Trapping of a phenoxyl radical at a non-haem high-spin iron(II) centre.

The activation of dioxygen at haem and non-haem metal centres, and subsequent functionalization of unactivated C‒H bonds, has been a focal point of much research. In iron-mediated oxidation reactions, O binding at an iron(II) centre is often accompanied by an oxidation of the iron centre. Here we demonstrate dioxygen activation by sodium tetraphenylborate and protons in the presence of an iron(II) complex to form a reactive radical species, whereby the iron oxidation state remains unaltered in the presence of a highly oxidizing phenoxyl radical and O.

A high-spin alkylperoxo-iron(iii) complex with -anionic ligands: implications for the superoxide reductase mechanism.

The NO macrocycle of the 12-TMCO ligand stabilizes a high spin ( = 5/2) [Fe(12-TMCO)(OOBu)Cl] (3-Cl) species in the reaction of [Fe(12-TMCO)(OTf)] (1-(OTf)) with -butylhydroperoxide (BuOOH) in the presence of tetraethylammonium chloride (NEtCl) in acetonitrile at -20 °C. In the absence of NEtCl the oxo-iron(iv) complex 2 [Fe(12-TMCO)(O)(CHCN)] is formed, which can be further converted to 3-Cl by adding NEtCl and BuOOH. The role of the -chloride ligand in the stabilization of the Fe-OOBu moiety can be extended to other anions including the thiolate ligand relevant to the enzyme superoxide reductase (SOR).

A New Thiolate-Bound Dimanganese Cluster as a Structural and Functional Model for Class Ib Ribonucleotide Reductases.

In class Ib ribonucleotide reductases (RNRs) a dimanganese(II) cluster activates superoxide (O ⋅ ) rather than dioxygen (O ), to access a high valent Mn -O -Mn species, responsible for the oxidation of tyrosine to tyrosyl radical. In a biomimetic approach, we report the synthesis of a thiolate-bound dimanganese complex [Mn (BPMT)(OAc) ](ClO) (BPMT=(2,6-bis{[bis(2-pyridylmethyl)amino]methyl}-4-methylthiophenolate) (1) and its reaction with O ⋅ to form a [(BPMT)MnO Mn] complex 2. Resonance Raman investigation revealed the presence of an O-O bond in 2, while EPR analysis displayed a 16-line S =1/2 signal at g=2 typically associated with a Mn Mn core, as detected in class Ib RNRs.

Evidence of Sulfur Non-Innocence in [Co (dithiacyclam)] -Mediated Catalytic Oxygen Reduction Reactions.

In many metalloenzymes, sulfur-containing ligands participate in catalytic processes, mainly via the involvement in electron transfer reactions. In a biomimetic approach, we now demonstrate the implication of S-ligation in cobalt mediated oxygen reduction reactions (ORR). A comparative study between the catalytic ORR capabilities of the four-nitrogen bound [Co(cyclam)] (1; cyclam=1,5,8,11-tetraaza-cyclotetradecane) and the S-containing analog [Co(S N -cyclam)] (2; S N -cyclam=1,8-dithia-5,11-diaza-cyclotetradecane) reveals improved catalytic performance once the chalcogen is introduced in the Co coordination sphere.

Temporal trends in treatment strategies and clinical outcomes among patients with advanced chronic kidney disease and ST-elevation myocardial infarctions: results from the Bremen STEMI registry.

Background: Although the detrimental effects of advanced chronic kidney disease (CKD) on prognosis in coronary artery disease is known, there are few data on the efficacy and safety of modern interventional therapies and medications in patients with advanced CKD, because this special patient cohort is often excluded or underrepresented in randomized trials.

Methods: In the present study all patients admitted with ST-elevation myocardial infarctions (STEMI) from the region of Bremen/Germany treated between 2006 and 2019 were analyzed. Advanced CKD was defined as glomerular filtration rate < 45 ml/min.

The influence of secondary interactions on the [Ni(O)] mediated aldehyde oxidation reactions.

A rate enhancement of one to two orders of magnitude can be obtained in the aldehyde deformylation reactions by replacing the -N(CH) groups of [Ni(O)(Me[12]aneN)] (Me[12]aneN = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane) and [Ni(O)(Me[13]aneN)] (Me[13]aneN = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclotridecane) complexes by -NH in [Ni(O)([12]aneN)] (2; [12]aneN = 1,4,7,10-tetraazacyclododecane) and [Ni(O)([13]aneN)] (4; [13]aneN = 1,4,7,10-tetraazacyclotridecane). Based on detailed spectroscopic, reaction-kinetics and theoretical investigations, the higher reactivities of 2 and 4 are attributed to the changes in the secondary-sphere interactions between the [Ni(O)] and [12]aneN or [13]aneN moieties, which open up an alternative electrophilic pathway for the aldehyde oxidation reaction. Identification of primary kinetic isotope effects on the reactivity and stability of 2 when the -NH groups of the [12]aneN ligand are deuterated may also suggest the presence of secondary interaction between the -NH groups of [12]aneN and [Ni(O)] moieties, although, such interactions are not obvious in the DFT calculated optimized structure at the employed level of theory.

Spectroscopic Characterization of a Reactive [Cu (μ-OH) ] Intermediate in Cu/TEMPO Catalyzed Aerobic Alcohol Oxidation Reaction.

Cu /TEMPO (TEMPO=2,2,6,6-tetramethylpiperidinyloxyl) catalyst systems are versatile catalysts for aerobic alcohol oxidation reactions to selectively yield aldehydes. However, several aspects of the mechanism are yet unresolved, mainly because of the lack of identification of any reactive intermediates. Herein, we report the synthesis and characterization of a dinuclear [L1 Cu ] complex 1, which in presence of TEMPO can couple the catalytic 4 H /4 e reduction of O to water to the oxidation of benzylic and aliphatic alcohols.

A bioinspired oxoiron(IV) motif supported on a NS macrocyclic ligand.

A mononuclear oxoiron(iv) complex 1-trans bearing two equatorial sulfur ligations is synthesized and characterized as an active-site model of the elusive sulfur-ligated FeIV[double bond, length as m-dash]O intermediates in non-heme iron oxygenases. The introduction of sulfur ligands weakens the Fe[double bond, length as m-dash]O bond and enhances the oxidative reactivity of the FeIV[double bond, length as m-dash]O unit with a diminished deuterium kinetic isotope effect, thereby providing a compelling rationale for nature's use of the cis-thiolate ligated oxoiron(iv) motif in key metabolic transformations.

A Pseudotetrahedral Terminal Oxoiron(IV) Complex: Mechanistic Promiscuity in C-H Bond Oxidation Reactions.

S=2 oxoiron(IV) species act as reactive intermediates in the catalytic cycle of nonheme iron oxygenases. The few available synthetic S=2 Fe =O complexes known to date are often limited to trigonal bipyramidal and very rarely to octahedral geometries. Herein we describe the generation and characterization of an S=2 pseudotetrahedral Fe =O complex 2 supported by the sterically demanding 1,4,7-tri-tert-butyl-1,4,7-triazacyclononane ligand.

After ten years of follow-up, no difference between supportive care plus immunosuppression and supportive care alone in IgA nephropathy.

The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria, end-stage kidney disease (ESKD), and death. The adapted primary endpoint was the time to first occurrence of a composite of death, ESKD, or a decline of over 40% in the estimated glomerular filtration rate (eGFR) compared to baseline at randomization into STOP-IgAN.

Catalytic dioxygen reduction mediated by a tetranuclear cobalt complex supported on a stannoxane core.

The synthesis, spectroscopic characterization (infrared, electron paramagnetic resonance and X-ray absorption spectroscopies) and density functional theoretical calculations of a tetranuclear cobalt complex CoL1 involving a nonheme ligand system, L1, supported on a stannoxane core are reported. CoL1, similar to the previously reported hexanuclear cobalt complex CoL2, shows a unique ability to catalyze dioxygen (O) reduction, where product selectivity can be changed from a preferential 4e/4H dioxygen-reduction (to water) to a 2e/2H process (to hydrogen peroxide) only by increasing the temperature from -50 to 30 °C. Detailed mechanistic insights were obtained on the basis of kinetic studies on the overall catalytic reaction as well as by low-temperature spectroscopic (UV-Vis, resonance Raman and X-ray absorption spectroscopies) trapping of the end-on μ-1,2-peroxodicobalt(iii) intermediate 1.

