Synthetic strategies towards water-stable, water-soluble lanthanoid cage clusters

This thesis aims to address the lack of control regarding the syntheses of lanthanoid oxo/hydroxo cage clusters, investigate the solution behaviour of these species and expand the scope of lanthanoid cluster chemistry. These aims are part of a broader goal, which is to identify lanthanoid cluster motifs with stability and structural profiles amenable to application as future in vivo contrast agents. The bulk of this work has been divided into four chapters: § A general introduction giving an overview of in vivo contrast media, concentrated on the current iodinated and lanthanoid based drugs. § An in-depth analysis of selected lanthanoid cluster syntheses focussed on gaining mechanistic insight into lanthanoid cluster formation. These insights then serve to guide our synthetic efforts, with our subsequent results in the field of lanthanoid cluster chemistry reported thereafter. § The implementation of in situ Fourier Transform infrared spectroscopy to metal based reactions aimed at identifying the solution-state behaviour of lanthanoid complexes and clusters. § A preliminary computed tomography (CT) study, in which the attenuation of selected mononuclear complexes and oligonuclear lanthanoid species are compared to Ultravist™, a commercial CT contrast agent. This study aims to validate our hypothesis that a high-nuclearity, lanthanoid based contrast agent could generate greater contrast than the current tri-iodinated contrast media. During our pursuit of water-soluble, water stable lanthanoid cluster species, a range of novel chiral, cationic, mono- and oligo-nuclear lanthanoid species were identified and characterised, with a range of catalytic, magnetic and luminescent properties investigated. Highlights include the identification of three new lanthanoid diketonate motifs, including the tetranuclear and dimeric motifs [Ln4(Cl)2(O)(hpb)6]Cl2 and [Ln2(hmb)5]Cl (Hhpb: (R/S,Z)-1'-hydroxy-3-(hydroxy(phenyl)methylene)bi(cyclopentan)-2-one; Hhmb: p-methoxyphenyl derivative), as well as an acetate containing chiral tetranuclear cluster [Ho4(OH)4(gme)7(Ac)(H2O)2] (Hgme: (Z)-4-hydroxy-4-((3αR,5R,5αR,8αS,8βR)-2,2,7,7-tetramethyltetrahydro-3αH-bis[1,3]dioxolo[4,5-δ:4',5'-δ]pyran-5-yl)but-3-en-2-one)). Progress has also been achieved regarding the controlled manipulation of cluster motif mediated by ligand design, exemplified by the synthesis of the cubane motif [Ln4(OH)4(H2O)n(X)8] where HX is an ortho substituted (Z)-4-hydroxy-4-phenylbut-3-en-2-one ligand. Further progress in this area could improve in the design and function of any application that employs lanthanoid cluster species. The ability of in situ Fourier Transform infrared spectroscopy to elucidate metal catalysed reactions, ligand to metal binding and intermolecular interactions between metal species has similarly been demonstrated. This novel means of monitoring reaction progress has yielded fundamental information regarding the solution behaviour of lanthanoid cluster species [Nd4(μ3-OH)2(PhacacPh)10] and [HNEt3][Tb9(m4-O)2(m3-OH)8(EtOacac)16]. Finally, a brief CT study measuring the attenuation of selected lanthanoid complexes and clusters in solution referenced against Ultravist™, a current iodinated CT contrast agent, is detailed. It has also been demonstrated that measuring attenuation values in solvents other than water can reasonably be achieved by applying a normalising factor to the resultant CT values.