Hydrolyse van biologisch relevante modelsystemen door metaal- gesubstitueerde polyoxometalaatcomplexen

Polyoxometalates (POMs) are described as inorganic metal-oxygen clusters that contain early transition metals (V, Nb, Ta, Mo and W) in their highest oxidation state. Their chemically robust nature and highly tunable chemical and physical properties including acidity, thermal stability, redox potential, solubility, size, shape, and charge resulted in their broad application in material science, magnetism, and catalysis. Several classes of POMs were known to have potent anti-tumor, anti-viral and anti-bacterial properties, which resulted in a substantial interest in the potential medicinal application of POMs. Previously, our research group examined the reactivity of several POMs towards different biologically relevant molecules and their model systems. For example, polyoxovanadates and -oxomolybadeswere found to be active towards phosphoester, carboxyester, and peptide bond hydrolysis. More interestingly, the incorporation of transition metal ions with high Lewis acidity such as Zr(IV) and Ce(IV) into heteropolyoxometalates of the Keggin, Wells-Dawson and Lindqvist type resulted in catalysts which showed activity towards hydrolysis of phosphoester and peptidebonds. In this thesis the aqueous speciation of several POMs including Zr(IV)-substituted Keggin POM (Et2NH2)8[{ -PW11O39Zr(µ-OH)(H2O)}2]·7H2O (ZrK 2:2), (Et2NH2)10[Zr(PW11O39)2]·7H2O (ZrK 1:2) and Ce(IV)-substituted Keggin POM, [Me2NH2]10[Ce(PW11O39)2]·14H2O (CeIV(PW11)2), Zr(IV)-substituted Wells-Dawson POM Na14[Zr4(P2W16O59)2(µ3-O)2(OH)2(H2O)4]·57H2O (ZrWD 4:2), was studied in detail. The kinetics of the hydrolysis of DNA model substrates 4-nitrophenyl phosphate (NPP) and bis-4-nitrophenyl phosphate (BNPP), RNA model substrate 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP), ATP, supercoiled plasmid pUC19 DNA was performed in detail. The results showed that all POMs promoted the hydrolysis of these substrates with high rate enhancement as compared to reactions in the absence of the catalyst. The mechanisms of hydrolytic reactions were proposed based on a combination of heteronuclear (1H and 31P) 1D and 2D NMR methods such as Diffusion Ordered NMR SpectroscopY (DOSY) and Exchange SpectroscopY (EXSY), kinetic data and density functional theory calculations. The results also clearly demonstrate that 31P DOSY NMR is a powerful technique to in situ determine the presence of reaction intermediates and products formed during the course of hydrolysis. In addition, 31P EXSY NMR has been proven to be a very useful technique to identify the exchange mechanism between the intermediates and the reaction products and to follow the reaction pathway.status: publishe