Photoinduced DNA Cleavage Promoted by Two Copper(II) Complexes of Tetracyclines and 1,10-Phenanthroline

In this report, we demonstrate how UV-light exposure can enhance DNA cleavage promoted by two copper(II) complexes of tetracyclines and 1,10-phenanthroline about 40 times in comparison to nonirradiated conditions. In addition, new aspects regarding their DNA binding properties, as well as the mechanism of the cleavage reaction, were also investigated

New La(III) Complex Immobilized on 3‑Aminopropyl-Functionalized Silica as an Efficient and Reusable Catalyst for Hydrolysis of Phosphate Ester Bonds

Described herein is the synthesis, structure, and monoesterase and diesterase activities of a new mononuclear [La^III(L¹)­(NO₃)₂] (<b>1</b>) complex (H₂L¹ = 2-bis­[{(2-pyridylmethyl)-aminomethyl}-6-[<i>N</i>-(2-pyridylmethyl) aminomethyl)])-4-methyl-6-formylphenol) in the hydrolysis of 2,4-bis­(dinitrophenyl)­phosphate (2,4-BDNPP). When covalently linked to 3-aminopropyl-functionalized silica, <b>1</b> undergoes disproportionation to form a dinuclear species (<b>APS-1</b>), whose catalytic efficiency is increased when compared to the homogeneous reaction due to second coordination sphere effects which increase the substrate to complex association constant. The anchored catalyst <b>APS-1</b> can be recovered and reused for subsequent hydrolysis reactions (five times) with only a slight loss in activity. In the presence of DNA, we suggest that <b>1</b> is also converted into the dinuclear active species as observed with <b>APS-1</b>, and both were shown to be efficient in DNA cleavage

Second-Coordination-Sphere Effects Increase the Catalytic Efficiency of an Extended Model for Fe^IIIM^II Purple Acid Phosphatases

Herein we describe the synthesis of a new heterodinuclear Fe^IIICu^II model complex for the active site of purple acid phosphatases and its binding to a polyamine chain, a model for the amino acid residues around the active site. The properties of these systems and their catalytic activity in the hydrolysis of bis­(2,4-dinitrophenyl)­phosphate are compared, and conclusions regarding the effects of the second coordination sphere are drawn. The positive effect of the polymeric chain on DNA hydrolysis is also described and discussed

Second-Coordination-Sphere Effects Increase the Catalytic Efficiency of an Extended Model for Fe^IIIM^II Purple Acid Phosphatases

Herein we describe the synthesis of a new heterodinuclear Fe^IIICu^II model complex for the active site of purple acid phosphatases and its binding to a polyamine chain, a model for the amino acid residues around the active site. The properties of these systems and their catalytic activity in the hydrolysis of bis­(2,4-dinitrophenyl)­phosphate are compared, and conclusions regarding the effects of the second coordination sphere are drawn. The positive effect of the polymeric chain on DNA hydrolysis is also described and discussed

Design of a Dinuclear Nickel(II) Bioinspired Hydrolase to Bind Covalently to Silica Surfaces: Synthesis, Magnetism, and Reactivity Studies

Presented herein is the design of a dinuclear Ni^II synthetic hydrolase [Ni₂(HBPPAMFF)­(μ-OAc)₂(H₂O)]­BPh₄ (<b>1</b>) (H₂BPPAMFF = 2-[(<i>N</i>-benzyl-<i>N</i>-2-pyridylmethylamine)]-4-methyl-6-[<i>N</i>-(2-pyridylmethyl)­aminomethyl)])-4-methyl-6-formylphenol) to be covalently attached to silica surfaces, while maintaining its catalytic activity. An aldehyde-containing ligand (H₂BPPAMFF) provides a reactive functional group that can serve as a cross-linking group to bind the complex to an organoalkoxysilane and later to the silica surfaces or directly to amino-modified surfaces. The dinuclear Ni^II complex covalently attached to the silica surfaces was fully characterized by different techniques. The catalytic turnover number (<i>k</i>_cat) of the immobilized Ni^IINi^II catalyst in the hydrolysis of 2,4-bis­(dinitrophenyl)­phosphate is comparable to the homogeneous reaction; however, the catalyst interaction with the support enhanced the substrate to complex association constant, and consequently, the catalytic efficiency (<i>E</i> = <i>k</i>_cat/<i>K</i>_M) and the supported catalyst can be reused for subsequent diester hydrolysis reactions

