acetate and phosphonate pendant arms. A lot of attention has been paid to the other members of this ligands series, but the information about cis-DO2A2P is still incomplete. In this thesis, the complexation properties of mentioned ligand were studied, as well as properties of its complexes with the lanthanide ions in solution. Key words Macrocycles; polydentate ligands; lanthanides; transition metals; organophosphorus acids

Macrocyclic complexes of H4dota-like ligands are used in various fields, mainly in medicine. e. g. as MRI contrast agents or luminescent probes. Their applications are greatly influenced by stereochemistry. Stereoisomers of these complexes mostly interconvert with each other in solution. This interconversion can be studied by NMR spectroscopy This work is intended to test 17 O NMR spectroscopy as a tool for monitoring dynamic processes where phosphonate group in the complexes of methylphosphonate derivatives of H4dota is involved. To this end, ligand H4do3apOEt and his LnIII -complexes (Ln ≠ Pm) containing 17 O-labeled phosphonate group were synthesized. Next, 17 O NMR spectra of these complexes were measured and analysed. In an analogy with H4dota complexes, signals of both non-coordinated and coordinated oxygen atoms (except GdIII ) in the complexes could be detected. Fraction of TSA (twisted square-antiprism) and SA (square-antiprism) isomers was determined from the acquired 17 O NMR spectrum for each complex. The determined values were compared with those obtained by analysing 1 H and 31 P NMR spectra of the complexes, which were also measured. The TbIII , DyIII and YbIII complexes (because of high resolution of their 17 O NMR spectra) and CeIII complex (because of anomalous properties of its...

Macrocyclic ligands are very efficient agents for complexation of paramagnetic metal ions in complexes possessing high kinetic inertness and thermodynamic stability. These properties are very useful for medical applications. The aim of this work is to prepare ligand cis- DO2A2P using a new synthetic approach. Cis-DO2A2P is the last ligand in the series of DOTA derivatives with mixed carboxylate and phosphonate pendant arms which does not have its complexes fully described. This thesis includes basic information known on the ligands from this series, about the structure and properties of their complexes, and synthesis of the cis-DO2A2P. Key words: macrocycles, polydentate ligands, lanthanides, transition metals, organophosphorus acids