The objective of this thesis is the chemical mimicry of dinuclear hydrolases via the design and synthesis of asymmetric dinucleating ligands and their homo- and heterodinuclear metallocomplexes. The chemical mimicry includes both structural and functional (biomimetic catalysis) aspects.
Two new asymmetric dinucleating ligands, HL (4-bromo-2-[(4-methylhomopiperazine-1-yl)methyl]-6-{[(pyridin-2-ylethyl)(pyridin-2-ylmethyl)amino]methyl}phenol) and H
2L' (4-bromo-2-[(4-methylhomopiperazine-1-yl)methyl]-6-{[(pyridin-2-ylethyl)(phenol-2-ylmethyl)amino]methyl}phenol), were designed and synthesized through a 5-step procedure with overall yield of ~20%. These two ligands were designed to provide two pendants with asymmetry in the type and number of donor atoms, as well as the different affinity to two metal ions.
Twenty one complexes with HL and H
2L' were synthesized and characterized. Among these, complex 1 was shown to be a good model in aqueous phase for homodinuclear hydrolases with both structural and functional features.
Synthesis of heterodinuclear coordination-position isomers, complexes 5 and 6, nicely demonstrated that HL binds two metal ions sequentially. The positions of metal ions in heterodinuclear complexes were controlled by the sequence of adding the desired metal ions in the synthesis.
Information obtained from the study of the crystal structures of the dinuclear complexes sheds light on the coordination chemistry of complexes with HL and H
2L' and provides us with a better picture in designing kinetic experiments and the elucidation of catalytic hydrolysis mechanism.
Homodinuclear complex 1 and the heterodinuclear complex (with Ni
2+ in homopiperazine pendant of L) were shown to effectively promote hydrolysis of P-O bond in BNPP in aqueous buffer. At pH 8.7 and 25 ℃, complex 1 promotes the hydrolysis of BNPP by a factor of ~2.0 x l0
6 times. The overall mechanism of catalytic hydrolysis of BNPP promoted by dinuclear complexes with L is proposed.
We have shown that although a bridging hydroxide is observed in the substrate bound complexes, it can not serve as a nucleophile in hydrolysis. The nucleophile comes from the terminal water bound at the Ni
2+ in homopiperazine pendant. The bridging hydroxide serves as a general base to activate the terminal nucleophile.
The major findings from the study of the catalytic activity of complex 1 on hydrolysis of BNPP are (i) both nickel ions work together to bind and activate the substrate, and (ii) the nickel ion in homopiperazine pendant is responsible to activate a terminal water molecule for the generation of a terminal hydroxide group that serves as the nucleophile.
The di-Zn(II) complex of HL displayed an interesting catalytic behavior. While its activity in aqueous buffer is only ~5% of di-Ni(II) complex 1, it showed a much improved activity in MeCN solvent, comparable to that of complex 1 in EtOH-H
2O buffer.
We also showed that complex 1 promotes the hydrolysis of P-O bonds in phosphate monoester such as NPP and C-N bonds in picolinamide and pyridine-2-carboxylic-(4-nitropheny1)amide. In all cases, complex 1 functions with a mechanism similar to that of BNPP hydrolysis.
The binding of small molecules such as HCO
3- and NO
2 - as well as the fixation of CO
2 by complex 1 were observed and studied by UV-vis spectrophotometric titration and X-ray crystallography.
The dinickel complex of ligand L' ([Ni
2L'(OH)]) displays a high catalytic activity towards the hydrolysis of P-O bonds. The catalytic mechanism is similar to that by complex 1 while the activity (at pH 9.3) is about 20 times higher. [Ni
2L'(OH)] can fix CO
2 from air to form CO
32- bridged complex 18. The formation of complex 18 inhibits the catalytic activity of [Ni
2L'(OH)].
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