Second-Sphere Effects in Dinuclear Fe^IIIZn^II Hydrolase Biomimetics: Tuning Binding and Reactivity Properties

Herein, we report the synthesis and characterization of two dinuclear Fe^IIIZn^II complexes [Fe^IIIZn^IILP1] (<b>1</b>) and [Fe^IIIZn^IILP2] (<b>2</b>), in which LP1 and LP2 are conjugated systems containing one and two pyrene groups, respectively, connected via the diamine −HN­(CH₂)₄NH– spacer to the well-known N₅O₂-donor H₂L ligand (H₂L = 2-bis­{[(2-pyridylmethyl)­aminomethyl]-6-[(2-hydroxybenzyl)­(2-pyridylmethyl)]­aminomethyl}-4-methylphenol). The complex [Fe^IIIZn^IIL1] (<b>3</b>), in which H₂L was modified to H₂L1, with a carbonyl group attached to the terminal phenol group, was included in this study for comparison purposes.¹ Both complexes <b>1</b> and <b>2</b> were satisfactorily characterized in the solid state and in solution. Extended X-ray absorption fine structure data for <b>1</b> and <b>3</b> in an acetonitrile solution show that the multiply bridged structure seen in the solid state of <b>3</b> is retained in solution. Potentiometric and UV–vis titration of <b>1</b> and <b>2</b> show that electrostatic interaction between the protonated amino groups and coordinated water molecules significantly decreases the p<i>K</i>_a of the iron­(III)-bound water compared to those of <b>3</b>. On the other hand, catalytic activity studies using <b>1</b> and <b>2</b> in the hydrolysis of the activated substrate bis­(2,4-dinitrophenyl)­phosphate (BDNPP) resulted in a significant increase in the association of the substrate (<i>K</i>_ass ≅ 1/<i>K</i>_M) compared to that of <b>3</b> because of electrostatic and hydrophobic interactions between BDNPP and the side-chain diaminopyrene of the ligands H₂LP1 and H₂LP2. In addition, the introduction of the pyrene motifs in <b>1</b> and <b>2</b> enhanced their activity toward DNA and as effective antitumor drugs, although the biochemical mechanism of the latter effect is currently under investigation. These complexes represent interesting examples of how to promote an increase in the activity of traditional artificial metal nucleases by introducing second-coordination-sphere effects

Synthesis, Magnetostructural Correlation, and Catalytic Promiscuity of Unsymmetric Dinuclear Copper(II) Complexes: Models for Catechol Oxidases and Hydrolases

