MODELLING STUDIES OF MAGNESIUM-DEPENDENT PHOSPHATE ESTER PROCESSING ENZYMES by

Chapter 1. Magnesium-dependent phosphate ester processing enzymes frequently employ a carboxylate-bridged dimetallic unit in their active sites. Biomimetic modelling chemistry of these magnesium centers has not been investigated previously. An brief introduction of the enzyme systems is presented, along with the focus of the present work. Chapter 2. Several dimagnesium(II) complexes were synthesized and characterized by employing the dinucleating ligand XDK, where H2XDK is m-xylylenediamine bis(Kemp's triacid imide), to stabilize the {Mg(4t-O2CR)}2 2+ unit. A [Mg2(XDK)(CH 3OH)4(H20) 2(NO 3)] complex has been prepared and allowed to react with one or two equivalents of diphenyl phosphate (DPP) to yield [Mg 2 (XDK)(DPP)(CH 3OH)3(H20)(NO3)] and [Mg2(XDK)(DPP)2(CH 3OH)3(H20)], respectively. These are the first structurally characterized phosphate ester-bridged dimagnesium complexes which are potential phosphatase models. Chapter 3. The phosphate ester exchange rate of free and bound diphenyl phosphate in [Mg 2(XDK)(DPP)2(CH 3OH)3(H20)] in methanol has been measured by variable temperature 3 1P{ 1H} NMR spectroscopy and compared to that of structurally analogous dizinc(II) and dicalcium(II) complexes. The synthesis and structural characterization of the dicalcium(II) complex is presented, along with a discussion on the differences between the carboxylateand phosphate ester-bridged dimagnesium, dizinc, and dicalcium centers. Chapter 4. Modelling studies of magnesium-dependent phosphatase enzymes were extended into aqueous media with the synthesis of a water-soluble XDK analog, WXDK. The synthesis and characterization of the carboxylate-bridged dimagnesium-WXDK complexes are described. The biological relevance of these modelling studies is discussed. Thesis Supervisor: Stephen J. Lippard Title: Arthur Amos Noyes Chair and Professor of Chemistry