Search

This work is concerned with the design and synthesis of the cheap, late first row transition metal complexes of Schiff base ligand systems. The prepared complexes readily afford systematic variation in order to probe potency and understand the role of metal, chelating ligands and anionic ligands when carrying out their cytotoxic effect. This study has lead to a better understanding of the action of these classes of complex and will be used to direct the design of new anti-cancer metallopharmaceuticals going forward. This thesis details the synthesis of a library of Schiff base macroacyclic ligands and their novel late first row transition metal complexes with varying anionic counterparts. The creation of a library with several degrees of variability provides a wide array of parameters to afford subtle variation in structure and chemistry e.g. denticity, co-ordination mode, chelate hole size, metal centred redox potentials, hydrolysis rates, co-ordinative saturation, lipophilicity, solubility and more. Complexation of the ligands was carried out by the free ligand and a novel macroacyclic metal template approach using the cheap late first row transition metal salts of Cobalt (II), Nickel (II), Copper (II) and Zinc (II) plus one Ru (III) complex. Structural studies of the 80 generated complexes was carried out by vibrational spectroscopy, elemental analysis, mass spectrometry, magnetic susceptibility and NMR. Single crystal X-ray structures have been determined with 20 reported in this thesis. All ligands act as tridentate ligands in all except one case to form monomeric distorted trigonal-bipyramidal, square-pyramidal or octahedral structures. In the case of zinc nitrate, the ligand L2PhMe acts as a tetradentate ligand to give a distorted octahedral structure. Paramagnetic NMR and solution magnetic susceptibility of paramagnetic complexes was achieved by the Evans NMR method and analysis of the solution NMR showed that L2R and L3R ligands display 2-fold symmetry and are likely either tetradentate in solution or a fast exchange between imine N-donar sites is occurring even down to -65°C. The majority of the resulting complexes of L1R were screened against a panel of three cancer cell lines. Several categories of complex were able to afford structure activity relationships. It was discovered that the ligand is indeed essential for activity of the metal salts against the panel of cell lines and it was largely discovered that the variation in 'tail group' and anionic coordinating ligands played little role in providing a dramatic variation in activity of the metal salt. In general all L1R complexes displayed moderate cytotoxicity showing a trend in activity with respect to the metal in the order RuIII≈CoII>CuII≈ZnII>NiII, over a 6 day exposure to the three cell panel RuIII was shown to be the most potent metal of the L1R series providing IC50 values of 4.6 (0.7) and 7.5 (1.2) μM against the DLD-1 and H460 cell lines respectively, which is Ca. 4.6 and 15 times less potent than cisplatin to the same cell panel respectively. RuIII was also discovered to be the only metal to provide an IC50 value from a 1 hour exposure to the DLD-1 cell panel. The value of 20.4 (3.5) μM is a moderate figure but again Ca. 10 fold less potent than cisplatin for the same test. The L2R and L3R complexes could not be screened by the same comprehension due to their low solubilities. However the lone screen that was possible from the very sparingly soluble complex [CuCl2(L3Bui)] gave the most exciting result and most potent complex of this thesis. After a 6 day exposure, [CuCl2(L3Bui)] gave IC50 values of 4.3 (0.1) and 2.9 (0.1) μM against the DLD-1 and H460 cell lines respectively. These values are merely 4 and 6 fold more than Cisplatin to the same cell lines respectively and demonstrates the potential of this class of complex as cytostatic agents. Further studies utilising a semi-quantitative DNA damaging assay, demonstrated that all first row complexes can damage DNA when in the presence of hydrogen peroxide, with the exception of ZnII complexes. CoII appeared to afford the greatest DNA damage with the most intsense bands for double strand breaks and the CuII complex of the ligand L3Bui also demonstrated a greater DNA damage as opposed to its L1Bui analogue.