Stoichiometric Formation of an Oxoiron(IV) Complex by a Soluble Methane Monooxygenase Type Activation of O at an Iron(II)-Cyclam Center.

In soluble methane monooxygenase enzymes (MMO), dioxygen (O) is activated at a diiron(II) center to form an oxodiiron(IV) intermediate that performs the challenging oxidation of methane to methanol. An analogous mechanism of O activation at mono- or dinuclear iron centers is rare in the synthetic chemistry. Herein, we report a mononuclear non-heme iron(II)-cyclam complex, -, that activates O to form the corresponding iron(IV)-oxo complex, -, via a mechanism reminiscent of the O activation process in MMO.

Zero Diffusive Sodium Balance in Hemodialysis Provided by an Algorithm-Based Electrolyte Balancing Controller: A Proof of Principle Clinical Study.

Restoring and controlling fluid volume homeostasis is still a challenge in contemporary end-stage kidney disease patients treated by intermittent hemodialysis (HD) or hemodiafiltration (HDF). This primary target is achieved by ultrafiltration (dry weight probing) and control of intradialytic sodium transfer (dialysate-plasma Na gradient). The latter task is mostly ignored in clinical practice by applying a dialysate sodium prescription uniform for all patients of the dialysis center but unaligned to individual plasma sodium levels.

The Photoconversion of Phytochrome Includes an Unproductive Shunt Reaction Pathway.

Phytochromes are modular bimodal photoswitches that control gene expression for morphogenetic processes in plants. These functions are triggered by photoinduced conversions between the inactive and active states of the photosensory module, denoted as Pr and Pfr, respectively. In the present time-resolved resonance Raman spectroscopic study of bacterial representatives of this photoreceptor family, we demonstrate that these phototransformations do not represent linear processes but include a branching reaction back to the initial state, prior to (de)activation of the output module.

Effects of Two Immunosuppressive Treatment Protocols for IgA Nephropathy.

The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.

Temperature Dependence of the Catalytic Two- versus Four-Electron Reduction of Dioxygen by a Hexanuclear Cobalt Complex.

The synthesis and characterization of a hexanuclear cobalt complex 1 involving a nonheme ligand system, L1, supported on a SnO stannoxane core are reported. Complex 1 acts as a unique catalyst for dioxygen reduction, whose selectivity can be changed from a preferential 4e/4H dioxygen-reduction (to water) to a 2e/2H process (to hydrogen peroxide) only by increasing the temperature from -50 to 25 °C. A variety of spectroscopic methods (Sn-NMR, magnetic circular dichroism (MCD), electron paramagnetic resonance (EPR), SQUID, UV-vis absorption, and X-ray absorption spectroscopy (XAS)) coupled with advanced theoretical calculations has been applied for the unambiguous assignment of the geometric and electronic structure of 1.

Reversible light-dependent molecular switches on Ag/AgCl nanostructures.

Nanostructured Ag/AgCl substrates were used to generate reversible and highly efficient light-dependent chemical switches based on adsorbed 4,4'-dimercaptoazobenzene (DMAB). DMAB was formed in situ via laser-induced dimerization either from 4-nitrothiophenol (4-NTP) or 4-aminothiophenol (4-ATP). The subsequent reaction pathways of DMAB, however, were quite different as monitored by surface enhanced Raman spectroscopy.

A New Domain of Reactivity for High-Valent Dinuclear [M(μ-O) M'] Complexes in Oxidation Reactions.

The strikingly different reactivity of a series of homo- and heterodinuclear [(M )(μ-O) (M )'] (M=Ni; M'=Fe, Co, Ni and M=M'=Co) complexes with β-diketiminate ligands in electrophilic and nucleophilic oxidation reactions is reported, and can be correlated to the spectroscopic features of the [(M )(μ-O) (M )'] core. In particular, the unprecedented nucleophilic reactivity of the symmetric [Ni (μ-O) Ni ] complex and the decay of the asymmetric [Ni (μ-O) Co ] core through aromatic hydroxylation reactions represent a new domain for high-valent bis(μ-oxido)dimetal reactivity.

Electrochemical and Resonance Raman Spectroscopic Studies of Water-Oxidizing Ruthenium Terpyridyl-Bipyridyl Complexes.

