Homo- and heterodinuclear metallocomplexes for biomimetic hydrolysis : design, synthesis, structure and catalytic activity

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 H2L' (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 H2L' 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 H2L' 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 Ni2+ 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 Ni2+ 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-H2O 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 HCO3- and NO2 - as well as the fixation of CO2 by complex 1 were observed and studied by UV-vis spectrophotometric titration and X-ray crystallography. The dinickel complex of ligand L' ([Ni2L'(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. [Ni2L'(OH)] can fix CO2 from air to form CO32- bridged complex 18. The formation of complex 18 inhibits the catalytic activity of [Ni2L'(OH)]

Synthesis, crystal structure, and photoluminescent property of a novel heterobimetallic Zn(II)-Ag(I) cyano-bridged coordination polymer incorporating,a pentameric unit [Ag(CN)(2-)](5) assembled by argentophilic interaction

A new photoluminescent heterobimetallic Zn(II)-Ag(I) cyano-bridged coordination polymer, [Ag5Zn2(tren)(2)(CN)(9)] (tren = tris(2-aminoethyl)amine) (1), has been synthesized and structurally characterized. It features rare linear pentameric unit of dicyanoargentate(I) ions assembled by d(10)-d(10) interaction as building blocks. Solid state emission spectrum of I shows strong ultraviolet luminescence with emission peak in the range of 376 nm. (C) 2006 Elsevier B.V. All rights reserved

¹H‑ENDOR Evidence for a Hydrogen-Bonding Interaction That Modulates the Reactivity of a Nonheme Fe^IVO Unit

We report that a novel use of 35 GHz ¹H-ENDOR spectroscopy establishes the presence in <b>1</b> of an Fe^IVO···H–O–Fe^III hydrogen bond predicted by density functional theory computations to generate a six-membered-ring core for <b>1</b>. The hydrogen bond rationalizes the difference in the C–H bond cleavage reactivity between <b>1</b> and <b>4</b>(OCH₃) (where a CH₃O group has replaced the HO on the Fe^III site). This result substantiates the seemingly paradoxical conclusion that the nonheme Fe^IVO unit of <b>1</b> not only has the electrophilic character required for H-atom abstraction but also retains sufficient nucleophilic character to accept a hydrogen bond from the Fe^III–OH unit

Evaluating the Identity and Diiron Core Transformations of a (μ-Oxo)diiron(III) Complex Supported by Electron-Rich Tris(pyridyl-2-methyl)amine Ligands

The composition of a (μ-oxo)­diiron­(III) complex coordinated by tris­[(3,5-dimethyl-4-methoxy)­pyridyl-2-methyl]­amine (R₃TPA) ligands was investigated. Characterization using a variety of spectroscopic methods and X-ray crystallography indicated that the reaction of iron­(III) perchlorate, sodium hydroxide, and R₃TPA affords [Fe₂(μ-O)­(μ-OH)­(R₃TPA)₂]­(ClO₄)₃ (<b>2</b>) rather than the previously reported species [Fe₂(μ-O)­(OH)­(H₂O)­(R₃TPA)₂]­(ClO₄)₃ (<b>1</b>). Facile conversion of the (μ-oxo)­(μ-hydroxo)­diiron­(III) core of <b>2</b> to the (μ-oxo)­(hydroxo)­(aqua)­diiron­(III) core of <b>1</b> occurs in the presence of water and at low temperature. When <b>2</b> is exposed to wet acetonitrile at room temperature, the CH₃CN adduct is hydrolyzed to CH₃COO^–, which forms the compound [Fe₂(μ-O)­(μ-CH₃COO)­(R₃TPA)₂]­(ClO₄)₃ (<b>10</b>). The identity of <b>10</b> was confirmed by comparison of its spectroscopic properties with those of an independently prepared sample. To evaluate whether or not <b>1</b> and <b>2</b> are capable of generating the diiron­(IV) species [Fe₂(μ-O)­(OH)­(O)­(R₃TPA)₂]³⁺ (<b>4</b>), which has previously been generated as a synthetic model for high-valent diiron protein oxygenated intermediates, studies were performed to investigate their reactivity with hydrogen peroxide. Because <b>2</b> reacts rapidly with hydrogen peroxide in CH₃CN but not in CH₃CN/H₂O, conditions that favor conversion to <b>1</b>, complex <b>1</b> is not a likely precursor to <b>4</b>. Compound <b>4</b> also forms in the reaction of <b>2</b> with H₂O₂ in solvents lacking a nitrile, suggesting that hydrolysis of CH₃CN is not involved in the H₂O₂ activation reaction. These findings shed light on the formation of several diiron complexes of electron-rich R₃TPA ligands and elaborate on conditions required to generate synthetic models of diiron­(IV) protein intermediates with this ligand framework

Spectroscopic and Theoretical Investigation of a Complex with an [OFe^IV–O–Fe^IVO] Core Related to Methane Monooxygenase Intermediate <b>Q</b>

