Redox-active ligand uranium complexes for approaches to multi-electron chemistry

While transition metal complexes are known to participate in multi-electron redox chemistry to facilitate important organometallic transformations, actinides, due to their low redox potentials, have a propensity to perform single electron chemistry. Because of its highly reducing nature, the ability to control the electronics of low-valent uranium is highly sought after as this may lead to unprecedented reactivity. Our lab has specifically been interested in mediating multi-electron transformations at uranium by employing redox-active ligands. Redox-active ligands can be used to facilitate multi-electron processes such as oxidative addition and reductive elimination at single metal centers. Using primarily 2,6-((Mes)N=CMe)2C5H3N) ( MesPDIMe) as a redox-active ligand, highly reduced uranium species bearing bulky cyclopentadienyl-based ancillary ligands, CpxU (MesPDIMe)(L) (x = P (1-(7,7-dimethylbenzyl)), * (1,2,3,4,5-pentamethyl); L = THF, HMPA), have been synthesized. These species have the ability to perform one, two, and four electron reduction of a variety of substrates. For examples, uranium mediated pinacol coupling of carbonylated substrates as well as oxidative addition toward two (X2, PhE-EPh, PhE-X) and four electron (Ar-N=N-Ar’, oxygen-atom transfer reagents) organic oxidants have been studied. with both radical and concerted addition pathways operable. Synthesis of a trans-dioxo species, Cp*UO2(MesPDIMe), has allowed for the study of the activation of the robust U=O double bonds—providing key insights into the necessary components for U=O bond scission. The lessons learned from the reductive silylation of this complex redox-active ligand species has allowed for application of these principles to simple UO 22+ systems

Exploration of a Unique Uranium Mediated Carbon-Carbon Radical Coupling Reaction

Designing an efficient nuclear fuel cycle has motivated decades of research on aqueous phase uranium chemistry. As such, studies are often limited by the formation of unreactive uranium oxides and/or solubility issues. Carrying out reactions in non-aqueous solvents addresses said problems and enables explorations into previously unattainable reactivity and fundamental properties of uranium. One such feat is the syntheses of uranium alkyls, as they permit research into bond interactions between uranium and carbon. Considering uranium’s oxophilicity, we investigated the relatively understudied uranium(III) alkyls—both their reactivity and reaction mechanism—towards oxygen-containing reagents. In an inert atmosphere, various uranium alkyl complexes were treated with substituted phosphine oxides, which provide electronic and steric modularity. Products were characterized via nuclear magnetic resonance (NMR), electronic absorption, and infrared spectroscopies. X-ray crystallographic data were obtained whenever possible. We observed the formation of a new carbon-carbon bond between the alkyl unit and phosphine oxide in a one-electron mechanism, while maintaining the U(III) oxidation state. This radical coupling was favored by electron-poor phosphine oxide and impeded by electron-rich analogs. The ability for the alkyl to form stable radicals drives the reaction forward. All attempts to capture the radical were unsuccessful, as the formation of the new uranium complexes appears to occur in concert with the homolytic cleavage of the U—C bond. To the best of our knowledge, such reactivity with phosphine oxides is unprecedented in the field of coordination chemistry

Estimating Prevalence, Demographics, and Costs of ME/CFS Using Large Scale Medical Claims Data and Machine Learning

Techniques of data mining and machine learning were applied to a large database of medical and facility claims from commercially insured patients to determine the prevalence, gender demographics, and costs for individuals with provider-assigned diagnosis codes for myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). The frequency of diagnosis was 519–1,038/100,000 with the relative risk of females being diagnosed with ME or CFS compared to males 1.238 and 1.178, respectively. While the percentage of women diagnosed with ME/CFS is higher than the percentage of men, ME/CFS is not a “women's disease.” Thirty-five to forty percent of diagnosed patients are men. Extrapolating from this frequency of diagnosis and based on the estimated 2017 population of the United States, a rough estimate for the number of patients who may be diagnosed with ME or CFS in the U.S. is 1.7 million to 3.38 million. Patients diagnosed with CFS appear to represent a more heterogeneous group than those diagnosed with ME. A machine learning model based on characteristics of individuals diagnosed with ME was developed and applied, resulting in a predicted prevalence of 857/100,000 (p > 0.01), or roughly 2.8 million in the U.S. Average annual costs for individuals with a diagnosis of ME or CFS were compared with those for lupus (all categories) and multiple sclerosis (MS), and found to be 50% higher for ME and CFS than for lupus or MS, and three to four times higher than for the general insured population. A separate aspect of the study attempted to determine if a diagnosis of ME or CFS could be predicted based on symptom codes in the insurance claims records. Due to the absence of specific codes for some core symptoms, we were unable to validate that the information in insurance claims records is sufficient to identify diagnosed patients or suggest that a diagnosis of ME or CFS should be considered based solely on looking for presence of those symptoms. These results show that a prevalence rate of 857/100,000 for ME/CFS is not unreasonable; therefore, it is not a rare disease, but in fact a relatively common one

A Bidentate Ligand Featuring Ditopic Lewis Acids in the Second Sphere for Selective Substrate Capture and Activation

We present a ligand platform featuring appended ditopic Lewis acids to facilitate capture/activation of diatomic substrates. We show that incorporation of two 9-borabicyclo[3.3.1]nonane (9-BBN) units on a single carbon tethered to a pyridine pyrazole scaffold maintains a set of unquenched nitrogen donors available to coordinate FeII, ZnII, and NiII. Using hydride ion affinity and competition experiments, we establish an additive effect for ditopic secondary sphere boranes, compared to the monotopic analogue. These effects are exploited to achieve high selectivity for binding NO2− in the presence of competitive anions such as F− and NO3−. Finally, we demonstrate hydrazine capture within the second-sphere of metal complexes, followed by unique activation pathways to generate hydrazido and diazene ligands on Zn and Fe, respectively.We report the synthesis of a bidentate ligand featuring secondary sphere ditopic Lewis acids. We verify a Lewis acid additivity effect for the ditopic boranes compared to a monotopic analogue using hydride ion affinity and competition studies. We show chemoselective nitrite capture in the presence of other anions. Pre-organized hydrazine adducts in the second sphere of Zn and Fe are functionalized to hydrazido and diazene ligands, respectively.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/176032/1/ange202218907.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/176032/2/ange202218907_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/176032/3/ange202218907-sup-0001-misc_information.pd

Hydrazine Capture and N–N Bond Cleavage at Iron Enabled by Flexible Appended Lewis Acids

Incorporation of two 9-borabicyclo[3.3.1]­nonyl substituents within the secondary coordination sphere of a pincer-based Fe­(II) complex provides Lewis acidic sites capable of binding 1 or 2 equiv of N₂H₄. Reduction of the 1:1 Fe:N₂H₄ species affords a rare Fe­(NH₂)₂ complex in which the amido ligands are stabilized through interactions with the appended boranes. The NH₂ units can be released as NH₃ upon protonation and exchanged with exogenous N₂H₄

Tailoring the Electronic Structure of Uranium Mono(imido) Species through Ligand Variation

Uranium mono­(imido) species have been prepared via the oxidation of Cp*U­(^MesPDI^Me)­(THF) (<b>1-Cp*</b>) and [Cp^PU­(^MesPDI^Me)]₂ (<b>1-Cp</b>^<b>P</b>), where Cp* = η⁵-1,2,3,4,5-pentamethylcyclopentadienide, Cp^P = 1-(7,7-dimethylbenzyl)­cyclopentadienide, ^MesPDI^Me = 2,6-[(Mes)­NCMe]₂C₅H₃N, and Mes = 2,4,6-trimethylphenyl, with organoazides. Treating either with N₃DIPP (DIPP = 2,6-diisopropylphenyl) formed uranium­(IV) mono­(imido) complexes, Cp^PU­(NDIPP)­(^MesPDI^Me) (<b>2-Cp</b>^<b>P</b>) and Cp*U­(NDIPP)­(^MesPDI^Me) (<b>2-Cp*</b>), featuring reduced [^MesPDI^Me]⁻. The addition of electron-donating 1-azidoadamantane (N₃Ad) to <b>1-Cp*</b> generated a dimeric product, [Cp*U­(NAd)­(^MesHPDI^Me)]₂ (<b>3</b>), from radical coupling at the <i>p</i>-pyridine position of the pyridine­(diimine) ligand and H-atom abstraction, formed through a monomeric intermediate that was observed in solution but could not be isolated. To support this, Cp*U­(^<i>t</i>Bu-^MesPDI^Me)­(THF) (<b>1-</b>^{<i><b>t</b></i>}<b>Bu</b>), which has a <i>tert</i>-butyl group protecting the <i>para</i> position, was also treated with N₃Ad, and the monomeric product, Cp*U­(NAd)­(^<i>t</i>Bu-^MesPDI^Me) (<b>2-</b>^{<i><b>t</b></i>}<b>Bu</b>), was isolated. All isolated complexes were analyzed spectroscopically and structurally, and the dynamic solution behavior was examined using electronic absorption spectroscopy

Hydrogen Bonds Dictate O₂ Capture and Release within a Zinc Tripod

Six directed hydrogen bonding (H-bonding) interactions allow for the reversible capture and reduction of dioxygen to a <i>trans</i>-1,2-peroxo within a tripodal zinc­(II) framework. Spectroscopic studies of the dizinc peroxides, as well as on model zinc diazides, suggest H-bonding contributions serve a dominant role for the binding/activation of these small molecules

A Uranium(IV) Triamide Species with Brønsted Basic Ligand Character: Metal–Ligand Cooperativity in the f Block

Deprotonation of the tridentate triamine ligand H₃N₃^Mes ((2,4,6-Me₃C₆H₂N­(H)­CH₂CH₂)₂NH) with 2 equiv of KCH₂Ph followed by treatment with 1 equiv of UCl₄ afforded the diamidoamine uranium complex (THF)₂UCl₂(HN₃^Mes) (<b>1-THF</b>). This species was further derivatized with either OPPh₃ or KCp* to generate (Ph₃PO)­UCl₂(HN₃^Mes) (<b>1-OPPh</b>_<b>3</b>) or Cp*UCl­(HN₃^Mes) (<b>2-Cl</b>), respectively. Deprotonation of <b>2-Cl</b> with ^<i>n</i>BuLi furnished the uranium­(IV) triamido compound Cp*U­(N₃^Mes-LiCl­(THF)₂) (<b>3-LiCl</b>), which is stabilized by the presence of LiCl. <b>3-LiCl</b> reacts readily with alcohols and thiols, including HOPh, HSPh, and HO^<i>t</i>Bu, to furnish the respective products Cp*U­(OPh)­(HN₃^Mes) (<b>2-OPh</b>), Cp*U­(SPh)­(HN₃^Mes) (<b>2-SPh</b>), and Cp*U­(O^<i>t</i>Bu)­(HN₃^Mes) (<b>2-O</b>^{<i><b>t</b></i>}<b>Bu</b>), which show cooperative addition of the H–E (E = O, S) bond across the U–N bond, serving to regenerate the diamidoamine ligand. Similar cooperative addition was noted for <b>3-LiCl</b> with benzophenone, furnishing Cp*U­(N₃^Mes-OCPh₂) (<b>3-OCPh</b>_<b>2</b>), which features new U–O and N–C bonds. The Brønsted basicity of the central nitrogen of <b>3-LiCl</b> was illustrated by addition of PhOAc, which favored α-carbon deprotonation over nucleophilic attack at the carbonyl. All species were subject to a complete spectroscopic and crystallographic analysis, confirming that the reactivity of <b>3-LiCl</b> in fact involves cooperation from the triamido ligand and uranium center

New Benzylpotassium Reagents and Their Utility for the Synthesis of Homoleptic Uranium(IV) Benzyl Derivatives

