Catalytically Relevant Organocopper(III) Complexes Formed through Aryl-Radical-Enabled Oxidative Addition.

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-CuIII species from CuI complexes. The process is enabled by the SET from a CuI species to an aryl diazonium salt to form a CuII 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 CuII species to form the alkyl-CuIII complex. The structure of resultant [(bpy)CuIII(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 CuII intermediate formed during the SET process has been identified as a four-coordinate complex, [CuII(CH3CN)2(CF3)2], through electronic paramagnetic resonance (EPR) studies. The catalytic relevance of the high-valent organo-CuIII has been demonstrated by the C-C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis of these formal CuIII complexes indicates inverted ligand fields in σ(Cu-CH2) bonds. These results demonstrate the stepwise oxidative addition in copper catalysis and provide a general strategy to investigate the elusive formal CuIII complexes.

Enabling Valence Delocalization in Iron(III) Macrocyclic Complexes through Ring Unsaturation.

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.

Revisit the E2 Domain of Amyloid Precursor Protein: Ferroxidase, Superoxide and Peroxynitrite Scavenging Activities.

Amyloid precursor protein (APP) is the biological precursor of ß-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.

Actinide-Oxygen Multiple Bonds from Air: Synthesis and Characterization of a Thorium Oxo Supported by Redox-Active Ligands.

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.