Oxinobactin and Sulfoxinobactin, Abiotic Siderophore Analogues to Enterobactin Involving 8‑Hydroxyquinoline Subunits: Thermodynamic and Structural Studies

The synthesis of two new iron chelators built on the tris-l-serine trilactone scaffold of enterobactin and bearing a 8-hydroxyquinoline (oxinobactin) or 8-hydroxyquinoline-5-sulfonate (sulfoxinobactin) unit has been described. The X-ray structure of the ferric oxinobactin has been determined, exhibiting a slightly distorted octahedral environment for Fe­(III) and a Δ configuration. The Fe­(III) chelating properties have been examined by potentiometric and spectrophotometric titrations in methanol–water 80/20% w/w solvent for oxinobactin and in water for sulfoxinobactin. They reveal the extraordinarily complexing ability (pFe^III values) of oxinobactin over the p­[H] range 2–9, the pFe value at p­[H] 7.4 being 32.8. This was supported by spectrophotometric competition showing that oxinobactin removes Fe­(III) from ferric enterobactin at p­[H] 7.4. In contrast, the Fe­(III) affinity of sulfoxinobactin was largely lower as compared to oxinobactin but similar to that of the ligand O-TRENSOX having a TREN backbone. These results are discussed in relation to the predisposition by the trilactone scaffold of the chelating units. Some comparisons are also made with other quinoline-based ligands and hydroxypyridinonate ligand (hopobactin)

Osmium(II) Complexes Bearing Chelating N‑Heterocyclic Carbene and Pyrene-Modified Ligands: Surface Electrochemistry and Electron Transfer Mediation of Oxygen Reduction by Multicopper Enzymes

We report the synthesis of original osmium­(II) complexes bearing chelating N-heterocyclic (NHC) and bipyridine ligands. The pincer ligand 1,1′-dimethyl-3,3′-methylenediimidazole-2,2′-diylidene was used to tune the redox properties of osmium complexes. Bipyridine ligands modified with pyrene groups were chosen to study the electrosynthesis of Os^II-NHC-based metallopolymers as well as the noncovalent immobilization of these complexes on carbon-nanotube (CNT) electrodes. Poly-[Os^II-NHC] polypyrene polymer was electrogenerated on a GC electrode, whereas the pyrene-modified [Os^II-NHC] could interact with the CNTs’ sidewalls through π–π interactions, allowing the immobilization of the NHC complexes at the surface of π-extended nanostructured electrodes. Furthermore, an Os^II-NHC complex was studied in water, showing electron transfer mediation with multicopper enzymes. UV–visible and electrochemical experiments demonstrate that redox properties of the Os^II-NHC complex provide sufficient driving force for electron transfer with bilirubin oxidase from <i>Myrothecium verrucaria</i> while achieving high potential electroenzymatic oxygen reduction at <i>E</i> = +0.45 V vs Ag/AgCl at pH 6.5

Osmium(II) Complexes Bearing Chelating N‑Heterocyclic Carbene and Pyrene-Modified Ligands: Surface Electrochemistry and Electron Transfer Mediation of Oxygen Reduction by Multicopper Enzymes

We report the synthesis of original osmium­(II) complexes bearing chelating N-heterocyclic (NHC) and bipyridine ligands. The pincer ligand 1,1′-dimethyl-3,3′-methylenediimidazole-2,2′-diylidene was used to tune the redox properties of osmium complexes. Bipyridine ligands modified with pyrene groups were chosen to study the electrosynthesis of Os^II-NHC-based metallopolymers as well as the noncovalent immobilization of these complexes on carbon-nanotube (CNT) electrodes. Poly-[Os^II-NHC] polypyrene polymer was electrogenerated on a GC electrode, whereas the pyrene-modified [Os^II-NHC] could interact with the CNTs’ sidewalls through π–π interactions, allowing the immobilization of the NHC complexes at the surface of π-extended nanostructured electrodes. Furthermore, an Os^II-NHC complex was studied in water, showing electron transfer mediation with multicopper enzymes. UV–visible and electrochemical experiments demonstrate that redox properties of the Os^II-NHC complex provide sufficient driving force for electron transfer with bilirubin oxidase from <i>Myrothecium verrucaria</i> while achieving high potential electroenzymatic oxygen reduction at <i>E</i> = +0.45 V vs Ag/AgCl at pH 6.5

