Pentamethylcyclopentadienyl Aminoborole Complexes of Hafnium

The tricyclophosphate ligand, (P₃O₉)³⁻, was investigated as an oxidation resistant ligand for ruthenium chemistry. The silver salt of tricyclophosphate, Ag₃(P₃O₉).H₂O, was found to be a useful synthon in the preparation of organic soluble tricyclophosphate salts. The complex [(P₃O₉)Ru(C₆H₆)]⁻ was prepared and characterized. In water, it was found that the tricyclophosphate ligand dissociated from the [(C₆H₆)Ru]²⁺ dication. Cyclic voltammatry in acetonitrile shows only a small irreversible oxidation at 0.95 V (Vs ferrocene). The rhenium carbonyl complex [(P₃O₉)Re(C0)₃]²⁻ was also investigated as a precursor to high valent tricyclophosphate rhenium complexes. Based on these results as well as related work by Klemperer and coworkers, it is concluded that the tricyclophosphate ligand is an exceptionally hard one that binds only weakly to transition metals. The preparations of chloro and allyl derivatives of pentamethylcyclopentadienyl aminoborole hafnium complexes are described. The chloro derivative, Cp*[C₄H₄BN(CHMe₂)₂]HfCl•LiCl, is prepared by treatment of Cp*HfCl₃ with Li₂(THF){C₄H₄BN(CHMe₂)₂}. The structures of the chloro derivatives Cp*[C₄H₄BN(CHMe₂)₂]HfCl•LiCl(Et₂O)₂ and {Cp*[C₄H₄BN(CHMe₂)₂]HfCl-LiCl}₂ were determined by single crystal X-ray analysis. Treatment of Cp*[C₄H₄BN(CHMe₂)₂]HfCl•LiCl with allyl magnesium bromide yields Cp*[C₄H₄BN(CHMe₂)₂]Hf(η³-C₃H₅), whose structure was determined by X-ray analysis. The allyl species was active for the polymerization of ethylene, but not for the polymerization of α-olefins. Addition of ligands to the allyl derivative results in the formation of Cp*[C₄H₄BN(CHMe₂)₂]Hf(C₃H₅)(L) (L = PMe₃, pyridine, CO). The structure of Cp*[C₄H₄BN(CHMe₂)₂]Hf(η³-C₃H₅)(CO) was determined. Treatment of Cp*[C₄H₄BN(CHMe₂)₂]Hf(η³-C₃H₅)(CO) with PMe₃ results in the formation of the dieneolate complex Cp*[C₄H₄BN(CHMe₂)₂]Hf(OCHCHCHCH₂) (PMe₃). The electronic spectra of several aminoborole complexes were investigated and the low energy transitions assigned as borole-metal LMCT transitions. The amphoteric complex Cp*{η⁵-C₄H₄BN(CHMe₂)₂}HfCl•LiCl heterolytically cleaves H-X bonds to form Cp*{η⁵-C₄H₄BNH(CHMe₂)₂}HfCl(X) (X = Cl, CCR). Cp*{η⁵-C₄H₄BNH(CHMe₂)₂}Hf(CCTMS)₂ is prepared from Cp*{η⁵-C₄H₄BN(CHMe₂)₂}Hf(η³-C₃H₅) and two equivalents of (trimethylsilyl)acetylene. Methyl iodide reacts with Cp{η⁵-C₄H₄BN(CHMe₂)₂}HfCl•LiCl to form Cp*{η⁵-C₄H₃MeBNH(CHMe₂)₂}HfClI. Control experiments using deuterium labelled substrates show heterolysis occurs with no incorporation of deuterium into the 2,5 positions of the borole heterocycle. The X-ray structure determinations of Cp*{η⁵-C₄H₄BNH(CHMe₂)₂}HfCl₂, Cp*{η⁵-C₄H₄BNH(CHMe₂)₂}HfCl(CCTMS), and Cp*{η⁵-C₄H₃MeBN(CHMe₂)₂}HfClI are reported.</p

Heterolysis of H−X Bonds by Pentamethylcyclopentadienyl−Aminoborole Complexes of Zirconium and Hafnium