The use of electrostatic interactions is fundamental in the the structure and function of biological enzymes, and has the potential to be a powerful tool in synthetic complexes as well. Electric fields generated by charged species have remarkable influence over electronic structure and intermolecular reactivity, and are capable of remarkable thermodynamic control in catalysis. Herein, a heterobimetallic platform consisting of a Schiff base binding site and an enchained crown ether ring is used to show a diverse range of effects that arise when a transition metal and a cation are placed in close proximity.In Chapter 1, spectroscopic and electrochemical techniques are used to demonstrate the role of electrostatic interactions on a nearby cobalt center. These experiments demonstrate the use of a wide range of cationic metals to impart significant shifts on the reduction potentials of a proximal transition metal center. Additionally, the role of solvent and anion coordination in the screening of electrostatic interactions are established.In Chapter 2, further studies are conducted with a nickel analogue of this heterobimetallic framework. Theoretical calculations are used to demonstrate the effect of electrostatics on the expanded molecular orbital manifold of metal Schiff base systems.In Chapter 3, a manganese complex is used to demonstrate the role of electrostatic interactions on reactivity. Extensive studies are carried out on the kinetic and thermodynamic considerations for the N-N coupling of Mn(V) nitrides, which showed that cationic charge is capable of stabilizing activated nitride species against bimolecular reactivity. The effect of proximal cations on ammonia oxidation and pKa are also explored.

The spectroscopy, photophysics, and photochemistry of organometallic complexes of the general type [Re(X)(CO)3(diimine)]0/+ (X= halogen, CN-, alkyl, benzyl, pyridyl, phosphine, isonitrile, or metal fragment group) have received much attention since the 1970s, when their excited state properties were recognized and presented by Wrighton. These organometallic complexes occupy an important position in the photophysics and photochemistry of transition-metal complexes due to their potential uses in many applications such as emission sensitizers, photosensitizers, photooxidants, photocatalysts and electrocatalysts. Due to their promising photophysical properties as well as their excellent thermal and chemical stabilities, ReI(CO)3 complexes have been incorporated into metal containing polymers and macromolecules as emitters in light emitting diodes (LEDs), photosensitizers in photovoltaic devices (PVs) and luminescent probes in biological systems.In the second and third chapters, the syntheses and characterization of monomeric and dimeric ReI(CO)3 complexes is described by using one-pot conditions via metal mediated Schiff base complexation. These compounds are fully characterized by X-ray crystallography, NMR, mass spectroscopy, UV-visible and cyclic voltammetry. Cyclic voltammetry experiments confirm that in dimeric complexes the bridging ligands unit do mediate coupling between the Re(CO)3X coordination complexes. Two-electron redox behaviour allows to calculate a comproportionation constant (Kc), which corresponds to the degree of coupling as the presence of an apparent inter-valence charge transfer (IVCT) band between the ReI(CO)3 centers. DFT and TDDFT calculations indicate that the reductions are ligand-centered, which support intra-ligand transitions for the IVCT bands.In the next chapter, the synthesis of series of main chain organometallic polymers (MCOPs) containing Re(CO)3Cl(diimine) cores is described. Three different types of polymerization reactions, including Yamamoto coupling, Heck coupling, and a new metal mediated Schiff base formation/condensation reaction, allowed for the formation of metal polymers with 100% metal complex incorporation and average molecular weights (Mn) ranging from 25 to 850 kDa.Finally, a study of the induction of E/Z isomerization in two Re(CO)3 diimine complexes with a pendant azobenzene group is presented. Time-resolved photophysical characterization reveales that excitation of the MLCT bands of the Re(CO)3 diimine fragments results in isomerization of the azo bonds in the pendant groups.

Furan derivatives have the potential to be an alternative resource since it can be obtained from biomass in large scale. Many monomers derived from furfural and 5-hydroxymethylfurfural (HMF), have been used in polymerization investigation in recent years. However, few studies in using 2,5-diformylfuran(DFF) as monomer has been reported, probably due to the limited availability of monmer. Polymeric Schiff bases (or polyimines) is a class of materials containing –CH=N- structural unit, which exhibit good thermal stability, useful mechanical properties. In this work, the polymeric Schiff bases obtained from polycondensation of DFF and aromatic, aliphatic diamines, and more comprehensive characterization study has been carried out. FT-IR and 13C Solid NMR study of products confirmed the formation of –CH=N- structural unit. And MALDI-TOF mass spectrum showed a typical polymer pattern, providing further understanding on the polymerization process. Thermal Analysis had also been carried out for both alphatic and aromatic polymeric Schiff Bases.