An investigation of transition metal complex chemistry: enzyme mimicry and Zn(II) detection.

This thesis presents research in the field of transition metal complex chemistry. The major project, reported in Part I, is focussed on the mimicking of enzymes in order to produce simple catalyst molecules that enhance the rate of ester hydrolysis. This work involved a systematic characterisation of a suite of potential enzyme mimics which were based on the simple template molecules tris(2-aminoethyl)amine (tren) and 1,4,7-triazacyclononane (tacn). The effects of substituting tren and tacn with methyl groups and β-cyclodextrin and then complexing these with Zn²⁺, Cu²⁺, Cd²⁺ and Ni²⁺ were examined. The aim was to produce stable complexes with lowered pKₐs for their associated aqua ligands (‘pKₐʜ₂ᴏ’), such that the catalytically active hydroxo ligands (responsible for the ester hydrolysis) were readily available over a broad pH range. The thirty two resulting transition metal complex systems were characterised by potentiometric titration under identical experimental conditions (aqueous NaClO₄ solution, I = 0.10 mol dm⁻³, 298.2 K). For selected systems which were characterised by large stability constants and relatively low aqua ligand pKₐʜ₂ᴏs, their ability to enhance the rate of hydrolysis of 4-nitrophenyl acetate was measured using UV-Visible spectroscopy. A modified Michaelis- Menten enzyme kinetics analysis was developed specifically for this study. Information about the possible mechanism of catalysis was also obtained by a qualitative investigation of the UV-Vis spectra of several systems over the course of the reaction. The chapters comprising Part I therefore describe the synthesis of the ligands (including two new compounds; 6ᴬ-{2-[bis(2-dimethylamino)ethyl]amino}-6ᴬ-deoxy-β-cyclodextrin (βCDMe₅tren) and 6ᴬ-(1,4,7-trimethyl-1,4,7-triazacyclononan-1-yl)-6ᴬ-deoxy-β-cyclodextrin (βCDMe₂tacn)), potentiometric titrations to establish speciation of the systems and the subsequent monitoring of the hydrolysis of 4-nitrophenyl acetate using UV-Vis spectroscopy. The secondary project, reported in Part II, is focussed on the detection of physiological Zn²⁺ using a newly characterised ligand; 2-((E)-2-phenyl)ethenyl-8-(N-4- methylbenzenesulfonyl)aminoquinol-6-yloxyacetic acid. A styryl functional group was added to the commercially available Zn²⁺-selective fluorophore “Zinquin” which detects physiological Zn²⁺ by complexing it and producing a fluorescent signal exclusively on Zn²⁺ binding. The intention of the styryl addition was to enhance the bulk of the Zinquin analogue and thereby hope to improve the selectivity of this fluorophore for free, intracellular Zn²⁺ over the Zn²⁺ found in the structures and catalytic centres of proteins and enzymes. This styryl Zinquin derivative was characterised using potentiometric titrimetry, UV-Vis spectroscopy and fluorimetry. This includes an analysis of the photoisomerism introduced by the styryl functionality. The absorbance and fluorescence characteristics of the free and Zn²⁺-complexed ligand were measured and stability constants for the Zn²⁺ complexes were determined. The results were compared to Zinquin under the same experimental conditions. Like Zinquin, the new styryl analogue was found to be Zn²⁺ selective.Thesis (Ph.D.) -- University of Adelaide, School of Physical Sciences, 201