Structural and Spectroscopic Investigation of an Anilinosalen Cobalt Complex with Relevance to Hydrogen Production

A Co­(II) anilinosalen catalyst containing proton relays in the first coordination sphere has been synthesized that catalyzes the electrochemical production of hydrogen from acid in dichloromethane and acetonitrile solutions. The complex has been spectroscopically and theoretically characterized in different protonation and redox states. We show that both coordinated anilido groups of the neutral Co­(II) complex can be protonated into aniline form. Protonation induces an anodic shift of more than 1 V of the reduction wave, which concomitantly becomes irreversible. Hydrogen evolution that originates from the aniline protons located in the first coordination sphere is observed upon bulk electrolysis at −1.5 V of the protonated complex in absence of external acid. Structures for intermediates in the catalytic reaction have been identified based on this data

Carl von Linné fil. to Peter Simon Pallas

Square planar cobalt­(II) complexes of salen ligands <i>N</i>,<i>N</i>′-bis­(3-<i>tert</i>-butyl-5<i>R</i>-salicylidene)-1,2-cyclohexanediamine), where R = OMe (<b>1</b>) and <i>tert</i>-butyl (<b>2</b>), were prepared. <b>1</b> and <b>2</b> were electrochemically reversibly oxidized into cations <b>[1-H</b>_<b>2</b><b>O]</b>^<b>+</b> and <b>[2-H</b>_<b>2</b><b>O]</b>^<b>+</b> in CH₂Cl₂. The chemically generated <b>[1-H</b>_<b>2</b><b>O]­(SbF</b>_<b>6</b><b>)·0.68 H</b>_<b>2</b><b>O·0.82CH</b>_<b>2</b><b>Cl</b>_<b>2</b> and <b>[2-H</b>_<b>2</b><b>O]­(SbF</b>_<b>6</b><b>)·0.3H</b>_<b>2</b><b>O·0.85CH</b>_<b>2</b><b>Cl</b>_<b>2</b> were characterized by X-ray diffraction and NIR spectroscopy. Both complexes are paramagnetic species containing a square pyramidal cobalt ion coordinated at the apical position by an exogenous water molecule. They exhibit remarkable NIR bands at 1220 (7370 M^–1 cm^–1) and 1060 nm (5560 M^–1 cm^–1), respectively, assigned to a CT transition. DFT calculations and magnetic measurements confirm the paramagnetic (<i>S</i> = 1) ground spin state of the cations. They show that more than 70% of the total spin density in <b>[1-H</b>_<b>2</b><b>O]</b>^<b>+</b> and <b>[2-H</b>_<b>2</b><b>O]</b>^<b>+</b> is localized on the metal, the remaining spin density being distributed over the aromatic rings (30% phenoxyl character). In the presence of <i>N</i>-methylimidazole <b>1</b> and <b>2</b> are irreversibly oxidized by air into the genuine octahedral cobalt­(III) bis­(phenolate) complexes <b>[1-im</b>_<b>2</b><b>]</b>^<b>+</b> and <b>[2-im</b>_<b>2</b><b>]</b>^<b>+</b>, the former being structurally characterized. Neither <b>[1-im</b>_<b>2</b><b>]</b>^<b>+</b> nor <b>[2-im</b>_<b>2</b><b>]</b>^<b>+</b> exhibits a NIR feature in its electronic spectrum. <b>1</b> and <b>2</b> were electrochemically two-electron oxidized into <b>[1]</b>^<b>2+</b> and <b>[2]</b>^<b>2+</b>. The cations were identified as Co­(III)–phenoxyl species by their characteristic absorption band at ca. 400 nm in the UV–vis spectrum. Coordination of the phenoxyl radical to the cobalt­(III) metal ion is evidenced by the EPR signal centered at <i>g</i> = 2.00

Asymmetric Approach to Hyacinthacines B₁ and B₂

Naturally occurring hyacinthacines B₁ and B₂ have been prepared from a common, easily available, advanced intermediate. The approach features several highly stereoselective transformations: inter alia, a dichloroketene–enol ether [2 + 2] cycloaddition, a Bruylants alkylation, and an amino-nitrile alkylation–reduction

Exploring the Interaction of N/S Compounds with a Dicopper Center: Tyrosinase Inhibition and Model Studies

