Facile Synthetic Access Towards Sulfur- and Selenium-Functionalized Boron-Based Multiresonance TADF Emitters.

Thermally activated delayed fluorescence (TADF) materials with high photoluminescence quantum yields and a fast reverse intersystem crossing (RISC) are of the highest interest for organic light-emitting diodes (OLEDs). In the past decade, triaryl boranes with multiple resonance effect (MR) have captured significant attention. The efficiency of MR-TADF emitters strongly depends on small singlet-triplet energy gaps (ΔE), but also on large reverse intersystem crossing (RISC) rate constants (k).

Gold(i) and gold(iii) carbene complexes from the marine betaine norzooanemonin: inhibition of thioredoxin reductase, antiproliferative and antimicrobial activity.

The natural marine betaine norzooanemonin (1,3-dimethylimidazolim-4-carboxylate) and its methyl and ethyl esters were used as ligand precursors to prepare a systematic series (12 members) of neutral monocarbene gold(i/iii) and cationic dicarbene gold(i/iii) complexes. The complexes were evaluated as inhibitors of bacterial thioredoxin reductase and for their antiproliferative and antimicrobial activities. While gold complexes with the parent norzooanemonin scaffold resulted in overall poor performance, the more lipophilic esters proved to be highly bioactive agents, related to their higher cellular uptake.

CryoET of β-amyloid and tau within postmortem Alzheimer's disease brain.

A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the deposition of β-amyloid and tau with disease-specific conformations. The in situ structure of amyloid in the human brain is unknown.

Synthesis of N-heterocyclic carbene gold(I) complexes from the marine betaine 1,3-dimethylimidazolium-4-carboxylate.

The marine natural product norzooanemonin (1,3-dimethylimidazolium-4-carboxylate) has been used to prepare a series of carboxyl- or carboxylate-functionalized N-heterocyclic carbene (NHC) gold(I) complexes from [(MeS)AuCl] in the presence of potassium carbonate. The potential of the resulting mono- and dicarbene complexes to act as cytotoxic or antibacterial drugs was investigated.

Iminoboranes With Parent B=NH Entity: Imino Group Metathesis, Nucleophilic Reactivity and N-N Coupling.

While R C=N-R double bonds in organic imines are well established, the related iminoboranes R-B=N-R are either prone to oligomerization or can only be stabilized at sufficient steric congestion. In particular, the examples of unsubstituted parent B=N-H entity are rare. We demonstrate that the amino imidazoline-2-imine ligand system (HAmIm) not only gives rise to the isolation of a parent (AmIm)B=N-H iminoborane, but also to species of type (AmIm)B=N-SiMe with concomitant stabilization by lithium bromide.

The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain.

Amyloid plaques composed of Aβ fibrils are a hallmark of Alzheimer's disease (AD). However, the molecular architecture of amyloid plaques in the context of fresh mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the in situ molecular architecture of Aβ fibrils in the App familial AD mouse model containing the Arctic mutation and an atomic model of ex vivo purified Arctic Aβ fibrils.

Bridging length scales from molecules to the whole organism by cryoCLEM and cryoET.

Resolving atomic structures of isolated proteins has uncovered mechanisms and fundamental processes in biology. However, many functions can only be tested in the context of intact cells and tissues that are many orders of magnitude larger than the macromolecules on which they depend. Therefore, methods that interrogate macromolecular structure provide a means of directly relating structure to function across length scales.

Reductive Al-B σ-Bond Formation in Alumaboranes: Facile Scission of Polar Multiple Bonds.

We present facile access to an alumaborane species with electron precise Al-B σ-bond. The reductive rearrangement of 1-(AlI ), 8-(BMes ) naphthalene (Mes=2,4,6-Me C H ) affords the alumaborane species cyclo-(1,8-C H )-[1-Al(Mes)(OEt )-8-B(Mes)] with a covalent Al-B σ-bond. The Al-B σ-bond performs the reductive scission of multiple bonds: S=C(NiPrCMe) affords the naphthalene bridged motif B-S-Al(NHC), NHC=N-heterocyclic carbene, while O=CPh is deoxygenated to afford an B-O-Al bridged species with incorporation of the remaining ≡CPh fragment into the naphthalene scaffold.

Reactions of a Four-Membered Borete with Carbon, Silicon, and Gallium Donor Ligands: Fused and Spiro-Type Boracycles.

Donor-acceptor cyclopropanes or cyclobutanes are dipolar reagents, which are widely used in the synthesis of complex organic (hetero)cycles in ring expansion reactions. Applying this concept to boron containing heterocycles, the four-membered borete cyclo-iPr N-BC H reacted with the carbon donor ligands 2,6-xylylisonitrile and the carbene IMes :C(NMesCH) with ring expansion and ring fusion, respectively. In particular, the tetracyclic structure formed with IMes displays zwitterionic character and absorption in the visible region.

Multidimensional Dynamics of the Proteome in the Neurodegenerative and Aging Mammalian Brain.

The amount of any given protein in the brain is determined by the rates of its synthesis and destruction, which are regulated by different cellular mechanisms. Here, we combine metabolic labeling in live mice with global proteomic profiling to simultaneously quantify both the flux and amount of proteins in mouse models of neurodegeneration. In multiple models, protein turnover increases were associated with increasing pathology.

Correction: "Give me five"- an amino imidazoline-2-imine ligand stabilises the first neutral five-membered cyclic triel(i) carbenoids.

Correction for '"Give me five"- an amino imidazoline-2-imine ligand stabilises the first neutral five-membered cyclic triel(i) carbenoides' by Lars Denker et al., Chem. Commun.

"Give me five" - an amino imidazoline-2-imine ligand stabilises the first neutral five-membered cyclic triel(I) carbenoides.

We present the first cyclic five-membered triel(i) carbenoides E(AmIm) for E = Ga, In, Tl; AmIm = amido imidazoline-2-imine, which fill the current gap between four- and six-membered triel(i) carbenoides supported by HGiso and HNacNac. Ga(AmIm) can act as a strong σ-donor ligand in transition metal complexes, while the intermediacy of the Al(i) carbenoide Al(AmIm) is rationalised based on the isolation of an Al(iii) insertion product.

Superseding β-Diketiminato Ligands: An Amido Imidazoline-2-Imine Ligand Stabilizes the Exhaustive Series of B=X Boranes (X=O, S, Se, Te).

Boron reluctantly forms B=X (X=O, S, Se, Te) moieties, which has stimulated the quest for such species in the past few years. Based on the N,N'-chelating β-diketiminato ligand (HNacNac), a new amido imidazoline-2-imine ligand system (HAmIm) is presented, giving rise to the isolation of an exhaustive series of Lewis acid free, monomeric chalcogen B=X boranes with documented π-bond character between boron and the chalcogen. The chalcogenoboranes are isoelectronic and isolobal to the respective ketones.

Two π-Electrons Make the Difference: From BODIPY to BODIIM Switchable Fluorescent Dyes.

(aza-)BODIPY dyes (boron dipyrromethene dyes) are well-established fluorophores due to their large quantum yields, stability, and diversity, which led to promising applications including imaging techniques, sensors, organic (opto)electronic materials, or biomedical applications. Although the control of the optical properties in (aza-)BODIPY dyes by peripheral functional groups is well studied, we herein present a novel approach to modify the 12 π-electron core of the dipyrromethene scaffold. The replacement of two carbon atoms in the β-position of a BODIPY dye by two nitrogen atoms afforded a 14 π-electron system, which was termed BODIIM (boron diimidazolylmethene) in systematic analogy to the BODIPY dyes.

Benzyl Borane NHC Adducts: Beyond B-C Bond Scission.

Benzyl-substituted boronates and borates are widely employed as mild sources in radical or anionic transfer reactions of benzyl entities. In this process the B-C bond to the benzyl moiety is essentially ruptured. In contrast, reactions with retention of the B-C bond are poorly investigated although several other reactive sites in benzyl-boron systems are clearly inherent.

-Heterocyclic Carbene Adducts of Alkynyl Functionalized 1,3,2-Dithioborolanes.

Alkynyl functionalized boron compounds are versatile intermediates in the areas of medicinal chemistry, materials science, and optical materials. In particular, alkynyl boronate esters [R-C≡C-B(OR)] are of interest since they provide reactivity at both the alkyne entity, with retention of the B-C bond or alkyne transfer to electrophilic substrates with scission of the latter. The boron atom is commonly well stabilized due to (i) the extraordinary strength of two B-O bonds, and (ii) the chelate effect exerted by a bifunctional alcohol.

A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits.

Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of actin polymerization during CME.

Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence.

Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice.

Completing the series of boron-nucleophilic cyanoborates: boryl anions of type NHC-B(CN).

Since the first seminal report of boron-centred nucleophiles, the area of boryl anions has developed only sporadically and requires further systematisation. The boryl anions of type NHC-B(CN) (NHC = N-heterocyclic carbene) described herein complete a consistent series with the known anions cAAC-B(CN) [cAAC = cyclic(alkyl)(amino)carbene] and B(CN). A novel approach towards NHC-stabilised cyanoboranes based on alkylthio-cyano exchange at boron is presented, and in contrast to other methods affords the products in better purity and yield.

Supramolecular organization of NMDA receptors and the postsynaptic density.

The postsynaptic density (PSD) of all vertebrate species share a highly complex proteome with ∼1000 conserved proteins that function as sophisticated molecular computational devices. Here, we review recent studies showing that this complexity can be understood in terms of the supramolecular organization of proteins, which self-assemble within a hierarchy of different length scales, including complexes, supercomplexes and nanodomains. We highlight how genetic and biochemical approaches in mice are being used to uncover the native molecular architecture of the synapse, revealing hitherto unknown molecular structures, including highly selective mechanisms for specifying the assembly of NMDAR-MAGUK supercomplexes.

Hierarchical organization and genetically separable subfamilies of PSD95 postsynaptic supercomplexes.

PSD95 is an abundant postsynaptic scaffold protein in glutamatergic synapses that assembles into supercomplexes composed of over 80 proteins including neurotransmitter receptors, ion channels and adhesion proteins. How these diverse constituents are organized into PSD95 supercomplexes in vivo is poorly understood. Here, we dissected the supercomplexes in mice combining endogenous gene-tagging, targeted mutations and quantitative biochemical assays.