The pentamethylcyclopentadienyl−aminoborole chloro complexes Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl·LiCl (Cp* = (η^5-C_5Me_5); M = Zr, Hf) heterolytically cleave H−X bonds to form Cp*{η^5-C_4H_4BNH(CHMe_2)_2}MCl(X) (X = OR, SR, C⋮CR). Control experiments using deuterium-labeled substrates show heterolysis occurs with no incorporation of deuterium into the 2,5 positions of the borole heterocycle. Cp*{η^5-C_4H_4BNH(CHMe_2)_2}Hf(C⋮CSiMe_3)_2 is prepared from Cp*{η^^5-C_4H_4BN(CHMe_2)_2}Hf(η^3-C_3H_5) and 2 equiv of (trimethylsilyl)acetylene. Treatment of Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl·LiCl (M = Zr, Hf) with donor ligands L yields the LiCl-free complexes Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl(L) (M = Zr, L = NMe2H; M = Hf, L = PMe_3). Cp*{η^5-C_4H_4BN(CHMe_2)_2}HfCl(PMe_3) reacts with (trimethylsilyl)acetylene with loss of HN(CHMe_2)_2 to form Cp*{η^5-C_4H_4B(C⋮CSiMe_3)}HfCl(PMe_3), resulting from formal migration of acetylide from hafnium to boron. X-ray structure determinations of Cp*{η^5-C_4H_4BNH(CHMe_2)_2}HfCl(C⋮CSiMe_3), Cp*{η^5-C_4H_4BN(CHMe_2)_2}HfCl(PMe_3), and Cp*{η^5-C_4H_4B(C⋮CSiMe_3)}HfCl(PMe_3) are reported

Pentamethylcyclopentadienyl Aminoborollide Derivatives of Zirconium and Hafnium: A New Class of Amphoteric Molecule Having Both Lewis Acidic and Lewis Basic Sites

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Pentamethylcyclopentadienyl Aminoborollide Derivatives of Zirconium and Hafnium: A New Class of Amphoteric Molecule Having Both Lewis Acidic and Lewis Basic Sites

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Heterolysis of H−X Bonds by Pentamethylcyclopentadienyl−Aminoborole Complexes of Zirconium and Hafnium

The pentamethylcyclopentadienyl−aminoborole chloro complexes Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl·LiCl (Cp* = (η^5-C_5Me_5); M = Zr, Hf) heterolytically cleave H−X bonds to form Cp*{η^5-C_4H_4BNH(CHMe_2)_2}MCl(X) (X = OR, SR, C⋮CR). Control experiments using deuterium-labeled substrates show heterolysis occurs with no incorporation of deuterium into the 2,5 positions of the borole heterocycle. Cp*{η^5-C_4H_4BNH(CHMe_2)_2}Hf(C⋮CSiMe_3)_2 is prepared from Cp*{η^^5-C_4H_4BN(CHMe_2)_2}Hf(η^3-C_3H_5) and 2 equiv of (trimethylsilyl)acetylene. Treatment of Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl·LiCl (M = Zr, Hf) with donor ligands L yields the LiCl-free complexes Cp*{η^5-C_4H_4BN(CHMe_2)_2}MCl(L) (M = Zr, L = NMe2H; M = Hf, L = PMe_3). Cp*{η^5-C_4H_4BN(CHMe_2)_2}HfCl(PMe_3) reacts with (trimethylsilyl)acetylene with loss of HN(CHMe_2)_2 to form Cp*{η^5-C_4H_4B(C⋮CSiMe_3)}HfCl(PMe_3), resulting from formal migration of acetylide from hafnium to boron. X-ray structure determinations of Cp*{η^5-C_4H_4BNH(CHMe_2)_2}HfCl(C⋮CSiMe_3), Cp*{η^5-C_4H_4BN(CHMe_2)_2}HfCl(PMe_3), and Cp*{η^5-C_4H_4B(C⋮CSiMe_3)}HfCl(PMe_3) are reported

Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation

Background: We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson’s disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. Results: All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant α-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal α-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had α-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated α-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Conclusions: Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication

RACK-1 Acts with Rac GTPase Signaling and UNC-115/abLIM in Caenorhabditis elegans Axon Pathfinding and Cell Migration

Migrating cells and growth cones extend lamellipodial and filopodial protrusions that are required for outgrowth and guidance. The mechanisms of cytoskeletal regulation that underlie cell and growth cone migration are of much interest to developmental biologists. Previous studies have shown that the Arp2/3 complex and UNC-115/abLIM act redundantly to mediate growth cone lamellipodia and filopodia formation and axon pathfinding. While much is known about the regulation of Arp2/3, less is known about regulators of UNC-115/abLIM. Here we show that the Caenorhabditis elegans counterpart of the Receptor for Activated C Kinase (RACK-1) interacts physically with the actin-binding protein UNC-115/abLIM and that RACK-1 is required for axon pathfinding. Genetic interactions indicate that RACK-1 acts cell-autonomously in the UNC-115/abLIM pathway in axon pathfinding and lamellipodia and filopodia formation, downstream of the CED-10/Rac GTPase and in parallel to MIG-2/RhoG. Furthermore, we show that RACK-1 is involved in migration of the gonadal distal tip cells and that the signaling pathways involved in this process might be distinct from those involved in axon pathfinding. In sum, these studies pinpoint RACK-1 as a component of a novel signaling pathway involving Rac GTPases and UNC-115/abLIM and suggest that RACK-1 might be involved in the regulation of the actin cytoskeleton and lamellipodia and filopodia formation in migrating cells and growth cones

Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention