Peroxynitrite (ONOO-) is a highly reactive nitrogen species that can cause significant damage to proteins, lipids, and DNA. Various enzymes, including metalloenzymes, play crucial roles in reducing ONOO- concentrations to protect cellular components. While the interaction of ONOO- with heme proteins is well known, the reduction by Cu-containing proteins is less studied. Amyloid precursor protein (APP), implicated in Alzheimer's disease, has an E2 domain that binds copper ions with a dissociation constant of KD similar to 10-12 M and is proposed to be involved in iron homeostasis, copper trafficking, and oxidative stress response. Our recent studies using EXAFS, UV-Vis, and EPR spectroscopy revealed a previously unidentified labile water ligand in the Cu(ii) site of the E2 domain, suggesting reactivity with anionic substrates like ONOO-. Experimental data showed that Cu(i)-E2 reduces ONOO- at a significant rate (1.1 x 105 M-1 s-1), comparable to native peroxynitrite scavengers, while maintaining active site integrity through multiple redox cycles. This study further investigates the mechanism of ONOO- reduction by Cu(i)-E2 using the Griess assay, demonstrating that reduction occurs via single electron transfer, forming nitrite and nitrate. This process aligns with previous findings that Cu(i)-E2 is oxidized to Cu(ii)-E2 upon ONOO- reduction. Mutations at Lys435, affecting secondary sphere interactions, revealed that factors beyond electrostatics are involved in substrate recruitment. MD simulations suggest that steric hindrance from a newly formed hydrogen bond also plays a role. Understanding ONOO- reduction by the E2 domain of APP expands our knowledge of copper proteins in mitigating oxidative stress and elucidates their physiological and pathological roles, particularly in Alzheimer's disease.

The bis-alkynyl complexes based on Fe-III(TIM) (TIM = 2,3,9,10-tetramethyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene) are reported herein. A modified synthesis of trans-[Fe(TIM)Cl-2]PF6 ([1]PF6) in a 90% yield was developed. The reaction between [1]PF6 and LiC2R (R = Ph, SiEt3, or (SiPr3)-Pr-i) resulted in the bis-alkynyl complexes, trans-[Fe(TIM)(C2R)(2)]PF6, in good yields, 43% for 2 (R = Ph), 29% for 3 (R = SiEt3), and 18% for 4 (R = (SiPr3)-Pr-i). X-ray diffraction studies yielded molecular structures of complexes 1-3, which feature a tightened Fe-N-4 coordination in comparison with analogous Fe(cyclam) complexes. Electron paramagnetic resonance studies confirmed that the complex ions [Fe(TIM)Cl-2](+) and [Fe(TIM)(C2R)(2)](+) are low-spin d(5) species with S = 1/2 ground states. Electronic absorption spectra of bis-alkynyl complexes 2-4 all feature intense LMCT (pi(C equivalent to C) -> d pi(Fe)) bands in the visible region, and the assignment was supported by the time-dependent density functional theory analysis. These complexes undergo multiple one-electron redox processes, and the first one-electron reduction is reversible in all four complexes and assigned as an Fe(+3/+2) couple. Spectroelectrochemical studies of 1 and 2 reveal that the first one-electron reduction leads to the emergence of intense metal-to-ligand charge transfer (d pi(Fe) -> pi*(alpha-diimine)) bands and the concurrent disappearance of the ligand-to-metal charge transfer bands.

Lanthanide (Ln) elements are critical materials that are typically extracted/mined together. Their separation by solvent extraction from acidic media is well known; however, there are few studies in basic media with carbonate anions. We investigated the complexation of Eu(III) and Tb(III) carbonates as solids and solutions in alkaline K2CO3, wherein we sought to access a Tb(IV) carbonate complex through ozonolysis. L3‐edge XANES of Eu and Tb carbonate solids, colorless solutions, and a red‐hued Tb solution (obtained by ozonolysis) all showed Ln(III) cations. The absence of evidence for a Tb(IV) complex was confirmed through XAS and EPR analyses, despite the solution exhibiting a deep red color. For solids and solutions, EXAFS results indicate molecular Ln(III)‐carbonato anions. In terms of the Eu(III) carbonate coordination number, the coordination does not change upon dissolution of the solid sample. Furthermore, EXAFS for the solutions revealed evidence for the association of potassium cations with the Ln(III)‐carbonato anions. This direct observation of contact ion pairing by EXAFS at room temperature is rare. The insights into Ln(III) carbonate complexation and solution speciation afforded by XANES‐EXAFS, FT‐IR, and EPR provides perspectives that serve as benchmarks for future computational and experimental efforts focused on caustic‐side solvent extraction of Ln(III) ions.

Stereochemical-controlled hydrogen bond donors play essential roles in the pharmaceutical industry. Consequently, organic molecules that bear difluoromethyl (CF2H) groups at chiral centers are emerging as pivotal components in pharmaceuticals due to their distinct hydrogenbonding property. However, a general approach for introducing CF2H groups in an enantioselective manner remained elusive. Here, we show that enantioconvergent difluoromethylation of racemic alkyl electrophiles, through alkyl radical intermediates, represents a new strategy for constructing CF2H-containing stereocenters. This strategy is enabled by using copper catalysts bound with a chiral diamine ligand bearing electron-deficient phenyl groups, and a nucleophilic difluoromethyl-zinc reagent. This method allows for the high-yield conversion of a diverse range of alkyl halides into their alkyl-CF2H analogs with excellent enantioselectivity (up to 99% e.e.). Mechanistic studies, supported by DFT calculations, revealed a route involving asymmetric difluoromethylation of alkyl radicals and crucial non-covalent interactions in the enantio-determining steps.

Stepwise oxidative addition of copper(I) complexes to form copper(III) species via single electron transfer (SET) events has been widely proposed in copper catalysis. However, direct observation and detailed investigation of these fundamental steps remain elusive owing largely to the typically slow oxidative addition rate of copper(I) complexes and the instability of the copper(III) species. We report herein a novel aryl-radical-enabled stepwise oxidative addition pathway that allows for the formation of well-defined alkyl-Cu-III species from Cu-I complexes. The process is enabled by the SET from a Cu-I species to an aryl diazonium salt to form a Cu-II species and an aryl radical. Subsequent iodine abstraction from an alkyl iodide by the aryl radical affords an alkyl radical, which then reacts with the Cu-II species to form the alkyl-Cu-III complex. The structure of resultant [(bpy)Cu-III(CF3)(2)(alkyl)] complexes has been characterized by NMR spectroscopy and X-ray crystallography. Competition experiments have revealed that the rate at which different alkyl iodides undergo oxidative addition is consistent with the rate of iodine abstraction by carbon-centered radicals. The Cu-II intermediate formed during the SET process has been identified as a four-coordinate complex, [Cu-II(CH3CN)(2)(CF3)(2)], through electronic paramagnetic resonance (EPR) studies. The catalytic relevance of the high-valent organo-Cu-III has been demonstrated by the C-C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis of these formal Cu-III complexes indicates inverted ligand fields in sigma(Cu-CH2) bonds. These results demonstrate the stepwise oxidative addition in copper catalysis and provide a general strategy to investigate the elusive formal Cu-III complexes.

The syntheses and characterization of Fe and Co complexes supported by a new tetra-imine macrocycle, TEIM (2,3,9,10-tetraethyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene), are reported. Templating with Co (OAc)2 & sdot;4H2O yielded trans-[Co(TEIM)Cl 2 ][PF 6 ] (1a), which was converted to trans-[Co(TEIM)X 2 ][PF 6 ] (X = N3 (2a) and NO2 (3a)) through reactions with NaX (X = N3 or NO2). Templating with Fe generated trans-[Fe(TEIM) (NCCH3)2][PF6]2, which was oxidized to trans-[Fe(TEIM)Cl 2 ][PF 6 ] (1b). The reaction of 1b with NaN3 formed [Fe(TEIM)(N3)2][PF6] (2b) while the reaction with [Fe(TEIM)(NCCH3)2][PF6]2 and NaNO2 yielded trans-[Fe (TEIM)(NO2)2] (3b). Single crystal X-ray diffraction studies revealed a pseudo-octahedral geometry around the Co / Fe centers with the ethyl groups oriented above or below the plane of the TEIM ring. The absorption spectra of 1b displays weak charge transfer bands near the UV to visible region, while 2b and 3b displayed intense charge transfer bands within the visible region. Cyclic voltammograms of 1a revealed four 1 e- reductions while those of 2a and 3a display only three cathodically shifted reductions. Analogous studies of 1b and 2b revealed two 1 e- reductions while 3b displays only an oxidation event. EPR studies of ferric complexes 1b and 2b indicated a low spin d 5 electronic figuration with S = 1 / 2 ground state.

