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 (O2⋅−) rather than dioxygen (O2), to access a high valent MnIII−O2−MnIV species, responsible for the oxidation of tyrosine to tyrosyl radical. In a biomimetic approach, we report the synthesis of a thiolate-bound dimanganese complex [MnII2(BPMT)(OAc)2](ClO)4 (BPMT=(2,6-bis{[bis(2-pyridylmethyl)amino]methyl}-4-methylthiophenolate) (1) and its reaction with O2⋅− to form a [(BPMT)MnO2Mn]2+ complex 2. Resonance Raman investigation revealed the presence of an O−O bond in 2, while EPR analysis displayed a 16-line St=1/2 signal at g=2 typically associated with a MnIIIMnIV core, as detected in class Ib RNRs. Unlike all other previously reported Mn−O2−Mn complexes, generated by O2⋅− activation at Mn2 centers, 2 proved to be a capable electrophilic oxidant in aldehyde deformylation and phenol oxidation reactions, rendering it one of the best structural and functional models for class Ib RNRs

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 (O2⋅−) rather than dioxygen (O2), to access a high valent MnIII−O2−MnIV species, responsible for the oxidation of tyrosine to tyrosyl radical. In a biomimetic approach, we report the synthesis of a thiolate‐bound dimanganese complex [MnII2(BPMT)(OAc)2](ClO)4 (BPMT=(2,6‐bis{[bis(2‐pyridylmethyl)amino]methyl}‐4‐methylthiophenolate) (1) and its reaction with O2⋅− to form a [(BPMT)MnO2Mn]2+ complex 2. Resonance Raman investigation revealed the presence of an O−O bond in 2, while EPR analysis displayed a 16‐line St=1/2 signal at g=2 typically associated with a MnIIIMnIV core, as detected in class Ib RNRs. Unlike all other previously reported Mn−O2−Mn complexes, generated by O2⋅− activation at Mn2 centers, 2 proved to be a capable electrophilic oxidant in aldehyde deformylation and phenol oxidation reactions, rendering it one of the best structural and functional models for class Ib RNRs.Peer Reviewe

Beweis von Schwefel‐non‐Innocence in [CoII(Dithiacyclam)]2+ ‐vermittelten, katalytischen Sauerstoff‐Reduktions‐Reaktionen

In vielen Metallenzymen sind Schwefel-enthaltende Liganden an Elektronen-Transfer-Reaktionen beteiligt. In dem hier diskutierten biomimetischen Ansatz wird der Einfluss einer Schwefelkoordination auf eine Kobalt-katalysierte Sauerstoff-Reduktionsreaktion (ORR) demonstriert. Ein Vergleich des ORR-Vermögens eines vierfach Stickstoff-koordinierten [Co(Cyclam]2+-Komplexes (1; Cyclam=1,5,8,11-Tetraaza-cyclotetradecan) und dessen Schwefel-Analogons [Co(S2N2-Cyclam)]2+ (2; S2N2-Cyclam=1,8-Dithia-5,11-diazacyclotetradecan) zeigt verbesserte katalytische Eigenschaften mit dem in die Ligandensphäre am Kobalt eingeführten Chalkogen. Isolierung und Charakterisierung der Intermediate, die sich im Zuge der Sauerstoffaktivierung an den Kobalt(II)-Zentren von 1 und 2 bilden, identifizieren eine Beteiligung des Schwefels am O2-Reduktionsprozess als entscheidenden Faktor für die verbesserten Eigenschaften von 2 bei der katalytischen ORR

Experimental and computational investigation of heteroatom substitution in nucleolytic Cu(ii) cyclen complexes for balancing stability and redox activity

Cu(II) complexes of cyclen-based ligands CuL1–CuL6 were synthesized and characterized. The corresponding ligands L1–L6 comprise different donor sets including S and O atoms. Whereas cyclen (L1) is commercially available, L2–L6 were synthesized according to protocols available in the literature. Cleavage activity of the complexes towards plasmid DNA was tested in the presence and absence of ascorbate as a reducing agent (oxidative vs. hydrolytic cleavage). As previously shown, the substitution of N donor atoms with hard donor O atoms leads to efficient oxidative nucleases, but dissociation of the complex upon reduction. We thus opted for S substitution (soft donors) to stabilize the reduced Cu(I) species. Increasing the S content, however, leads to species that are difficult to reoxidize in order to ensure efficient oxidative DNA cleavage. We are showing by experimental (cyclic voltammetry) and computational means (DFT) that the rational combination of O and S atoms next to two nitrogen donors within the macrocycle (oxathiacyclen complex CuL6) leads to the stabilization of both redox states. The complex thus exhibits the highest oxidative DNA cleavage activity within this family of cyclen-based Cu(II) complexes – without leaching of the metal ion during reduction

