A π-extended ß-diketiminate ligand via a templated Scholl approach.

We report a templated Scholl oxidation strategy for the preparation of the first ß-diketiminate (BDI) ligands embedded within a 24-electron π-system backbone. The resulting benzo[f,g]tetracene BDI ligand was coordinated to a zinc centre and electrochemical studies showed the redox active nature of the ligand.

Coordination of a Phosphine-Tethered Aminoborane to Group 10 Metals.

While π-complexes of C=C bonds are ubiquitous in organometallic chemistry, analogous complexes of the isoelectronic but strongly polarized B=N double bond of aminoboranes are extremely scarce. To address this gap, a diphosphine-aminoborane ligand (PhDPBAiPr) is introduced and its coordination with group 10 metals is investigated. The B=N bond does not coordinate to the metal in Pt(0) and Pd(II) complexes. In contrast, side-on coordination of the B=N bond is observed in the Ni(0) complex (PhDPBAiPr)Ni(NCPh), and the X-ray crystal structure reveals B-N bond elongation compared to the free ligand. The choice of co-ligand strongly influences the presence or absence of side-on coordination at Ni(0) as evidenced by NMR spectroscopy. While the B=N π-complex is geometrically similar to C=C analogues, a bonding analysis reveals that the interaction of the B=N motif with the electron-rich Ni(0) center is best described as 3c4e hyperbond, in which Ni and N are competing for the empty orbital on B.

Understanding the Remarkable Stability of Well-Defined Dinuclear Copper(I) Carbene Complexes.

The synthesis of a well-defined dicopper carbene complex supported by the PNNP (2,7-bis(di-tert-butylphosphaneyl)methyl-1,8-naphthyridine) expanded pincer ligand is reported. This carbene complex is remarkably stable, even in the presence of air and water. The reactivity of this complex was explored towards typical carbene transfer substrates and its electronic structure was investigated. Using a combination of experiments and DFT calculations, the principles that underly the stability of dinuclear carbene complexes are probed.

Pendulum-like hemilability in a Ti-based frustrated Lewis Trio.

We describe the first experimental example of a theoretically predicted Frustrated Lewis Trio (FLT). A tetradentate PNNP ligand is used to stabilise a highly electrophilic [TiCl3]+ fragment in a way that results in two equally long and frustrated Ti-P bonds. A combined experimental and computational approach revealed a distinct role of each Lewis basic phosphine in the heterolytic activation of chemical bonds. This dual functionality is characterised by a pendulum-like hemilability, where one of the phosphines acts as a nucleophile while the other serves as a hemilabile ligand that dynamically tunes the Ti-P distance as a function of the required electron density at the Ti centre.

Reactivity of Nickel Complexes Bearing P(C=X)P Ligands (X = O, N) Toward Diazoalkanes: Evidence for Phosphorus Ylide Intermediates.

Nickel carbenes are attracting attention for the development of more sustainable catalysts, among others, for cyclopropanation. Intramolecular trapping of a nickel carbene intermediate with an olefin incorporated in a P(C=C)P Ni pincer complex had previously allowed the isolation of a nickelacyclobutane intermediate and a detailed characterization of its reactivity. Herein, we report the reactivity of related nickel pincer complexes bearing a ketone P(C=O)P or an imine P(C=N)P with diazoalkanes as the carbene precursor. The observed reactivity suggests, in both cases, the reaction of the transient nickel carbene with one of the phosphine arms to form phosphorus ylides that subsequently react with the unsaturated backbone. Density functional theory (DFT) calculations are used to shed light on the mechanisms of these reactions.

Polar X-H Bond (X=O, S, N) Activation at a Cage Silanide.

