Direct tests of cytochrome and functions in the electron transport chain of malaria parasites.

The mitochondrial electron transport chain (ETC) of malaria parasites is a major antimalarial drug target, but critical cytochrome (cyt) functions remain unstudied and enigmatic. Parasites express two distinct cyt homologs ( and -2) with unusually sparse sequence identity and uncertain fitness contributions. cyt -2 is the most divergent eukaryotic cyt homolog currently known and has sequence features predicted to be incompatible with canonical ETC function.

Direct Tests of Cytochrome Function in the Electron Transport Chain of Malaria Parasites.

Unlabelled: The mitochondrial electron transport chain (ETC) of malaria parasites is a major antimalarial drug target, but critical cytochrome functions remain unstudied and enigmatic. Parasites express two distinct cyt homologs ( and -2) with unusually sparse sequence identity and uncertain fitness contributions. cyt -2 is the most divergent eukaryotic cyt homolog currently known and has sequence features predicted to be incompatible with canonical ETC function.

New Role for Radical SAM Enzymes in the Biosynthesis of Thio(seleno)oxazole RiPP Natural Products.

Ribosomally synthesized post-translationally modified peptides (RiPPs) are ubiquitous and represent a structurally diverse class of natural products. The ribosomally encoded precursor polypeptides are often extensively modified post-translationally by enzymes that are encoded by coclustered genes. Radical -adenosyl-l-methionine (SAM) enzymes catalyze numerous chemically challenging transformations.

Molecular and Electronic Structures and Single-Molecule Magnet Behavior of Tris(thioether)-Iron Complexes Containing Redox-Active α-Diimine Ligands.

Incorporating radical ligands into metal complexes is one of the emerging trends in the design of single-molecule magnets (SMMs). While significant effort has been expended to generate multinuclear transition metal-based SMMs with bridging radical ligands, less attention has been paid to mononuclear transition metal-radical SMMs. Herein, we describe the first α-diiminato radical-containing mononuclear transition metal SMM, namely, [κ-PhTt]Fe(AdNCHCHNAd) (), and its analogue [κ-PhTt]Fe(CyNCHCHNCy) () (PhTt = phenyltris(butylthiomethyl)borate, Ad = adamantyl, and Cy = cyclohexyl).

Exceptionally High O-H Bond Dissociation Free Energy of a Dicopper(II) μ-Hydroxo Complex and Insights into the Geometric and Electronic Structure Origins Thereof.

The strength of the relevant bonds in bond-making and bond-breaking processes can directly affect the overall efficiency of the process. Copper-oxygen sites are known to catalyze reactions with some of the most recalcitrant C-H bonds found in nature as quantified by the bond dissociation free energy (BDFE), yet only a handful of copper-bound O-H bond strengths have been defined. Equally important in the design of synthetic catalysts is an understanding of the geometric and electronic structure origins of these thermodynamic parameters.

Substituted Benzothietes: Synthesis and a Quantum Chemical Investigation of Their Cycloreversion Properties.

A flexible synthesis for highly substituted benzothietes that does not require flash-vacuum pyrolysis was developed. This allows for the use of a number of functional groups and nonvaporizable molecules. Highly stabilized derivatives were isolated.

Understanding Hydrogen Bonding Interactions in Crosslinked Methylammonium Lead Iodide Crystals: Towards Reducing Moisture and Light Degradation Pathways.

Methylammonium lead halide perovskite-based solar cells have demonstrated efficiencies as high as 24.2 %, highlighting their potential as inexpensive and solution-processable alternatives to silicon solar cell technologies. Poor stability towards moisture, ultraviolet irradiation, heat, and a bias voltage of the perovskite layer and its various device interfaces limits the commercial feasibility of this material for outdoor applications.

A Tricopper(I) Complex Competent for O Atom Transfer, C-H Bond Activation, and Multiple O Activation Steps.

Oxygenation of a tricopper(I) cyclophanate (1) affords reactive transients competent for C-H bond activation and O atom transfer to various substrates (including toluene, dihydroanthracene, and ethylmethylsulfide) based on H NMR, gas chromatography/mass spectrometry (MS), and electrospray ionization (ESI)/MS data. Low product yields (<1%) are determined for C-H activation substrates (e.g, toluene, ethylbenzene), which we attribute to competitive ligand oxidation.

Thermodynamics of a μ-oxo Dicopper(II) Complex for Hydrogen Atom Abstraction.

The mono-μ-hydroxo complex {[Cu(tmpa)]-(μ-OH)} (1) can undergo reversible deprotonation at -30 °C to yield {[Cu(tmpa)]-(μ-O)} (2). This species is basic with a pK of 24.3.

Electrocatalytic Water Oxidation by a Homogeneous Copper Catalyst Disfavors Single-Site Mechanisms.

Deployment of solar fuels derived from water requires robust oxygen-evolving catalysts made from earth abundant materials. Copper has recently received much attention in this regard. Mechanistic parallels between Cu and single-site Ru/Ir/Mn water oxidation catalysts, including intermediacy of terminal Cu oxo/oxyl species, are prevalent in the literature; however, intermediacy of late transition metal oxo species would be remarkable given the high d-electron count would fill antibonding orbitals, making these species high in energy.

Phenol-Induced O-O Bond Cleavage in a Low-Spin Heme-Peroxo-Copper Complex: Implications for O Reduction in Heme-Copper Oxidases.

This study evaluates the reaction of a biomimetic heme-peroxo-copper complex, {[(DCHIm)(F)Fe]-(O)-[Cu(AN)]} (1), with a phenolic substrate, involving a net H-atom abstraction to cleave the bridging peroxo O-O bond that produces Fe═O, Cu-OH, and phenoxyl radical moieties, analogous to the chemistry carried out in heme-copper oxidases (HCOs). A 3D potential energy surface generated for this reaction reveals two possible reaction pathways: one involves nearly complete proton transfer (PT) from the phenol to the peroxo ligand before the barrier; the other involves O-O homolysis, where the phenol remains H-bonding to the peroxo O in the transition state (TS) and transfers the H after the barrier. In both mechanisms, electron transfer (ET) from phenol occurs after the PT (and after the barrier); therefore, only the interaction with the H is involved in lowering the O-O cleavage barrier.

Perception of the plant hormone ethylene: known-knowns and known-unknowns.

The gaseous phytohormone ethylene is implicated in virtually all phases of plant growth and development and thus has a major impact on crop production. This agronomic impact makes understanding ethylene signaling the Philosopher's Stone of the plant biotechnology world in applications including post-harvest transport of foodstuffs, consistency of foodstuff maturity pre-harvest, decorative flower freshness and longevity, and biomass production for biofuel applications. Ethylene is biosynthesized by plants in response to environmental factors and plant life-cycle events, and triggers a signaling cascade that modulates over 1000 genes.

Peroxo and Superoxo Moieties Bound to Copper Ion: Electron-Transfer Equilibrium with a Small Reorganization Energy.

Oxygenation of [Cu2(UN-O(-))(DMF)](2+) (1), a structurally characterized dicopper Robin-Day class I mixed-valent Cu(II)Cu(I) complex, with UN-O(-) as a binucleating ligand and where dimethylformamide (DMF) binds to the Cu(II) ion, leads to a superoxo-dicopper(II) species [Cu(II)2(UN-O(-))(O2(•-))](2+) (2). The formation kinetics provide that kon = 9 × 10(-2) M(-1) s(-1) (-80 °C), ΔH(‡) = 31.1 kJ mol(-1) and ΔS(‡) = -99.

Observation of a Cu(II)(2) (μ-1,2-peroxo)/Cu(III)(2) (μ-oxo)(2) equilibrium and its implications for copper-dioxygen reactivity.

Synthesis of small-molecule Cu2 O2 adducts has provided insight into the related biological systems and their reactivity patterns including the interconversion of the Cu(II) 2 (μ-η(2) :η(2) -peroxo) and Cu(III) 2 (μ-oxo)2 isomers. In this study, absorption spectroscopy, kinetics, and resonance Raman data show that the oxygenated product of [(BQPA)Cu(I) ](+) initially yields an "end-on peroxo" species, that subsequently converts to the thermodynamically more stable "bis-μ-oxo" isomer (Keq =3.2 at -90 °C).

Structure/function correlations among coupled binuclear copper proteins through spectroscopic and reactivity studies of NspF.

The terminal step of 4-hydroxy-3-nitrosobenzamide biosynthesis in Streptomyces murayamaensis is performed by NspF, a mono-oxygenase that converts o-aminophenols to the corresponding nitroso product (hydroxyanilinase activity). Previous biochemical characterization of the resting form of NspF suggested that this enzyme belonged to the coupled binuclear copper enzyme (CBC) family. Another member of this enzyme family, tyrosinase, is able to mono-oxygenate monophenols (monophenolase activity) but not o-aminophenols.

Electronic structure of a low-spin heme/Cu peroxide complex: spin-state and spin-topology contributions to reactivity.

This study details the electronic structure of the heme–peroxo–copper adduct {[(F8)Fe(DCHIm)]-O2-[Cu(AN)]}+ (LS(AN)) in which O2(2–) bridges the metals in a μ-1,2 or “end-on” configuration. LS(AN) is generated by addition of coordinating base to the parent complex {[(F8)Fe]-O2-[Cu(AN)]}+ (HS(AN)) in which the O2(2–) bridges the metals in an μ-η2:η2 or “side-on” mode. In addition to the structural change of the O2(2–) bridging geometry, coordination of the base changes the spin state of the heme fragment (from S = 5/2 in HS(AN) to S = 1/2 in LS(AN)) that results in an antiferromagnetically coupled diamagnetic ground state in LS(AN).