Ein neuer Thiolat‐gebundener Dimangan‐Cluster als strukturelles und funktionales Modell der Class Ib Ribonukleotidreduktasen

In Class Ib Ribonukleotidreduktasen (RNRs) aktiviert ein Dimangan(II)-Cluster Superoxid (O2⋅−) anstelle von molekularem Sauerstoff (O2), um eine hochvalente MnIII-O2-MnIV-Spezies zu bilden, die für die Oxidation von Tyrosin zum Tyrosyl-Radikal verantwortlich ist. Im vorliegenden biomimetischen Ansatz wird ein Thiolat-gebundener Dimangan-Komplex [MnII2(BPMT)(OAc)2](ClO)4 (BPMT=(2,6-Bis{[bis(2-pyridylmethyl)amino]methyl}-4-methylthiophenolat) (1) synthetisiert und dessen Reaktion mit O2⋅− zur Bildung des [(BPMT)MnO2Mn]2+-Komplexes 2 gezeigt. Resonanz-Raman-Untersuchungen zeigen das Vorliegen einer O-O-Bindung in 2, während die ESR-Analyse ein Signal bei g=2 mit 16 Linien für St=urn:x-wiley:00448249:media:ange202217076:ange202217076-math-0001 aufzeigt, das typischerweise mit einem MnIIIMnIV-Kern assoziiert wird, wie es auch in Class Ib RNR detektiert wurde. Anders als zuvor publizierte Mn-O2-Mn-Komplexe, die durch O2⋅−-Aktivierung an Mn2-Zentren gebildet wurden, ist 2 ein geeignetes elektrophiles Oxidationsmittel für Aldehyd-Deformylierungsreaktionen und Phenol-Oxidationsreaktionen, sodass es eines der besten strukturellen und funktionalen Modelle der Class Ib RNRs darstellt.Peer Reviewe

Beweis von Schwefel‐non‐Innocence in [CoII(Dithiacyclam)]2+‐vermittelten, katalytischen Sauerstoff‐Reduktions‐Reaktionen

In vielen Metallenzymen sind Schwefel-enthaltende Liganden an Elektronen-Transfer-Reaktionen beteiligt. In dem hier diskutierten biomimetischen Ansatz wird der Einfluss einer Schwefelkoordination auf eine Kobalt-katalysierte Sauerstoff-Reduktionsreaktion (ORR) demonstriert. Ein Vergleich des ORR-Vermögens eines vierfach Stickstoff-koordinierten [Co(Cyclam]2+-Komplexes (1; Cyclam=1,5,8,11-Tetraaza-cyclotetradecan) und dessen Schwefel-Analogons [Co(S2N2-Cyclam)]2+ (2; S2N2-Cyclam=1,8-Dithia-5,11-diazacyclotetradecan) zeigt verbesserte katalytische Eigenschaften mit dem in die Ligandensphäre am Kobalt eingeführten Chalkogen. Isolierung und Charakterisierung der Intermediate, die sich im Zuge der Sauerstoffaktivierung an den Kobalt(II)-Zentren von 1 und 2 bilden, identifizieren eine Beteiligung des Schwefels am O2-Reduktionsprozess als entscheidenden Faktor für die verbesserten Eigenschaften von 2 bei der katalytischen ORR.Peer Reviewe

A Clostridium difficile outbreak in an Italian hospital: the efficacy of the multi-disciplinary and multifaceted approach

Introduction: We described an outbreak of C. difficile that occurred in the Internal Medicine department of an Italian hospital and assessed the efficacy of the measures adopted to manage the outbreak.Methods: The outbreak involved 15 patients and was identified by means of continuous integrated microbiological surveillance, starting with laboratory data (alert organism surveillance).Diarrheal fecal samples from patients with suspected infection by C. difficile underwent rapid membrane immuno-enzymatic testing, which detects both the presence of the glutamate dehydrogenase antigen and the presence of the A and B toxins.Extensive microbiological sampling was carried out both before and after sanitation of the environment, in order to assess the efficacy of the sanitation procedure.Results: The outbreak lasted one and a half month, during which time the Committee for the Prevention of Hospital Infections ordered the implementation of multiple interventions, which enabled the outbreak to be controlled and the occurrence of new cases to be progressively prevented.The strategies adopted mainly involved patient isolation, reinforcement of proper hand hygiene techniques, antimicrobial stewardship and environmental decontamination by means of chlorine-based products. Moreover, the multifaceted management of the outbreak involved numerous sessions of instruction/training for nursing staff and socio-sanitary operatives during the outbreak.Sampling of environmental surfaces enabled two sites contaminated by C. difficile to be identified.Conclusions: Joint planning of multiple infection control practices, together with effective communication and collaboration between the Hospital Infections Committee and the ward involved proved to be successful in controlling the outbreak