Low-valent silicon compounds such as neutral silylenes display versatile reactivity for the activation of small molecules. In contrast, their anionic congeners silanides ([R3 Si- ]) have primarily been investigated for their nucleophilic reactivity. Here we show that incorporating a silanide center in a bicyclic cage structure allows for formal oxidative addition of polar element-hydrogen bonds (RX-H, R=aromatic residue, X=O, S, NH). The resulting hydrosilicates were isolated and characterized structurally and spectroscopically. Density Functional Theory (DFT) calculations and experimental observations support an ionic mechanism for RX-H bond activation. Finally, the reactivity of the RS-H bond adduct was further investigated, revealing that it behaves as a Lewis pair upon facile heterolytic cleavage of the Si-S bond.

Cooperative H2 activation at a nickel(0)-olefin centre.

Catalytic olefin hydrogenation is ubiquitous in organic synthesis. In most proposed homogeneous catalytic cycles, reactive M-H bonds are generated either by oxidative addition of H2 to a metal centre or by deprotonation of a non-classical metal dihydrogen (M-H2) intermediate. Here we provide evidence for an alternative H2-activation mechanism that instead involves direct ligand-to-ligand hydrogen transfer (LLHT) from a metal-bound H2 molecule to a metal-coordinated olefin. An unusual pincer ligand that features two phosphine ligands and a central olefin supports the formation of a non-classical Ni-H2 complex and the Ni(alkyl)(hydrido) product of LLHT, in rapid equilibrium with dissolved H2. The usefulness of this cooperative H2-activation mechanism for catalysis is demonstrated in the semihydrogenation of diphenylacetylene. Experimental and computational mechanistic investigations support the central role of LLHT for H2 activation and catalytic semihydrogenation. The product distribution obtained is largely determined by the competition between (E)-(Z) isomerization and catalyst degradation by self-hydrogenation.

Synthesis, Structure and Reactivity of a Mononuclear N,N,O-Bound Fe(II) α-Keto-Acid Complex.

A bulky, tridentate phenolate ligand (ImPh2 NNOtBu ) was used to synthesise the first example of a mononuclear, facial, N,N,O-bound iron(II) benzoylformate complex, [Fe(ImPh2 NNOtBu )(BF)] (2). The X-ray crystal structure of 2 reveals that the iron centre is pentacoordinate (τ=0.5), with a vacant site located cis to the bidentate BF ligand. The Mössbauer parameters of 2 are consistent with high-spin iron(II), and are very close to those reported for α-ketoglutarate-bound non-heme iron enzyme active sites. According to NMR and UV-vis spectroscopies, the structural integrity of 2 is retained in both coordinating and non-coordinating solvents. Cyclic voltammetry studies show that the iron centre has a very low oxidation potential and is more prone to electrochemical oxidation than the redox-active phenolate ligand. Complex 2 reacts with NO to form a S=3 /2 {FeNO}7 adduct in which NO binds directly to the iron centre, according to EPR, UV-vis, IR spectroscopies and DFT analysis. Upon O2 exposure, 2 undergoes oxidative decarboxylation to form a diiron(III) benzoate complex, [Fe2 (ImPh2 NNOtBu )2 (µ2 -OBz)(µ2 -OH)2 ]+ (3). A small amount of hydroxylated ligand was also observed by ESI-MS, hinting at the formation of a high-valent iron(IV)-oxo intermediate. Initial reactivity studies show that 2 is capable of oxygen atom transfer reactivity with O2 , converting methyl(p-tolyl)sulfide to sulfoxide.

Reactions of Nickel(0)-Olefin Pincer Complexes with Terminal Alkynes: Cooperative C-H Bond Activation and Alkyne Coupling.

Metal-ligand cooperation can facilitate the activation of chemical bonds, opening reaction pathways of interest for catalyst development. In this context, olefins occupying the central position of a diphosphine pincer ligand (PC=CP) are emerging as reversible H atom acceptors, e.g., for H2 activation. Here, we report on the reactivity of nickel complexes of PC=CP ligands with a terminal alkyne, for which two competing pathways are observed. First, cooperative and reversible C-H bond activation generates a Ni(II) alkyl/alkynyl complex as the kinetic product. Second, in the absence of a bulky substituent on the olefin, two alkyne molecules are incorporated in the ligand structure to form a conjugated triene bound to Ni(0). The mechanisms of these processes are studied by density functional theory calculations supported by experimental observations.

