OP-5: Cronies and Enemies - The Current Philippine Scene

This series consists of two papers, "Who Controls the Philippine Economy?" by John F. Doherty, and "The Extradition Treaty between the Philippines and the United States: Facts and Implications," by Jovito R. Salonga

Spectroscopic and catalytic characterization of a functional (FeFeII)-Fe-III biomimetic for the active site of uteroferrin and protein cleavage

A mixed-valence complex, [Fe(III)Fe(II)L1(mu-OAc)(2)]BF4 center dot H2O, where the ligand H(2)L1 = 2-{[[3-[((bis-(pyridin-2-ylmethyl)amino)methyl)-2-hydroxy-5-methylbenzyl](pyridin-2-ylmethyl)amino]methyl]phenol}, has been studied with a range of techniques, and, where possible, its properties have been compared to those of the corresponding enzyme system purple acid phosphatase. The (FeFeII)-Fe-III and Fe-2(III) oxidized species were studied spectroelectrochemically. The temperature-dependent population of the S = 3/2 spin states of the heterovalent system, observed using magnetic circular dichroism, confirmed that the dinuclear center is weakly antiferromagnetically coupled (H = -2JS(1).S-2, where J = -5.6 cm(-1)) in a frozen solution. The ligand-to-metal charge-transfer transitions are correlated with density functional theory calculations. The (FeFeII)-Fe-III complex is electron paramagnetic resonance (EPR)-silent, except at very low temperatures

Catalytic promiscuity: Catecholase-like activity and hydrolytic DNA cleavage promoted by a mixed-valence Fe(III)Fe(II) complex

Catalytic promiscuity has emerged as an important property of many enzymes since the relationship of this property to enzymatic evolution became clear. Simultaneously, the development of suitable biomimetic catalytic systems capable of mimicking the promiscuous catalytic properties of such enzymes represents a new challenge for bioinorganic chemists. In this paper we report on the X-ray structure, the solution studies and the promiscuous catalytic activity of the mixed-valence complex [(bpbpmp)Fe-III(mu-OAc)(2)Fe-II](ClO4), (1), containing the unsymmetrical dinucleating ligand 2-{[(2-hydroxybenzyl)(2-pyridylmethyl)aminomethyl]-4-methyl-6-[bis(2-pyridylmethyl)aminomethyl]}phenol (H(2)bpbpmp). Potentiometric and spectrophotometric titrations and kinetics studies showed that this coordination compound generates active species that promote hydrolytic cleavage of double strand DNA (dsDNA), with a rate enhancement of 1.9x10(8) over the non-catalyzed reaction, as well as promote oxidation of 3,5-di-tert-butylcatechol (3,5-dtbc), with k(cat) = 1.16 x 10(-2)s(-1) and K-M = 7.1 x 10(-4) mol L-1. Thus, complex 1 shows both hydrolase and oxidoreductase activities and can be regarded as a man-made model for studying catalytic promiscuity

Art. Meyerin, Ursula

Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear Fe(II)M(II) center (M(II) = Fe, Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of phosphoric acid esters. The dinuclear complex [(H(2)O)Fe(III)(mu-OH)Zn(II)(L-H)](CIO(4))(2) (2) with the ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl-6-[N-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl]phenol (H(2)L-H) has recently been prepared and is found to closely mimic the coordination environment of the Fe(III)Zn(II) active site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a variety of structural, spectroscopic, and computational techniques the electronic structure of the Fe(III) center of this biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted Fe(III)N(2)O(4) octahedron with a dominant tetragonal compression align ad along the mu-OH-Fe-O(phenolate) direction. To probe the role of the Fe-O(phenolate) bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (-CH(3), -H, -Br, -NO(2)) in the 5-position. Tie effects of the substituents on the electronic properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This study establishes benchmarks against accurate crystallographic struck ral information using spectroscopic techniques that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase activity increases in the order -NO(2)<- Br <- H <- CH(3) when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear free energy relationship is found when log(k(cat)/k(0)) is plotted against the Hammett parameter a. However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes containing the electron-withdrawing -NO(2) and electron-donating CH3 groups are the most active while the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups

Electronic Structure and Spectro-Structural Correlations of FeIIIZnII Biomimetics for Purple Acid Phosphatases: Relevance to DNA Cleavage and Cytotoxic Activity

Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear FeIIIMII center (MII = Fe, Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of phosphoric acid esters. The dinuclear complex [(H2O)FeIII( μ-OH)ZnII(L-H)](ClO4)2 (2) with the ligand 2-[N-bis(2-pyridylmethyl)aminomethyl]-4-methyl- 6-[N0-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl]phenol (H2L-H) has recently been prepared and is found to closely mimic the coordination environment of the FeIIIZnII active site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a variety of structural, spectroscopic, and computational techniques the electronic structure of the FeIII center of this biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted FeIIIN2O4 octahedron with a dominant tetragonal compression aligned along the μ-OH-Fe-Ophenolate direction. To probe the role of the Fe-Ophenolate bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (-CH3, -H, -Br, -NO2) in the 5-position. The effects of the substituents on the electronic properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This study establishes benchmarks against accurate crystallographic structural information using spectroscopic techniques that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase activity increases in the order-NO2rBrrHrCH3 when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear free energy relationship is found when log(kcat/k0) is plotted against the Hammett parameter σ. However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes containing the electron-withdrawing-NO2 and electron-donating-CH3 groups are the most active while the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups

A potentially polymerizable heterodinuclear FeIIIZnII purple acid phosphatase mimic. Synthesis, characterization, and phosphate ester hydrolysis studies