Synthesis, Characterization, and Reactivity of a Series of Homo‐ and Hetero‐dinuclear Complexes based on an Asymmetric FloH Ligand System

In a previous communication we reported the site‐directed generation of a heterodinuclear FeIIICuII complex (1 ) by using an asymmetric dinucleating ligand FloH. The iron(III) ion was introduced first on the preferential metal‐binding site of the ligand that led to the formation of the thermodynamically favored five‐membered chelate ring upon metal‐binding. Copper(II) was introduced in the next step. The stepwise metalation strategy reported previously has now been extended to synthesize a series of heterodinuclear FeIIIMII [M = Mn (2 ), Fe (3 ), Co (4 ), and Ni (5 )] and FeIICuI (1a ) as well as the homodinuclear CuICuI (6 ) complexes. The complexes were characterized by X‐ray crystallography (except for 1a and 6 ), and by a limited number of spectroscopic methods. Complex 1 with a labile solvent binding site at FeIII reacted with H2O2 to form a transient intermediate that showed reactivity typical of metal peroxide complexes. The metal centers in the complexes 2 –5 are coordinatively saturated, and hence they showed no reactivity with H2O2. Complex 1a reacted with O2 via an intermolecular pathway to form a μ‐oxo bridged tetrameric complex 1b , which was structurally characterized. This is in contrast to the homodinuclear CuICuI and heme FeIICuI cores, which prefer an intramolecular pathway for O2 activation.Peer Reviewe

An All-Organic Photochemical Magnetic Switch with Bistable Spin States

Controlling the electronic spin state in single-molecules through an external stimulus is of interest in developing devices for information technology, such as data storage and quantum computing. We report the synthesis and operation mode of two all-organic molecular spin state switches that can be photochemically switched from a diamagnetic (EPR silent) to a paramagnetic (EPR active) form at cryogenic temperatures due to a reversible electrocyclic reaction of its carbon skeleton. Facile synthetic substitution of a configurationally stable 1,14-dimethyl-[5]helicene with radical stabilizing groups at the 4,11-positions afforded two spin state switches as 4,11-dioxo or 4,11-bis(dicyanomethylidenyl) derivatives in a closed diamagnetic form. After irradiation with an LED light source at cryogenic temperatures a stable paramagnetic state is readily obtained, rendering this system a bistable magnetic switch that can reversibly react back to its diamagnetic form through a thermal stimulus. The switching can be monitored with UV/Vis spectroscopy, EPR spectroscopy, or induced by electrochemical reduction and reoxidation. Variable-temperature EPR spectroscopy of the paramagnetic species revealed an open-shell triplet ground state with an experimentally determined triplet–singlet energy gap of < 0.1 kcal/mol. The inherent chirality and the ability to separate the enantiomers turns this helical motif into a potential chiroptical spin state switch. The herein developed 4,11-substitution pattern on the dimethyl[5]helicene introduces a platform for designing future generations of organic molecular photomagnetic switches that might find applications in spintronics and related fields

Imido Cobalt Complexes with Imidyl Character

We report on the synthesis of a variety of trigonal imido cobalt complexes [Co(NAryl)L2)–, (L = N(Dipp)SiMe3), Dipp = 2,6-diisopropylphenyl) bearing very long Co–NAryl bonds of around 1.75 Å. The electronic structure was interrogated using a variety of physical and spectroscopic methods indicating the first authenticated examples of cobalt bound imidyl species. Computational studies corroborate these findings and reveal that the high-spin state of these complexes gives rise to unpaired spin-density on the imide nitrogen and leads to its imidyl character. Obtained complexes are capable of intermolecular H atom abstraction from C–H bonds that yields the corresponding cobalt amides. Exchange of the Dipp-substituent on the imide by the smaller mesityl function (2,4,6-trimethylphenyl) effectuates the unexpected Me3Si shift from the ancillary ligand set to the imide nitrogen, followed by intramolecular C–H bond activation.<br /