Efficient synthesis of fully renewable, furfural-derived building blocks via formal Diels-Alder cycloaddition of atypical addends.

Diels-Alder (DA) cycloaddition of furanics is emerging as a key transformation in circular chemistry, providing access to highly versatile, biobased platform molecules. Further development of this technology into viable industrial applications faces major challenges, a notorious one being the lack of reactivity of the most readily available furans, i.e. the furfural derivatives. Herein we describe the remarkably-facile intramolecular DA reaction of allyl acetals of different furfurals to efficiently afford formal DA adducts with the atypical, unreactive dienophile allyl alcohol. Our methodology gives access to unprecedented oxanorbornene derivatives in high chemo-, regio- and stereoselectivity, which can be readily diversified into valuable products. This offers the potential of scalable production of renewable chemical building blocks from cheap, bioderived platform molecules.

Homoleptic Fe(III) and Fe(IV) Complexes of a Dianionic C3-Symmetric Scorpionate.

High-valent iron species have been implicated as key intermediates in catalytic oxidation reactions, both in biological and synthetic systems. Many heteroleptic Fe(IV) complexes have now been prepared and characterized, especially using strongly π-donating oxo, imido, or nitrido ligands. On the other hand, homoleptic examples are scarce. Herein, we investigate the redox chemistry of iron complexes of the dianonic tris-skatylmethylphosphonium (TSMP2-) scorpionate ligand. One-electron oxidation of the tetrahedral, bis-ligated [(TSMP)2FeII]2- leads to the octahedral [(TSMP)2FeIII]-. The latter undergoes thermal spin-cross-over both in the solid state and solution, which we characterize using superconducting quantum inference device (SQUID), Evans method, and paramagnetic nuclear magnetic resonance spectroscopy. Furthermore, [(TSMP)2FeIII]- can be reversibly oxidized to the stable high-valent [(TSMP)2FeIV]0 complex. We use a variety of electrochemical, spectroscopic, and computational techniques as well as SQUID magnetometry to establish a triplet (S = 1) ground state with a metal-centered oxidation and little spin delocalization on the ligand. The complex also has a fairly isotropic g-tensor (giso = 1.97) combined with a positive zero-field splitting (ZFS) parameter D (+19.1 cm-1) and very low rhombicity, in agreement with quantum chemical calculations. This thorough spectroscopic characterization contributes to a general understanding of octahedral Fe(IV) complexes.

Crystal structure of the second extracellular domain of human tetraspanin CD9: twinning and diffuse scattering.

Remarkable features are reported in the diffraction pattern produced by a crystal of the second extracellular domain of tetraspanin CD9 (deemed CD9EC2), the structure of which has been described previously [Oosterheert et al. (2020 ▸), Life Sci. Alliance, 3, e202000883]. CD9EC2 crystallized in space group P1 and was twinned. Two types of diffuse streaks are observed. The stronger diffuse streaks are related to the twinning and occur in the direction perpendicular to the twinning interface. It is concluded that the twin domains scatter coherently as both Bragg reflections and diffuse streaks are seen. The weaker streaks along c* are unrelated to the twinning but are caused by intermittent layers of non-crystallographic symmetry related molecules. It is envisaged that the raw diffraction images could be very useful for methods developers trying to remove the diffuse scattering to extract accurate Bragg intensities or using it to model the effect of packing disorder on the molecular structure.

The greatest air quality experiment ever: Policy suggestions from the COVID-19 lockdown in twelve European cities.