A family of cerium complexes featuring a redox-active ligand in different oxidation states has been synthesized, including the the iminosemiquinone (isq)1- compound, Ce(dippisq)3 (1-Ceisq), and the amidophenolate (ap)2- species CeIII(dippap)3K3 (2-Ceap), [CeIII(dippap)3K][K(18-c-6)]2 (2-Ceap 18c6), and [CeIII(dippap)3K][K(15-c-5)2]2 (2-Ceap 15c5). Treating 2-Ceap 15c5 with dioxogen furnishes the cerium(IV) derivative [CeIV(dippap)3][K(15-c-5)2]2 (3-Ceap 15c5), and an analogous synthesis can be used to generate [CeIV(dippap)3][K(crypt)]2 (3-Ceap crypt). Similarly, addition of hexamethyldisiloxane produces an interesting bis(amidophenolate) species, [(Me3SiO)2CeIV(dippap)2][K(15-c-5)2]2 (4-CeOSiMe3). Full spectroscopic and structural characterization of each derivative was performed to establish the oxidation states of both the ligands and the cerium ions. Cerium(III) complexes with redox-active ligands in oxidation states L1- and L2- have been synthesized and fully characterized. Multielectron movement has been achieved by redox chemistry at the ligands. Sequestering counterions also introduces exciting reactivity, forming Ce(IV) species with dioxygen and oxidative addition of hexamethyldisiloxane to form a bis(siloxide) cerium(IV) species. image

Amyloid precursor protein (APP) is the biological precursor of β-amyloids, a known histopathological hallmark associated with Alzheimer's disease (AD). The function of APP is of great interest yet remains elusive. One of the extracellular domains of APP, the E2 domain, has been proposed to possess ferroxidase activity and affect neuronal iron homeostasis. However, contradicting evidence has been reported, and its precise role remains inconclusive. Here, we studied the Cu-binding site of the E2 domain using extended X-ray absorption fine structure (EXAFS), UV-vis, and electron paramagnetic resonance (EPR) and discovered that a new labile water ligand coordinates to the Cu(II) cofactor in addition to the four known histidines. We explored the proposed ferroxidase activity of the Cu(II)-E2 domain through reactions with ferrous iron and observed single-turnover ferrous oxidation activity with a rate up to 1.0 × 102 M-1 s-1. Cu(I)-E2 reacted with molecular oxygen at a rate of only 5.3 M-1 s-1, which would restrict any potential multiturnover ferroxidase activity to this slow rate and prevents observation of activity under multiturnover conditions. The positive electrostatic potential surface of the protein indicates possible reactivity with negatively charged small substrates such as superoxide radicals (O2•-) and peroxynitrite (ONOO-) that are major contributors to the oxidative stress prevalent in the extracellular environment. Our assays showed that Cu(I)-E2 can remove O2•- at a rate of 1.6 × 105 M-1 s-1, which is slower than the rates of native SODs. However, the reaction between Cu(I)-E2 and ONOO- achieved a rate of 1.1 × 105 M-1 s-1, comparable to native ONOO- scavenger peroxiredoxins (105-107 M-1 s-1). Therefore, the E2 domain of APP can serve as an enzymatic site that may function as a ferroxidase under substrate-limiting conditions, a supplemental O2•- scavenger, and an ONOO- remover in the vicinity of the cellular iron efflux channel and protect neuron cells from reactive oxygen species (ROS) and reactive nitrogen species (RNS) damage.

Plants associated with traditional forms of coppice management are affected by changes in, or cessation of, stand management which produce differences in structure, usually in the direction of high forest. The habitat structure, ground flora richness, and composition of an ancient woodland in southern England were compared across three distinct management treatments: traditional Coppice (the cyclical cutting of underwood on rotations), Limited Intervention (representing the effective cessation of management), and Irregular High Forest silviculture (a form of continuous cover forestry using single and small group selective tree harvesting). Coppice and Irregular silviculture showed a more complex woody stand structure whereas Limited Intervention was strongly correlated with closed-canopy, single-storied structures and no developing understorey. Increased bramble Rubus fruticosus cover was strongly associated with Irregular silviculture, bare ground mostly with the limited intervention closed-canopy stands. Distinct plant-habitat associations were identified across stand management types with the greatest differences between Limited Intervention and the two active interventions. Overall vascular plant species and Coppice group species were lowest in Limited Intervention stands. Using ancient woodland indicator and Coppice plant species and groups, we found a similar community pattern between Coppice and Irregular silviculture. More ancient woodland species were accommodated within the comparatively heterogenous woodland habitat associated with active silvicultural interventions of Coppice and Irregular High Forest management. The study indicates that the introduction of Irregular silviculture as practiced here can conserve most ancient woodland and Coppice plants associated with traditional coppicing, a practice which has declined significantly in the UK since the late 19th Century.