Tyrosinase (Ty) is a copper-containing enzyme widely present in plants, bacteria, and humans, where it is involved in biosynthesis of melanin-type pigments. Development of Ty inhibitors is an important approach to control the production and the accumulation of pigments in living systems. In this paper, we focused our interest in phenylthiourea (PTU) and phenylmethylene thiosemicarbazone (PTSC) recognized as inhibitors of tyrosinase by combining enzymatic studies and coordination chemistry methods. Both are efficient inhibitors of mushroom tyrosinase and they can be considered mainly as competitive inhibitors. Computational studies verify that PTSC and PTU inhibitors interact with the metal center of the active site. The <i>K</i>_IC value of 0.93 μM confirms that PTSC is a much more efficient inhibitor than PTU, for which a <i>K</i>_IC value of 58 μM was determined. The estimation of the binding free energies inhibitors/Ty confirms the high inhibitor efficiency of PTSC. Binding studies of PTSC along with PTU to a dinuclear copper­(II) complex ([Cu₂(μ-BPMP)­(μ-OH)]­(ClO₄)₂ (<b>1</b>); H-BPMP = 2,6-bis-[bis­(2-pyridylmethyl)­aminomethyl]-4-methylphenol) known to be a structural and functional model for the tyrosinase catecholase activity, have been performed. Interactions of the compounds with the dicopper model complex <b>1</b> were followed by spectrophotometry and electrospray ionization (ESI). The molecular structure of <b>1</b>-PTSC and <b>1</b>-PTU adducts were determined by single-crystal X-ray diffraction analysis showing for both an unusual bridging binding mode on the dicopper center. These results reflect their adaptable binding mode in relation to the geometry and chelate size of the dicopper center

Interaction of Polycationic Ni(II)-Salophen Complexes with G‑Quadruplex DNA

A series of nine Ni­(II) salophen complexes involving one, two, or three alkyl-imidazolium side-chains was prepared. The lengths of the side-chains were varied from one to three carbons. The crystal structure of one complex revealed a square planar geometry of the nickel ion. Fluorescence resonance energy transfer melting of G-quadruplex structures in the presence of salophen complex were performed. The G-quadruplex DNA structures were stabilized in the presence of the complexes, but a duplex DNA was not. The binding constants of the complexes for parallel and antiparallel G-quadruplex DNA, as well as hairpin DNA, were measured by surface plasmon resonance. The compounds were selective for G-quadruplex DNA, as reflected by equilibrium dissociation constant <i>K</i>_D values in the region 0.1–1 μM for G-quadruplexes and greater than 2 μM for duplex DNA. Complexes with more and shorter side-chains had the highest binding constants. The structural basis for the interaction of the complexes with the human telomeric G-quadruplex DNA was investigated by computational studies: the aromatic core of the complex stacked over the last tetrad of the G-quadruplex with peripherical cationic side chains inserted into opposite grooves. Biochemical studies (telomeric repeat amplification protocol assays) indicated that the complexes significantly inhibited telomerase activity with IC₅₀ values as low as 700 nM; the complexes did not significantly inhibit polymerase activity

Interaction of Polycationic Ni(II)-Salophen Complexes with G‑Quadruplex DNA

A series of nine Ni­(II) salophen complexes involving one, two, or three alkyl-imidazolium side-chains was prepared. The lengths of the side-chains were varied from one to three carbons. The crystal structure of one complex revealed a square planar geometry of the nickel ion. Fluorescence resonance energy transfer melting of G-quadruplex structures in the presence of salophen complex were performed. The G-quadruplex DNA structures were stabilized in the presence of the complexes, but a duplex DNA was not. The binding constants of the complexes for parallel and antiparallel G-quadruplex DNA, as well as hairpin DNA, were measured by surface plasmon resonance. The compounds were selective for G-quadruplex DNA, as reflected by equilibrium dissociation constant <i>K</i>_D values in the region 0.1–1 μM for G-quadruplexes and greater than 2 μM for duplex DNA. Complexes with more and shorter side-chains had the highest binding constants. The structural basis for the interaction of the complexes with the human telomeric G-quadruplex DNA was investigated by computational studies: the aromatic core of the complex stacked over the last tetrad of the G-quadruplex with peripherical cationic side chains inserted into opposite grooves. Biochemical studies (telomeric repeat amplification protocol assays) indicated that the complexes significantly inhibited telomerase activity with IC₅₀ values as low as 700 nM; the complexes did not significantly inhibit polymerase activity