COVID-19 (Coronavirus disease 2019) hit Europe in January 2020. By March, Europe was the active centre of the pandemic. As a result, widespread "lockdown" measures were enforced across the various European countries, even if to a different extent. Such actions caused a dramatic reduction, especially in road traffic. This event can be considered the most significant experiment ever conducted in Europe to assess the impact of a massive switch-off of atmospheric pollutant sources. In this study, we focus on in situ concentration data of the main atmospheric pollutants measured in twelve European cities, characterized by different climatology, emission sources, and strengths. We propose a methodology for the fair comparison of the impact of lockdown measures considering the non-stationarity of meteorological conditions and emissions, which are progressively declining due to the adoption of stricter air quality measures. The analysis of these unmatched circumstances allowed us to estimate the impact of a nearly zero-emission urban transport scenario on air quality in 12 European cities. The clearest result, common to all the cities, is that a dramatic traffic reduction effectively reduces NO2 concentrations. In contrast, each city's PM and ozone concentrations can respond differently to the same type of emission reduction measure. From the policy point of view, these findings suggest that measures targeting urban traffic alone may not be the only effective option for improving air quality in cities.

E-selective Semi-hydrogenation of Alkynes under Mild Conditions by a Diruthenium Hydride Complex.

The synthesis, characterization and catalytic activity of a new class of diruthenium hydrido carbonyl complexes bound to the tBu PNNP expanded pincer ligand is described. Reacting tBu PNNP with two equiv of RuHCl(PPh3 )3 (CO) at 140 °C produces an insoluble air-stable complex, which was structurally characterized as [Ru2 (tBu PNNP)H(µ-H)Cl(µ-Cl)(CO)2 ] (1) using solid-state NMR, IR and X-ray absorption spectroscopies and follow-up reactivity. A reaction with KOtBu results in deprotonation of a methylene linker to produce [Ru2 (tBu PNNP* )H(µ-H)(µ-OtBu)(CO)2 ] (3) featuring a partially dearomatized naphthyridine core. This enables metal-ligand cooperative activation of H2 analogous to the mononuclear analogue, [Ru(tBu PNP*)H(CO)]. In contrast to the mononuclear system, the bimetallic analogue 3 catalyzes the E-selective semi-hydrogenation of alkynes at ambient temperature and atmospheric H2 pressure with good functional group tolerance. Monitoring the semi-hydrogenation of diphenylacetylene by 1 H NMR spectroscopy shows the intermediacy of Z-stilbene, which is subsequently isomerized to the E-isomer. Initial findings into the mode of action of this system are provided, including the spectroscopic characterization of a polyhydride intermediate and the isolation of a deactivated species with a partially hydrogenated naphthyridine backbone.

Motor evoked potentials versus Macrostimulation in predicting the postoperative motor threshold in STN Deep brain stimulation.

INTRODUCTION: Accuracy is crucial in Deep Brain Stimulation (DBS). Electrophysiological and image-based techniques are used to avoid suboptimal positioning. Macrostimulation is the gold standard to delineate the therapeutic window intraoperatively. Despite this, electrode revision rates due to malpositioning are as high as 17%. The goal was to compare motor evoked potentials (MEPs) with the gold standard of Macrostimulation. We assessed accuracy and precision as well as the correlation in predicting motor side effects at the initial mapping 4 weeks postoperatively. METHODS: In this prospective study intraoperative MEPs from 94 contacts in 16 patients undergoing STN DBS under local anesthesia were correlated to the postoperative threshold for stimulation-induced motor side effects and compared to intraoperative Macrostimulation. Analysis of accuracy, precision and correlation (Pearson) was performed. RESULTS: MEPs of the upper extremity had a mean percentage error of 25% (SD 38.8%) and correlated significantly with the motor threshold at postoperative mapping (R=0.235). Macrostimulation was less accurate and precise with a mean percentage error of - 68% (SD 78.8%) but had a higher correlation (R=0.388). MEPs rarely (3%) overestimated the threshold by maximally 1 mA. In contrast, Macrostimulation overestimated the threshold by over 1 mA in 69% leading to a false sense of security. CONCLUSION: MEPs are feasible in an awake setting during Deep Brain Stimulation in the STN for PD patients. MEPs of the upper extremity are more accurate and precise predicting the motor threshold and avoid a false sense of security in comparison to the gold standard of Macrostimulation.