The irreversible conversion of single-site water-oxidation catalysts (WOC) into more rugged catalysts structurally related to [(trpy)(5,5'-X -bpy)Ru (μ-O)Ru (trpy)(O)(H O)] (X=H, 1-dn ; X=F, 2-dn ; bpy=2,2'-bipyridine; trpy=2,2':6',2"-terpyridine) represents a critical issue in the development of active and durable WOCs. In this work, the electrochemical and acid-base properties of 1-dn and 2-dn were evaluated. In situ resonance Raman spectroscopy was employed to characterize the species formed upon the stoichiometric oxidation of the single-site catalysts and demonstrated the formation of high-oxidation-state mononuclear Ru=O and RuO-O complexes.

Using Separable Nonnegative Matrix Factorization Techniques for the Analysis of Time-Resolved Raman Spectra.

The key challenge of time-resolved Raman spectroscopy is the identification of the constituent species and the analysis of the kinetics of the underlying reaction network. In this work we present an integral approach that allows for determining both the component spectra and the rate constants simultaneously from a series of vibrational spectra. It is based on an algorithm for nonnegative matrix factorization that is applied to the experimental data set following a few pre-processing steps.

Changing the chemical and physical properties of high valent heterobimetallic bis-(μ-oxido) Cu-Ni complexes by ligand effects.

Two new heterobimetallic [LNiOCu(RPY2)] (RPY2 = N-substituted bis 2-pyridyl(ethylamine) ligands with R = indane, 3a or R = Me, 3b) complexes have been spectroscopically trapped at low temperatures. They were prepared by reacting the mononuclear side-on LNi superoxo precursor bearing a β-diketiminate ligand (L = [HC-(CMeNCH(iPr))]) with the Cu(i) complexes. In contrast to the oxo groups in known high-valent [M(μ-O)] (M = Fe, Co, Ni, Cu) cores that display electrophilic reactivities, 3a and 3b display rather nucleophilic oxo cores active in aldehyde deformylation reactions.

Intensive Supportive Care plus Immunosuppression in IgA Nephropathy.

Background: The outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain.

Methods: We conducted a multicenter, open-label, randomized, controlled trial with a two-group, parallel, group-sequential design. During a 6-month run-in phase, supportive care (in particular, blockade of the renin-angiotensin system) was adjusted on the basis of proteinuria.

Light-Dark Adaptation of Channelrhodopsin Involves Photoconversion between the all-trans and 13-cis Retinal Isomers.

Channelrhodopsins (ChR) are light-gated ion channels of green algae that are widely used to probe the function of neuronal cells with light. Most ChRs show a substantial reduction in photocurrents during illumination, a process named "light adaptation". The main objective of this spectroscopic study was to elucidate the molecular processes associated with light-dark adaptation.

Resonance Raman Spectroscopic Analysis of the [NiFe] Active Site and the Proximal [4Fe-3S] Cluster of an O2-Tolerant Membrane-Bound Hydrogenase in the Crystalline State.

We have applied resonance Raman (RR) spectroscopy on single protein crystals of the O2-tolerant membrane-bound [NiFe] hydrogenase (MBH from Ralstonia eutropha) which catalyzes the splitting of H2 into protons and electrons. RR spectra taken from 65 MBH samples in different redox states were analyzed in terms of the respective component spectra of the active site and the unprecedented proximal [4Fe-3S] cluster using a combination of statistical methods and global fitting procedures. These component spectra of the individual cofactors were compared with calculated spectra obtained by quantum mechanics/molecular mechanics (QM/MM) methods.

Surface Enhanced Resonance Raman Spectroscopy Reveals Potential Induced Redox and Conformational Changes of Cytochrome c Oxidase on Electrodes.

Immobilization of Cytochrome c oxidase (CcO) on electrodes makes voltage-driven reduction of oxygen to water possible. Efficient catalytic turnover in CcO/electrode systems is, however, often observed at large overpotentials that cannot be rationalized by the redox properties of the enzyme itself. To understand the structural basis for this observation, CcO was electrostatically adsorbed on amino-functionalized Ag electrodes, and the redox transitions of heme a and a3 were monitored via surface enhanced resonance Raman spectroscopy (SERRS) as a function of applied potential.