Previous efforts to model the diiron­(IV) intermediate <b>Q</b> of soluble methane monooxygenase have led to the synthesis of a diiron­(IV) TPA complex, <b>2</b>, with an O=Fe^IV–O–Fe^IV–OH core that has two ferromagnetically coupled S_loc = 1 sites. Addition of base to <b>2</b> at −85 °C elicits its conjugate base <b>6</b> with a novel OFe^IV–O–Fe^IVO core. In frozen solution, <b>6</b> exists in two forms, <b>6a</b> and <b>6b</b>, that we have characterized extensively using Mössbauer and parallel mode EPR spectroscopy. The conversion between <b>2</b> and <b>6</b> is quantitative, but the relative proportions of <b>6a</b> and <b>6b</b> are solvent dependent. <b>6a</b> has two equivalent high-spin (<i>S</i>_loc = 2) sites, which are antiferromagnetically coupled; its quadrupole splitting (0.52 mm/s) and isomer shift (0.14 mm/s) match those of intermediate <b>Q</b>. DFT calculations suggest that <b>6a</b> assumes an anti conformation with a dihedral OFe–FeO angle of 180°. Mössbauer and EPR analyses show that <b>6b</b> is a diiron­(IV) complex with ferromagnetically coupled <i>S</i>_loc = 1 and <i>S</i>_loc = 2 sites to give total spin <i>S</i>_t = 3. Analysis of the zero-field splittings and magnetic hyperfine tensors suggests that the dihedral OFe–FeO angle of <b>6b</b> is ∼90°. DFT calculations indicate that this angle is enforced by hydrogen bonding to both terminal oxo groups from a shared water molecule. The water molecule preorganizes <b>6b</b>, facilitating protonation of one oxo group to regenerate <b>2</b>, a protonation step difficult to achieve for mononuclear Fe^IVO complexes. Complex <b>6</b> represents an intriguing addition to the handful of diiron­(IV) complexes that have been characterized

Hydrogen-Bonding Effects on the Reactivity of [X–Fe^III–O–Fe^IVO] (X = OH, F) Complexes toward C–H Bond Cleavage

Complexes <b>1</b>–OH and <b>1</b>–F are related complexes that share similar [X–Fe^III–O–Fe^IVO]³⁺ core structures with a total spin <i>S</i> of ¹/₂, which arises from antiferromagnetic coupling of an <i>S</i> = ⁵/₂ Fe^III–X site and an <i>S</i> = 2 Fe^IVO site. EXAFS analysis shows that <b>1</b>–F has a nearly linear Fe^III–O–Fe^IV core compared to that of <b>1</b>–OH, which has an Fe–O–Fe angle of ∼130° due to the presence of a hydrogen bond between the hydroxo and oxo groups. Both complexes are at least 1000-fold more reactive at C–H bond cleavage than <b>2</b>, a related complex with a [OH–Fe^IV–O–Fe^IVO]⁴⁺ core having individual <i>S</i> = 1 Fe^IV units. Interestingly, <b>1</b>–F is 10-fold more reactive than <b>1</b>–OH. This raises an interesting question about what gives rise to the reactivity difference. DFT calculations comparing <b>1</b>–OH and <b>1</b>–F strongly suggest that the H-bond in <b>1</b>–OH does not significantly change the electrophilicity of the reactive Fe^IVO unit and that the lower reactivity of <b>1</b>–OH arises from the additional activation barrier required to break its H-bond in the course of H-atom transfer by the oxoiron­(IV) moiety

Evaluating the Identity and Diiron Core Transformations of a (μ-Oxo)diiron(III) Complex Supported by Electron-Rich Tris(pyridyl-2-methyl)amine Ligands

The composition of a (μ-oxo)diiron(III) complex coordinated by tris[(3,5-dimethyl-4-methoxy)pyridyl-2-methyl]amine (R[subscript 3]TPA) ligands was investigated. Characterization using a variety of spectroscopic methods and X-ray crystallography indicated that the reaction of iron(III) perchlorate, sodium hydroxide, and R[subscript 3]TPA affords [Fe[subscript 2](μ-O)(μ-OH)(R[subscript 3]TPA)[subscript 2]](ClO[subscript 4])[subscript 3] (2) rather than the previously reported species [Fe[subscript 2](μ-O)(OH)(H[subscript 2]O)(R[subscript 3]TPA)[subscript 2]](ClO[subscript 4])[subscript 3] (1). Facile conversion of the (μ-oxo)(μ-hydroxo)diiron(III) core of 2 to the (μ-oxo)(hydroxo)(aqua)diiron(III) core of 1 occurs in the presence of water and at low temperature. When 2 is exposed to wet acetonitrile at room temperature, the CH[subscript 3]CN adduct is hydrolyzed to CH[subscript 3]COO[superscript –], which forms the compound [Fe[subscript 2](μ-O)(μ-CH[subscript 3]COO)(R[subscript 3]TPA)[subscript 2]](ClO[subscript 4])[subscript 3] (10). The identity of 10 was confirmed by comparison of its spectroscopic properties with those of an independently prepared sample. To evaluate whether or not 1 and 2 are capable of generating the diiron(IV) species [Fe[subscript 2](μ-O)(OH)(O)(R[subscript 3]TPA)[subscript 2]][superscript 3+] (4), which has previously been generated as a synthetic model for high-valent diiron protein oxygenated intermediates, studies were performed to investigate their reactivity with hydrogen peroxide. Because 2 reacts rapidly with hydrogen peroxide in CH[subscript 3]CN but not in CH[subscript 3]CN/H[subscript 2]O, conditions that favor conversion to 1, complex 1 is not a likely precursor to 4. Compound 4 also forms in the reaction of 2 with H[subscript 2]O[subscript 2] in solvents lacking a nitrile, suggesting that hydrolysis of CH[subscript 3]CN is not involved in the H[subscript 2]O[subscript 2] activation reaction. These findings shed light on the formation of several diiron complexes of electron-rich R[subscript 3]TPA ligands and elaborate on conditions required to generate synthetic models of diiron(IV) protein intermediates with this ligand framework.National Institute of General Medical Sciences (U.S.) (Grant GM-032134