An analogue of the purple acid phosphatase biomimetic 2-((bis(pyridin-2-ylmethyl)amino)methyl)-6-(((2-hydroxybenzyl)(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol has been synthesized. The analogue, 2-((bis(pyridin-2-ylmethyl)amino)methyl)-6-(((2-hydroxy-4-(4-vinylbenzyloxy)benzyl)(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (H2BPBPMPV) possesses a pendant olefin suitable for copolymerization. Complexation with Fe-III/Zn-II resulted in the complex [(FeZnII)-Zn-III (BPBPMPV)(CH3COO)(2)](ClO4), characterized with mass spectrometry, microanalysis, UV/vis, and IR spectrometry. The catalytic activity of the complex toward bis-(2,4-dinitrophenyl) phosphate was determined, resulting in K-m of 4.1 +/- 0.6 mM, with k(cat) 3.8 +/- 0.2 x 10(-3) s(-1) and a bell-shaped pH-rate profile with pK(a) values of 4.31, 5.66, 8.96, the profile exhibiting residual activity above pH 9.5

Spectroscopic and Catalytic Characterization of a Functional Fe^IIIFe^II Biomimetic for the Active Site of Uteroferrin and Protein Cleavage

A mixed-valence complex, [Fe^IIIFe^II<b>L1</b>(μ-OAc)₂]­BF₄·H₂O, where the ligand H₂<b>L1</b> = 2-{[[3-[((bis­(pyridin-2-ylmethyl)­amino)­methyl)-2-hydroxy-5-methylbenzyl]­(pyridin-2-ylmethyl)­amino]­methyl]­phenol}, has been studied with a range of techniques, and, where possible, its properties have been compared to those of the corresponding enzyme system purple acid phosphatase. The Fe^IIIFe^II and Fe^III₂ oxidized species were studied spectroelectrochemically. The temperature-dependent population of the <i>S</i> = ³/₂ spin states of the heterovalent system, observed using magnetic circular dichroism, confirmed that the dinuclear center is weakly antiferromagnetically coupled (<i>H</i> = −2<i>JS</i>₁·<i>S</i>₂, where <i>J</i> = −5.6 cm^–1) in a frozen solution. The ligand-to-metal charge-transfer transitions are correlated with density functional theory calculations. The Fe^IIIFe^II complex is electron paramagnetic resonance (EPR)-silent, except at very low temperatures (<2 K), because of the broadening caused by the exchange coupling and zero-field-splitting parameters being of comparable magnitude and rapid spin–lattice relaxation. However, a phosphate-bound Fe^III₂ complex showed an EPR spectrum due to population of the <i>S</i>_tot = 3 state (<i>J</i>= −3.5 cm^–1). The phosphatase activity of the Fe^IIIFe^II complex in hydrolysis of bis­(2,4-dinitrophenyl)­phosphate (<i>k</i>_cat. = 1.88 × 10^–3 s^–1; <i>K</i>_m = 4.63 × 10^–3 mol L^–1) is similar to that of other bimetallic heterovalent complexes with the same ligand. Analysis of the kinetic data supports a mechanism where the initiating nucleophile in the phosphatase reaction is a hydroxide, terminally bound to Fe^III. It is interesting to note that aqueous solutions of [Fe^IIIFe^II<b>L1</b>(μ-OAc)₂]⁺ are also capable of protein cleavage, at mild temperature and pH conditions, thus further expanding the scope of this complex’s catalytic promiscuity

Spectroscopic and Catalytic Characterization of a Functional Fe^IIIFe^II Biomimetic for the Active Site of Uteroferrin and Protein Cleavage

A mixed-valence complex, [Fe^IIIFe^II<b>L1</b>(μ-OAc)₂]­BF₄·H₂O, where the ligand H₂<b>L1</b> = 2-{[[3-[((bis­(pyridin-2-ylmethyl)­amino)­methyl)-2-hydroxy-5-methylbenzyl]­(pyridin-2-ylmethyl)­amino]­methyl]­phenol}, has been studied with a range of techniques, and, where possible, its properties have been compared to those of the corresponding enzyme system purple acid phosphatase. The Fe^IIIFe^II and Fe^III₂ oxidized species were studied spectroelectrochemically. The temperature-dependent population of the <i>S</i> = ³/₂ spin states of the heterovalent system, observed using magnetic circular dichroism, confirmed that the dinuclear center is weakly antiferromagnetically coupled (<i>H</i> = −2<i>JS</i>₁·<i>S</i>₂, where <i>J</i> = −5.6 cm^–1) in a frozen solution. The ligand-to-metal charge-transfer transitions are correlated with density functional theory calculations. The Fe^IIIFe^II complex is electron paramagnetic resonance (EPR)-silent, except at very low temperatures (<2 K), because of the broadening caused by the exchange coupling and zero-field-splitting parameters being of comparable magnitude and rapid spin–lattice relaxation. However, a phosphate-bound Fe^III₂ complex showed an EPR spectrum due to population of the <i>S</i>_tot = 3 state (<i>J</i>= −3.5 cm^–1). The phosphatase activity of the Fe^IIIFe^II complex in hydrolysis of bis­(2,4-dinitrophenyl)­phosphate (<i>k</i>_cat. = 1.88 × 10^–3 s^–1; <i>K</i>_m = 4.63 × 10^–3 mol L^–1) is similar to that of other bimetallic heterovalent complexes with the same ligand. Analysis of the kinetic data supports a mechanism where the initiating nucleophile in the phosphatase reaction is a hydroxide, terminally bound to Fe^III. It is interesting to note that aqueous solutions of [Fe^IIIFe^II<b>L1</b>(μ-OAc)₂]⁺ are also capable of protein cleavage, at mild temperature and pH conditions, thus further expanding the scope of this complex’s catalytic promiscuity