Mechanistic insights into the C55-P targeting lipopeptide antibiotics revealed by structure-activity studies and high-resolution crystal structures.

The continued rise of antibiotic resistance is a global concern that threatens to undermine many aspects of modern medical practice. Key to addressing this threat is the discovery and development of new antibiotics that operate by unexploited modes of action. The so-called calcium-dependent lipopeptide antibiotics (CDAs) are an important emerging class of natural products that provides a source of new antibiotic agents rich in structural and mechanistic diversity. Notable in this regard is the subset of CDAs comprising the laspartomycins and amphomycins/friulimicins that specifically target the bacterial cell wall precursor undecaprenyl phosphate (C55-P). In this study we describe the design and synthesis of new C55-P-targeting CDAs with structural features drawn from both the laspartomycin and amphomycin/friulimicin classes. Assessment of these lipopeptides revealed previously unknown and surprisingly subtle structural features that are required for antibacterial activity. High-resolution crystal structures further indicate that the amphomycin/friulimicin-like lipopeptides adopt a unique crystal packing that governs their interaction with C55-P and provides an explanation for their antibacterial effect. In addition, live-cell microscopy studies provide further insights into the biological activity of the C55-P targeting CDAs highlighting their unique mechanism of action relative to the clinically used CDA daptomycin.

A Well-Defined Anionic Dicopper(I) Monohydride Complex that Reacts like a Cluster.

Low-nuclearity copper hydrides are rare and few well-defined dicopper hydrides have been reported. Herein, we describe the first example of a structurally characterized anionic dicopper hydride complex. This complex does not display typical reactivity associated with low-nuclearity copper hydrides, such as alcoholysis or insertion reactions. Instead, its stoichiometric and catalytic reactivity is akin to that of copper hydride clusters. The distinct reactivity is ascribed to the robust dinuclear core that is bound tightly within the dinucleating ligand scaffold.

Combining metal-metal cooperativity, metal-ligand cooperativity and chemical non-innocence in diiron carbonyl complexes.

Several metalloenzymes, including [FeFe]-hydrogenase, employ cofactors wherein multiple metal atoms work together with surrounding ligands that mediate heterolytic and concerted proton-electron transfer (CPET) bond activation steps. Herein, we report a new dinucleating PNNP expanded pincer ligand, which can bind two low-valent iron atoms in close proximity to enable metal-metal cooperativity (MMC). In addition, reversible partial dearomatization of the ligand's naphthyridine core enables both heterolytic metal-ligand cooperativity (MLC) and chemical non-innocence through CPET steps. Thermochemical and computational studies show how a change in ligand binding mode can lower the bond dissociation free energy of ligand C(sp3)-H bonds by ∼25 kcal mol-1. H-atom abstraction enabled trapping of an unstable intermediate, which undergoes facile loss of two carbonyl ligands to form an unusual paramagnetic (S = ) complex containing a mixed-valent iron(0)-iron(i) core bound within a partially dearomatized PNNP ligand. Finally, cyclic voltammetry experiments showed that these diiron complexes show catalytic activity for the electrochemical hydrogen evolution reaction. This work presents the first example of a ligand system that enables MMC, heterolytic MLC and chemical non-innocence, thereby providing important insights and opportunities for the development of bimetallic systems that exploit these features to enable new (catalytic) reactivity.

The Ruthenium Nitrosyl Moiety in Clusters: Trinuclear Linear µ-Hydroxido Magnesium(II)-Diruthenium(II), µ3-Oxido Trinuclear Diiron(III)-Ruthenium(II), and Tetranuclear µ4-Oxido Trigallium(III)-Ruthenium(II) Complexes.

