Macrocyclic Lanthanide Complexes As Mri Contrast Agents

The aims of this project are to synthesise macrocyclic ligand complexes using various chemistry processes and to test them out on live cells and compare their effects to each other. The macrocyclic ligands were based on the primary ligand, cyclen (1,4,7,10 tetraazacyclodecane). The macrocyclic ligands were successfully synthesised and the various chemistry used in this research to synthesise them were amide bond formation and reduction, click chemistry, fluorescein tagging and selective deprotection. The results confirmed by the H-NMR, C-NMR, fluorescence spectra and TLC plates confirmed the physical characteristics of the macrocyclic ligands. Due to limited amount of time we were unable to test out these results on live cells and compare them with each other; however the success of synthesising these compounds indicates that they may have potential applications as contrast agents in magnetic resonance imaging. Magnetic resonance imaging relies on NMR signals produced by hydrogen nuclei in water and its modifications which are influenced by its surrounding chemical environments. As a result three-dimensional, high resolution images are produced making MRI a powerful technique used in medical clinical diagnosis and biomedical research. Contrast agents (CA) in MRI improve the contrast between pathological tissues by accelerating the relaxation time of adjacent water molecules. Contrast in MRI is usually based on T1 or T2 relaxations which are influenced by the CA. Gadolinium based complexes are the most commonly employed CAs, they produce a positive contrast by decreasing T1 thus elevating T1 signal intensity. Gadolinium has the longest electronic relaxation time of the lanthanide series. It is strongly paramagnetic and possesses 7 unpaired f-electrons making it ideal as a relaxation agent. However, Free Gd3+ is a toxic heavy metal which can accumulate in bones and various tissues, and is associated with NSF. Thus, it is imperative that the gadolinium metal is held strongly by suitable molecular scaffold-like structure in order to be administered intravenously. There are currently nine approved gadolinium based contrast agents available commercially in different regions of the world. Three of these classes of drugs gadovist, prohance and dotarem are macrocyclic in structure (cyclen based) whereas the others are open chains e.g. omniscan. Macrocycles form highly stable complexes due to their macrocyclic effect, and high kinetics of decomplexations. Other lanthanides commonly used include terbium and europium, when bound to chromophore-chelating group they undergo lanthanide luminescence which can be used in microscopy and bioanalysis. The main area of concern for MRI is safety. Other areas of research are the synthesis of novel macrocyclic ligands to be used in bone imaging, cellular imaging and blood pool imaging.