The complexes [FeIII(HMC)(C2DMA)2]CF3SO3 ([2]OTf) and [FeIII(HMTI)(C2Y)2]CF3SO3 ([3a-c]OTf) have been prepared and thoroughly characterized (HMC = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; HMTI = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-1,3,8,10-tetraene; Y = Fc (ferrocenyl, [3a]OTf), 4-(N,N-dimethyl)anilino (DMA, [3b]OTf), or 4-(N,N-bis(4-methoxyphenyl)anilino (TPA, [3c]OTf); OTf- = CF3SO3-)). Vibrational and electronic absorption spectroelectrochemical analyses following one-electron oxidation of the ethynyl substituent Y revealed evidence of strong coupling in the resultant mixed valent species for all HMTI-based complexes. However, the analogous mixed valent ion based on [2]OTf appeared to be more localized. Thus, the tetra-imino macrocycle HMTI has enabled significant valence delocalization along the -C2-FeIII-C2- bridge. Electron paramagnetic resonance and Mössbauer spectroscopic studies of [3b]OTf reveal that the π-acidity of HMTI lowers the energy of the FeIII dπ orbitals compared to the purely σ-donating HMC. This observation provides a basis for the interpretation of the macrocycle-dependent valence (de)localization.

The first non-uranyl, f-element oxo complex synthesized from dioxygen in dry air is presented in this work. The synthesis was accomplished by treating the redox-active thorium amidophenolate complex, [Th(dippap)3][K(15-c-5)2]2 (1-ap crown), with dioxygen in dry air, forming a rare terminal thorium oxo, [O═Th(dippisq)2(dippap)][K(15-c-5)2]2 (2-oxo). Compound 1-ap crown was regenerated by treating 2-oxo with potassium graphite. X-ray crystallography of 2-oxo revealed a comparatively longer bond length for the thorium-oxygen double bond when compared to other thorium oxos. As such, several thorium-oxygen single bonds were synthesized for comparison, including Th(dippisq)2(OSiMe3)2(THF) (4-OSiMe3), Th(OSiMe3)4(bipy)2 (5-OSiMe3), and [Th(OH)2 (dippHap)4][K(15-c-5)2]2 (6-OH). Full spectroscopic and structural characterization of the complexes was performed via 1H NMR spectroscopy, X-ray crystallography, EPR spectroscopy, and electronic absorption spectroscopy as well as SQUID magnetometry, which all confirmed the electronic structure of these complexes.

Changing economics in the 20th century led to losses and fragmentation of semi-natural woodland in Britain and to a reduction in active woodland management with many becoming increasingly neglected, even-aged and with closed canopy. Lack of woodland management is known to contribute to declines in some taxonomic groups, for example birds. However, the response of bats to changes in woodland structure are poorly understood. We compared two measures of bat activity, derived from static acoustic recorders across 120 sample plots in coppice, irregular high forest (uneven-aged, continuous cover) and limited intervention (under-managed, even-aged) management stands, within a large tract of ancient woodland in southern England. Bat species richness was highest in irregular high forest stands, and there were significant differences in occupancy rates for most bat species across stand management types. Coppice recorded low activity of several bat species and irregular high forest showed high occupancy rates, including for Barbastelle Barbastella barbastellus, which is IUCN listed as near threatened. The occupancy rates in stand management types differed for some bat species between mid- and late summer counts, suggesting seasonal variation in habitat use. Within stands, most bat species were associated with opened canopy, lower growing stocks and reduced densities of understorey, and to a lesser extent, with large-girthed trees and presence of deadwood snags. In some cases, species responded to a given habitat variable similarly across the three stand management types, whereas in others, the response differed among stand management types. For example, increased numbers of large-girthed trees benefitted a number of bat species within coppice where these were least common, but not in irregular stands. Irregular silviculture high forest appears to provide many of the structural attributes that positively influence occupancy of several woodland bat species, including Barbastella barbastellus.