The ruthenium nitrosyl moiety, {RuNO}6, is important as a potential releasing agent of nitric oxide and is of inherent interest in coordination chemistry. Typically, {RuNO}6 is found in mononuclear complexes. Herein we describe the synthesis and characterization of several multimetal cluster complexes that contain this unit. Specifically, the heterotrinuclear µ3-oxido clusters [Fe2RuCl4(µ3-O)(µ-OMe)(µ-pz)2(NO)(Hpz)2] (6) and [Fe2RuCl3(µ3-O)(µ-OMe)(µ-pz)3(MeOH)(NO)(Hpz)][Fe2RuCl3(µ3-O)(µ-OMe)(µ-pz)3(DMF)(NO)(Hpz)] (7·MeOH·2H2O) and the heterotetranuclear µ4-oxido complex [Ga3RuCl3(µ4-O)(µ-OMe)3(µ-pz)4(NO)] (8) were prepared from trans-[Ru(OH)(NO)(Hpz)4]Cl2 (5), which itself was prepared via acidic hydrolysis of the linear heterotrinuclear complex {[Ru(µ-OH)(µ-pz)2(pz)(NO)(Hpz)]2Mg} (4). Complex 4 was synthesized from the mononuclear Ru complexes (H2pz)[trans-RuCl4(Hpz)2] (1), trans-[RuCl2(Hpz)4]Cl (2), and trans-[RuCl2(Hpz)4] (3). The new compounds 4-8 were all characterized by elemental analysis, ESI mass spectrometry, IR, UV-vis, and 1H NMR spectroscopy, and single-crystal X-ray diffraction, with complexes 6 and 7 being characterized also by temperature-dependent magnetic susceptibility measurements and Mössbauer spectroscopy. Magnetometry indicated a strong antiferromagnetic interaction between paramagnetic centers in 6 and 7. The ability of 4 and 6-8 to form linkage isomers and release NO upon irradiation in the solid state was investigated by IR spectroscopy. A theoretical investigation of the electronic structure of 6 by DFT and ab initio CASSCF/NEVPT2 calculations indicated a redox-noninnocent behavior of the NO ancillary ligand in 6, which was also manifested in TD-DFT calculations of its electronic absorption spectrum. The electronic structure of 6 was also studied by an X-ray charge density analysis.

Low emission zones reduced PM10 but not NO2 concentrations in Berlin and Munich, Germany.

Low emission zones (LEZs) aiming at improving the air quality in urban areas have been implemented in many European cities. However, studies are limited in evaluating the effects of LEZ, and most of which used simple methods. In this study, a general additive mixed model was utilized to account for confounders in the atmosphere and validate the effects of LEZ on PM10 and NO2 concentrations in two German cities. In addition, the effects of LEZ on elemental carbon (EC) and total carbon (TC) in Berlin were also evaluated. The LEZ effects were estimated after taking into account air pollutant concentrations at a reference site located in the regional background, and adjusting for hour of the week, public holidays, season, and wind direction. The LEZ in Berlin, and the LEZ in combination with the heavy-duty vehicle (HDV) transit ban in Munich significantly reduced the PM10 concentrations, at both traffic sites (TS) and urban background sites (UB). The effects were greater in LEZ stage 3 than in LEZ stages 2 and 1. Moreover, compared with PM10, LEZ was more efficient in reducing EC, a component that is considered more toxic than PM10 mass. In contrast, the LEZ had no consistent effect on NO2 levels: no effects were observed in Berlin; in Munich, the combination of the LEZ and the HDV transit ban reduced NO2 at UB site in LEZ stage 1, but without further reductions in subsequent stages of the LEZ. Overall, our study indicated that LEZs, which target the major primary air pollution source in the highly populated city center could be an effective way to improve urban air quality such as PM mass concentration and EC level.