Copper dioxygen (bio)inorganic chemistry.

Cu/O2 intermediates in biological, homogeneous, and heterogeneous catalysts exhibit unique spectral features that reflect novel geometric and electronic structures that make significant contributions to reactivity. This review considers how the respective intermediate electronic structures overcome the spin-forbidden nature of O2 binding, activate O2 for electrophilic aromatic attack and H-atom abstraction, catalyze the 4 e- reduction of O2 to H2O, and discusses the role of exchange coupling between Cu ions in determining reactivity.

Sulfur donor atom effects on copper(I)/O(2) chemistry with thioanisole containing tetradentate N(3)S ligand leading to μ-1,2-peroxo-dicopper(II) species.

To better understand the effect of thioether coordination in copper-O(2) chemistry, the tetradentate N(3)S ligand L(ASM) (2-(methylthio)-N,N-bis((pyridin-2-yl)methyl)benzenamine) and related alkylether ligand L(EOE) (2-ethoxy-N,N-bis((pyridin-2-yl)methyl)ethanamine) have been studied. The corresponding copper(I) complexes, [(L(ASM))Cu(I)](+) (1a) and [(L(EOE))Cu(I)](+) (3a), were studied as were the related compound [(L(ESE))Cu(I)](+) (2a, L(ESE) = (2-ethylthio-N,N-bis((pyridin-2-yl)methyl)ethanamine). The X-ray structure of 1a and its solution conductivity reveal a monomeric molecular structure possessing thioether coordination which persists in solution.

Heme-copper-dioxygen complexes: toward understanding ligand-environmental effects on the coordination geometry, electronic structure, and reactivity.

The nature of the ligand is an important aspect of controlling the structure and reactivity in coordination chemistry. In connection with our study of heme-copper-oxygen reactivity relevant to cytochrome c oxidase dioxygen-reduction chemistry, we compare the molecular and electronic structures of two high-spin heme-peroxo-copper [Fe(III)O(2)(2-)Cu(II)](+) complexes containing N(4) tetradentate (1) or N(3) tridentate (2) copper ligands. Combining previously reported and new resonance Raman and EXAFS data coupled to density functional theory calculations, we report a geometric structure and more complete electronic description of the high-spin heme-peroxo-copper complexes 1 and 2, which establish mu-(O(2)(2-)) side-on to the Fe(III) and end-on to Cu(II) (mu-eta(2):eta(1)) binding for the complex 1 but side-on/side-on (mu-eta(2):eta(2)) mu-peroxo coordination for the complex 2.

Spectroscopic and computational studies of a trans-mu-1,2-disulfido-bridged dinickel species, [{(tmc)Ni}(2)(S(2))](OTf)(2): comparison of end-on disulfido and peroxo bonding in (Ni(II))(2) and (Cu(II))(2) species.

A powerful means of enhancing our understanding of the structures and functions of enzymes that contain nickel-sulfur bonds, such as Ni superoxide dismutase, acetyl-coenzyme A synthase/carbon monoxide dehydrogenase, [NiFe] hydrogenase, and methyl-CoM reductase, involves the investigation of model compounds with similar structural and/or electronic properties. In this study, we have characterized a trans-mu-1,2-disulfido-bridged dinickel(II) species, [{(tmc)Ni}(2)(S(2))](2+) (1, tmc = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) by using electronic absorption, magnetic circular dichroism (MCD), and resonance Raman (rR) spectroscopic techniques, as well as density functional theory (DFT) and time-dependent DFT computational methods. Our computational results, validated on the basis of the experimental MCD data and previously reported (1)H NMR spectra, reveal that 1 is best described as containing two antiferromagnetically coupled high-spin Ni(II) centers.

A Series of Cyanide-Bridged Binuclear Complexes.

A series of cyanide-bridged binuclear complexes, ('S(3)')Ni-CN-M[Tp(tBu)] ('S(3)' = bis(2-mercaptophenyl)sulfide, Tp(tBu) = hydrotris(3-tert-butylpyrazolyl)borate, M = Fe (2-Fe), Co (2-Co), Ni (2-Ni), Zn (2-Zn)) was prepared by the coupling of K[('S(3)')Ni(CN)] with [Tp(tBu)]MX. The isostructural series of complexes was structurally and spectroscopically characterized. A similar coupling strategy was used to synthesize the anionic copper(I) analogue, Et4N{('S3')Ni-CN-Cu[Tp(tBu)]}, 2-Cu.

Synthetic analogs for evaluating the influence of N-H...S hydrogen bonds on the formation of thioester in acetyl coenzyme A synthase.

A series of square planar methylnickel(II) complexes, (dppe)Ni(Me)(SAr) (dppe = 1,2-bis(diphenylphosphino)ethane); 2. Ar = phenyl; 3. Ar = pentafluorophenyl; 4.