Herein, we report the synthesis and characterization, through elemental analysis, electronic spectroscopy, electrochemistry, potentiometric titration, electron paramagnetic resonance, and magnetochemistry, of two dinuclear copper­(II) complexes, using the unsymmetrical ligands <i>N</i>′,<i>N</i>′,<i>N</i>-tris­(2-pyridylmethyl)-<i>N</i>-(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol (<b>L1</b>) and <i>N</i>′,<i>N</i>′-bis­(2-pyridylmethyl)-<i>N</i>,<i>N</i>-(2-hydroxybenzyl)­(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol (<b>L2</b>). The structures of the complexes [Cu₂(<b>L1</b>)­(μ-OAc)]­(ClO₄)₂·(CH₃)₂CHOH (<b>1</b>) and [Cu₂(<b>L2</b>)­(μ-OAc)]­(ClO₄)·H₂O·(CH₃)₂CHOH (<b>2</b>) were determined by X-ray crystallography. The complex [Cu₂(<b>L3</b>)­(μ-OAc)]²⁺ [<b>3</b>; <b>L3</b> = <i>N</i>-(2-hydroxybenzyl)-<i>N</i>′,<i>N</i>′,<i>N</i>-tris­(2-pyridylmethyl)-1,3-propanediamin-2-ol] was included in this study for comparison purposes only (Neves et al. <i>Inorg. Chim. Acta</i> <b>2005</b>, <i>358</i>, 1807–1822). Magnetic data show that the Cu^II centers in <b>1</b> and <b>2</b> are antiferromagnetically coupled and that the difference in the exchange coupling <i>J</i> found for these complexes (<i>J</i> = −4.3 cm^–1 for <b>1</b> and <i>J</i> = −40.0 cm^–1 for <b>2</b>) is a function of the Cu–O–Cu bridging angle. In addition, <b>1</b> and <b>2</b> were tested as catalysts in the oxidation of the model substrate 3,5-di-<i>tert</i>-butylcatechol and can be considered as functional models for catechol oxidase. Because these complexes possess labile sites in their structures and in solution they have a potential nucleophile constituted by a terminal Cu^II-bound hydroxo group, their activity toward hydrolysis of the model substrate 2,4-bis­(dinitrophenyl)­phosphate and DNA was also investigated. Double electrophilic activation of the phosphodiester by monodentate coordination to the Cu^II center that contains the phenol group with <i>tert</i>-butyl substituents and hydrogen bonding of the protonated phenol with the phosphate O atom are proposed to increase the hydrolase activity (<i>K</i>_ass. and <i>k</i>_cat.) of <b>1</b> and <b>2</b> in comparison with that found for complex <b>3</b>. In fact, complexes <b>1</b> and <b>2</b> show both oxidoreductase and hydrolase/nuclease activities and can thus be regarded as man-made models for studying catalytic promiscuity

Synthesis, Magnetostructural Correlation, and Catalytic Promiscuity of Unsymmetric Dinuclear Copper(II) Complexes: Models for Catechol Oxidases and Hydrolases

Herein, we report the synthesis and characterization, through elemental analysis, electronic spectroscopy, electrochemistry, potentiometric titration, electron paramagnetic resonance, and magnetochemistry, of two dinuclear copper­(II) complexes, using the unsymmetrical ligands <i>N</i>′,<i>N</i>′,<i>N</i>-tris­(2-pyridylmethyl)-<i>N</i>-(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol (<b>L1</b>) and <i>N</i>′,<i>N</i>′-bis­(2-pyridylmethyl)-<i>N</i>,<i>N</i>-(2-hydroxybenzyl)­(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol (<b>L2</b>). The structures of the complexes [Cu₂(<b>L1</b>)­(μ-OAc)]­(ClO₄)₂·(CH₃)₂CHOH (<b>1</b>) and [Cu₂(<b>L2</b>)­(μ-OAc)]­(ClO₄)·H₂O·(CH₃)₂CHOH (<b>2</b>) were determined by X-ray crystallography. The complex [Cu₂(<b>L3</b>)­(μ-OAc)]²⁺ [<b>3</b>; <b>L3</b> = <i>N</i>-(2-hydroxybenzyl)-<i>N</i>′,<i>N</i>′,<i>N</i>-tris­(2-pyridylmethyl)-1,3-propanediamin-2-ol] was included in this study for comparison purposes only (Neves et al. <i>Inorg. Chim. Acta</i> <b>2005</b>, <i>358</i>, 1807–1822). Magnetic data show that the Cu^II centers in <b>1</b> and <b>2</b> are antiferromagnetically coupled and that the difference in the exchange coupling <i>J</i> found for these complexes (<i>J</i> = −4.3 cm^–1 for <b>1</b> and <i>J</i> = −40.0 cm^–1 for <b>2</b>) is a function of the Cu–O–Cu bridging angle. In addition, <b>1</b> and <b>2</b> were tested as catalysts in the oxidation of the model substrate 3,5-di-<i>tert</i>-butylcatechol and can be considered as functional models for catechol oxidase. Because these complexes possess labile sites in their structures and in solution they have a potential nucleophile constituted by a terminal Cu^II-bound hydroxo group, their activity toward hydrolysis of the model substrate 2,4-bis­(dinitrophenyl)­phosphate and DNA was also investigated. Double electrophilic activation of the phosphodiester by monodentate coordination to the Cu^II center that contains the phenol group with <i>tert</i>-butyl substituents and hydrogen bonding of the protonated phenol with the phosphate O atom are proposed to increase the hydrolase activity (<i>K</i>_ass. and <i>k</i>_cat.) of <b>1</b> and <b>2</b> in comparison with that found for complex <b>3</b>. In fact, complexes <b>1</b> and <b>2</b> show both oxidoreductase and hydrolase/nuclease activities and can thus be regarded as man-made models for studying catalytic promiscuity