A new family of benzylpotassium reagents, KBn′(<b>1-Bn</b>′) (Bn′ = <i>p</i>-^<i>i</i>PrBn, <i>p</i>-^<i>t</i>BuBn, <i>p</i>-NMe₂Bn, <i>p</i>-SMeBn, <i>m-</i>OMeBn, <i>o-</i>OMeBn, 2-picolyl), was synthesized using a modified literature procedure and characterized by multinuclear NMR spectroscopy. Combining four equivalents of <b>1-Bn</b>′ with UCl₄ at low temperature in THF afforded the homoleptic uranium­(IV) derivatives <b>2-Bn</b>′ (<b>2-</b><i><b>p</b></i><b>-</b>^{<b><i>i</i></b>}<b>Pr</b>,<b> 2-</b><i><b>p</b></i><b>-</b>^{<b><i>t</i></b>}<b>Bu</b>,<b> 2-</b><i><b>p</b></i><b>-NMe</b>_<b>2</b>, <b>2-</b><i><b>p</b></i><b>-SMe</b>,<b> 2-</b><i><b>o</b></i><b>-Picolyl</b>, <b>2-</b><i><b>m</b></i><b>-OMe</b>, <b>2-</b><i><b>o</b></i><b>-OMe</b>). In addition to ¹H NMR spectroscopic characterization, structural studies of five of these organouranium compounds (<b>2-</b><i><b>p</b></i><b>-</b>^{<b><i>i</i></b>}<b>Pr</b>,<b> 2-</b><i><b>p</b></i><b>-</b>^{<b><i>t</i></b>}<b>Bu</b>,<b> 2-</b><i><b>o</b></i><b>-Picolyl</b>, <b>2-</b><i><b>m</b></i><b>-OMe</b>, <b>2-</b><i><b>o</b></i><b>-OMe</b>) were performed, showing that in many cases the benzyl groups are coordinated in an η⁴-fashion, lending stability to these otherwise low-coordinate molecules. In the cases of U­(<i>o-</i>OMeBn)₄ (<b>2-</b><i><b>o</b></i><b>-OMe</b>) and U­(2-picolyl)₄ (<b>2-</b><i><b>o</b></i><b>-Picolyl</b>), heteroatom coordination to the uranium center is observed

New Benzylpotassium Reagents and Their Utility for the Synthesis of Homoleptic Uranium(IV) Benzyl Derivatives

A new family of benzylpotassium reagents, KBn′(<b>1-Bn</b>′) (Bn′ = <i>p</i>-^<i>i</i>PrBn, <i>p</i>-^<i>t</i>BuBn, <i>p</i>-NMe₂Bn, <i>p</i>-SMeBn, <i>m-</i>OMeBn, <i>o-</i>OMeBn, 2-picolyl), was synthesized using a modified literature procedure and characterized by multinuclear NMR spectroscopy. Combining four equivalents of <b>1-Bn</b>′ with UCl₄ at low temperature in THF afforded the homoleptic uranium­(IV) derivatives <b>2-Bn</b>′ (<b>2-</b><i><b>p</b></i><b>-</b>^{<b><i>i</i></b>}<b>Pr</b>,<b> 2-</b><i><b>p</b></i><b>-</b>^{<b><i>t</i></b>}<b>Bu</b>,<b> 2-</b><i><b>p</b></i><b>-NMe</b>_<b>2</b>, <b>2-</b><i><b>p</b></i><b>-SMe</b>,<b> 2-</b><i><b>o</b></i><b>-Picolyl</b>, <b>2-</b><i><b>m</b></i><b>-OMe</b>, <b>2-</b><i><b>o</b></i><b>-OMe</b>). In addition to ¹H NMR spectroscopic characterization, structural studies of five of these organouranium compounds (<b>2-</b><i><b>p</b></i><b>-</b>^{<b><i>i</i></b>}<b>Pr</b>,<b> 2-</b><i><b>p</b></i><b>-</b>^{<b><i>t</i></b>}<b>Bu</b>,<b> 2-</b><i><b>o</b></i><b>-Picolyl</b>, <b>2-</b><i><b>m</b></i><b>-OMe</b>, <b>2-</b><i><b>o</b></i><b>-OMe</b>) were performed, showing that in many cases the benzyl groups are coordinated in an η⁴-fashion, lending stability to these otherwise low-coordinate molecules. In the cases of U­(<i>o-</i>OMeBn)₄ (<b>2-</b><i><b>o</b></i><b>-OMe</b>) and U­(2-picolyl)₄ (<b>2-</b><i><b>o</b></i><b>-Picolyl</b>), heteroatom coordination to the uranium center is observed