Synthesis, Magnetostructural Correlation, and Catalytic Promiscuity of Unsymmetric Dinuclear Copper(II) Complexes: Models for Catechol Oxidases and Hydrolases

Herein, we report the synthesis and characterization, through elemental analysis, electronic spectroscopy, electrochemistry, potentiometric titration, electron paramagnetic resonance, and magnetochemistry, of two dinuclear copper­(II) complexes, using the unsymmetrical ligands <i>N</i>′,<i>N</i>′,<i>N</i>-tris­(2-pyridylmethyl)-<i>N</i>-(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol (<b>L1</b>) and <i>N</i>′,<i>N</i>′-bis­(2-pyridylmethyl)-<i>N</i>,<i>N</i>-(2-hydroxybenzyl)­(2-hydroxy-3,5-di-<i>tert</i>-butylbenzyl)-1,3-propanediamin-2-ol (<b>L2</b>). The structures of the complexes [Cu₂(<b>L1</b>)­(μ-OAc)]­(ClO₄)₂·(CH₃)₂CHOH (<b>1</b>) and [Cu₂(<b>L2</b>)­(μ-OAc)]­(ClO₄)·H₂O·(CH₃)₂CHOH (<b>2</b>) were determined by X-ray crystallography. The complex [Cu₂(<b>L3</b>)­(μ-OAc)]²⁺ [<b>3</b>; <b>L3</b> = <i>N</i>-(2-hydroxybenzyl)-<i>N</i>′,<i>N</i>′,<i>N</i>-tris­(2-pyridylmethyl)-1,3-propanediamin-2-ol] was included in this study for comparison purposes only (Neves et al. <i>Inorg. Chim. Acta</i> <b>2005</b>, <i>358</i>, 1807–1822). Magnetic data show that the Cu^II centers in <b>1</b> and <b>2</b> are antiferromagnetically coupled and that the difference in the exchange coupling <i>J</i> found for these complexes (<i>J</i> = −4.3 cm^–1 for <b>1</b> and <i>J</i> = −40.0 cm^–1 for <b>2</b>) is a function of the Cu–O–Cu bridging angle. In addition, <b>1</b> and <b>2</b> were tested as catalysts in the oxidation of the model substrate 3,5-di-<i>tert</i>-butylcatechol and can be considered as functional models for catechol oxidase. Because these complexes possess labile sites in their structures and in solution they have a potential nucleophile constituted by a terminal Cu^II-bound hydroxo group, their activity toward hydrolysis of the model substrate 2,4-bis­(dinitrophenyl)­phosphate and DNA was also investigated. Double electrophilic activation of the phosphodiester by monodentate coordination to the Cu^II center that contains the phenol group with <i>tert</i>-butyl substituents and hydrogen bonding of the protonated phenol with the phosphate O atom are proposed to increase the hydrolase activity (<i>K</i>_ass. and <i>k</i>_cat.) of <b>1</b> and <b>2</b> in comparison with that found for complex <b>3</b>. In fact, complexes <b>1</b> and <b>2</b> show both oxidoreductase and hydrolase/nuclease activities and can thus be regarded as man-made models for studying 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